“Progressive loss of brain gray matter (GM) has been reported in childhood-onset schizophrenia; however, it is uncertain whether these changes are shared by pediatric patients with different psychoses,” the authors write as background information in the study.

Researchers examined the progression of brain changes in first-episode early-onset psychosis and the relationship to diagnosis and prognosis at two-year follow-up among patients at six child and adolescent psychiatric units in Spain. The authors performed magnetic resonance imaging (MRI) of the brain for 61 patients (25 diagnosed with schizophrenia, 16 with bipolar disorder and 20 with other psychoses) and 70 healthy control participants. MRI scans were conducted at study baseline and after two years of follow-up.

Compared with control patients, those diagnosed with schizophrenia showed greater gray matter volume loss in the frontal lobe during the two-year follow-up. Patients with schizophrenia also showed cerebrospinal fluid increase in the left frontal lobe. Additionally, changes for total brain gray matter and left parietal gray matter were significantly different in patients with schizophrenia compared with patients in the control group.

Among patients with schizophrenia, progressive brain volume changes in certain areas were related to markers of poorer prognosis, such as more weeks of hospitalization during follow-up and less improvement in negative symptoms. Greater left frontal gray matter volume loss was related to more weeks of hospitalization whereas severity of negative symptoms correlated with cerebrospinal fluid increase in patients with schizophrenia.

The authors did not find any significant changes in patients with bipolar disorder compared to control patients, and longitudinal brain changes in the control group were consistent with the expected pattern described for healthy adolescents.

“In conclusion, we found progression of gray matter volume loss after a two-year follow-up in patients who ended up with a diagnosis of schizophrenia but not bipolar disease compared with healthy controls,” the authors write. “Some of these pathophysiologic processes seem to be markers of poorer prognosis. To develop therapeutic strategies to counteract these pathologic progressive brain changes, future studies should focus on their neurobiological underpinnings.”

Material adapted from American Medical Association (AMA).

Reference
Arch Gen Psychiatry. 2012;69[1]:16-26.

The authors used functional MRI images to study each participant on three occasions after administration of Δ9-THC, CBD, or placebo. Study participants performed a visual oddball task of pressing buttons according to the direction arrows on a screen were pointing, as a measure of attentional salience processing.

“Pairwise comparisons revealed that Δ9-THC significantly increased the severity of psychotic symptoms compared with placebo and CBD whereas there was no significant difference between the CBD and placebo conditions,” the authors conclude.

Δ9-THC had a greater effect than placebo on reaction time to nonsalient relative to salient stimuli. This was associated with modulation of both prefrontal and striatal function by Δ9-THC, augmenting (increasing) activation in the former region and attenuating (weakening) it in the latter.

“Moreover, in the present study, the magnitude of Δ9-THC’s effect on response times to nonsalient stimuli was correlated with its effect on activation in the right caudate, the region where the physiological effect of Δ9-THC was linked to its induction of psychotic symptoms,” the authors write.

They conclude that “collectively, these observations suggest that Δ9-THC may increase the aberrant attribution of salience and induce psychotic symptoms through its effects on the striatum and lateral prefrontal cortex.”

When the effects of CBD were contrasted with Δ9-THC and placebo with respect to the visual task there was a “significant effect” in the left caudate with CBD augmenting (increasing) the response and Δ9-THC attenuating (weakening) it.

“These effects suggest that CBD may also influence the effect of cannabis use on salience processing – and hence psychotic symptoms – by having an opposite effect, enhancing the appropriate response to salient stimuli,” the authors wrote.

Material adapted from Archives of General Psychiatry.

Reference
Arch of Gen Psychiatry. 2012;69[1]:27-36)

Previous fMRI studies that scanned the brains of soldiers exposed to violent combat situations have shown the same pattern of heightened activation in these two areas of the brain, which are associated with threat detection. The authors suggest that both maltreated children and soldiers may have adapted to be ‘hyper-aware’ of danger in their environment.

However, the anterior insula and amygdala are also areas of the brain implicated in anxiety disorders. Neural adaptation in these regions may help explain why children exposed to family violence are at greater risk of developing anxiety problems later in life.

Dr. Eamon McCrory, lead author from the UCL Division of Psychology and Language Sciences and the Anna Freud Centre, said: “We are only now beginning to understand how child abuse influences functioning of the brain’s emotional systems. This research is important because it provides our first clues as to how regions in the child’s brain may adapt to early experiences of abuse in the home”.

Dr. McCrory added: “All the children studied were healthy and none were suffering from a mental health problem. What we have shown is that exposure to family violence is associated with altered brain functioning in the absence of psychiatric symptoms and that these alterations may represent an underlying neural risk factor. We suggest these changes may be adaptive for the child in the short term but may increase longer term risk”.

In the study, which is published in the journal Current Biology, 43 children had their brains scanned using an fMRI scanner. 20 children who had been exposed to documented violence at home were compared with 23 matched peers who had not experienced family violence. The average age of the maltreated children was 12 years old and they had all been referred to local social services in London.

When the children were in the scanner they were presented with pictures of male and female faces showing sad, calm or angry expressions. The children had only to decide if the face was male or female – processing the emotion on the face was incidental. As described, the children who had been exposed to violence at home showed increased brain activity in the anterior insula and amygdala in response to the angry faces.

Professor Peter Fonagy, Chief Executive of the Anna Freud Centre and professor of psychology at UCL, said: “Dr McCrory’s groundbreaking research has undoubtedly taken us an important step closer to understanding the devastation which exposing children to violence can leave in its wake. His exciting findings confirm the traumatic effects these experiences have on brain development.

Professor Fonagy added: “The report should energize clinicians and social workers to double their efforts to safeguard children from violence. By helping us understand the consequences of maltreatment the findings also offer fresh inspiration for the development of effective treatment strategies to protect children from the consequences of maltreatment.”

Dr. McCrory said: “Even though we know that maltreatment represents one of the most potent environmental risk factors associated with anxiety and depression, relatively little is known how such adversity ‘gets under the skin’ and increases a child’s later vulnerability.”

“The next step for us is to try and understand how stable these changes are. Not every child exposed to family violence will go on to develop a mental health problem; many bounce back and lead successful lives. We want to know much more about those mechanisms that help some children become resilient.”

Material adapted from University College London.

“The ability to identify people who are not showing memory problems and other symptoms but may be at a higher risk for cognitive decline is a very important step toward developing new ways for doctors to detect Alzheimer’s disease,” said Susan Resnick, PhD, with the National Institute on Aging in Baltimore, who wrote an accompanying editorial.

For the study, researchers used brain scans to measure the thickness of regions of the brain’s cortex in 159 people free of dementia with an average age of 76. The brain regions were chosen based on prior studies showing that they shrink in patients with Alzheimer’s dementia. Of the 159 people, 19 were classified as at high risk for having early Alzheimer’s disease due to smaller size of particular regions known to be vulnerable to Alzheimer’s in the brain’s cortex, 116 were classified as average risk and 24 as low risk. At the beginning of the study and over the next three years, participants were also given tests that measured memory, problem solving and ability to plan and pay attention.

The study found that 21 percent of those at high risk experienced cognitive decline during three years of follow-up after the MRI scan, compared to seven percent of those at average risk and none of those at low risk.

“Further research is needed on how using MRI scans to measure the size of different brain regions in combination with other tests may help identify people at the greatest risk of developing early Alzheimer’s as early as possible,” said study author Bradford Dickerson, MD, of Massachusetts General Hospital in Boston and a member of the American Academy of Neurology.

The study also found 60 percent of the group considered most at risk for early Alzheimer’s disease had abnormal levels of proteins associated with the disease in cerebrospinal fluid, which is another marker for the disease, compared to 36 percent of those at average risk and 19 percent of those at low risk.

The study, performed by Dickerson and collaborator David Wolk, MD, of University of Pennsylvania in Philadelphia and a member of the AAN, using data collected as part of the Alzheimer’s Disease Neuroimaging Initiative, was supported by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (both part of the National Institutes of Health), Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., the Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration and the Dana Foundation. Funding for this particular data analysis came from the NIA and the Alzheimer’s Association.

Material adapted from American Academy of Neurology (AAN).

“Patients with Parkinson disease (PD) are at an increased risk of developing dementia (PDD), with cumulative prevalence rates of up to 80 percent,” the authors write as background information in the article. “Approximately 25 percent of non-demented PD patients meet neuropsychological criteria for mild cognitive impairment (PD-MCI), which converts to PDD in many cases, and even mild cognitive deficits in PD are associated with functional impairments and worse quality of life.”

Researchers sought to assess the regions and patterns of brain atrophy in patients with PD with normal cognition (PD-NC), patients with PD with mild cognitive impairment (PD-MCI) and patients with PD with dementia-level cognitive deficits (PDD). Data were collected as part of the University of Pennsylvania Center of Excellence for Research on Neurodegenerative Diseases, and the study population included 84 patients with PD (61 PD-NC, 12 PD-MCI and 11 PDD) and 23 healthy control individuals, who all underwent magnetic resonance imaging (MRI) of the brain.

After controlling for other factors (such as patient age, sex and education level), the authors found no between-group differences in regional brain volumes for PD-NC patients compared with participants in the control group. Among patients with PD, there were cognitive group-level differences in hippocampal and medial temporal lobe volumes. Patients in the PD-MCI and PDD groups had smaller hippocampal volumes compared with PD-NC patients, but no differences were observed between patients in the PD-MCI and PDD groups. Patients in the PDD group, but not patients in the PD-MCI group, also had medial temporal lobe atrophy compared with patients in the PD-NC group. The authors found no between-group differences for other brain regions.

Patients in the PD-MCI group had a different pattern of brain atrophy compared to patients in the PD-NC group, but was similar to that of PDD patients. This pattern was characterized by atrophy in hippocampal volume, prefrontal cortex gray and white matter, occipital lobe gray and white matter, and parietal lobe white matter. In non-demented PD patients, the authors found a correlation between memory-encoding performance and hippocampal volume, “suggesting heterogeneity in the neural substrate of memory impairment.”

“With growing recognition of Parkinson disease with mild cognitive impairment as common and clinically significant, it will be important to develop consensus diagnostic criteria, validate assessment instruments for use in clinical care and research, and test treatments for their symptomatic and disease-modifying effects,” the authors conclude. “Use of a pattern classification approach may allow identification of diffuse regions of cortical gray and white matter atrophy early in the course of cognitive decline.”

Material adapted from JAMA.

Reference
Arch Neurol. 2011;[12]:1562-1568).

“An estimated 3.7 million children are assessed for childhood maltreatment (CM) each year in the United States; because many cases do not come to professional attention, this likely is an underestimate of the number of children experiencing maltreatment,” the authors write as background information in the article. “Converging data support adverse effects of early life stress on morphologic development of corticostriatal-limbic structures. Magnetic resonance imaging studies show decreased corticostriatal-limbic gray matter volume in children and adults reporting exposure to CM.”

Erin E. Edmiston, B.A., then of Yale University, New Haven, Conn., now with Vanderbilt University, Nashville, Tenn., and colleagues compiled data on 42 adolescents (age range 12 to 17 years) without a psychiatric diagnosis to examine the association between exposure to childhood maltreatment and cerebral gray matter volume abnormalities. Participants were recruited from a sample of children identified at birth to be at high risk for CM, and additional participants were also recruited to allow for a sample of adolescents reporting a spectrum of CM severity. Data were collected through a self-report questionnaire, and included questions related to five subtypes of CM: physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse.

Self-reported scores on the Childhood Trauma Questionnaire (CTQ) were associated with a negative correlation with cerebral gray matter volume in the prefrontal cortex, striatum, amygdala, sensory association cortices and cerebellum. The authors also found that self-reported physical abuse, physical neglect and emotional neglect subtypes of CM were all associated with reductions in gray matter volume of the rostral prefrontal cortex. No significant results were found for emotional abuse or for sexual abuse.

“Although preliminary, results of exploratory analyses support prominent reductions in prefrontal cortex volume common across physical abuse, physical neglect, and emotional neglect CM subtypes, as well as patterns of additional regional gray matter volume decreases in the CM subtypes,” the authors write. “Findings in girls were in regions associated with emotion regulation, whereas findings in boys were in regions subserving impulse control.”

“Together, these results highlight the critical need for improved understanding of effects of childhood abuse and neglect in adolescents and of possible differences in the effects of different CM subtypes on brain development,” the authors conclude. “Although adolescents with a history of CM may have symptoms and behaviors that may not yet meet criteria for psychiatric diagnoses, detection and early intervention may help improve functioning and reduce risk for the development of mood, addictive, and other psychiatric disorders.”

Material adapted from JAMA.

Reference
Arch Pediatr Adolesc Med. 2011;165[12]:1069-1077.

In the first reported study of 3D-TV and children with epilepsy, researchers at the University of Munich, Germany and the University of Salzburg, Austria, exposed 140 consecutive young patients (median age 12) to a standard test for photosensitivity, called photo-paroxysmal stimulation, and to 15 minutes of 3D-TV viewing. The viewing was on a 50” 3D-Plasma TV with 3D shutter glasses at a distance of about two meters (approx. six and one-half feet). Responses to the two forms of stimulation were recorded on an EEG and evaluated by two independent professionals.

“In our cohort of children with a risk of epilepsy or with known epilepsy fifteen minutes of 3D television viewing did not increase epileptiform activity on EEG, nor were there any apparent seizures,” says lead author Herbert Plischke. “We conclude that the chance for people with undiagnosed epilepsy to have an epileptic seizure provoked by 3D-TV is unlikely.”

Seizures that are provoked by television appear not to be a matter of technology, according to the investigators, but a matter of content, for example, color, contrast, pattern, and flicker, independent of whether the viewing medium is a 2D- or 3D-TV. A significant number of patients (20%) did present with other symptoms like nausea, headache and dizziness.

Material adapted from American Epilepsy Society (AES).

Research Director David Amaral and Assistant Professor Christine Wu Nordahl

The study was led by Christine Wu Nordahl, a researcher at the UC Davis MIND Institute and an assistant professor in the Department of Psychiatry and Behavioral Sciences and David G. Amaral, Beneto Foundation Chair, MIND Institute Research Director and University of California Distinguished Professor in the Department of Psychiatry and Behavioral Sciences.

“The finding that boys with regressive autism show a different form of neuropathology than boys with early onset autism is novel,” Nordahl said. “Moreover, when we evaluated girls with autism separately from boys, we found that no girls – regardless of whether they had early onset or regressive autism – had abnormal brain growth.”

Brain enlargement has been observed in previous studies of autism. However, prior to this study, little was known about how many and which children with autism have abnormally large brains.

“This adds to the growing evidence that there are multiple biological subtypes of autism, with different neurobiological underpinnings,” Amaral said.

Autism is a neurodevelopmental disorder whose symptoms include deficits in language and social interaction and communication. The condition affects 1 in 110 children born today, according to the U.S. Centers for Disease Control and Prevention. It is diagnosed more frequently in male children than female children – at a ratio of 4 to 1.

The current study is one of the first published from data collected by the UC Davis MIND Institute Autism Phenome Project (APP). The project’s goal is to recruit and enroll as many very young children as possible in order to collect sufficient biological and behavioral information to characterize different autism subgroups and to explore different neural, immunologic, and genetic signatures of autism.

For the study, the authors enrolled a total of 180 children between age 2 and 4. One hundred and fourteen of the participants had autism spectrum disorder; the remaining participants were 66 age-matched typically developing controls. Of the children with autism, 54 percent were diagnosed with the regressive form and 46 with the non-regressive type.

The researchers collected magnetic resonance imaging (MRI) scans on 180 participants at age 3. To evaluate the rate of brain growth prior to age 3, they analyzed head circumference measurements taken from pediatric well-baby visits from birth through 18 months. Roughly half of the children with autism were reported by their parents as having experienced a regression, characterized by the loss of previously acquired language and social skills.

