Subcortical brain atrophy in

Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

GWI is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon. The highest atrophy was observed in the brainstem, followed by left cerebellum and right thalamus, then by right cerebellum and left thalamus. These findings indicate graded atrophy of regions anatomically connected through the brainstem via the crossed superior cerebellar peduncle (left cerebellum → right thalamus, right cerebellum → left thalamus). This distribution of atrophy, together with the observed systematic reduction in volume of other subcortical...
read more

Dr. Georgopoulos presented American Legion's Highest Award

Dr. Apostolos Georgopoulos was presented The American Legion's Distinguished Service Medal. American Legion National Commander Charles E. Schmidt said Georgopoulos is responsible for research involving , , Alzheimer's disease, schizophrenia, alcohol abuse and other areas. The American Legion Distinguished Service Medal recognizes outstanding service to the nation and programs of The American Legion.

---

Original Story BelowThe American Legion's Board of Directors announced on May 10 the that Apostolos Georgopoulos, Director of the Minneapolis VA Brain Sciences Center, has been awarded by unanimous vote the American Legion's highest award, the Distinguished Service Medal for his "achievements in research on Gulf War illness as it affects an estimated 300,000 veterans and military personnel who served in Iraq and Afghanistan". The medal is based on outstanding service to the community, state, and nation and has been awarded since 1921. Past recipients include Jonas Salk, Babe Ruth, General Eisenhower, Bob Hope, and Presidents Truman,...
read more

The Beautiful Brain and the Influence of Santiago Ramón y Cajal on Medicine

The Beautiful Brain: The Drawings of Ramón y Cajal is an aptly titled exhibit featuring drawings of brain cells by Santiago Ramón y Cajal, the grand master of neurohistology who flourished more than 100 years ago. The exhibit opened at the Weisman Art Museum of the University of Minnesota in January 2017 and will travel to university museums and galleries in Canada and the United States through the spring of 2019. The exhibit consists of 82 exquisitely detailed drawings of brain cells and neural elements from other tissues selected from more than 3200 drawings. The exhibit is exceptionally well conceived, executed, and presented, and the accompanying catalog is of the highest quality.

A question of who, not if: Psychological disorders in Holocaust survivors' children

Objective: Because findings on the mental health status of Holocaust survivors' offspring have been inconsistent, we aimed to identify factors that place some offspring at greater risk for developing mood or anxiety disorders. Method: Using a web-based survey and structured clinical interviews with adult children of survivors, we attempted to predict disorders from offspring's circumstances, perceptions of parents' posttrauma adaptational styles, and self-reported reparative adaptational impacts. Posttrauma adaptational styles encompass intrafamilial and interpersonal psychological, social and behavioral coping, mastery, and defense mechanisms used by each parent. Reparative adaptational impacts reflect the offspring's self-reported insecurity about their own competence, reparative protectiveness, need for control, obsession with the Holocaust, defensive psychosocial constriction, and immature dependency. Results: Of the disorders studied, generalized anxiety disorder was most frequent, followed by major depressive episode and . Only 2 variables independently predicted these disorders: participants' age and reparative adaptational impacts. Parents' styles were correlated...
read more

Researchers pinpoint reductions in brain volume of ill Gulf War Vets

The at the Minneapolis VA Health Care System has evolved into one of the leading facilities in the country for researching , a condition that is of major concern to the Veteran community.Researchers at the center have made what they believe to be key breakthroughs with .

Minnesota Trauma Project and

Posttraumatic Stress Disorder

Posttraumatic Stress Disorder (PTSD)

A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.

Awareness Day

It's that time of year when we burst with national pride. It's worth remembering that many people including many of those who fought for our country, struggle with symbolic bombs bursting in air. Psychologists Brian Engahl and Ryan Van Wyk talked with KARE 11 about Post Traumatic Stress Disorder on June 27, a day dedicated to Post Traumatic Stress Awareness...

Apolipoprotein E

Apolipoprotein E (ApoE)

a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.

: the resilience gene

The gene has been implicated in various conditions, most notably Alzheimer's disease and coronary artery disease. A predisposing role of the 4 isoform and a protective role of 2 isoform in those diseases have been documented. Here we investigated the role of in resilience to trauma.

