Neuroscience

UC Santa Barbara has reported an important discovery in the interdisciplinary study of split-brain research. The findings uncover dynamic changes in brain coordination patterns between left and right hemispheres.

Split-brain research has been conducted for decades, and scientists have long ago shown that language processing is largely located in the left side of the brain. When words appear only in the left visual field –– an area processed by the right side of the brain –– the right brain must transfer that information to the left brain, in order to interpret it. The new study at UCSB shows that healthy test subjects respond less accurately when information is shown only to the right brain.

While hemispheric specialization is considered accurate, the new study sheds light on the highly complex interplay –– with neurons firing back and forth between distinct areas in each half of the brain. The findings rely on extremely sensitive neuroscience equipment and analysis techniques from network science, a fast-growing field that draws on insights from sociology, mathematics, and physics to understand complex systems composed of many interacting parts. These tools can be applied to systems as diverse as earthquakes and brains.

Fifty years ago, UC Santa Barbara neuroscientist Michael S. Gazzaniga moved the field forward when he was a graduate student at the California Institute of Technology and first author of a groundbreaking report on split-brain patients. The study, which became world-renowned, was published in the Proceedings of the National Academy of Sciences (PNAS) in August 1962. This week, in the very same journal, Gazzaniga and his team announced major new findings in split-brain research. The report is an example of the interdisciplinary science for which UCSB is well known.

"The occasion of this paper is on the 50th anniversary of the first report on human split-brain research reported in PNAS," said Gazzaniga. "That study showed how surgically dividing the two hemispheres of the human brain –– in an attempt to control epilepsy –– allowed for studying how each isolated half-brain was specialized for cognitive function.

"In the present study, new techniques –– not present 50 years ago –– begin to allow for an understanding of how the normal, undivided brain integrates the special functions of each half brain. It is a new beginning and very exciting," said Gazzaniga, professor of psychology in UCSB’s Department of Psychological and Brain Sciences, and director of UCSB’s SAGE Center for the Study of Mind.

There are a growing number of clues that immune and inflammatory mechanisms are important for the biology of schizophrenia. In a new study in Biological Psychiatry, Dr. Mar Fatjó-Vilas and colleagues explored the impact of the interleukin-1β gene (IL1β) on brain function alterations associated with schizophrenia.

Fatjó-Vilas said that “this study is a contribution to the relatively new field of ‘functional imaging genetics’ which appears to be potentially powerful for the study of schizophrenia, where genetic factors are of established importance and cognitive impairment – affecting particularly executive function and long-term memory – is increasingly recognized as a core feature of the disorder.”

To conduct this study, they recruited patients with schizophrenia and healthy volunteers, all of whom completed a working memory task while undergoing a functional magnetic resonance imaging scan in the laboratory. This allowed the researchers to determine which areas of the brain became activated during the task. Each participant was also genotyped to determine which allelic combination of the -511C/T polymorphism at the promoter region of the IL1β gene they carry: CC, TT, or CT.

Patients who were homozygous for the C allele (CC) showed reduced prefrontal cortex activation associated with working memory than patients who had at least one copy of the T allele. Among the healthy volunteers, frontal brain activation did not differ according to genotype.

“The analyzed genetic variant exerts an influence on prefrontal cortex function and this influence is different in healthy subjects and patients with schizophrenia,” summarized Fatjó-Vilas.

An important issue is that the -511C/T seems to have a role in regulating the levels of IL1B expression, in which case it would influence neuronal activity dependent on the protein availability. This means that the T allele has been reported to be more active than the C allele, suggesting that a tendency for greater expression of IL1β is associated with greater compromise of frontal cortical functions underlying cognition.

Interleukin-1β is released in the blood under stressful conditions and its release is one of the ways that stress promotes inflammation. IL-1β levels in the blood are altered, for example, in patients with depression and other neuropsychiatric disorders.

Apart from having a role in the immune system, interleukins are also involved in a variety of developmental and functioning processes of the central nervous system. Thus, this study provides further clues for identifying specific biological mechanisms of the disorder associated with both neurodevelopmental processes and immunological and stress response functions.