The MRIs were carried out on study participants during natural, nighttime sleep using protocols developed specifically for the Autism Phenome Project by Nordahl.

“Obtaining MRI scans in 3-year-old children without the use of sedation may seem quite challenging. But, by working closely with the parents, we actually were successful more than 85 percent of the time. Patience on the part of everyone and the dedication of the families was critical for our success,” Nordahl said.

The study found that accelerated head growth and brain enlargement was consistently observed only in the subset of children diagnosed with regressive autism. Specifically, total brain volume in 3-year-old males with regressive autism was more than 6 percent larger than that of age-matched typically developing peers. Twenty-two percent of boys with regressive autism, as opposed to 5 percent of boys without regressive autism, had enlarged brains, the study found.

Changes in brain size were not apparent in boys who did not experience a regression. Girls with autism, regardless of autism onset status, also did not show abnormal brain growth. The study findings suggest that abnormalities in overall brain growth are specific to male children with the regressive type of autism, and that rapid brain growth may be a risk factor for regression, the researchers said.

While brain size was clearly larger at age 3, the study also determined when the precocious growth began, by examining records of head circumference that provides a reasonable estimate of brain size in young children. These analyses clearly indicated that brain growth diverged from normal at around 4 to 6 months of age. This is of particular interest, because many families believe that the trigger that led to their child’s regression took place close to the time that the regression happened. But the data reported in this paper indicate that the process leading to the enlarged brain, which presumably also is associated with the onset of autism, started when the child was a newborn.

Much remains to be elucidated regarding brain changes associated with autism, the authors note. In the current study, not all boys with regression demonstrate the precocious brain growth. The investigative team also continues efforts to define the underlying brain pathology in children with early onset autism and in girls with autism.

“It is not clear how many different types of autism will be identified,” Amaral said. “The purpose of defining different types of autism is to more effectively study the cause of each type and eventually determine effective preventative measures and better, individualized treatments. This is a first step in defining autism subtypes based on the data from the Autism Phenome Project, but it certainly will not be the last. There are already indications that other subtypes of autism will be more closely associated with immunological differences or genetic alterations.”

The study’s other authors are Nicholas Lange of the Department of Psychiatry and Biostatistics at Harvard University Schools of Medicine and Public Health McLean Hospital; Deana D. Li, Lou Ann Barnett, Aaron Lee, Tony J. Simon, Sally Rogers and Sally Ozonoff of the UC Davis MIND Institute and the Department of Psychiatry and Behavioral Sciences in the UC Davis School of Medicine; and Michael H. Buonocore of the Department of Radiology, UC Davis School of Medicine.

Material adapted from UC Davis Health System.

The researchers used diffusion tensor imaging (DTI), an advanced MRI-based imaging technique, on 38 amateur soccer players (average age: 30.8 years) who had all played the sport since childhood. They were asked to recall the number of times they headed the ball during the past year. (Heading is when players deliberately hit or field the soccer ball with their head.) Researchers ranked the players based on heading frequency and then compared the brain images of the most frequent headers with those of the remaining players. They found that frequent headers showed brain injury similar to that seen in patients with concussion, also known as mild traumatic brain injury (TBI).

The findings are especially concerning given that soccer is world’s most popular sport with popularity growing in the U.S., especially among children. Of the 18 million Americans who play soccer, 78 percent are under the age of eighteen. Soccer balls are known to travel at speeds as high as 34 miles per hour during recreational play, and more than twice that during professional play.

After confirming the potentially damaging impact of frequent heading, “Our goal was to determine if there is a threshold level for heading frequency that, when surpassed, resulted in detectable brain injury,” said lead author Michael Lipton, M.D., Ph.D., director of Einstein’s Gruss Magnetic Resonance Research Center and medical director of MRI services at Montefiore. Further analysis revealed a threshold level of approximately 1,000 to 1,500 heads per year. Once players in the study exceeded that number, researchers observed significant injury.

“While heading a ball 1,000 or 1,500 times a year may seem high to those who don’t participate in the sport, it only amounts to a few times a day for a regular player,” observed Dr. Lipton, who is also associate professor of radiology, of psychiatry and behavioral sciences, and of the Dominick P. Purpura Department of Neuroscience at Einstein.

“Heading a soccer ball is not an impact of a magnitude that will lacerate nerve fibers in the brain,” said Dr. Lipton. “But repetitive heading may set off a cascade of responses that can lead to degeneration of brain cells.”

Researchers identified five areas, in the frontal lobe (behind the forehead) and in the temporo-occipital region (the bottom-rear areas) of the brain that were affected by frequent heading – areas that are responsible for attention, memory, executive functioning and higher-order visual functions. In a related study, Dr. Lipton and colleague Molly Zimmerman, Ph.D., assistant professor in the Saul R. Korey Department of Neurology at Einstein, gave the same 38 amateur soccer players tests designed to assess their neuropsychological function. Players with the highest annual heading frequency performed worse on tests of verbal memory and psychomotor speed (activities that require mind-body coordination, like throwing a ball) relative to their peers.

“These two studies present compelling evidence that brain injury and cognitive impairment can result from heading a soccer ball with high frequency,” Dr. Lipton said. “These are findings that should be taken into consideration in planning future research to develop approaches to protect soccer players.”

Heading is an essential part of soccer and is unlikely to be eliminated from practice or play.

As there appears to be a safe range for heading frequency, additional research can help refine this number, which can then be used to establish heading guidelines. As in other sports, the frequency of potentially harmful actions in practice and games could be monitored and restricted based on confirmed unsafe exposure thresholds.

“In the past, pitchers in Little League Baseball sustained shoulder injuries at a rate that was alarming,” Dr. Lipton noted. “But ongoing research has helped shape various approaches, including limits on the amount of pitching a child performs, which have substantially reduced the incidence of these injuries.”

“Brain injury due to heading in children, if we confirm that it occurs, may not show up our radar because the impairment will not be immediate and can easily be attributed to other causes like ADHD or learning disabilities,” continued Dr. Lipton. “We, including the agencies that supervise and encourage soccer play, need to do the further research to precisely define the impact of excessive heading on children and adults in order to develop parameters within which soccer play will be safe over the long term.”

In addition to Drs. Lipton and Zimmerman, other authors on these studies include Namhee Kim, Ph.D., Richard Lipton, M.D., Edwin Gulko, M.D., and Craig Branch, Ph.D., all at Einstein, and Walter Stewart, Ph.D., at Geisinger Health System.

Material adapted from Albert Einstein College of Medicine of Yeshiva University.

The results were published the week of Nov. 21 in the Proceedings of the National Academy of Sciences.

Understanding how meditation works will aid investigation into a host of diseases, Brewer said. “Meditation has been shown to help in variety of health problems, such as helping people quit smoking, cope with cancer, and even prevent psoriasis,” he added.

The Yale team conducted functional magnetic resonance imaging scans on both experienced and novice meditators as they practiced three different meditation techniques.

Experienced meditators seem to switch off areas of the brain associated with wandering thoughts, anxiety and some psychiatric disorders such as schizophrenia. Researchers used fMRI scans to determine how the brains of meditators differed from subjects who were not meditating. The areas shaded in blue highlight areas of decreased activity in the brains of meditators. Credit: courtesy of yale

The scans also showed that when the default mode network was active, brain regions associated with self-monitoring and cognitive control were co-activated in experienced meditators but not novices. This may indicate that meditators are constantly monitoring and suppressing the emergence of “me” thoughts, or mind-wandering. In pathological forms, these states are associated with diseases such as autism and schizophrenia.

The meditators did this both during meditation, and also when just resting — not being told to do anything in particular. This may indicate that meditators have developed a “new” default mode in which there is more present-centered awareness, and less “self”-centered, say the researchers.

“Meditation’s ability to help people stay in the moment has been part of philosophical and contemplative practices for thousands of years,” Brewer said. “Conversely, the hallmarks of many forms of mental illness is a preoccupation with one’s own thoughts, a condition meditation seems to affect. This gives us some nice cues as to the neural mechanisms of how it might be working clinically.”

Other Yale researchers involved in this study were Patrick D. Worhunsky, Jeremy R. Gray and Hedy Kober.

Material adapted from Yale University.

The study showed that psychopaths have reduced connections between the ventromedial prefrontal cortex (vmPFC), the part of the brain responsible for sentiments such as empathy and guilt, and the amygdala, which mediates fear and anxiety. Two types of brain images were collected. Diffusion tensor images (DTI) showed reduced structural integrity in the white matter fibers connecting the two areas, while a second type of image that maps brain activity, a functional magnetic resonance image (fMRI), showed less coordinated activity between the vmPFC and the amygdala.

“This is the first study to show both structural and functional differences in the brains of people diagnosed with psychopathy,” says Michael Koenigs, assistant professor of psychiatry in the University of Wisconsin School of Medicine and Public Health. “Those two structures in the brain, which are believed to regulate emotion and social behavior, seem to not be communicating as they should.”

The study, which took place in a medium-security prison in Wisconsin, is a unique collaborative between three laboratories,

UW-Madison psychology Professor Joseph Newman has had a long term interest in studying and diagnosing those with psychopathy and has worked extensively in the Wisconsin corrections system. Dr. Kent Kiehl, of the University of New Mexico and the MIND Research Network, has a mobile MRI scanner that he brought to the prison and used to scan the prisoners’ brains. Koenigs and his graduate student, Julian Motzkin, led the analysis of the brain scans.

The study compared the brains of 20 prisoners with a diagnosis of psychopathy with the brains of 20 other prisoners who committed similar crimes but were not diagnosed with psychopathy.

“The combination of structural and functional abnormalities provides compelling evidence that the dysfunction observed in this crucial social-emotional circuitry is a stable characteristic of our psychopathic offenders,’’ Newman says. “I am optimistic that our ongoing collaborative work will shed more light on the source of this dysfunction and strategies for treating the problem.”

Newman notes that none of this work would be possible without the extraordinary support provided by the Wisconsin Department of Corrections, which he called “the silent partner in this research.” He says the DOC has demonstrated an unprecedented commitment to supporting research designed to facilitate the differential diagnosis and treatment of prisoners.

The study, published in the most recent Journal of Neuroscience, builds on earlier work by Newman and Koenigs that showed that psychopaths’ decision-making mirrors that of patients with known damage to their ventromedial prefrontal cortex (vmPFC). This bolsters evidence that problems in that part of the brain are connected to the disorder.

“The decision-making study showed indirectly what this study shows directly – that there is a specific brain abnormality associated with criminal psychopathy,’’ Koenigs adds.

Material adapted from University of Wisconsin-Madison.

“The new technology we have created can conform to the brain’s unique geometry, and records and maps activity at resolutions that have not been possible before,” says Brian Litt, MD, the study’s senior author and Associate Professor of Neurology at the Perelman School of Medicine and Bioengineering at the University of Pennsylvania. “Using this device, we can explore the brain networks underlying normal function and disease with much more precision, and its likely to change our understanding of memory, vision, hearing and many other normal functions and diseases.” For our patients, implantable brain devices could be inserted in less invasive operations and, by mapping circuits involved in epilepsy, paralysis, depression and other ‘network brain disorders’ in sufficient detail, this could allow us to intervene to make patients better, Litt said.

High-resolution, flexible, active electrode array with 360 amplified and multiplexed electrodes. Only 39 wires are needed to sample from all of the 360 electrodes simultaneously. The electrode array is ultrathin and flexible, allowing close contact with the brain and high-resolution recordings of seizures. Credit: Travis Ross and Yun Soung Kim, University of Illinois at Urbana-Champaign (click to enlarge)

Monitoring and studying the brain’s constant electrical activity, or to alter it when it goes awry, often requires the placement of electrodes deep within specific regions of the brain. These currently used devices can be clumsy and of low resolution, and those used for neuromotor prostheses can cause tissue inflammation and hemorrhages.

Study collaborators including lead author Jonathan Viventi, PhD, an assistant professor at the Polytechnic Institute of New York University who worked with Litt on the project as a postdoctoral fellow at Penn, and colleagues John Rogers from the University of Illinois Urbana-Champaign, and Dae-Hyeong Kim from Seoul National University, worked together to conceive and build the array, believed to be the first device of its kind to be used as a brain interface.

In animal models, researchers observed responses to visual stimuli and recorded previously unknown details of sleep patterns and brain activity during epileptic seizures. The array recorded spiral waves during seizure activity that have not been previously recorded in whole brain. These patterns are similar to those seen in the heart during ventricular fibrillation, raising the possibility of fighting epilepsy with some of the same methods used to treat cardiac arrhythmias, like focal destruction or ablation of abnormal circuits.

The extreme flexibility of the device allowed it to be folded in half without damage, forming a unique double-sided recording device. This device can be used to interface with rarely explored brain regions, such as the interior of sulci and in-between the brain hemispheres. Credit: Yun Soung Kim, University of Illinois at Urbana-Champaign (click to enlarge)

Ultimately, the researchers expect that flexible electrode arrays can be perfected for use for various therapeutic and research purposes throughout the body. They could serve as neuroprostheses, pacemakers, ablative devices, or neuromuscular stimulators. Their versatility, sensitivity, and reduced effect on surrounding tissues puts them in the forefront of the next generation of brain-computer interfaces.

In addition to the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS), the research was supported by the National Science Foundation, the Division of Materials Sciences at the U.S. Department of Energy, Citizens United for Research in Epilepsy, the Dr. Michel and Mrs. Anna Mirowski Discovery Fund for Epilepsy Research, and NIH’s National Heart, Lung, and Blood Institute.

Material adapted from Penn Medicine.

Two studies now appear in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association and Neurology, the medical journal of the American Academy of Neurology.

ASL-MRI can be used to measure neurodegenerative changes in a similar way that fluorodeoxyglucose Positron emission tomography (FDG-PET) scans are currently being used to measure glucose metabolism in the brain. Both tests correlate with cognitive decline in patients with Alzheimer’s disease.

“In brain tissue, regional blood flow is tightly coupled to regional glucose consumption, which is the fuel the brain uses to function. Increases or decreases in brain function are accompanied by changes in both blood flow and glucose metabolism,” explained John A. Detre, MD, professor of Neurology and Radiology at Penn, senior author on the papers, who has worked on ASL-MRI for the past 20 years. “We designed ASL-MRI to allow cerebral blood flow to be imaged noninvasively and quantitatively using a routine MRI scanner.”

When Alzheimer’s disease is suspected, patients typically receive an MRI initially to look for structural changes that could indicate other medical causes, such as a stroke or brain tumor. Adding about 10-20 minutes to the test time, ASL can be incorporated into the routine MRI and capture functional measures to detect Alzheimer’s disease upfront, turning a routine clinical test (structural MRI) into both a structural and functional test.

Comparison of arterial spin labeling (ASL) and fluorodeoxyglucose (FDG) images. Representative images from control subjects (top row) and AD patients (bottom row) comparing structural magnetic resonance imaging images (T1 and fluid-attenuated inversion recovery), arterial spin labeling magnetic resonance imaging (ASL-MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). All four patients were diagnosed correctly by both readers using both modalities. White arrows highlight areas of concordant hypometabolism on FDG-PET and hypoperfusion on ASL-MRI. (click to enlarge)

The studies being reported this week show a comparison of ASL-MRI and FDG-PET in a group of Alzhiemer’s patients and age-matched controls. Cerebral blood flow and glucose metabolism were measured simultaneously by injecting the PET tracer during the MRI study. The data were then analyzed two different ways.

In the first study, now online in Alzheimer’s and Dementia, ASL-MRI and FDG-PET images from 13 patients diagnosed with Alzheimer’s and 18 age-matched controls were analyzed by visual inspection. Independent, blinded review of the two tests by expert nuclear medicine physicians demonstrated similar abilities to rule out (sensitivity) and diagnose (specificity) Alzheimer’s. Neither ASL-MRI nor FDG-PET showed a clear advantage from quantitative testing.

