The effects of Human Leukocyte Antigen DRB1*13 and Apolipoprotein E on age-related variability of Synchronous Neural Interactions in healthy women
permalinkEBioMedicine - 2018-09-01James L, Dolan S, Leuthold A, Engdahl B, Georgopoulos A, Georgopoulos AP10.1016/j.ebiom.2018.08.026BackgroundAge-related brain changes are well-documented and influenced by genetics. Extensive research links
Apolipoprotein Eto brain function, with the E4 allele serving as a risk factor for brain disease, including Alzheimer's disease, and the E2 allele conferring protection. Recent evidence also supports protective effects of another gene,
Human Leukocyte AntigenDRB1*13, on brain disease and age-related brain atrophy in cognitively healthy adults. Here we investigated the effects of
HLADRB1*13 on brain function by examining changes in neural network properties with age in healthy adults.MethodsOne hundred seventy-eight cognitively healthy women (28-99 y old) underwent a magnetoencephalography scan and provided a blood sample for genetic analysis. Age-related changes in neural network variability in genetic subgroups of DRB1*13 X
ApoEgenotype combinations were assessed using linear regression of network variability against age.FindingsFor individuals lacking a DRB1*13 allele and/or carrying an
ApoE4 allele, network variability increased significantly with age. In...
Personality Factors and Their Impact on Posttraumatic Stress Disorder and Post-traumatic Growth is Mediated by Coping Style Among Operation Iraqi Freedom/Operation Enduring Freedom - Afghanistan Veterans
Posttraumatic Stress Disorder). However, some individuals may also experience positive changes following trauma exposure. These changes are known as post-traumatic growth (PTG). Dispositional and situational factors are likely at play in determining both severity of
PTSDsymptoms and whether and to what degree an individual experiences PTG. This study examined how coping style and personality traits interact to influence
PTSDand PTG.Materials and MethodsTwo hundred and seventy-one
Operation Iraqi Freedom/Operation Enduring Freedom veterans not engaged in mental health treatment completed self-report measures of trauma exposure, personality traits, coping styles,
PTSDsymptoms, and PTG. The study was approved by the Minneapolis VAHCS Institutional Review Board.ResultsAdaptive coping and positive personality traits such as openness were positively correlated with PTG. Maladaptive coping and neuroticism were positively correlated with
PTSDsymptoms. Regression analyses indicated that an inverted-U (quadratic) curve characterized the relationship between
Invariant and heritable local cortical organization as revealed by Functional Magnetic Resonance Imaging
Functional Magnetic Resonance Imagingtime series decreased with distance as a power law. The rate of decrease, b, varied among individuals by ~1.9x, was highly correlated between hemispheres, but differed among areas (by ~1.2x) in a systematic fashion, becoming progressively less steep from frontal to occipital areas. With respect to twin status, b was significantly correlated between monozygotic twins, less so between dizygotic twins or nontwin siblings, and not at all in nonrelated individuals. These results quantify the lawful, distance-related cortical interactions and demonstrate, for the first time, the heritability of their power...
Brain Function in Gulf War Illness and Associated Mental Health Comorbidities
permalinkJ Neurol Neuromedicine - 2018-07-19Engdahl B, James L, Miller R, Leuthold A, Lewis S, Carpenter A, Georgopoulos APGWI has affected a substantial number of Gulf War (GW) veterans. The disease involves several organ systems among which the brain is most prominent. Neurological, cognitive and mood-related (NCM) symptoms frequently dominate and are at the root of chronic ill-health and disability in veterans suffering from
Gulf War Illness. In addition, such symptoms frequently co-occur with diagnosable mental health disorders, predominantly
PTSD. Here we investigated the possibility that increased
GWIseverity leads, above a threshold, to a diagnosable mental health disorder (excluding psychosis). For this purpose, we used, in separate analyses, symptom severity scores and resting-state brain functional connectivity patterns, as determined by
Magnetoencephalography. Two-hundred-thirty GW-era veterans participated in this study. They completed diagnostic interviews to establish the presence of
GWIand assess mental health status. This distinguished 3 groups: healthy controls (N = 41), veterans with
GWIand no mental illness (
GWIgroup, N = 91), and veterans...
Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia
Minnesota Women's Healthy Brain Aging Project: Past, Present, and Future
permalink2018-06-12Lisa James, PhD, holder of the , presented her work at the University of Minnesota on June 12th, 2018. She, along with the project coordinator, Stacy Dolan, RN are shown describing and seeking support from an appreciative audience. Two attendees are shown with project assistant Rachel Johnson (right).To learn more about our work and how you can support it, visit !-->!-->!-->!-->!-->!-->!-->
Encoding of Serial Order in Working Memory: Neuronal Activity in Motor, Premotor, and Prefrontal Cortex during a Memory Scanning Task
permalinkJournal of Neuroscience - 2018-05-23Carpenter A, Baud-Bovy G, Georgopoulos AP, Pellizzer G10.1523/JNEUROSCI.3294-17.2018We have adapted Sternberg's context-recall task to investigate the neural mechanisms of encoding serial order information in working memory, in 2 male rhesus monkeys. We recorded from primary motor, premotor, and dorsolateral prefrontal cortex while the monkeys performed the task. In each cortical area, most neurons displayed marked modulation of activity during the list presentation period of the task, whereas the serial order of the stimuli needed to be encoded in working memory. The activity of many neurons changed in a consistent manner over the course of the list presentation period, without regard to the location of the stimuli presented. Remarkably, these neurons encoded serial position information in a relative (rather than absolute) manner across different list lengths. In addition, many neurons showed activity related to both location and serial position, in the form of an interaction effect. Surprisingly, the activity of these neurons was often modulated by the location of...
Kare 11 explores Posttraumatic Stress Disorder and PTSD research involving the Brain Sciences Center
permalinkKare 11 - 2018-05-18Join Kare 11 as they explore Former Army infantryman Brian Zimmerman's experience with
PTSD, its treatment, and potential
PTSDresearch at the
Brain Sciences Center.Watch the trailer video, part 1, and part 2
Adverse effects of Gulf War Illness serum on neural cultures and their prevention by healthy serum
permalinkJ Neurol Neuromedicine - 2018-04-27Georgopoulos AP, Tsilibary EC, Souto EP, James L, Engdahl B, Georgopoulos AGWI is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW). Here we tested the hypothesis that brain damage may be caused by circulating harmful substances to which GW veterans were exposed but which could not be eliminated due to lack of specific immunity. We assessed the effects of serum from
GWIpatients on function and morphology of brain cultures in vitro, including cultures of embryonic mouse brain and neuroblastoma N2A line. Blood serum from
GWIand healthy GW veterans was added, alone and in combination, to the culture and its effects on the function and morphology of the culture assessed. Neural network function was assessed using electrophysiological recordings from multielectrode arrays in mouse brain cultures, whereas morphological assessments (neural growth and cell apoptosis) were done in neuroblastoma cultures. In contrast to healthy serum, the...
Protective Effect of Human Leukocyte Antigen Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women
permalinkEBioMedicine - 2018-03-01James L, Christova P, Lewis S, Engdahl B, Georgopoulos A, Georgopoulos AP10.1016/j.ebiom.2018.02.005BackgroundReduction of brain volume (brain atrophy) during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the
HLAallele DRB1*13:02 which prevents brain atrophy in
GWI(James et al., 2017).MethodsSeventy-one cognitively healthy women (32-69 years old) underwent a
Structural Magnetic Resonance Imagingscan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB1*13:02 allele (No DRB1*13:02 group, N = 60) or carried the DRB1*13:02 allele (N = 11). We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume) was the dependent variable and age was the independent variable.FindingsIn...