Dr. John Krystal, Editor of Biological Psychiatry, commented, “We are just beginning to explore the functional impact of inflammatory mechanisms in schizophrenia and the current findings increase our curiosity about these novel mechanisms.”

Research led by Chu Chen, PhD, Associate Professor of Neuroscience at LSU Health Sciences Center New Orleans, has identified an enzyme called Monoacylglycerol lipase (MAGL) as a new therapeutic target to treat or prevent Alzheimer’s disease. The study was published online November 1, 2012 in the Online Now section of the journal Cell Reports.

The research team found that inactivation of MAGL, best known for its role in degrading a cannabinoid produced in the brain, reduced the production and accumulation of beta amyloid plaques, a pathological hallmark of Alzheimer’s disease. Inhibition of this enzyme also decreased neuroinflammation and neurodegeneration, and improved plasticity of the brain, learning and memory.

"Our results suggest that MAGL contributes to the cause and development of Alzheimer’s disease and that blocking MAGL represents a promising therapeutic target," notes Dr. Chu Chen, who is also a member of the Department of Otolaryngology at LSU Health Sciences Center New Orleans.

The researchers blocked MAGL with a highly selective and potent inhibitor in mice using different dosing regimens and found that inactivation of MAGL for eight weeks was sufficient to decrease production and deposition of beta amyloid plaques and the function of a gene involved in making beta amyloid toxic to brain cells. They also measured indicators of neuroinflammation and neurodegeneration and found them suppressed when MAGL was inhibited. The team discovered that not only did the integrity of the structure and function of synapses associated with cognition remain intact in treated mice, but MAGL inactivation appeared to promote spatial learning and memory, measured with behavioral testing.

Alzheimer’s disease is a neurodegenerative disorder characterized by accumulation and deposition of amyloid plaques and neurofibrillary tangles, neuroinflammation, synaptic dysfunction, progressive deterioration of cognitive function and loss of memory in association with widespread nerve cell death. The most common cause of dementia among older people, more than 5.4 million people in the United States and 36 million people worldwide suffer with Alzheimer’s disease in its various stages. Unfortunately, the few drugs that are currently approved by the Food and Drug Administration have demonstrated only modest effects in modifying the clinical symptoms for relatively short periods, and none has shown a clear effect on disease progression or prevention.

"There is a great public health need to discover new therapies to prevent and treat this devastating disorder," Dr. Chen concludes. The research was supported by grants from the National Institutes of Health. In addition to scientists from LSU Health Sciences Center New Orleans, the research team also included investigators from the Massachusetts Institute of Technology.

In a new study appearing this month in the Journal of Neuroscience, researchers have unlocked the complex cellular mechanics that instruct specific brain cells to continue to divide. This discovery overcomes a significant technical hurdle to potential human stem cell therapies; ensuring that an abundant supply of cells is available to study and ultimately treat people with diseases. 

“One of the major factors that will determine the viability of stem cell therapies is access to a safe and reliable supply of cells,” said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., lead author of the study. “This study demonstrates that – in the case of certain populations of brain cells – we now understand the cell biology and the mechanisms necessary to control cell division and generate an almost endless supply of cells.”

The study focuses on cells called glial progenitor cells (GPCs) that are found in the white matter of the human brain. These stem cells give rise to two cells found in the central nervous system: oligodendrocytes, which produce myelin, the fatty tissue that insulates the connections between cells; and astrocytes, cells that are critical to the health and signaling function of oligodendrocytes as well as neurons.

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New research in The FASEB Journal suggests that dysfunction in the SRGAP3 protein may lead to schizophrenia, hydrocephalus, mental retardation and some forms of autism in childhood

A new research discovery has the potential to revolutionize the biological understanding of some childhood psychiatric disorders. Specifically, scientists have found that when a single protein involved in brain development, called “SRGAP3,” is malformed, it causes problems in the brain functioning of mice that cause symptoms that are similar to some mental health and neurological disorders in children. Because this protein has similar functions in humans, it may represent a “missing link” for several disorders that are part of an illness spectrum. In addition, it offers researchers a new target for the development of treatments that can correct the biological cause rather than treat the symptoms. This discovery was published in November 2012 print issue of The FASEB Journal.