In the second study, published in Neurology, the ASL-MRI and FDG-PET images were compared statistically at each location in the brain by computerized analysis. Data from 15 AD patients were compared to 19 age-matched healthy adults. The patterns of reduction in cerebral blood flow were nearly identical to the patterns of reduced glucose metabolism by FDG-PET, both of which differed from the patterns of reduction in gray matter seen in AD.

“Given that ASL-MRI is entirely non-invasive, has no radiation exposure, is widely available and easily incorporated into standard MRI routines, it is potentially more suitable for screening and longitudinal disease tracking than FDG-PET,” said the Neurology study authors.

Additional studies will focus on larger sample sizes including patients with mild cognitive impairment and other kinds of neurodegenerative conditions.

Study collaborators from Penn included Erik S. Musiek, MD, PhD; Marc Korczykowski, Babak Saboury, Patricia M. Martinez; Janet S. Reddin, PhD; Abass Alavi, MD; Daniel Y. Kimberg; Joel Greenberg, PhD; and Steven E. Arnold, MD. An additional researcher from and Astra-Zeneca also contributed to the research.

Material adapted from Perelman School of Medicine at the University of Pennsylvania.

The research was reported online in the journal Magnetic Resonance Imaging.

Bazarian and colleagues used a cutting edge statistical approach to analyze before-and-after images of the players’ brains from diffusion tensor imaging (DTI). A DTI scan is similar to an MRI but it does not relay pictures, rather it captures and relays quantitative data that must be decoded and interpreted.

Collaborators and co-authors Tong Zhu, Ph.D., and Jianhui Zhong, Ph.D., uniquely applied a novel (wild bootstrap) statistical method to the DTI imaging study and detected the small but noteworthy changes in the white matter of the teenagers.

“Although this was a very small study, if confirmed it could have broad implications for youth sports,” Bazarian said. “The challenge is to determine whether a critical number of head hits exists above which this type of brain injury appears, and then to get players and coaches to agree to limit play when an athlete approached that number.”

Nine athletes and six people in a control group from Rochester, N.Y., volunteered to take part in the research during the 2006-2007 sports season. Among the nine athletes, only one was diagnosed with a sports-related concussion that season, but six others sustained many sub-concussive blows and showed abnormalities on their post-season DTI scans that were closer to the concussed brain than to the normal brains in the control group.

The imaging changes also strongly correlated with the number of head hits (self-reported in a diary), the symptoms experienced, and independent of cognitive test results, Bazarian said.

The URMC study is unique because it was able to compare brain scans from the same player, pre-season and post-season. Most other studies compare the injured brain of one person to the normal brain of another person from a control group. However, that becomes a problem when searching for very subtle changes, Bazarian said, because so much natural variation exists in every individual’s brain.

Indeed, among athletes there is no easy, objective way to diagnose concussions. High schools, colleges, and professional programs routinely administer pre-season, computer-based cognitive tests. Yet some athletes have become adept at tricking the test, Bazarian said. They intentionally do poorly on the baseline so that a mild concussion will not show up if re-tested later.

The DTI scan provides detailed information of axonal injury at the cellular level by measuring the motion of water in the brain. Axons, which are like cables woven throughout brain tissue, swell up when injury occurs. As the swelling impacts the movement of water, scientists can measure changes in flow and volume and thus make an educated guess at the extent of axonal injury.

Measurements in the study at hand showed many changes in the brain of the player with the diagnosed concussion; however an intermediate level of changes also occurred among the players who reported anywhere from 26 to 399 total sub-concussive blows. The fewest changes occurred in the control group, as expected.

A key objective of the study was to determine if this statistical approach worked, and the preliminary results showed that white matter changes among the intermediate group were three times higher than the controls.

Efforts to further understand the significance of study results are already underway. Bazarian and collaborators at the Rochester Center for Brain Imaging, the URMC Department of Emergency Medicine, Department of Athletics and Recreation, and the Department of Imaging Sciences, are working on an NFL-funded study of UR football players this fall. Ten players agreed to wear helmets with special sensors that objectively detect the number of head hits they sustain, the velocity and angle. Each player is also receiving a pre-season and 2 post-season DTI scans, and the data downloaded from the helmet sensors will be correlated with information from the images.

“Our studies are taking important steps toward personalized medicine for traumatic brain injury,” Bazarian said. “In the future we’d like to be able to have a baseline image of a brain and clearly know the significance of changes that occur later.”

Material adapted from University of Rochester Medical Center.

Previous research has suggested that plaque and tangle deposits in the brain — hallmarks of Alzheimer’s disease and many dementias — are associated not only with memory loss but also with mild symptoms of depression and anxiety in middle-aged and older individuals. The team wanted to see what the brain-scanning technique developed at UCLA would find in older people with MDD.

UCLA researchers have created a chemical marker called FDDNP that binds to both plaque and tangle deposits, which can then be viewed through a positron emission tomography (PET) brain scan, providing a “window into the brain.” Using this method, researchers are able to pinpoint where in the brain these abnormal protein deposits are accumulating.

Researchers compared the FDDNP brain scans of 20 older adults between ages 60 to 82 who had been diagnosed with MDD with the scans of 19 healthy controls of similar age, education and gender. They found that in patients with MDD, FDDNP binding was significantly higher throughout the brain and in critical brain regions, including the posterior cingulate and lateral temporal areas, that are involved in decision-making, complex reasoning, memory and emotions.
 
“This is the first study using FDDNP to assess the abnormal protein levels in brains of older adults with severe depression,” said the study’s senior author, Dr. Gary Small, UCLA’s Parlow-Solomon Professor on Aging and a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. “The findings suggest that the higher protein load in critical brain regions may contribute to the development of severe depression in late life.”

Researchers also found that similar protein deposit patterns in the lateral temporal and posterior cingulate areas in patients were associated with different clinical symptoms. Some patients demonstrated indicators of depression only, while others displayed symptoms of mild cognitive impairment as well.

Dr. Small noted that previous research has shown that depression may be a risk factor for or a precursor to memory loss, such as mild cognitive impairment, which can later lead to dementia.

Brain images demonstrate higher FDDNP binding (yellow areas) and thus more abnormal proteins in a patient with major depressive disorder compared with a healthy control.

According to Kumar and Small, more follow-up over time is needed to evaluate the significance of the outcomes of the study’s patient subgroups. Such research will help further assess if depression later in life might be a precursor to mild cognitive impairment and dementia.

In addition, the researchers said, FDDNP used with PET may also be helpful in identifying new treatments and in tracking the effectiveness of current antidepressant therapy and medications designed to help reduce abnormal protein build-up in the brain.

The team is planning larger studies involving investigators at UCLA and the University of Illinois that will address the impact of the genetic marker APOE-4, which is a risk factor for dementia and Alzheimer’s disease.

Additional authors include Prabha Siddarth of the UCLA Department of Psychiatry and Biobehavioral Sciences; Vladimir Kepe of the UCLA Department of Molecular and Medical Pharmacology; and Vicki Manoukian and Virginia Elderkin-Thompson of the Semel Institute for Neuroscience and Human Behavior at UCLA.

Material adapted from University of California, Los Angeles (UCLA), Health Sciences.

Many patients recover from psychosis with minimal symptoms, but for others, the psychosis can be persistent and can affect their ability to function well and lead a normal life. At present, psychiatrists have no clear method of assessing a person’s risk of future episodes and predicting how the disease will progress. This is important in terms of guiding patients’ and their clinicians’ choices about appropriate treatments.

Now, a study led by Dr Paola Dazzan and Dr Janaina Mourao-Miranda at the Institute of Psychiatry, King’s College London in collaboration with the Computer Science Department at University College London and published today in the journal Psychological Medicine reports the successful use of computer algorithms to analyze MRI scans and predict a patient’s outcome.

Algorithms that quantify the risk of further episodes of disease are common in areas of medicine such as cardiovascular medicine and oncology, but no accurate tests are available to psychiatrists. Researchers have previously used MRI to predict outcome in psychosis, based on the analysis of specific brain regions. However, the changes in the brain associated with psychosis are often subtle and difficult to detect, and these approaches have therefore been of limited benefit for clinical practice.

Dr. Dazzan and colleagues worked with a cohort of 100 patients, taking MRI brain scans when they presented to clinical services with a first psychotic episode. In addition, the researchers scanned the brains of a control group of 91 healthy individuals. The patients were followed up around six years later and classified as having developed a continuous, episodic or intermediate illness course, depending on whether their symptoms remitted or not during this time.

From this larger sample, the researchers then analyzed scans from twenty-eight subjects with a continuous course of illness, the same number from patients with an episodic course and again, the same number from healthy controls. They used these scans as data to ‘train’ a software developed by a group led by Dr. Mourao-Miranda based on pattern recognition (a statistical approach that uses data from the whole brain rather than from a specific region) and to distinguish between the different severities of the illness. The algorithm, applied to the scans collected at the first episode of psychosis, was able to differentiate between patients who then went on to develop continuous psychosis and those who went on to develop a more benign, episodic psychosis in seven out of ten cases.

“Although we have some way to go to improve the accuracy of these tests and validate the results on independent large samples, we have shown that in principle it should be possible to use brain scans to identify at the first episode of illness both patients who are likely to go on to have a continuous psychotic illness and those who will develop a less severe form of the illness,” says Dr Mourao-Miranda, a Wellcome Trust Research Career Development Fellow. “This suggests that even by the time that they have their first episode of psychosis, significant changes have already occurred to their brains.”

“This is the first step towards being able to use brain imaging to provide tangible benefit to patients affected by psychosis,” says Dr Dazzan. “This could in future offer a fast and reliable way of predicting the outcome for an individual patient allowing us to optimize treatments for those most in need, while avoiding long-term exposure to antipsychotic medications in those with very mild forms.

“Structural MRI scans can be obtained in as little as ten minutes and so this technique could be incorporated into routine clinical investigations. The information this provides could help inform the treatment options available to each patient and help us better manage their illness.”

Material adapted from Wellcome Trust.

The study’s results are published in the scientific journal Biological Psychology.

“First-person shooter” games have been discussed in connection with violence over and over. Participants take on the role of a shooter fighting opponents in a war-like situation using different weapons. The Norwegian killer is said to have participated in such worlds intensely before he killed dozens of people in Oslo’s government district and on the vacation island of Utoya. And after the shooting sprees in Erfurt, Emsdetten and Winnenden, the debate whether violent games lower the inhibition threshold and result in violent behavior was revived again.

Psychologists, epileptologists and neurologists from the University of Bonn studied the effect of shoot ‘em up game images and other emotionally charged photos on the brain activity of heavy gamers. “Compared to people who abstain from first-person shooters, they show clear differences in how emotions are controlled,” reported lead author Dr. Christian Montag from the Institute of Psychology at the University of Bonn.

Excessive first-person shooting of about 15 hours a week
The 21 subjects ranging in age from 20 to 30 years played first-person shooters for about 15 hours per week on average. During this study, they were shown a standardized catalog of photos that reliably trigger emotions in human brains, using video glasses. At the same time, the researchers recorded the responses in their brains using one of the brain scanners at the Life & Brain Center of the University of Bonn. The images included photos as they are used in the violent games, but also shots of accident and disaster victims.

“This mix of images allowed us to transport the subjects both to the fictitious first-person shooter world they are familiar with and to also trigger emotions via real images,” explained Dr. Montag. This catalog of photos was also shown to a control group of 19 persons who had no experience with violent video games.

When the subjects regarded the real, negative pictures, there was greatly increased activity in their amygdalas. This region of the brain is strongly involved in processing negative emotions. “Surprisingly, the amygdalas in the subjects as well as in the control group were similarly stimulated,” reported Montag. “This shows that both groups responded to the photos with similarly strong emotions.” But the left medial frontal lobes were clearly less activated in the users of violent games than in the control subjects. This is the brain structure humans use to control their fear or aggression.

“First-person shooters do not respond as strongly to the real, negative image material because they are used to it from their daily computer activities,” Montag concluded. “One might also say that they are more desensitized than the control group.” On the other hand, while processing the computer game images, the first-person shooters showed higher activity in brain regions associated with memory recall and working memory than the control group members. “This indicates that the gamers put themselves into the video game due to the computer game images and were looking for a potential strategy to find a solution for the game status shown,” said Dr. Montag.

Violent games as a cause for changes in brain activity?
One question raised while interpreting the results is whether the users showed altered brain activity due to the games, or whether they were more tolerant of violence from the start and as a consequence, preferred first-person shooter games. The researchers from the University of Bonn were able to suggest an answer to this question based on the fact that they took into account various personality traits such as fearfulness, aggressiveness, callousness or emotional stability.

“There were no differences between the subjects and the control group in this area,” reported Dr. Montag. “This is an indication that the violent games are the cause of the difference in information processing in the brain.”

From the results, Dr. Montag has concluded that emotional desensitization does not only occur while playing computer games. “We were ultimately able to find the decreased control of emotions in first-person shooters for the real images, too,” he said. That is why he thinks these responses are not just limited to these virtual worlds. While there are many studies on video games and aggressive behavior, surprisingly few exist that look at their effect on the brain. “Our results provide indications that the extensive use of first-person shooters is not without its problems,” said Dr. Montag. “But we will need additional studies to shed some more light on the connections between violent games, brain activity, and actual behavior.”

Material adapted from University of Bonn.

Reference
Does excessive play of violent first-person-shooter-video-games dampen brain activity in response to emotional stimuli?, Biological Psychology, DOI:10.1016/j.biopsycho.2011.09.014

“Advances in brain imaging techniques mean we are able to investigate different and specific areas of the human brain and see how they regulate people’s behavior,” explained Dr. Frederic Boy, who led the research. “What is clear is that the way people behave results from a complex interaction between a number of genetic, social and environmental factors.”

The scientists studied males with no history of psychiatric disorders or substance dependence, who completed a questionnaire which helped assess different aspects of impulsivity, an important component of self-control. They underwent a specialized magnetic resonance spectroscopy brain scan, an imaging technique that allows measurement of the amount of GABA in small regions of the brain.

The team found that men with more GABA in their dorsolateral prefrontal cortex had lower scores in one aspect of impulsivity called the “feeling of urgency” or the tendency to act rashly in response to distress or other strong emotions and urges. Inversely, men with lower GABA tended to have higher urgency ratings. These findings add to evidence that “low GABA may be a risk factor for cortical dysfunction across a number of disorders, as depression and panic disorder are associated with low cortical GABA,” commented Dr. John Krystal, Editor of Biological Psychiatry, which published the research. These findings may also hold true in women, but women were not included in this study due to the possible effect of natural hormonal fluctuations.

The authors note that the next stages of research need to focus on further disentangling this relationship between GABA and the dorsolateral prefrontal cortex.

“After that we can start evaluating whether there’s any way in which we could treat a GABA deficit in this area. I suspect this could be difficult, as GABA is present throughout the brain, and raising the level indiscriminately may have all sorts of unforeseen consequences,” said Dr. Boy. “The other area which needs further research is whether GABA levels in the dorsolateral prefrontal cortex fluctuate over time, as this study is simply a snapshot of levels on one given day.” This future research will be important to help further uncover the links between behavior and possible cortical dysfunction.

Material adapted from Elsevier.

Reference
The article is “Dorsolateral Prefrontal γ-Aminobutyric Acid in Men Predicts Individual Differences in Rash Impulsivity” by Frederic Boy, C. John Evans, Richard A.E. Edden, Andrew D. Lawrence, Krish D. Singh, Masud Husain, and Petroc Sumner. Boy, Evans, Lawrence, Singh, and Sumner are affiliated with Cardiff University, Cardiff, United Kingdom. Husain is affiliated with University College London, London, United Kingdom. Edden is affiliated with The Johns Hopkins University and Kennedy Krieger Institute, both in Baltimore, Maryland. The article appears in Biological Psychiatry, Volume 70, Number 9 (November 1, 2011), published by Elsevier.