Function of basal ganglia in tauG-guiding action

Nervous systems control purposeful movement, both within and outside the body, which is essential for the survival of an animal. The movement control functions of globus pallidus (GP), subthalamic nucleus (STN) and zona incerta (ZI) were analyzed in monkeys reaching for seen targets. Temporal profiles of the hand movements of monkeys and the synchronized flow of electrochemical energy through these basal ganglia were analyzed in terms of a theory of goal-directed movement. Theoretical and empirical analysis indicated: (i) the neural information for controlling movement is the relative-rate-of-change of flow of electrochemical energy in neurons rather than the flow itself; (ii) GP is involved in creating prospective electrochemical flow to guide movement; (iii) STN is involved in registering the perceptual electrochemical flow monitoring the movement; (iv) ZI is involved in integrating the prospective and perceptual electrochemical flows to power the muscles and thence the movement. Possible implications for PD are discussed.

Cutaneous cryptococcosis in a patient taking fingolimod for multiple sclerosis: Here come the opportunistic infections?

Background:Fingolimod is an oral disease-modifying therapy for relapsing forms of multiple sclerosis, which acts by sequestering lymphocytes within lymph nodes.Objective:To describe a case of extrapulmonary cryptococcosis in a patient taking fingolimod.Methods:Case report.Results:A 47-year-old man developed a non-healing skin lesion approximately 16 months after starting treatment with fingolimod. Biopsy revealed cryptococcosis. Fingolimod was discontinued and the lesion resolved with antifungal therapy.Conclusion:Despite few reported opportunistic infections in the pivotal clinical trials and first few years post-marketing, there has been a recent increase in reported AIDS-defining illnesses in patients taking fingolimod. Neurologists should be alert for opportunistic infections in their patients using this medication.

In Minnesota, the promise of a test for

Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

BSC member Dr. Brian Engdahl and colleagues met with The American Legion's Ken Olsen to discuss and new developments in ways to test for . "In Minnesota, the promise of a test for

GWI

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

"

Multiple sclerosis: integration of modeling with biology, clinical and imaging measures to provide better monitoring of disease progression and prediction of outcome

Multiple Sclerosis (MS) is a major cause of neurological disability in adults and has an annual cost of approximately $28 billion in the United States. MS is a very complex disorder as demyelination can happen in a variety of locations throughout the brain; therefore, this disease is never the same in two patients making it very hard to predict disease progression. A modeling approach which combines clinical, biological and imaging measures to help treat and fight this disorder is needed. In this paper, I will outline MS as a very heterogeneous disorder, review some potential solutions from the literature, demonstrate the need for a biomarker and will discuss how computational modeling combined with biological, clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism.

Successful treatment of paroxysmal ataxia and dysarthria in multiple sclerosis with levetiracetam

BackgroundParoxysmal ataxia and dysarthria (PAD) is a relatively rare symptom in Multiple Sclerosis patients. PAD involves transient dysfunction in control, coordination and initiation of speech and/or limb movements.ObjectiveTo describe the successful use of levetiracetam for the treatment of PAD.MethodsCase report.ResultsA 37-year-old woman with MS developed PAD approximately 3 months after a multifocal MS relapse. Brain MRI showed a lesion in the posterior aspect of the midbrain as well as in the right posterior internal capsule, both of which were adjacent to the red nucleus. Attack frequency was reduced after starting levetiracetam at a dose of 500 mg twice daily, and attacks stopped completely once the dose was increased to 750 mg twice daily.ConclusionsGiven its advantages (in terms of side effects, safety profile and ease of use compared to other anticonvulsants), we suggest that levetiracetam be considered for management of PAD, and perhaps for other paroxysmal MS symptoms as well.

Cortical miscommunication after prenatal exposure to alcohol

We report on the effects of prenatal alcohol exposure on resting-state brain activity as measured by . We studied 37 subjects diagnosed with fetal alcohol spectrum disorder in one of three categories: fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder. For each subject, the signal was recorded for 60 s during rest while subjects lay supine. Using time series analysis, we calculated the for all pair-wise combinations of 248 sensors resulting in 30,628 partial correlations for each subject. We found significant differences from control subjects in 6.19 % of the partial zero-lag crosscorrelations (; Georgopoulos et al. in J Neural Eng 4:349-355, 2007), with these differences localized in the right posterior frontal, right parietal, and left parietal/posterior frontal regions. These results show that can detect functional brain differences in the individuals affected by prenatal exposure to alcohol. Furthermore, these...
read more

Brain Correlates of

Human Leukocyte Antigen

Human Leukocyte Antigen (HLA)

Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.

