Posts tagged neurobiology
Articles and news from the latest research reports.
Neurobiology of Attention Deficit/Hyperactivity Disorder
Attention deficit/hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder, has been associated with various structural and functional CNS abnormalities but findings about neurobiological mechanisms linking genes to brain phenotypes are just beginning to emerge. Despite the high heritability of the disorder and its main symptom dimensions, common individual genetic variants are likely to account for a small proportion of the phenotype’s variance. Recent findings have drawn attention to the involvement of rare genetic variants in the pathophysiology of ADHD, some being shared with other neurodevelopmental disorders. Traditionally, neurobiological research on ADHD has focused on catecholaminergic pathways, the main target of pharmacological treatments. However, more distal and basic neuronal processes in relation with cell architecture and function might also play a role, possibly accounting for the coexistence of both diffuse and specific alterations of brain structure and activation patterns. This article aims to provide an overview of recent findings in the rapidly evolving field of ADHD neurobiology with a focus on novel strategies regarding pathophysiological analyses.
Decision Making: From Neuroscience to Psychiatry
Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker’s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson’s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders.
Opposites attract: How cells and cell fragments move in electric fields
Like tiny, crawling compass needles, whole living cells and cell fragments orient and move in response to electric fields — but in opposite directions, scientists at the University of California, Davis, have found. Their results, published April 8 in the journal Current Biology, could ultimately lead to new ways to heal wounds and deliver stem cell therapies.
When cells crawl into wounded flesh to heal it, they follow an electric field. In healthy tissue there’s a flux of charged particles between layers. Damage to tissue sets up a “short circuit,” changing the flux direction and creating an electrical field that leads cells into the wound. But exactly how and why does this happen? That’s unclear.
"We know that cells can respond to a weak electrical field, but we don’t know how they sense it," said Min Zhao, professor of dermatology and ophthalmology and a researcher at UC Davis’ stem cell center, the Institute for Regenerative Cures. "If we can understand the process better, we can make wound healing and tissue regeneration more effective.”
The researchers worked with cells that form fish scales, called keratocytes. These fish cells are commonly used to study cell motion, and they also readily shed cell fragments, wrapped in a cell membrane but lacking a nucleus, major organelles, DNA or much else in the way of other structures.
In a surprise discovery, whole cells and cell fragments moved in opposite directions in the same electric field, said Alex Mogilner, professor of mathematics and of neurobiology, physiology and behavior at UC Davis and co-senior author of the paper.
It’s the first time that such basic cell fragments have been shown to orient and move in an electric field, Mogilner said. That allowed the researchers to discover that the cells and cell fragments are oriented by a “tug of war” between two competing processes.
Think of a cell as a blob of fluid and protein gel wrapped in a membrane. Cells crawl along surfaces by sliding and ratcheting protein fibers inside the cell past each other, advancing the leading edge of the cell while withdrawing the trailing edge.
Assistant project scientist Yaohui Sun found that when whole cells were exposed to an electric field, actin protein fibers collected and grew on the side of the cell facing the negative electrode (cathode), while a mix of contracting actin and myosin fibers formed toward the positive electrode (anode). Both actin alone, and actin with myosin, can create motors that drive the cell forward.
The polarizing effect set up a tug-of-war between the two mechanisms. In whole cells, the actin mechanism won, and the cell crawled toward the cathode. But in cell fragments, the actin/myosin motor came out on top, got the rear of the cell oriented toward the cathode, and the cell fragment crawled in the opposite direction.
The results show that there are at least two distinct pathways through which cells respond to electric fields, Mogilner said. At least one of the pathways — leading to organized actin/myosin fibers — can work without a cell nucleus or any of the other organelles found in cells, beyond the cell membrane and proteins that make up the cytoskeleton.
Upstream of those two pathways is some kind of sensor that detects the electric field. In a separate paper to be published in the same journal issue, Mogilner and Stanford University researchers Greg Allen and Julie Theriot narrow down the possible mechanisms. The most likely explanation, they conclude, is that the electric field causes certain electrically charged proteins in the cell membrane to concentrate at the membrane edge, triggering a response.
New Research on the Effects of Traumatic Brain Injury (TBI)
Considerable opportunity exists to improve interventions and outcomes of traumatic brain injury (TBI) in older adults, according to three studies published in the recent online issue of NeuroRehabilitation by researchers from the Icahn School of Medicine at Mount Sinai.
An Exploration of Clinical Dementia Phenotypes Among Individuals With and Without Traumatic Brain Injury
Some evidence suggests that a history of TBI is associated with an increased risk of dementia later in life, but the clinical features of dementia associated with TBI have not been well investigated. Researchers at the Icahn School of Medicine as well as other institutions analyzed data from elderly individuals with dementia with and without a history of TBI to characterize the clinical profiles of patients with post-TBI dementia.
The results of the study indicate that compared to older adults with dementia with no history of TBI, those with a history of TBI had higher fluency and verbal memory scores and later onset of decline. However, their general health was worse, they were more likely to have received medical attention for depression, and were more likely to have a gait disorder, falls, and motor slowness. These findings suggest that dementia among individuals with a history of TBI may represent a unique clinical phenotype that is distinct from that seen among elderly individuals who develop dementia without a history of TBI.
"Our study indicates that individuals with dementia and without a history of TBI may present clinical characteristics that differ in subtle but meaningful ways," said Kristen Dams-O’Connor, PhD, first author of the study and an Assistant Professor of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai. "It is imperative that clinicians take a history of TBI into account when making dementia diagnoses."