Researchers measured the status of the endocannabinoid system indirectly by determining whether there was an increase or decrease in the density of endocannabinoid receptors, called the CB1 receptor, in several brain regions using positron emission tomography, or PET, imaging. They compared these densities in women with anorexia or bulimia with those of healthy women.

They found global increases in ligand binding to CB1 receptors in the brains of women with anorexia nervosa. This finding is consistent with a compensatory process engaged by deficits in endocannabinoid levels or reduced CB1 receptor function.

CB1R availability was also increased in the insula in both anorexia and bulimia patients. The insula “is a region that integrates body perception, gustatory information, reward and emotion, functions known to be disturbed in these patients,” explained Dr. Koen Van Laere, the study’s lead author.

“The role of endocannabinoids in appetite control is clearly important. These new data point to important connections between this system and eating disorders,” added Dr. John Krystal, Editor of Biological Psychiatry.

Additional research is now needed to establish whether the observed changes are caused by the disease or whether these are neurochemical alterations that serve as risk factors for developing an eating disorder.

Furthermore, since very few effective treatments exist for these disorders, these data indicate that the endocannabinoid system may be a potential new target for developing drugs to treat eating disorders. Such new therapies are currently being investigated in animal models.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. Gérard, Goffin, and Van Laere are affiliated with Division of Nuclear Medicine, University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium. Pieters is affiliated with University Psychiatric Centre, Katholieke Universiteit Leuven, Eating Disorder Clinic Kortenberg, Kortenberg, Belgium. Bormans is with the Laboratory for Radiopharmacy, Katholieke Universiteit Leuven, Leuven, Belgium.

Material adapted from Elsevier.

Reference
The article is “Brain Type 1 Cannabinoid Receptor Availability in Patients with Anorexia and Bulimia Nervosa” (DOI 10.1016/j.biolpsych.2011.05.010) by Nathalie Gérard, Guido Pieters, Karolien Goffin, Guy Bormans, and Koen Van Laere.

The researchers have shown that its activity can be modulated depending on the subject’s genetic makeup, personal history and cognition. These results suggest that the effects of psychotherapies on the cerebral activity of patients could vary according to their genetic traits. This work makes the cover story of the November 2011 issue of Human Brain Mapping.

Several studies published over the past decade point to the possibility that the 5-HTTLPR gene, which codes for the serotonin (a substance involved in emotional regulation) transporter, could play an important role in depression. The promoter of this gene can be in either long or short form, and the short version can accentuate the emotional impact of stressful events. Although this hypothesis remains controversial, it is accepted that the short form of the gene triggers a more intense activation of the amygdala, also known as the cerebellar tonsil, a brain structure involved in emotions and in the recognition of danger signals.

For this new project, the researchers studied the impact of psychological and environmental factors on the “genetic” effect by carrying out functional MRI brain scans on 45 healthy individuals, including carriers of both the short and long form of the gene. During the scans, the subjects were shown photographs of pleasant or unpleasant images and were asked either to indicate whether they found the effect pleasing or displeasing, or to think about the links between the images and themselves.

The results of the scans proved to be different depending on the form of the gene: carriers of the short form showed a higher activation of the amygdala when associating a photo with themselves than when deciding whether an image was pleasing or displeasing. The opposite was observed in the subjects who did not carry the short form. In other words, the activity of the amygdala varied according not only to the form of the gene, but also to the type of mental activity — whether it was an “objective” description of the image or an association with one’s personal history.

Prior to the scans, the subjects were interviewed about any negative events that may have occurred in their lives during the previous year, such as professional difficulties, separation, bereavement, etc. The results showed that the stress experienced during the year also affected the influence of the gene on the activation of the amygdala — such “genetic-environmental” interaction being itself modified by the individual’s mental activity.

The results show that while the subjects’ genetic makeup affects their brain functions, its influence is modulated by both personal history and psychological condition. Extrapolated to the field of depression, these results also suggest that psychotherapy — in particular, cognitive therapy, which consists in helping depressed patients to perceive the world differently — could have diverse cerebral effects depending on certain genes. Researchers are on the case.

Material adapted from CNRS (Délégation Paris Michel-Ange).

Reference
Cognitive Appraisal and Life Stress Moderate the Effects of the 5-HTTLPR Polymorphism on Amygdala Reactivity. Cédric Lemogne, Philip Gorwood, Claudette Boni, Mathias Pessiglione, Stéphane Lehéricy, and Philippe Fossati. Human Brain Mapping, November 2011.

Reporting in the current online edition of the journal Human Brain Mapping, senior author Jennifer G. Levitt, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA; first author Xua Hua, a UCLA postdoctoral researcher; and colleagues found aberrant growth rates in areas of the brain implicated in the social impairment, communication deficits and repetitive behaviors that characterize autism.

Autism is thought to affect one in 110 children in the U.S., and many experts believe the numbers are growing. Despite its prevalence, little is known about the disorder, and no cure has been discovered.

Normally, as children grow into teenagers, the brain undergoes major changes. This highly dynamic process depends on the creation of new connections, called white matter, and the elimination, or “pruning,” of unused brain cells, called gray matter. As a result, our brains work out the ideal and most efficient ways to understand and respond to the world around us.
Although most children with autism are diagnosed before they are 3 years old, this new study suggests that delays in brain development continue into adolescence.

“Because the brain of a child with autism develops more slowly during this critical period of life, these children may have an especially difficult time struggling to establish personal identity, develop social interactions, and refine emotional skills,” Hua said. “This new knowledge may help to explain some of the symptoms of autism and could improve future treatment options.”

The researchers used a type of brain-imaging scan called a T1-weighted MRI, which can map structural changes during brain development. To study how the brains of boys with autism changed over time, they scanned 13 boys diagnosed with autism and a control group of seven non-autistic boys on two separate occasions. The boys ranged in age from 6 to 14 at the time of the first scan; on average, they were scanned again approximately three years later. By scanning the boys twice, the scientists were able to create a detailed picture of how the brain changes during this critical period of development.

For the first time, UCLA researchers have shown that the connections between brain regions that are important for language and social skills grow much more slowly in boys with autism than in non-autistic children.

Besides seeing that the white-matter connections between those brain regions that are important for language and social skills were growing much slower in the boys with autism, they found a second anomaly: In two areas of the brain — the putamen, which is involved in learning, and the anterior cingulate, which helps regulate both cognitive and emotional processing — unused cells were not properly pruned away.

“Together, this creates unusual brain circuits with cells that are overly connected to their close neighbors and under-connected to important cells further away making it difficult for the brain to process information in a normal way,” Hua said. “The brain regions where growth rates were found to be the most altered were associated with the problems autistic children most often struggle with — social impairment, communication deficits and repetitive behavior,” she added.

Future studies using alternative neuroscience techniques should attempt to identify the source of this white-matter impairment, the researchers said.

“This study provides a new understanding of how the brains of children with autism are growing and developing in a unique way,” Levitt said. “Brain imaging could be used to determine if treatments are successful at addressing the biological difference. The delayed brain growth in autism may also suggest a different approach for educational intervention in adolescent and adult patients, since we now know their brains are wired differently to perceive information.”

Other authors on the study included Paul M. Thompson, Alex D. Leow, Sarah K. Madsen, Rochelle Caplan, Jeffry R. Alger, Joseph O’Neill, Kishori Joshi, Susan L. Smalley and Arthur W. Toga, all of UCLA. Support was provided by the National Institutes of Health, the National Alliance for Autism Research, the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke. The authors report no conflict of interest.

Material adapted from University of California, Los Angeles (UCLA), Health Sciences.

“In babies born preterm, the more the cerebral cortex grows early in life the better children perform complex tasks when they reach six years old,” said study author A. David Edwards, DSc, of Imperial College in London. “The period before a full-term birth is critical for brain development. Problems occurring at this time have long-term consequences, and it appears that preterm birth affects brain growth.”

The study looked at brain growth rates of 82 infants who were born before 30 weeks gestational age using MRI scans of their brain between 24-44 weeks. Brain scans were collected repeatedly from immediately after the babies were born until their full-term due date. Their cognitive abilities were tested at two years old and again at six years old.

The study found that the faster the rate of cerebral cortex growth in infancy, the higher their scores were on the developmental and intelligence tests as children. A five to 10 percent reduction in the surface area of the cerebral cortex at full-term age predicted approximately one standard deviation lower score on the intelligence tests in later childhood. Motor skills were not correlated with the rate of cerebral cortex growth, and the overall brain size was not related to general cognitive ability.

“These findings show we should focus on the growth of specific regions of the brain like the cortex when trying to understand or diagnose potential problems in babies and fetuses,” said Edwards.

The study was supported by the Health Foundation, the Garfield Weston Foundation, Wellbeing of Women and the NIHR Imperial College Healthcare Comprehensive Biomedical Research Center.

Material adapted from American Academy of Neurology (AAN).

Understanding the neural basis of reinforcement and punishment processing is of paramount importance to cognitive neuroscience,” explains primary study author Dr. Timothy Vickery from the Department of Psychology at Yale University. “Most perceptual and cognitive functions are served by discrete brain structures, and thus the focus in the reward literature has been on understanding specialized circuits that process reward, such as the basal ganglia. In our study, we tested whether signals related to decision outcomes, encompassing both reinforcement and punishment, may be represented more extensively beyond the traditional reward- and penalty-processing areas that have been described.”

Dr. Vickery and colleagues imaged the brains of human subjects as they engaged in either matching-pennies or rock-paper-scissors games and used a sophisticated pattern analysis to analyze brain responses. The researchers were surprised to discover that both reinforcement and punishment representations were pervasive throughout the entire cortex. This suggests that reward and punishment may influence a much more widespread range of cognitive and perceptual processes than was previously imagined. Interestingly, the findings also indicated that the distribution of punishment signals and reinforcement signals are largely similar. This is in contrast to previous studies suggesting that there are limited regions encoding punishment and far more regions associated with reward.

Taken together, the findings provide evidence that both positive and negative outcomes can directly influence neural processing throughout the entire brain. “While it is likely that the basal ganglia and its projections are responsible for the core functions of reward-related processing, many other brain regions are at least provided with this information,” concludes Dr. Vickery. “This suggests an imperative to study the effects of reinforcement and punishment in domains where they are not usually considered as important factors—from low-level sensory systems to high-level social reasoning. Such distributed representations would have adaptive value for optimizing many types of cognitive processes and behavior in the natural world.”

Material adapted from Cell Press.

Professor Jianfeng Feng

The researchers used MRI scanners to scan the brain activity in 39 depressed people (23 female 16 male) and 37 control subjects who were not depressed (14 female 23 male). The researchers found the fMRI scans revealed significant differences in the brain circuitry of the two groups. The greatest difference observed in the depressed patients was the uncoupling of the so-called “hate circuit” involving the superior frontal gyrus, insula and putamen. Other major changes occurred in circuits related to risk and action responses, reward and emotion, attention and memory processing.

The hate circuit was first clearly identified in 2008 by UCL Professor Semir Zeki who found that a circuit which seemed to connect three regions in the brain (the superior frontal gyrus, insula and putamen) when test subjects were shown pictures of people they hated.

The new University of Warwick led research found that in significant numbers of the depressed test subjects they examined by fMRI that this hate circuit had become decoupled. Those depressed people also seemed to have experienced other significant disruptions to brain circuits associated with: risk and action, reward and emotion, and attention and memory processing. The researchers found that in the depressed subjects:

• The Hate circuits were 92% per cent likely to be decoupled
• The Risk/Action circuit was 92% likely to be decoupled
• The Emotion/Reward circuit was 82% likely to be decoupled

Professor Jianfeng Feng, from the University of Warwick’s Department of Computer studies said that:

“The results are clear but at first sight are puzzling as we know that depression is often characterized by intense self loathing and there is no obvious indication that depressives are less prone to hate others. One possibility is that the uncoupling of this hate circuit could be associated with impaired ability to control and learn from social or other situations which provoke feelings of hate towards self or others. This in turn could lead to an inability to deal appropriately with feelings of hate and an increased likelihood of both uncontrolled self-loathing and withdrawal from social interactions. It may be that this is a neurological indication that is more normal to have occasion to hate others rather than hate ourselves.”

Material adapted from University of Warwick.

The study, initiated by Centre for Cognitive Neuroscience (CCN) at University of Turku, was methodologically unique combining the expertice in brain imaging (National PET-Center and CCN), measurements and modeling of radiation (Radiation and Nuclear Safety Authority in Finland, STUK) and measurements of skin temperature (Finnish Institute of Occupational Health, TTL). No conclusions concerning health risks can be made based on the result.

The study was financed by Finnish Technology Agency (Tekes) as part of the national Wirecom (wireless communication) research program. The results were published in Journal of Blood Circulation and Metabolism (advance online publication, 14 September 2011).

Material adapted from Suomen Akatemia (Academy of Finland).

Reference
Journal of Blood Circulation and Metabolism (advance online publication, 14 September 2011).

They show that brain activity in the face of noise is controlled by specific brain waves during sleep. In particular, waves called sleep ‘spindles’ prevent the transmission of sounds to auditory brain regions. Conversely, when sounds are associated with brain waves called ‘K-complexes’, activation of auditory areas is larger. Our perception of the environment is therefore not continuously reduced during sleep, but rather varies throughout sleep under the influence of particular brain waves.

Left panels : Auditory brain regions remain active in response to sounds during human non-rapid eye movement sleep. Right panels : When sounds occur during brain waves called sleep ‘spindles’, their transmission to the auditory cortex is distorted. Only a small region in the brainstem (arrow) remains activated in response to sounds. (c) ULg CRC (click to enlarge)

Conversely, sounds can induce the production during sleep of brain waves called ‘K-complexes’. The results brought by this new study demonstrate that production of K-complexes by sounds is associated with a larger activation of auditory brain areas. While spindles prevent the transmission of sounds, K-complexes reflect a more important transmission of sounds to the sleeping brain.

The effects of noise on sleep are therefore controlled by specific brain waves. In particular, the human brain is isolated from the environment during sleep spindles, which might allow essential sleep functions to operate such as the consolidation of memory for previously acquired information. These brain waves thus play a crucial role in sleep quality and stability in the face of noise.

Material adapted from University of Liège.

Reference
“Interplay between spontaneous and induced brain activity during human non-rapid eye movement sleep”, PNAS, 2011, doi 10.1073, by T.T. Dang-Vu, M. Bonjean, M. Schabus, M. Boly, A. Darsaud, M. Desseilles, C. Degueldre, E. Balteau, C. Phillips, A. Luxen, T. Sejnowski et P. Maquet.

As yet, the technology can only reconstruct movie clips people have already viewed. However, the breakthrough paves the way for reproducing the movies inside our heads that no one else sees, such as dreams and memories, according to researchers.

“This is a major leap toward reconstructing internal imagery,” said Professor Jack Gallant, a UC Berkeley neuroscientist and coauthor of the study to be published online Sept. 22 in the journal Current Biology. “We are opening a window into the movies in our minds.”

Eventually, practical applications of the technology could include a better understanding of what goes on in the minds of people who cannot communicate verbally, such as stroke victims, coma patients and people with neurodegenerative diseases.

It may also lay the groundwork for brain-machine interface so that people with cerebral palsy or paralysis, for example, can guide computers with their minds.

However, researchers point out that the technology is decades from allowing users to read others’ thoughts and intentions, as portrayed in such sci-fi classics as “Brainstorm,” in which scientists recorded a person’s sensations so that others could experience them.

Previously, Gallant and fellow researchers recorded brain activity in the visual cortex while a subject viewed black-and-white photographs. They then built a computational model that enabled them to predict with overwhelming accuracy which picture the subject was looking at.