Protection in

Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

BackgroundWe recently reported that six alleles from class II genes of the confer protection from (Georgopoulos et al., 2015). The most significant effect is exerted on Neurological-Cognitive-Mood (NCM), Pain, and Fatigue symptoms, such that higher number of copies of the protective alleles are associated with lower symptom severity. Here we tested the hypothesis that this effect is exerted by modulating the strength of neural synchronicity.MethodsEighty-one Gulf War veterans (65 with and 16 healthy controls) underwent a scan to assess the strength of brain synchronicity by computing zero-lag crosscorrelations (and their Fisher z transforms) between prewhitened time series. A high-resolution genotyping determined the number of copies, k, of the 6 protective alleles above in each participant. We tested the hypothesis above by regressing NCM, Pain and Fatigue symptom severity against the interaction term, k x z (-related effect), while...
read more

Using model systems to understand errant plasticity mechanisms in psychiatric disorders

In vivo model systems are a critical tool for gaining insight into the pathology underlying psychiatric disorders. Although modern functional imaging tools allow study of brain correlates of behavior in clinical groups and genome-wide association studies are beginning to uncover the complex genetic architecture of psychiatric disorders, there is less understanding of pathology at intervening levels of organization. Several psychiatric disorders derive from pathological neural plasticity, and studying the mechanisms that underlie these processes, including reinforcement learning and spike-timing-dependent plasticity, requires the use of animals. It will be particularly important to understand how individual differences in plasticity mechanisms at a cellular level confer resilience on some but lead to disease in others.

A Magnetoencephalographic (

Magnetoencephalography

Magnetoencephalography (MEG)

A noninvasive technique that detects magnetic fields above the surface of the head produced by postsynaptic potentials in the brain.

) Study of

Gulf War Illness

Gulf War Illness (GWI)

Shortly after the Gulf War (1990^aEUR"91), veterans started to report a variety of health problems that began during, or soon after returning from, deployment, prompting investigation into the epidemiology and etiology of the complaints. Those investigations revealed that diffuse symptoms such as fatigue, musculoskeletal pain, mood and neurocognitive complaints, gastrointestinal problems, and rashes were most commonly reported. The constellation of symptoms, now commonly referred to as Gulf War Illness (GWI), has affected a substantial number of Gulf War veterans. Several population-based studies have demonstrated that these symptoms occur at significantly higher rates in deployed Gulf War veterans relative to their nondeployed peers and other veterans, raising the issue about possible in-theater exposures and stress as contributing factors. However, these symptoms are also present in non-deployed military personnel, leading some to suspect other causes, including reactions to vaccine adjuvants. In summary, GWI is now a recognized constellation of symptoms of unclear etiology, also co-occurring with psychiatric disorders.

BackgroundGulf War Illness () has affected many Gulf War veterans. It involves several organs, most notably the brain. Neurological-cognitive-mood-related symptoms frequently dominate and are at the root of chronic ill-health and disability in . Here we investigated the neural mechanisms underlying brain dysfunction in in the absence of mental health disorders.MethodsEighty-six veterans completed diagnostic interviews to establish the presence of and assess mental health status. Participants diagnosed with met both Center for Disease Control and Kansas criteria. We studied 46 healthy controls and 40 veterans with without mental illness. They all underwent a resting-state magnetoencephalographic () scan to assess brain communication based on (; Georgopoulos et al., 2007).FindingsWe found substantial differences in between control and groups centered on the cerebellum and frontal cortex. In addition, using the maxima and minima of per sensor as predictors, we successfully classified 94.2% of the...
read more

Defining the cognitive enhancing properties of video games: Steps Towards Standardization and Translation

Ever since video games were available to the general public, they have intrigued brain researchers for many reasons. There is an enormous amount of diversity in the video game research, ranging from types of video games used, the amount of time spent playing video games, the definition of video gamer versus non-gamer to the results obtained after playing video games. In this paper, our goal is to provide a critical discussion of these issues, along with some steps towards generalization using the discussion of an article published by Clemenson and Stark (2005) as the starting point. The authors used a distinction between 2D versus 3D video games to compare their effects on the learning and memory in humans. The primary hypothesis of the authors is that the exploration of virtual environments while playing video games is a human correlate of environment enrichment. Authors found that video gamers performed better than the...
read more

Block design enhances classification of 3D reach targets from electroencephalographic signals

To date, decoding accuracy of actual or imagined pointing movements to targets in 3D space from electroencephalographic (EEG) signals has remained modest. The reason may pertain to the fact that these movements activate essentially the same neural networks. In this study, we aimed at testing whether repetitive pointing movements to each of the targets promotes the development of segregated neural patterns, resulting in enhanced decoding accuracy. Six human subjects generated slow or fast repetitive pointing movements with their right dominant arm to one of five targets distributed in 3D space, followed by repetitive imagery of movements to the same target or to a different target. Nine naive subjects generated both repetitive and non-repetitive slow actual movements to each of the five targets to test the effect of block design on decoding accuracy. In order to assure that base line drift and low frequency motion artifacts do not contaminate the data, the...
read more