For this study, researchers used data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) collected between September 2005 and May 2012 to analyze 332 elderly individuals with dementia and a history of TBI and 664 elderly individuals without dementia who do have a history of TBI. Statistical analyses focused on evaluating differences in the areas of neurocognitive functioning, psychiatric functioning, medical history and health, clinical characteristics of dementia, and dementia diagnosis using data collected at the baseline (first) NACC study visit.
Mortality of Elderly Individuals with TBI in the First 5 Years Following Injury
After observing a high rate of mortality among patients over the age of 55 in the first five years after sustaining a TBI, researchers at the Icahn School of Medicine at Mount Sinai were interested in learning more about the precise causes for what may be considered a premature death.
The results of this study indicate that for approximately a third of the patients, death one to five years after TBI resulted from health conditions that were present at the time of injury before the onset of TBI, suggesting a continuation of an already ongoing process. The remainder of patients died from conditions that appeared to unfold in the years after injury. According to the authors, each cause of death in this sample would have required pro-active medical management, medical intervention and medication compliance.
"Like those with other chronic health conditions, individuals with TBI could benefit from the development of a disease management model of primary care," said one of the study authors, Wayne Gordon, PhD, Jack Nash Professor and Vice Chair of the Department of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai and Chief of the Rehabilitation Psychology and Neuropsychology service. "This study suggests that close medical management and lifestyle interventions may help to prevent premature death among elderly survivors of TBI in the future."
Researchers reviewed the charts of 30 individuals over the age of 55 who completed inpatient acute rehabilitation during the period from 2003-2009 and who died one to four years after TBI, and then compared that data to a matched sample of 30 patients who did not die. They found that 53 percent of deceased subjects had been diagnosed with gait abnormalities, 32 percent were taking respiratory medications at admission, and 17 percent were taking respiratory medications at discharge. Compared to patients who survived several years after injury, deceased patients were discharged from the hospital with significantly more medications.
Inpatient Rehabilitation for Traumatic Brain Injury: The Influence of Age on Treatments and Outcomes
For this study, researchers analyzed the difference in treatment and outcomes between elderly and younger patients with TBI. They found that patients over 65 had lower brain injury severity and a shorter length of stay in acute care. Elderly patients also received fewer hours of rehabilitation therapy, due to a shorter length of stay, and fewer hours of treatment per day, especially from psychology and therapeutic recreation. They gained less functional ability during and after rehabilitation, and had a very high mortality rate.
"We know significantly more about the treatment received by adolescents and young adults with TBI than we do about those over 65," said Marcel Dijkers, PhD, lead author and Research Professor in the Department of Rehabilitation Medicine at Mount Sinai. "Our data indicates that elderly people can be rehabilitated successfully, but it raises a number of questions. For instance: is the high mortality due to the TBI or is it the result of the continuation of a condition that began pre-TBI?"
The researchers analyzed data on 1,419 patients with TBI admitted to nine TBI rehabilitation inpatient programs across the country between 2009 and 2011. They collected data through abstracting of medical records, point-of-care forms completed by therapists, and interviews conducted three and nine months after discharge.
Low incidence of venous insufficiency in MS
Results of a study using several imaging methods showed that CCSVI (chronic cerebrospinal venous insufficiency) occurs at a low rate in both people with multiple sclerosis (MS) and non-MS volunteers, contrary to some previous studies. The research by an interdisciplinary team at The University of Texas Health Science Center at Houston (UTHealth) was published in a recent early online edition of the Annals of Neurology.
“Our results in this phase of the study suggest that findings in the major veins that drain the brain consistent with CCSVI are uncommon in individuals with MS and quite similar to those found in our non-MS volunteers,” said Jerry Wolinsky, M.D., principal investigator and the Bartels Family and Opal C. Rankin Professor of Neurology at The UTHealth Medical School. “This makes it very unlikely that CCSVI could be the cause of MS, or contribute in an important manner to how the disease can worsen over time.” Wolinsky is also a member of the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston and director of the UTHealth MS Research Group.
CCSVI has been described by Italian neurosurgeon Paolo Zamboni, M.D., as a new disorder in which veins draining the central nervous system are abnormal. Zamboni’s published research linked CCSVI to MS. Not all researchers have been able to duplicate his results.
UTHealth was one of three institutions in the United States to receive an initial grant to study CCSVI in multiple sclerosis (MS). The grant was part of a $2.3 million joint commitment from the National MS Society and the MS Society of Canada.
The UTHealth team tested several imaging methods including ultrasound, magnetic resonance imaging with an intravenous contrast agent, and direct radiologic investigation of the major veins by direct injection of veins with radio-opaque contrast. The goal was to validate a consistent, reliable diagnostic approach for CCSVI, determine whether CCSVI was specific to MS and if CCSVI contributed to disease activity.
The team was blinded to the participant’s diagnosis throughout the study. Doppler ultrasound was used to investigate venous drainage in 276 people with and without MS. Using the criteria described by Zamboni for the diagnosis of CCVSI, UTHealth researchers found less prevalence of CCVSI than in some previous studies and no statistical difference between those with MS and those without MS. Detailed experience with the other imaging approaches are being readied for publication.
Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system, interrupting the flow of information within the brain and from the brain to the body. It affects more than 400,000 people in the United States and 2.1 million in the world.