In their latest experiment, researchers say they have solved a much more difficult problem by actually decoding brain signals generated by moving pictures.

“Our natural visual experience is like watching a movie,” said Shinji Nishimoto, lead author of the study and a post-doctoral researcher in Gallant’s lab. “In order for this technology to have wide applicability, we must understand how the brain processes these dynamic visual experiences.”

Nishimoto and two other research team members served as subjects for the experiment, because the procedure requires volunteers to remain still inside the MRI scanner for hours at a time.

They watched two separate sets of Hollywood movie trailers, while fMRI was used to measure blood flow through the visual cortex, the part of the brain that processes visual information. On the computer, the brain was divided into small, three-dimensional cubes known as volumetric pixels, or “voxels.”

“We built a model for each voxel that describes how shape and motion information in the movie is mapped into brain activity,” Nishimoto said.

The brain activity recorded while subjects viewed the first set of clips was fed into a computer program that learned, second by second, to associate visual patterns in the movie with the corresponding brain activity.

Brain activity evoked by the second set of clips was used to test the movie reconstruction algorithm. This was done by feeding 18 million seconds of random YouTube videos into the computer program so that it could predict the brain activity that each film clip would most likely evoke in each subject.

Finally, the 100 clips that the computer program decided were most similar to the clip that the subject had probably seen were merged to produce a blurry yet continuous reconstruction of the original movie.

Reconstructing movies using brain scans has been challenging because the blood flow signals measured using fMRI change much more slowly than the neural signals that encode dynamic information in movies, researchers said. For this reason, most previous attempts to decode brain activity have focused on static images.

“We addressed this problem by developing a two-stage model that separately describes the underlying neural population and blood flow signals,” Nishimoto said.

Ultimately, Nishimoto said, scientists need to understand how the brain processes dynamic visual events that we experience in everyday life.

“We need to know how the brain works in naturalistic conditions,” he said. “For that, we need to first understand how the brain works while we are watching movies.”

Material adapted from University of California – Berkeley.

Lebel recently moved to the United States to work at UCLA, where she is a post-doctoral fellow working with an expert in brain-imaging research. “This is the first long-range study, using a type of imaging that looks at brain wiring, to show that in the white matter there are still structural changes happening during young adulthood,” says Lebel. “The white matter is the wiring of the brain; it connects different regions to facilitate cognitive abilities. So the connections are strengthening as we age in young adulthood.”

The duo recently published their findings in the Journal of Neuroscience. For their research they used magnetic resonance imaging or MRIs to scan the brains of 103 healthy people between the ages of five and 32. Each study subject was scanned at least twice, with a total of 221 scans being conducted overall. The study demonstrated that parts of the brain continue to develop post-adolescence within individual subjects.

The research results revealed that young adult brains were continuing to develop wiring to the frontal lobe; tracts responsible for complex cognitive tasks such as inhibition, high-level functioning and attention. The researchers speculated in their article that this may be due to a plethora of life experiences in young adulthood such as pursing post-secondary education, starting a career, independence and developing new social and family relationships.

An important observation the researchers made when reviewing the brain-imaging scan results was that in some people, several tracts showed reductions in white matter integrity over time, which is associated with the brain degrading. The researchers speculated in their article that this observation needs to be further studied because it may provide a better understanding of the relationship between psychiatric disorders and brain structure. These disorders typically develop in adolescence or young adulthood.

“What’s interesting is a lot of psychiatric illness and other disorders emerge during adolescence, so some of the thought might be if certain tracts start to degenerate too soon, it may not be responsible for these disorders, but it may be one of the factors that makes someone more susceptible to developing these disorders,” says Beaulieu.

“It’s nice to provide insight into what the brain is doing in a healthy control population and then use that as a springboard so others can ask questions about how different clinical disorders like psychiatric disease and neurological disease may be linked to brain structure as the brain progresses with age.”

Material adapted from University of Alberta Faculty of Medicine & Dentistry.

Scientists have long known that functional specificity exists in certain domains: In the motor system, for example, there is one patch of neurons that controls the fingers of your left hand, and another that controls your tongue. But what about more complex functions such as recognizing faces, using language or doing math? Are there special brain regions for those activities, or do they use general-purpose areas that serve whatever task is at hand?

The researchers use an innovative method to analyze fMRI data subject by subject, allowing them to discern individual patterns of brain activity. Photo: Patrick Gillooly

But according to Fedorenko and her co-authors — Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience, and undergraduate student Michael Behr — this apparent overlap may simply be due to flaws in methodology, i.e., how fMRI data is traditionally gathered and analyzed. In their new study, published in this week’s Proceedings of the National Academy of Sciences, they used an innovative technique they have been developing over the past few years; the new method yielded evidence that there are, in fact, bits of the brain that do language and nothing else.

Forget the forest, it is all in the trees
fMRI studies of language are typically done by group analysis, meaning that researchers test 10, 20 or even 50 subjects, then average data together onto a common brain space to search for regions that are active across brains.

But Fedorenko says this is not an ideal way to do things, mainly because the fine-grained anatomical differences between brains can cause data “smearing,” making it look as if one region is active in two different tasks when in reality, the tasks activate two neighboring — but not overlapping — regions in each individual subject.

A map of the different brain areas that are active while a subject performs a language task (red) and a cognitive control task (blue), showing that nearby but distinct regions are used for each activity. Image courtesy of Fedorenko et al. (click to enlarge)

It is the same way for brains. “Brains are different in their folding patterns, and where exactly the different functional areas fall relative to these patterns,” Fedorenko says. “The general layout is similar, but there isn’t fine-grained matching.” So, she says, analyzing data by “aligning brains in some common space … is just never going to be quite right.”

Ideally, then, data would be analyzed for each subject individually; that is, patterns of activity in one brain would only ever be compared to patterns of activity from that same brain. To do this, the researchers spend the first 10 to 15 minutes of each fMRI scan having their subject do a fairly sophisticated language task while tracking brain activity. This way, they establish where the language areas lie in that individual subject, so that later, when the subject performs other cognitive tasks, they can compare those activation patterns to the ones elicited by language.

From left, MIT undergraduate Michael Behr, principal investigator Nancy Kanwisher and research scientist Evelina Fedorenko in front of the fMRI machine they use to measure real-time brain activity associated with language and other cognitive tasks. Photo: Patrick Gillooly

Out of the nine regions they analyzed — four in the left frontal lobe, including the region known as Broca’s area, and five further back in the left hemisphere — eight uniquely supported language, showing no significant activation for any of the seven other tasks. These findings indicate a “striking degree of functional specificity for language,” as the researchers report in their paper.

Future studies will test the newly identified language areas with even more non-language tasks to see if their functional specificity holds up; the researchers also plan to delve deeper into these areas to discover which particular linguistic jobs each is responsible for.

Fedorenko says the results do not imply that every cognitive function has its own dedicated piece of cortex; after all, we are able to learn new skills, so there must be some parts of the brain that are both high-level and functionally flexible. Still, she says, the results give hope to researchers looking to draw some distinctions within in the human cortex: “Brain regions that do related things may be nearby … [but] it’s not just all one big mushy multifunctional thing in there.”

Material adapted from Massachusetts Institute of Technology.

This ruminative thinking can be either passive and maladaptive (i.e., worrying) or active and solution-focused (i.e., coping). New research by Stanford University researchers, published in Elsevier’s Biological Psychiatry, provides insights into how these types of rumination are represented in the brains of depressed persons.

The interactions of two distinct and competing neural networks, the default mode network (DMN) and the task positive network (TPN), are particularly relevant to this question. Whereas the DMN supports passive, self-related thought, the TPN underlies active thinking required for solving problems, explained study author J. Paul Hamilton.

Using brain imaging technology, Hamilton and his colleagues found that, in depressed patients, increasing levels of activity in the DMN relative to the TPN are associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination. These findings indicate that the DMN and TPN interact in depression to promote depression-related thinking, with stronger DMN influence associated with more worrying, less effective coping, and more severe depression.

“It makes sense that non-productive ruminations would engage default-mode networks in the brain as these systems enable the brain to ‘idle’ when humans are not focused on specific tasks,” commented Dr. John Krystal, editor of Biological Psychiatry. “Better understanding the factors that control the switch between these modes of function may provide insights into depression and its treatment.”

Material adapted from Elsevier.

Reference
The article is “Default-Mode and Task-Positive Network Activity in Major Depressive Disorder: Implications for Adaptive and Maladaptive Rumination” by J. Paul Hamilton, Daniella J. Furman, Catie Chang, Moriah E. Thomason, Emily Dennis, and Ian H. Gotlib. The authors are affiliated with Stanford University, Stanford, California. The article appears in Biological Psychiatry, Volume 70, Number 4 (August 15, 2011), DOI 10.1016/j.biopsych.2011.02.003, published by Elsevier.

The researchers report in the journal Frontiers in Human Neuroscience that they used functional magnetic resonance imaging (fMRI) to identify areas of the brain activated when study participants thought about physical objects such as a carrot, a horse or a house. The researchers then generated a list of topics related to those objects and used the fMRI images to determine the brain activity that words within each topic shared. For instance, thoughts about “eye” and “foot” produced similar neural stirrings as other words related to body parts.

Once the researchers knew the brain activity a topic sparked, they were able to use fMRI images alone to predict the subjects and words a person likely thought about during the scan. This capability to put people’s brain activity into words provides an initial step toward further exploring themes the human brain touches upon during complex thought.

“The basic idea is that whatever subject matter is on someone’s mind — not just topics or concepts, but also, emotions, plans or socially oriented thoughts — is ultimately reflected in the pattern of activity across all areas of his or her brain,” said the team’s senior researcher, Matthew Botvinick, an associate professor in Princeton’s Department of Psychology and in the Princeton Neuroscience Institute.

“The long-term goal is to translate that brain-activity pattern into the words that likely describe the original mental ‘subject matter,’” Botvinick said. “One can imagine doing this with any mental content that can be verbalized, not only about objects, but also about people, actions and abstract concepts and relationships. This study is a first step toward that more general goal.

“If we give way to unbridled speculation, one can imagine years from now being able to ‘translate’ brain activity into written output for people who are unable to communicate otherwise, which is an exciting thing to consider. In the short term, our technique could be used to learn more about the way that concepts are represented at the neural level — how ideas relate to one another and how they are engaged or activated.”

The research, which was published Aug. 23, was funded by a grant from the National Institute of Neurological Disease and Stroke, part of the National Institutes of Health.

Depicting a person’s thoughts through text is a “promising and innovative method” that the Princeton project introduces to the larger goal of correlating brain activity with mental content, said Marcel Just, a professor of psychology at Carnegie Mellon University. The Princeton researchers worked from brain scans Just had previously collected in his lab, but he had no active role in the project.

“The general goal for the future is to understand the neural coding of any thought and any combination of concepts,” Just said. “The significance of this work is that it points to a method for interpreting brain activation patterns that correspond to complex thoughts.”

Tracking the brain’s ‘semantic threads’
Largely designed and conducted in Botvinick’s lab by lead author and Princeton postdoctoral researcher Francisco Pereira, the study takes a currently popular approach to neuroscience research in a new direction, Botvinick said. He, Pereira and coauthor Greg Detre, who earned his Ph.D. from Princeton in 2010, based their work on various research endeavors during the past decade that used brain-activity patterns captured by fMRI to reconstruct pictures that participants viewed during the scan.

“This ‘generative’ approach — actually synthesizing something, an artifact, from the brain-imaging data — is what inspired us in our study, but we generated words rather than pictures,” Botvinick said.

“The thought is that there are many things that can be expressed with language that are more difficult to capture in a picture. Our study dealt with concrete objects, things that are easy to put into a picture, but even then there was an interesting difference between generating a picture of a chair and generating a list of words that a person associates with ‘chair.’”

Those word associations, lead author Pereira explained, can be thought of as “semantic threads” that can lead people to think of objects and concepts far from the original subject matter yet strangely related.

“Someone will start thinking of a chair and their mind wanders to the chair of a corporation then to Chairman Mao — you’d be surprised,” Pereira said. “The brain tends to drift, with multiple processes taking place at the same time. If a person thinks about a table, then a lot of related words will come to mind, too. And we thought that if we want to understand what is in a person’s mind when they think about anything concrete, we can follow those words.”

Pereira and his co-authors worked from fMRI images of brain activity that a team led by Just and fellow Carnegie Mellon researcher Tom Mitchell, a professor of computer science, published in the journal Science in 2008. For those scans, nine people were presented with the word and picture of five concrete objects from 12 categories. The drawing and word for the 60 total objects were displayed in random order until each had been shown six times. Each time an image and word appeared, participants were asked to visualize the object and its properties for three seconds as the fMRI scanner recorded their brain activity.

Princeton researchers developed a method to determine the probability of various words being associated with the object a person thought about during a brain scan. They produced color-coded figures that illustrate the probability of words within the Wikipedia article about the object the participant saw during the scan actually being associated with the object. The more red a word is, the more likely a person is to associate it, in this case, with "cow." On the other hand, bright blue suggests a strong correlation with "carrot." Black and grey "neutral" words had no specific association or were not considered at all. Credit: Courtesy of Francisco Pereira

The computer ultimately created a database of topics and associated words that were free from the researchers’ biases, Pereira said.

“We let the software discern the factors that make up meaning rather than stipulating it ourselves,” he said. “There is always a danger that we could impose our preconceived notions of the meaning words have. Plus, I can identify and describe, for instance, a bird, but I don’t think I can list all the characteristics that make a bird a bird. So instead of postulating, we let the computer find semantic threads in an unsupervised manner.”

The topic database let the researchers objectively arrange the fMRI images by subject matter, Pereira said. To do so, the team searched the brain scans of related objects for similar activity to determine common brain patterns for an entire subject, Pereira said. The neural response for thinking about “furniture,” for example, was determined by the common patterns found in the fMRI images for “table,” “chair,” “bed,” “desk” and “dresser.” At the same time, the team established all the words associated with “furniture” by matching each fMRI image with related words from the Wikipedia-based list.

Based on the similar brain activity and related words, Pereira, Botvinick and Detre concluded that the same neural response would appear whenever a person thought of any of the words related to furniture, Pereira said. And a scientist analyzing that brain activity would know that person was thinking of furniture. The same would follow for any topic.

Using images to predict the words on a person’s mind
Finally, to ensure their method was accurate, the researchers conducted a blind comparison of each of the 60 fMRI images against each of the others. Without knowing the objects the pair of scans pertained to, Pereira and his colleagues estimated the presence of certain topics on a participant’s mind based solely on the fMRI data. Knowing the applicable Wikipedia topics for a given brain image, and the keywords for each topic, they could predict the most likely set of words associated with the brain image.

The researchers found that they could confidently determine from an fMRI image the general topic on a participant’s mind, but that deciphering specific objects was trickier, Pereira said. For example, they could compare the fMRI scan for “carrot” against that for “cow” and safely say that at the time the participant had thought about vegetables in the first example instead of animals. In turn, they could say that the person most likely thought of other words related to vegetables, as opposed to words related to animals.

On the other hand, when the scan for “carrot” was compared to that for “celery,” Pereira and his colleagues knew the participant had thought of vegetables, but they could not identify related words unique to either object.

One aim going forward, Pereira said, is to fine-tune the group’s method to be more sensitive to such detail. In addition, he and Botvinick have begun performing fMRI scans on people as they read in an effort to observe the various topics the mind accesses.

“Essentially,” Pereira said, “we have found a way to generally identify mental content through the text related to it. We can now expand that capability to even further open the door to describing thoughts that are not amenable to being depicted with pictures.”

Material adapted from Princeton University.