"Developmental brain disorders such as schizophrenia, hydrocephalus, mental retardation and autism are among the most devastating diseases in children and young adults," said Dusan Bartsch, Ph.D., a researcher involved in the work from the Department of Molecular Biology at the Central Institute of Mental Health at the University of Heidelberg in Mannheim, Germany. "We hope that our findings will contribute to a better understanding, and in the end, to better treatments for these disorders."

Bartsch and colleagues made this discovery using mice with the SRGAP3 protein inactivated. Then they conducted several experiments comparing these mice to normal mice. The mice with inactive SRGAP3 showed clear changes in their brains’ anatomy, which resulted in altered behavior similar to certain symptoms in human neurological and psychiatric diseases. An involvement of SRGAP3 in different brain disorders could indicate that these disorders are possibly connected, as SRGAP3 is a key player in brain development. These different disorders could be connected via the SRGAP3 protein because they all emerge from disturbed development of the nervous system.

"Since Freud put biological psychiatry on the map, we’ve slowly increased our understanding of how mental health is dictated by chemistry," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Eventually we’ll understand the complex biology underlying most psychiatric illnesses, from genes to proteins to cell signaling to overt behaviors. Along the way, as in this report, we’re likely to find single targets close to the roots of apparently different mental illnesses."

(Image: bzztbomb)

Researchers at the University of Minnesota’s Center for Magnetic Resonance Research (CMRR) have found a small population of neurons that is involved in measuring time, which is a process that has traditionally been difficult to study in the lab.

In the study, which is published October 30 in the open access journal PLOS Biology, the researchers developed a task in which monkeys could only rely on their internal sense of the passage of time. Their task design eliminated all external cues which could have served as “clocks”.

The monkeys were trained to move their eyes consistently at regular time intervals without any external cues or immediate expectation of reward. Researchers found that despite the lack of sensory information, the monkeys were remarkably precise and consistent in their timed behaviors. This consistency could be explained by activity in a specific region of the brain called the lateral intraparietal area (LIP). Interestingly, the researchers found that LIP activity during their task was different from activity in previous studies that had failed to eliminate external cues or expectation of reward.

"In contrast to previous studies that observed a build-up of activity associated with the passage of time, we found that LIP activity decreased at a constant rate between timed movements," said lead researcher Geoffrey Ghose, Ph.D., associate professor of neuroscience at the University of Minnesota. "Importantly, the animals’ timing varied after these neurons were more, or less, active. It’s as if the activity of these neurons was serving as an internal hourglass."

By developing a model to help explain the differences in timing signals they see relative to previous studies, their study also suggests that there is no “central clock” in the brain that is relied upon for all tasks involving timing. Instead, it appears as though each of the brain’s circuits responsible for different actions are capable of independently producing an accurate timing signal.

One important direction for future research is to explore how such precise timing signals arise as a consequence of practice and learning, and whether, when the signals are altered, there are clear effects on behavior.

In the largest prospective study to date of children with early and later manifestation of autism spectrum disorders (ASD) compared to children without ASD, researchers found two distinct patterns of language, social and motor development in the children with ASD. Published in the journal Child Development, the study found that early in development, children who display early signs of ASD show greater initial delay across multiple aspects of development compared to children whose ASD symptoms emerge later. However at 36 months of age, the early differences between these groups are no longer obvious. By the third birthday, the level of impairment between these symptom onset groups of children with ASD is comparable. Additionally, researchers uncovered a preclinical phase of ASD in which the signs of delay are not easily detected with existing clinical tests.

Previous research by Kennedy Krieger Institute researchers found that approximately half of all children with ASD can be diagnosed around the first birthday, while the remaining half do not show diagnostic indicators until later. The current study builds upon these findings by further evaluating motor and language development in a wider age span of children diagnosed with ASD (6 to 36 months), and examining how development unfolds differently in each group.

“Regardless of diagnosis, the development of children with and without ASD appears similar at six months of age on clinical tests,” says Dr. Rebecca Landa, lead author and director of Kennedy Krieger’s Center for Autism and Related Disorders. “However, for those children who went on to develop autism, the earliest signs of atypical development were non-specific to autism, such as general communication or motor delay.”

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