Patients who ruminate and activate the brain’s frontal lobes are more likely to relapse into depression than those who respond with acceptance and activate visual areas in the back of the brain. Part of what makes depression such a devastating disorder is the high rate of relapse: each time a person becomes clinically depressed, increases their chances of becoming depressed by 16%. However, the fact that some patients are able to fully maintain their recovery points to the possibility that differences in the way they respond to everyday emotional challenges may reduce their chances of relapse.

Using functional magnetic resonance imaging to examine that possibility, researchers presented sixteen formerly-depressed patients with sad movie clips while taking pictures of their brain activity. Over the next year and a half, nine of the sixteen patients relapsed into depression. The researchers compared the brain activity of relapsing patients against those who remained healthy and against another group of people who had never been depressed.

When faced with sadness, relapsing patients showed more activity in a frontal region of the brain known as the medial prefrontal gyrus. Responses in this frontal region were also linked to higher rumination scores, the tendency to think obsessively about negative events. Patients who did not relapse showed more activity in the rear part of the brain responsible for processing visual information. Responses in this visual area were also linked to greater feelings of acceptance and non-judgment of experience. Both the frontal and visual responses to sadness were atypical in that they were not found in people who had never been depressed.

“Despite achieving an apparent recovery from the symptoms of depression, this study suggests that there are important differences in how formerly depressed people respond to emotional challenges that predict future well-being,” explained author Dr. Norman Farb. “For a person with a history of depression, using the frontal brain’s ability to analyze and interpret sadness may actually be an unhealthy reaction that can perpetuate the chronic cycle of depression.”

Dr. John Krystal, editor of Biological Psychiatry added, “Relapse is one of the most vexing problems in depression treatment. Having a biomarker for relapse could guide a new generation of treatment research.”

Further evaluation is needed to determine whether the brain’s reaction to sadness can predict a person’s risk for future depression on an individual, case-by-case basis. It will also be important to examine whether people identified as being at risk for relapse can be trained to change their way of responding to negative emotion or whether treatment strategies can be developed that would target the hyperactivity of this cortical region when processing sad or other negative stimuli.

Material adapted from Elsevier.

Reference
The article is “Mood-Linked Responses in Medial Prefrontal Cortex Predict Relapse in Patients with Recurrent Unipolar Depression” by Norman A.S. Farb, Adam K. Anderson, Richard T. Bloch, and Zindel V. Segal. The authors are affiliated with University of Toronto, Toronto, Ontario, Canada. Farb and Anderson are also with Rotman Research Institute, Baycrest, Toronto, Ontario, Canada. The article appears in Biological Psychiatry, Volume 70, Number 4 (August 15, 2011), DOI 10.1016/j.biopysch.2011.03.009, published by Elsevier.

Researcher John Gabrieli

The new study, published in the journal NeuroImage, found that when the PHC was very active before people were shown an image, they were less likely to remember it later. “When that area is busy, for some reason or another, it’s less ready to learn something new,” says Gabrieli, the Grover Hermann Professor of Health Sciences and Technology and Cognitive Neuroscience and a principal investigator at the McGovern Institute for Brain Research at MIT.

The PHC, which has previously been linked to recollection of visual scenes, wraps around the hippocampus, a part of the brain critical for memory formation. However, this study is the first to investigate how PHC activity before a scene was presented would affect how well the scene was remembered. Lead author of the paper is Julie Yoo, a postdoc at the McGovern Institute.

Subjects were shown 250 color photographs of indoor and outdoor scenes as they lay in a functional magnetic resonance imaging (fMRI) scanner. They were later shown 500 scenes — including the 250 they had already seen — as a test of their recollection of the first batch of images. The fMRI scans revealed that images were remembered better when there was lower activity in the PHC before the scenes were presented.

The precise area of activation was slightly different in each person studied, but was always located in the PHC.

In a second experiment, the researchers used real-time fMRI, which can monitor subjects’ brain states from moment to moment, to determine when the brain was “ready” or “not ready” to recall images. Those states were used as triggers to present new visual scenes. As expected, images presented while the brain was in a “ready” state were better remembered.

In theory, this method could be used to determine when a student is best prepared to learn new material, or to monitor workers who need to stay alert. “That’s what we would like to think — that we are able to measure states of receptivity for learning, or preparedness for learning,” Gabrieli says. “In terms of how that would be translated to real life, there are still a few steps to go.”

The main hurdle is that fMRI scanners are very large, and at this point, they cannot be made into small, portable devices. A possible alternative is using electroencephalography (EEG), a more easily miniaturized technology that measures electrical activity along the scalp. The researchers are now working on ways to use EEG to measure activity in the PHC.

Material adapted from MIT.

The study was the first to look at sub-regions in the part of the brain known as the hippocampus. Abnormalities in the hippocampus are among the most consistent findings in schizophrenia research and are also implicated in bipolar disorder. Certain areas of the hippocampus (cornu ammonis regions 2 and 3) were found to be different, in terms of how their proteins are affected, in people with schizophrenia and bipolar disorder compared to the general population. The differences observed in these regions were found to be almost identical in both conditions.

A process which controls how information is transmitted by the shuttling of proteins to and from the synapse (a junction that permits a neuron to pass a signal to another cell) was also found to be is affected in both illnesses.

Professor David Cotter, Department of Psychiatry, RCSI and Beaumont Hospital commented: “Our study is the first to show the depth of protein similarities between schizophrenia and bipolar disorder as they appear in the brain and the processes associated with them. Although, the two conditions present with different symptoms, the research has shown that they are almost identical in terms of how they present in the brain,” Professor Cotter concluded.

Material adapted from Royal College of Surgeons in Ireland (RCSI).

Reference
Melanie Föcking, Patrick Dicker, Jane A. English, K. Oliver Schubert, Michael J. Dunn, David R. Cotter. Common Proteomic Changes in the Hippocampus in Schizophrenia and Bipolar Disorder and Particular Evidence for Involvement of Cornu Ammonis Regions 2 and 3. Archives of General Psychiatry. 68 (5): 477-88

The study of 311 people in their 70s and 80s with no cognitive problems from the population-based Mayo Clinic Study of Aging used an advanced brain imaging technique called proton MR spectroscopy to see if they had abnormalities in several brain metabolites that may be biomarkers for Alzheimer’s disease. They also had PET scans to assess the level of amyloid-beta deposits, or plaques, in the brain that are one of the first signs of changes in the brain due to Alzheimer’s disease. The participants were also given tests of memory, language and other skills.

“There is increasing evidence that Alzheimer disease is associated with changes in the brain that start many years before symptoms develop,” said Jonathan M. Schott, MD, of the Dementia Research Centre, University College London in England and a member of the American Academy of Neurology, who wrote an editorial accompanying the study. “If we could identify people in whom the disease process has started but symptoms have not yet developed, we would have a potential window of opportunity for new treatments—as and when they become available—to prevent or delay the start of memory loss and cognitive decline.”

The study found that 33 percent of the participants had significantly high levels of amyloid-beta deposits in their brains. Those with high levels of amyloid-beta deposits also tended to have high levels of the brain metabolites myoinositol/creatine and choline/creatine. People with high levels of choline/creatine were more likely to have lower scores on several of the cognitive tests, regardless of the amount of amyloid-beta deposits in their brains.

“This relationship between amyloid-beta deposits and these metabolic changes in the brain are evidence that some of these people may be in the earliest stages of the disease,” said study author Kejal Kantarci, MD, MSc, of the Mayo Clinic in Rochester, Minn., and a member of the American Academy of Neurology. “More research is needed that follows people over a period of years to determine which of these individuals will actually develop the disease and what the relationship is between the amyloid deposits and the metabolites.”

The study was supported by the Paul Beeson Award in Aging, National Institutes of Health and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation.

Material adapted from American Academy of Neurology (AAN).

Researcher Marcel Just

A new brain imaging study published in the journal “Brain” by scientists at Carnegie Mellon University provides an explanation as to why autistic individuals’ use of the wrong pronoun is more than simply a word choice problem. Marcel Just, Akiki Mizuno and their collaborators at CMU’s Center for Cognitive Brain Imaging (CCBI) found that errors in choosing a self-referring pronoun reflect a disordered neural representation of the self, a function processed by at least two brain areas — one frontal and one posterior.

“The psychology of self — the thought of one’s own identity — is especially important in social interaction, a facet of behavior that is usually disrupted in autism,” said Just, a leading cognitive neuroscientist and the D.O. Hebb Professor of Psychology at CMU who directs the CCBI. “Most children don’t need to receive any instruction in which pronoun to use. It just comes naturally, unless a child has autism.”

For the study, the research team used functional magnetic resonance imaging (fMRI) to compare the brain activation pattern and the synchronization of activation across brain areas in young adults with high-functioning autism with control participants during a language task that required rapid pronoun comprehension.

The results revealed a significantly diminished synchronization in autism between a frontal area (the right anterior insula) and a posterior area (precuneus) during pronoun use in the autism group. The participants with autism also were slower and less accurate in their behavioral processing of the pronouns. In particular, the synchronization was lower in autistic participants’ brains between the right anterior insula and precuneus when answering a question that contained the pronoun “you,” querying something about the participant’s view.

“Shifting from one pronoun to another, depending on who the speaker is, constitutes a challenge not just for children with autism but also for adults with high-functioning autism, particularly when referring to one’s self,” Just said. “The functional collaboration of two brain areas may play a critical role for perspective shifting by supporting an attention shift between oneself and others.

“Pronoun reversals also characterize an atypical understanding of the social world in autism. The ability to flexibly shift viewpoints is vital to social communication, so the autistic impairment affects not just language but social communication,” Just added.

Autism was documented for the first time in 1943, in a landmark article by Dr. Leo Kanner of Johns Hopkins University. In that first article, Kanner noted the puzzling misuse of pronouns by children with the disorder. “When he [the child] wanted his mother to pull his shoe off, he said: ‘Pull off your shoe.’” Kanner added that, “Personal pronouns are repeated [by the child with autism] just as heard, with no change to suit the altered situation.” Because his mother referred to him as “you,” so did the child.

Just’s previous brain imaging research in autism has shown that other facets of thinking that are disrupted in autism, such as social difficulties and language impairments, also may be attributed to a reduced communication bandwidth between the frontal and posterior parts of the brain. He refers to this as the “Theory of Frontal-Posterior Underconnectivity.” In each of these types of thinking, the processing is done by a set of different brain regions that includes key frontal regions, and the lower frontal-posterior bandwidth limits how well the frontal regions can contribute to the brain’s networked computations.

The brain’s communication network is its white matter, the 45 percent of the brain that consists of myelinated (insulated) axons that carry information between brain regions. An emerging view is that the white matter is compromised in autism, specifically in the frontal-posterior tracts. In a groundbreaking study published in 2009, Just and his colleagues showed for the first time that compromised white matter in children with reading difficulties could be repaired with extensive behavioral therapy. Their imaging study showed that the brain locations that had been abnormal prior to the remedial training improved to normal levels after the training, and the reading performance in individual children improved by an amount that corresponded to the amount of white matter change. Ongoing research at the CCBI is assessing the white matter in detail, measuring its integrity and topology, trying to pinpoint the difference in the autistic brain’s networks.

“This new understanding of what causes pronoun confusion in autism helps make sense of the larger problems of autism as well as the idiosyncrasies,” Just said. “Moreover, it points to new types of therapies that may help rehab the white matter in autism.”

In addition to Just and Mizuno, a psychology doctoral candidate and first author of the study, the research team included CMU’s Yanni Liu, a postdoctoral associate, and Timothy A. Keller, a senior research psychologist; Duquesne University’s Diane L. Williams, an assistant professor of speech-language pathology; and the University of Pittsburgh School of Medicine’s Nancy J. Minshew, a professor of psychiatry and neurology.

Material adapted from Carnegie Mellon University.

Researcher Charles DeCarli, M.D.

“This study provides evidence that identifying these risk factors early in middle age could be useful in screening people at risk of dementia and in encouraging them to make changes in their lifestyles before it’s too late,” said Charles DeCarli, a professor of neurology in the UC Davis School of Medicine and director of the UC Davis Alzheimer’s Disease Center.

The study examined the relationships between midlife vascular risk factors and markers for brain aging based on magnetic resonance imaging (MRI). The indicators are associated with cognitive decline and dementia later in life.

The current study was conducted with data from participants in the Framingham Offspring Cohort Study, a multi-site, prospective cohort study comprised of three generations of the offspring and spouses of participants in the Framingham Heart Study. Some 1,352 of the study participants were included in the current research. The study subjects had an average age of 54.

Study participants have been followed since 1978 to identify vascular disease risk factors, and were repeatedly assessed for those risk factors, which included an elevated body mass index, hypertension, obesity, diabetes and smoking.

Beginning in 1999, the researchers obtained measures of vascular disease such as the volume of white matter hyperintensities, or areas on MRI that appear bright white that are associated with increased vascular damage. Other measurements included changes in total brain volume and changes in cognitive tests of verbal and spatial memory and decision-making capabilities.

The study found that people with high blood pressure developed white matter hyperintensities at a faster rate than those with normal blood pressure and had a more rapid decline in scores on tests of executive function, or planning and decision making. Participants who were obese were more likely to be in the top 25 percent of people with a greater rate of decline in scores on tests of executive functioning abilities later in life.

The study also found that participants with diabetes in mid-life had lost brain volume in the hippocampus brain region at a faster rate than those without diabetes when they were older. Study subjects who smoked lost overall brain volume faster than non-smokers and also were more likely to have a rapid increase in white matter hyperintensities.

“These factors appeared to cause the brain to lose volume, to develop lesions secondary to presumed vascular injury, and also appeared to affect the brain’s ability to plan and make decisions as quickly as it had 10 years earlier,” said DeCarli, who is a fellow of the American Academy of Neurology.

Other study authors include Stephanie Debette, Sudha Seshadri, Alexa Besier, Jayandra Jung Himali, Carole Palumbo and Philip A. Wolf, all of Boston University.

Material adapted from UC Davis Health System.

Over twenty years ago, a team of scientists, led by Giacomo Rizzolatti at the University of Parma, discovered special brain cells, called mirror neurons, in monkeys. These cells appeared to be activated both when the monkey did something itself and when the monkey simply watched another monkey do the same thing.

The function of such mirror neurons in humans has since become a hot topic. In the latest issue of Perspectives on Psychological Science, a team of distinguished researchers debate whether the mirror neuron system is involved in such diverse processes as understanding speech, understanding the meaning of other people’s actions, and understanding other people’s minds.

Understanding Speech
The mirror neuron system probably plays some role in how we understand other people’s speech, but it’s likely that this role is much smaller than has been previously claimed. In fact, the role is small enough that it’s unlikely that mirror neurons would be causal factors in our ability to understand speech. Mirror neuron-related processes may only contribute to understanding what another person is trying to say if the room is very noisy or there are other complications to normal speech perception conditions.

Understanding Actions
Mirror neurons are believed to play a critical role in how and why we understand other people’s actions. There are many physical actions, like Tiger Woods’ golf swing, that we ourselves can’t do, but we understand those actions anyway. However, contrary to what some mirror neuron proponents have suggested, doing isn’t required for understanding. In fact, neuroimaging data reviewed in this article demonstrate that the actions we ourselves have the most experience doing — the actions we are best at doing and understand best — actually show less mirror neuron activity. Such findings suggest a need to reappraise the role of mirror neurons in guiding how we understand actions.

Understanding Minds
One of the most powerful roles suggested for the mirror neuron system in humans is that of understanding not just other people’s physical actions or speech, but their minds and their intentions. It has been suggested that some persons, such as persons with autism, have difficulty understanding other people’s minds and, therefore, might lack mirror neurons. However, numerous research studies reviewed in this article consistently show that persons with autism are highly capable of understanding the intentions of other people’s actions, suggesting that our intuitions about persons with autism and mirror neurons needs to be revised.

This article presents some of the toughest questions asked about mirror neurons to date. The answers to those questions, guided by hundreds of research studies, clarify the limits of the function of mirror neurons in humans.

Material adapted from Association for Psychological Science.

Researcher Charles DeCarli, M.D.

“These factors appeared to cause the brain to lose volume, to develop lesions secondary to presumed vascular injury, and also appeared to affect its ability to plan and make decisions as quickly as 10 years later. A different pattern of association was observed for each of the factors,” said study author Charles DeCarli, MD, with the University of California at Davis in Sacramento and a Fellow of the American Academy of Neurology. “Our findings provide evidence that identifying these risk factors early in people of middle age could be useful in screening people for at-risk dementia and encouraging people to make changes to their lifestyle before it’s too late.”

The study involved 1,352 people without dementia from the Framingham Offspring Study with an average age of 54. Participants had body mass and waist circumference measures taken and were given blood pressure, cholesterol and diabetes tests. They also underwent brain MRI scans over the span of a decade, the first starting about seven years after the initial risk factor exam. Participants with stroke and dementia at baseline were excluded, and between the first and last MRI exams, 19 people had a stroke and two developed dementia.

The study found that people with high blood pressure developed white matter hyperintensities, or small areas of vascular brain damage, at a faster rate than those with normal blood pressure readings and had a more rapid worsening of scores on tests of executive function, or planning and decision making, corresponding to five and eight years of chronological aging respectively.

People with diabetes in middle age lost brain volume in the hippocampus (measured indirectly using a surrogate marker) at a faster rate than those without diabetes. Smokers lost brain volume overall and in the hippocampus at a faster rate than nonsmokers and were also more likely to have a rapid increase in white matter hyperintensities.

People who were obese at middle age were more likely to be in the top 25 percent of those with the faster rate of decline in scores on tests of executive function, DeCarli said. People with a high waist-to-hip ratio were more likely to be in the top 25 percent of those with faster decrease in their brain volume.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke and the National Institute on Aging.

Material adapted from American Academy of Neurology (AAN).

Cigarette smoking is the second leading cause of preventable death and is an important risk factor for coronary artery disease, lung disease, suicide and cancer, according to background information in the article.

“Although many people who smoke cigarettes would like to quit, the effects of withdrawal frequently lead to relapse,” write the authors. “Relapse is particularly problematic in early withdrawal because 50 percent of people relapse within the first 3 days of quitting.”

Previous research into early cigarette withdrawal has focused on nicotine’s modulation of dopamine-releasing neurons. “However, other neural targets that may be important in cigarette withdrawal are affected by cigarette smoke,” write the authors. For instance, the enzyme monoamine oxidase A (MAO-A), which metabolizes mood-enhancing chemicals, has been shown to be affected by cigarette smoke. In regions of the brain that modulate affect (mood), such as the prefrontal cortex and anterior cingulate cortex, elevations in MAO-A binding are associated with depressive episodes. “The main hypothesis of this study,” the authors explain, “is that MAO-A binding increases during acute cigarette withdrawal in regions implicated in affect regulation, such as the prefrontal cortex and the anterior cingulate cortex.”

Researchers conducted a study of 24 healthy, nonsmoking individuals and 24 otherwise healthy cigarette-smoking individuals. Among the latter group, 12 were moderate smokers (15 to 24 cigarettes per day) and 12 were heavy smokers (25 or more cigarettes per day). Positron emission tomography (PET) scans were performed once in nonsmokers and twice in smokers (once after active cigarette smoking and once after acute withdrawal). Before scans were conducted, participants also completed an assessment of their mood, energy level, anxiety level and urge to smoke.

An elevation in MAO-A density during cigarette withdrawal was found in the heavy-smoking subgroup but not the moderate-smoking subgroup, with a magnitude of change of 23.7 percent and 33.3 percent in the prefrontal and anterior cingulate cortices, respectively. A highly significant interaction between smoking severity and condition (measurement of MAO-A density during active smoking and withdrawal) was noticed among participants who smoked heavily. The MAO-A density levels in the prefrontal and anterior cingulate cortex were also significantly greater during heavy smokers’ withdrawal period compared with healthy nonsmoking controls. In heavy-smoking individuals, researchers also noticed a change in depressed mood self-report between the withdrawal day and the active smoking day.

“These results have significant implications for quitting heavy smoking and for understanding what has previously appeared to be a paradoxical association of cigarette smoking with major depressive disorder and suicide,” state the authors. “Understanding the neurobiology of heavy cigarette smoking is important because those who smoke heavily are much more likely to have major depressive disorder and to experience medical complications resulting from cigarette smoking.”

The researchers also call for clinical trials of MAO-A inhibiting drugs among individuals in the earliest stages of quitting heavy cigarette smoking.

Material adapted from JAMA.

Reference
Arch Gen Psychiatry. 2011;68[8]:817-826.

“We are on track to develop, test and make available to the public- within the next few years – a safe, reliable, noninvasive brain computer interface that can bring life-changing technology to millions of people whose ability to move has been diminished due to paralysis, stroke or other injury or illness,” said Contreras-Vidal of the university’s School of Public Health.

Harsha Agashe, a Ph.D. student in Contreras-Vidal's lab wears the Brain Cap, a non-invasive, sensor-lined cap with neural interface software. Photo Credit - John Consoli, University of Maryland.

“We are doing something that few previously thought was possible,” said Contreras-Vidal, who is also an affiliate professor in Maryland’s Fischell Department of Bioengineering and the university’s Neuroscience and Cognitive Science Program. “We use EEG [electroencephalography] to non-invasively read brain waves and translate them into movement commands for computers and other devices.

Peer Reviewed
Contreras-Vidal and his team have published three major papers on their technology over the past 18 months, the latest a just released study in the Journal of Neurophysiology in which they successfully used EEG brain signals to reconstruct the complex 3-D movements of the ankle, knee and hip joints during human treadmill walking. In two earlier studies they showed (1) similar results for 3-D hand movement and (2) that subjects wearing the brain cap could control a computer cursor with their thoughts.

Alessandro Presacco, a second-year doctoral student in Contreras-Vidal’s Neural Engineering and Smart Prosthetics Lab, Contreras-Vidal and co-authors write that their Journal of Neurophysiology study indicated “that EEG signals can be used to study the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function.”

There are other brain computer interface technologies under development, but Contreras-Vidal notes that these competing technologies are either very invasive, requiring electrodes to be implanted directly in the brain, or, if noninvasive, require much more training to use than does UMD’s EEG-based, brain cap technology.

Partnering to Help Sufferers of Injury and Stroke 
Contreras-Vidal and his team are collaborating on a rapidly growing cadre projects with researchers at other institutions to develop thought-controlled robotic prosthetics that can assist victims of injury and stroke. Their latest partnership is supported by a new $1.2 million NSF grant. Under this grant, Contreras-Vidal’s Maryland team is embarking on a four-year project with researchers at Rice University, the University of Michigan and Drexel University to design a prosthetic arm that amputees can control directly with their brains, and which will allow users to feel what their robotic arm touches.

“There’s nothing fictional about this,” said Rice University co-principal investigator Marcia O’Malley, an associate professor of mechanical engineering. “The investigators on this grant have already demonstrated that much of this is possible. What remains is to bring all of it – non-invasive neural decoding, direct brain control and [touch] sensory feedback – together into one device.”

In a NIH-supported project underway, Contreras-Vidal and his colleagues are pairing their brain cap’s EEG-based technology with a DARPA-funded next-generation robotic arm designed by researchers at the Johns Hopkins Applied Physics Laboratory to function like a normal limb. And the UMD team is developing a new collaboration with the New Zealand’s start-up Rexbionics, the developer of a powered lower-limb exoskeleton called Rex that could be used to restore gait after spinal cord injury.

During research at the Veterans Affairs Medical Center in Baltimore, Alessandro Presacco, a graduate researcher in UMD's Neural Engineering and Smart Prosthetics Lab, gets hooked up to take data similar to that used to reconstruct the complex 3-D movements of the ankle, knee and hip joints during treadmill walking. Photo Credit - University of Maryland.

“There is a big push in brain science to understand what exercise does in terms of motor learning or motor retraining of the human brain,” says Larry Forrester, an associate professor of physical therapy and rehabilitation science at the University of Maryland School of Medicine.

For the more than a year, Forrester and the UMD team have tracked the neural activity of people on a treadmill doing precise tasks like stepping over dotted lines. The researchers are matching specific brain activity recorded in real time with exact lower-limb movements.

This data could help stroke victims in several ways, Forrester says. One is a prosthetic device, called an “anklebot,” or ankle robot, that stores data from a normal human gait and assists partially paralyzed people. People who are less mobile commonly suffer from other health issues such as obesity, diabetes or cardiovascular problems, Forrester says, “so we want to get [stroke survivors] up and moving by whatever means possible.”

The second use of the EEG data in stroke victims is more complex, yet offers exciting possibilities. “By decoding the motion of a normal gait,” Contreras-Vidal says, “we can then try and teach stroke victims to think in certain ways and match their own EEG signals with the normal signals.” This could “retrain” healthy areas of the brain in what is known as neuroplasticity.

One potential method for retraining comes from one of the Maryland research team’s newest members, Steve Graff, a first-year bioengineering doctoral student. He envisions a virtual reality game that matches real EEG data with on-screen characters. “It gives us a way to train someone to think the right thoughts to generate movement from digital avatars. If they can do that, then they can generate thoughts to move a device,” says Graff, who brings a unique personal perspective to the work. He has congenital muscular dystrophy and uses a motorized wheelchair. The advances he’s working on could allow him to use both hands – to put on a jacket, dial his cell phone or throw a football while operating his chair with his mind.

Alessandro Presacco, a graduate researcher in UMD's Neural Engineering and Smart Prosthetics Lab, adjust a version of Brain Cap headset worn by Steve Graff, a bioengineering doctoral student . Looking on is Lab director and Brain Cap creator José 'Pepe' Contreras-Vidal. Photo Credit - University of Maryland.

No Surgery Required
During the past two decades a great deal of progress has been made in the study of direct brain to computer interfaces, most of it through studies using monkeys with electrodes implanted in their brains. However, for use in humans such an invasive approach poses many problems, not the least of which is that most people don’t’ want holes in their heads and wires attached to their brains.

“EEG monitoring of the brain, which has a long, safe history for other applications, has been largely ignored by those working on brain-machine interfaces, because it was thought that the human skull blocked too much of the detailed information on brain activity needed to read thoughts about movement and turn those readings into movement commands for multi-functional high-degree of freedom prosthetics,” said Contreras-Vidal. He is among the few who have used EEG, MEG or other sensing technologies to develop non-invasive neural interfaces, and the only one to have demonstrated decoding results comparable to those achieved by researchers using implanted electrodes.

A paper Contreras-Vidal and colleagues published in the Journal of Neuroscience in March 2010 showed the feasibility of Maryland’s EEG-based technology to infer multidimensional natural movement from noninvasive measurements of brain activity. In their two latest studies, Contreras-Vidal and his team have further advanced the development of their EEG brain interface technology, and provided powerful new evidence that it can yield brain computer interface results as good as or better than those from invasive studies, while also requiring minimal training to use.

In a paper published in April in the Journal of Neural Engineering, the Maryland team demonstrated that people wearing the EEG brain cap, could after minimal training control a computer cursor with their thoughts and achieve performance levels comparable to those by subjects using invasive implanted electrode brain computer interface systems. Contreras-Vidal and his co-authors write that this study also shows that compared to studies of other noninvasive brain control interface systems, training time with their system was substantially shorter, requiring only a single 40-minute session.

Material adapted from University of Maryland, College Park.

Professor Rafael Malach

By scanning the brain activity of sleeping children, the scientists discovered that the autistic brains exhibited significantly weaker synchronization between brain areas tied to language and communication, compared to that of non-autistic children.

“Identifying biological signs of autism has been a major goal for many scientists around the world, both because they may allow early diagnosis, and because they can provide researchers with important clues about the causes and development of the disorder,” says postdoctoral fellow Dr. Ilan Dinstein, a member of the group of Prof. Rafael Malach, who headed this study in the Weizmann Institute’s Neurobiology Department. While many scientists believe that faulty lines of communication between different parts of the brain are involved in the spectrum of autism disorders, there was no way to observe this in very young children, who are unable to lie still inside an fMRI scanner while they are awake.

But work by Malach’s group and other research groups pointed to a solution. Their studies had shown that even during sleep, the brain does not actually switch off. Rather, the electrical activity of the brain cells switches over to spontaneous fluctuation. These fluctuations are coordinated across the two hemispheres of the brain such that each point on the left is synchronized with its corresponding point in the right hemisphere.

As compared to the control brain (top), the autistic brain (bottom) shows weaker inter-hemispheric synchronization in several areas, particularly the superior temporal gyrus (light blue) and the inferior frontal gyrus (red).

In sleeping autistic toddlers, the fMRI scans showed lowered levels of synchronization between the left and right brain areas known to be involved in language and communication. This pattern was not seen either in children with normal development or in those with delayed language development who were not autistic. In fact, the researchers found that this synchronization was strongly tied to the autistic child’s ability to communicate: The weaker the synchronization, the more severe were the symptoms of autism. On the basis of the scans, the scientists were able to identify 70% of the autistic children between the ages of one and three.

Dinstein: “This biological measurement could help diagnose autism at a very early stage. The goal for the near future is to find additional markers that can improve the accuracy and the reliability of the diagnosis.”

Material adapted from Weizmann Institute of Science.

The study “Aging of the Cerebral Cortex Differs Between Humans and Chimpanzees” is the first study of its kind in this field and will be published in the “Proceedings of the National Academy of Sciences” on July 25, 2011.

“Although other animals experience some cognitive impairment and brain atrophy as they age, it appears that human aging is marked by more dramatic degeneration,” said Dr. Sherwood, associate professor of anthropology in GW’s Columbian College of Arts and Sciences.

The researchers used magnetic resonance imaging (MRI) to measure the volume of the whole brain and numerous specific internal structures using a sample of 99 chimpanzee brains ranging from 10-51 years of age. This data were compared to brain structure volumes measured in 87 humans ranging from 22-88 years of age.

Measurements of the neocortical gray and white matter, frontal lobe gray and white matter, and the hippocampus were performed. In contrast to humans, who showed a decrease in the volume of all brain structures over the lifespan, chimpanzees did not display significant age-related changes. Furthermore, the effects of aging in humans were only evident after the maximum age of chimpanzees. As a result, the researchers concluded that the brain shrinkage seen in human aging is evolutionarily novel and is the result of an extended lifespan.

The hippocampus, the area of the brain responsible for encoding new memories and maintaining spatial navigation, was of specific interest to the researchers, as this area is especially vulnerable to age-associated atrophy in humans. In addition, the hippocampus is the region of the brain most prominently affected by Alzheimer’s disease (AD), an illness that is only seen in primarily older humans. AD is a form of dementia that is associated with a loss of brain function, impacting memory, thinking and behavior. AD is a result of neurodegeneration, which is the progressive loss of structure or function of neurons, including the death of neurons. The unique vulnerability seen in humans to develop AD may be in part due to the human tendency to show more pronounced brain atrophy than any other species, even in normal, healthy aging.

“What’s really unusual for humans is the combination of an extremely long life and a large brain,” said Dr. Sherwood. “While there are certainly benefits to both of these adaptations, it seems that more intense decline in brain volume in the elderly of our species is a cost.”

Material adapted from George Washington University.

German neuroscientists studied this effect by using neuroimaging to evaluate brain engagement in young and old adults while they performed a specialized cognitive task that included supposedly irrelevant pictures of either neutral, happy, sad, or fearful faces. During parts of the task when they did not have to pay as much attention, the elderly subjects were significantly more distracted by the happy faces. When this occurred, they had increased engagement in the part of the brain that helps control emotions and this stronger signal in the brain was correlated with those who showed the greatest emotional stability.

“Integrating our findings with the assumptions of life span theories we suggest that motivational goal-shifting in healthy aging leads to a self-regulated engagement in positive emotions even when this is not required by the setting,” explained author Dr. Stefanie Brassen. “In addition, our finding of a relationship between rostral anterior cingulate cortex activity and emotional stability further strengthens the hypothesis that this increased emotional control in aging enhances emotional well being.”

“The lessons of healthy aging seem to be similar to those of resilience, throughout life. As recently summarized in other work by Drs. Dennis Charney and Steven Southwick, when coping with extremely stressful life challenges, it is critical to realistically appraise the situation but also to approach it with a positive attitude,” noted Dr. John H. Krystal, the Editor of Biological Psychiatry.

Lifespan theories explain that positivity bias in later life reflects a greater emphasis on short-term rather than long-term priorities. The study by Dr. Brassen and colleagues now provides another clue to how the brain contributes to this age-related shift in priorities.

This makes aging successfully sound so simple – use your brain to focus on the positive.

Material adapted from Elsevier.

Reference / Abstract
The article is “Anterior Cingulate Activation Is Related to a Positivity Bias and Emotional Stability in Successful Aging” by Stefanie Brassen, Matthias Gamer, and Christian Büchel. The authors are affiliated with the Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. The article appears in Biological Psychiatry, Volume 70, Number 2 (July 1, 2011), published by Elsevier.

“If you meet these people on the street, they appear healthy and have no obvious cognitive problems,” says lead author Susan Stark, PhD, assistant professor of occupational therapy and neurology. “But they have changes in their brain that look similar to Alzheimer’s disease, and they have twice the typical annual rate of falls for their age group.”

Stark and her colleagues recruited 119 volunteers from studies of aging and health at Washington University’s Knight Alzheimer’s Disease Research Center. All the participants were 65 or older and cognitively normal.

Brain scans showed that 18 participants had high levels of amyloid plaques, a hallmark of Alzheimer’s. The other 101 volunteers had normal amyloid levels in the brain.

Participants were given a journal and asked to note any falls. When they did so, the researchers followed up with a questionnaire and a phone interview about the falls. This follow-up allowed researchers to gather information for future analyses that will compare and contrast the nature of the falls.

About one in three adults age 65 or older typically fall each year. But in the 18 participants with high amyloid levels in the brain, two-thirds fell within the first eight months of the study. High levels of amyloid in the brain were the best predictor of an increased risk of falls.

“Falls are a serious health concern for older adults,” Stark says. “Our study points to the notion that we may need to consider preclinical Alzheimer’s disease as a potential cause.”

Material adapted from Washington University School of Medicine.

Michela Gallagher, Krieger-Eisenhower Professor of Psychological and Brain Sciences at The Johns Hopkins University.

The researchers emphasize, however, that more studies are necessary before any such recommendation can be made to doctors and patients.

The effects seen in the study “could be like taking your foot off the accelerator or tapping the brakes, and possibly could slow the progression on that path [to Alzheimer's],” said principal investigator and neuroscientist Michela Gallagher. “We need further clinical studies with longer exposure to the drug to, first of all, make sure with rigorous evaluation that the drug is effective in the longer term and, equally important, that it does no harm.”

The new study, presented July 20 at the International Congress on Alzheimer’s Disease in Paris, also shows that excess brain activity in patients with a condition known as amnestic mild cognitive impairment, or aMCI, contributes to brain dysfunction that underlies memory loss. Previously, it had been thought that this hyperactivity was the brain’s attempt to “make up” for weakness in its ability to form new memories.

The clinical study, funded by the National Institutes of Health, tested 34 participants, some healthy older adults and others with aMCI, meaning that they had memory difficulties greater than would be expected at their age. Each person participated in a sequence of two treatment phases lasting two weeks each. Patients received a low dose of levetiracetam during one phase and a placebo during the other.

After each treatment phase, the researchers evaluated subjects’ memory and conducted functional magnetic resonance imaging of their brains. These scans were used to map brain activity during performance of a memory task, allowing the researchers to compare each individual’s status both on and off the drug. Compared to the normal participants, subjects with amnestic MCI who took the placebo had excess activity in the hippocampus, a part of the brain essential for memory. But when they had been taking levetiracetam for two weeks, the excess activity was reduced to the same level as that of the control subjects; memory performance in the task they performed also was improved to the level of the controls.

The findings have possible implications for the progression to Alzheimer’s disease. Studies showing excess activity in the hippocampus in patients with aMCI have found that if these patients are followed for a number of years, those with the greatest excess activation have the greatest further drop in memory and are more likely to receive a diagnosis of Alzheimer’s disease over the next four to six years.

Other recent research provides a clue as to why this might be the case, says Gallagher, the Krieger-Eisenhower Professor of Psychological and Brain Sciences in Johns Hopkins’ Krieger School of Arts and Sciences.

“Because some of the physiology that creates Alzheimer’s disease in the brain is driven by greater brain activity, this excess activity might be like having your foot on the accelerator if you are on the path to Alzheimer’s,” Gallagher said. “So the next step in this line of research will be to test that idea to see whether reducing excess activity might actually slow progression to Alzheimer’s for patients with aMCI.”

Between 8 and 15 percent of patients with aMCI progress to an Alzheimer’s diagnosis every year, making aMCI a stage of transition between normal aging and neurodegenerative disease. At present there is no effective treatment to modify this progression before irreversible damage has occurred in the brain. It would be a significant breakthrough to slow the progression of Alzheimer’s, a disease that is expected to affect as many as 16 million Americans by 2050.

Levetiracetam, the drug used in the study, is an anticonvulsant that decreases abnormally high activity in the brain. It is combined with other drugs to treat certain types of epileptic seizures.

The team that conducted the Johns Hopkins study included Marilyn Albert and Gregory Krauss, both professors of neurology at the Johns Hopkins University School of Medicine, and Arnold Bakker, a graduate student in Gallagher’s laboratory, who presented the findings at the Alzheimer’s conference.

Gallagher is the founder of, and a member of the scientific board of, AgeneBio, a biotechnology company focused on developing treatments for diseases that have an impact on memory, such as amnestic mild cognitive impairment and Alzheimer’s disease. The company is headquartered in Indianapolis. Gallagher owns AgeneBio stock, which is subject to certain restrictions under Johns Hopkins policy. She is entitled to shares of any royalties received by the university on sales of products related to her inventorship of intellectual property. The terms of these arrangements are managed by the university in accordance with its conflict-of-interest policies.

Material adapted from Johns Hopkins University .

A new study published in Biological Psychiatry has approached that problem by following a large population of elderly individuals over a 10 year period. Researchers performed an initial imaging scan on subjects to obtain a baseline measurement of their hippocampal volume and then performed follow-up scans 5 and 10 years later. During this time, they also repeatedly assessed the individuals for both depressive symptoms and depressive disorders.

Corresponding author Dr. Tom den Heijer explains their findings: “We found that persons with a smaller hippocampus were not at higher risk to develop depression. In contrast, those with depression declined in volume over time. Our study therefore suggests that a small hippocampal volume in depressed patients is more likely an effect of the depression rather than a cause.”

“The principal importance of this type of research is that it may provide insight into age-related impairments in the function of the hippocampus,” reflected Dr. John Krystal, Editor of Biological Psychiatry. “For example, in Alzheimer’s disease, memory problems and disorientation are prominent symptoms, reflecting among other things the impaired function of the hippocampus.”

Future studies will be needed to better understand whether current treatments protect the hippocampus and hippocampal function.

Material adapted from Elsevier.

Reference
“A Study of the Bidirectional Association Between Hippocampal Volume on Magnetic Resonance Imaging and Depression in the Elderly” by Tom den Heijer, Henning Tiemeier, Hendrika J. Luijendijk, Fedde van der Lijn, Peter J. Koudstaal, Albert Hofman, and Monique M.B. Breteler. The authors are affiliated with Erasmus Medical Center, Rotterdam, the Netherlands. den Heijer is also from Sint Franciscus Gasthuis, Rotterdam, the Netherlands. Luijendijk is also from Bavo, Europoort, the Netherlands. The article appears in Biological Psychiatry, Volume 70, Number 2 (July 15, 2011), published by Elsevier.

The research was conducted by professor Michael Kahana of the Department of Psychology in the School of Arts and Sciences and graduate student Jeremy R. Manning, of the Neuroscience Graduate Group in Penn’s Perelman School of Medicine. They collaborated with Gordon Baltuch and Brian Litt of the departments of Neurology and Psychology at the medical school and Sean M. Polyn of Vanderbilt University.

“Theories of episodic memory suggest that when I remember an event, I retrieve its earlier context and make it part of my present context,” Kahana said. “When I remember my grandmother, for example, I pull back all sorts of associations of a different time and place in my life; I’m also remembering living in Detroit and her Hungarian cooking. It’s like mental time travel. I jump back in time to the past, but I’m still grounded in the present.”

To investigate the neurobiological evidence for this theory, the Penn team combined a centuries-old psychological research technique — having subjects memorize and recall a list of unrelated words — with precise brain activity data that can only be acquired via neurosurgery.

A diagram of electrode placements.

“We can do direct brain recordings in monkeys or rats, but with humans one can only obtain these recordings when neurosurgical patients, who require implanted electrodes for seizure mapping, volunteer to participate in memory experiments,” Kahana said. “With these recordings, we can relate what happens in the memory experiment on a millisecond-by-millisecond basis to what’s changing in the brain.”

The memory experiment consisted of patients memorizing lists of 15 unrelated words. After seeing a list of the words in sequence, the subjects were distracted by doing simple arithmetic problems. They were then asked to recall as many words as they could in any order. Their implanted electrodes measured their brain activity at each step, and each subject read and recalled dozens of lists to ensure reliable data.

“By examining the patterns of brain activity recorded from the implanted electrodes,” Manning said, “we can measure when the brain’s activity is similar to a previously recorded pattern. When a patient recalls a word, their brain activity is similar to when they studied the same word. In addition, the patterns at recall contained traces of other words that were studied prior to the recalled word.”

“What seems to be happening is that when patients recall a word, they bring back not only the thoughts associated with the word itself but also remnants of thoughts associated with other words they studied nearby in time,” he said.

The findings provide a brain-based explanation of a memory phenomenon that people experience every day.

“This is why two friends you met at different points in your life can become linked in your memory,” Kahana said. “Along your autobiographical timeline, contextual associations will exist at every time scale, from experiences that take place over the course of years to experiences that take place over the course of minutes, like studying words on a list.”

Material adapted from University of Pennsylvania.

In a paper published online by Cerebral Cortex, USC researcher Lisa Aziz-Zadeh furthered her ongoing work in mapping out the way the brain generates empathy, even for those who differ physically from themselves.

According to Aziz-Zadeh’s findings, empathy for someone to whom you can directly relate — or example, because they are experiencing pain in a limb that you possess — is mostly generated by the intuitive, sensory-motor parts of the brain. However, empathy for someone to whom you cannot directly relate relies more on the rationalizing part of the brain.

Though they are engaged to differing degrees depending on the circumstance, it appears that both the intuitive and rationalizing parts of the brain work in tandem to create the sensation of empathy, said Aziz-Zadeh, assistant professor at USC’s Division of Occupational Science and Occupational Therapy.

“People do it automatically,” she said.

In an experiment, Aziz-Zadeh and a team from USC showed videos of tasks being performed by hands, feet, and a mouth to a woman who had been born without arms or legs and also to a group of 13 typically developed women. Videos showed activities such as a mouth eating and a hand grasping an object.

Researchers also showed videos of pain, in the form of an injection, being inflicted on parts of the body.

While the participants watched the videos, their brains were scanned using functional magnetic imaging (fMRI), and then those scans were compared, revealing the differing sources of empathy.

In an additional finding, Aziz-Zadeh discovered that when the congenital amputee viewed videos of tasks being performed that she could also perform but using body parts that she did not have, the sensory-motor parts of her brain were still strongly engaged. For example, the participant can hold objects, but uses a stump in conjunction with her chin to do so rather than a hand.

If the goal of the action was impossible for her, then another set of brain regions involved in deductive reasoning were also activated.

Material adapted from University of Southern California.

Results will be published in the October 2011 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“Even though adolescents might physically appear grown up, their brains are continuing to significantly develop and mature, particularly in frontal brain regions that are associated with higher-level thoughts, like planning and organization,” said Susan F. Tapert, acting chief of psychology at the VA San Diego Healthcare System as well as professor of psychiatry at the University of California, San Diego. “Heavy alcohol use could interrupt normal brain cell growth during adolescence, particularly in these frontal brain regions, which could interfere with teens’ ability to perform in school and sports, and could have long-lasting effects, even months after the teen uses.”

Tapert, who is also the corresponding author for this study, explained that “working memory” is a term that refers to using and working with information that is held in your mind, such as adding numbers in your head. “Working memory is critical to logical thinking and reasoning,” she said.

Spatial working memory is the ability to perceive the space around you, she added, and then remember and work with this information. “We chose to examine spatial working memory because previous studies have shown it is impaired in adults and adolescents who heavily drink alcohol,” she said. “Deficits on tasks of spatial working memory could relate to difficulties with driving, figural reasoning (like geometry class), sports (remembering and enacting complex plays), using a map, or remembering how to get to places.”

Tapert and her colleagues recruited 95 participants from San Diego-area public schools as part of ongoing longitudinal studies: 40 binge drinking (27 males, 13 females) and 55 control (31 males, 24 females) adolescents 16 to 19 years of age. All of the adolescents completed neuropsychological testing, substance use interviews, and a SWM task during functional magnetic resonance imaging (fMRI).

“Our study found that female teenage heavy drinkers had less brain activation in several brain regions than female non-drinking teens when doing the same spatial task,” said Tapert. “These differences in brain activity were linked to worse performance on other measures of attention and working memory ability. Male binge drinkers showed some but less abnormality as compared to male non-drinkers. This suggests that female teens may be particularly vulnerable to the negative effects of heavy alcohol use.”

“These findings remind us that adolescent boys and girls are biologically different and represent distinctive groups that require separate and parallel study,” noted Edith V. Sullivan, a professor in the department of psychiatry and behavioral sciences at Stanford University School of Medicine. “Adding alcohol to the mix of the developing brain and its multifaceted functions likely complicates the normal developmental trajectory, which is already sexually dimorphic.”

Tapert agreed there is a need to examine gender differences associated with alcohol use, particularly during adolescence, as alcohol seems to have a differential effect on the brain. “Females’ brains develop one to two years earlier than males, so alcohol use during a different developmental stage – despite the same age – could account for the gender differences,” she said. “Hormonal levels and alcohol-induced fluctuations in hormones could also account for the gender differences. Finally, the same amount of alcohol could more negatively affect females since females tend to have slower rates of metabolism, higher body fat ratios, and lower body weight. This is similar to what generally has been found in adult alcoholics: while both men and women are adversely affected, women are often more vulnerable than men to deleterious effects on the brain.”

These findings reflect “relatively normal healthy teens” who engage in social drinking, added Tapert, such as having four to five drinks at a party on the weekend but not using for weeks afterwards. “The teens we examined have relatively limited experience with alcohol, are drinking at levels that are widespread for kids their age – almost a quarter of all seniors admit to binge drinking in the preceding two weeks – have no diagnosable alcohol or drug disorder, do not use other drugs, and do not have any mental health disorders,” said Tapert.

“And yet binge-drinking is a dangerous activity for all youth,” observed Sullivan. “Long after a young person – middle school to college – enjoys acute recovery from a hang-over, this study shows that risk to cognitive and brain functions endures. The effects on the developing brain are only now being identified. ‘Why tamper with normal developmental trajectories that will likely set the stage for cognitive and motor abilities for the rest of one’s life?’”

Material adapted from Alcoholism: Clinical & Experimental Research.