Characterization of Hand Clenching in Human Sensorimotor Cortex Using High-, and Ultra-High Frequency Band Modulations of Electrocorticogram
permalinkFrontiers in Neuroscience - 2018-02-27Jiang T, Liu S, Pellizzer G, Aydoseli A, Karamursel S, Sabanci PA, Sencer A, Gurses C, Ince NF10.3389/fnins.2018.00110Functional mapping of eloquent cortex before the resection of a tumor is a critical procedure for optimizing survival and quality of life. In order to locate the hand area of the motor cortex in two patients with low-grade gliomas (LGG), we recorded electrocorticogram (ECoG) from a 113 channel hybrid high-density grid (64 large contacts with diameter of 2.7 mm and 49 small contacts with diameter of 1 mm) while they executed hand clenching movements. We investigated the spatio-spectral characteristics of the neural oscillatory activity and observed that, in both patients, the hand movements were consistently associated with a wide spread power decrease in the low frequency band (LFB: 8-32 Hz) and a more localized power increase in the high frequency band (HFB: 60-280 Hz) within the sensorimotor region. Importantly, we observed significant power increase in the ultra-high frequency band (UFB: 300-800 Hz) during hand movements of both patients within a restricted...
Abnormal cortical neural synchrony during working memory in schizophrenia
permalinkClinical Neurophysiology - 2018-01-01Kang SS, MacDonald III AW, Chafee M, Im CH, Bernat EM, Davenport ND, Sponheim S10.1016/j.clinph.2017.10.024ObjectiveTo better understand the origins of working memory (WM) impairment in schizophrenia we investigated cortical oscillatory activity in people with schizophrenia (PSZ) while they performed a WM task requiring encoding, maintenance, and retrieval/manipulation processes of spatial information.MethodsWe examined time-frequency synchronous energy of cortical source signals that were derived from
MEGlocalized to cortical regions using WM-related hemodynamic responses and individualized structural head-models.ResultsCompared to thirteen healthy controls (HC), twelve PSZ showed performance deficits regardless of WM-load or duration. During encoding, PSZ had early theta and delta event-related synchrony (ERS) deficits in prefrontal and visual cortices which worsened with greater memory load and predicted WM performance. During prolonged maintenance of material, PSZ showed deficient beta event-related desynchrony (ERD) in dorsolateral prefrontal, posterior parietal, and visual cortices. In retrieval, PSZ showed reduced delta/theta ERS in the anterior prefrontal and ventral visual cortices and diminished gamma ERS in the premotor and posterior parietal cortices.ConclusionsAlthough...
Human Leukocyte Antigen and Gulf War Illness: HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans
permalinkEBioMedicine - 2017-12-01James L, Christova P, Engdahl B, Lewis S, Carpenter A, Georgopoulos AP10.1016/j.ebiom.2017.11.005BackgroundGulf War Illness (
GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six
GWI(Georgopoulos et al., 2016) and their association with regional brain function (James et al., 2016). More recently, we reported on the presence of subcortical brain atrophy in
GWI(Christova et al., 2017) and discussed its possible relation to immune mechanisms. Here we focused on one of the six
HLAalleles, DRB1*13:02, which has been found to have a protective role in a broad range of autoimmune diseases (Furukawa et al., 2017), and tested its effects on brain volumes.MethodsSeventy-six Gulf War veterans (55 with
GWIand 21 healthy controls) underwent a
Indirect Relations Between Transgressive Acts and General Combat Exposure and Moral Injury
PTSD) symptoms, demoralization, self-handicapping, and self-injury. In this study, we tested a frequently cited model of moral injury and assessed the associations between potentially transgressive acts, moral injury outcomes, and guilt and fear. Additionally, we sought to clarify the relative contribution of transgressive and nontransgressive/general combat exposure to moral injury. On the basis of previous research and theory, we anticipated that the transgressive acts would be related to outcomes through guilt and that nontransgressive combat exposure would be related to outcomes through fear. Materials and Methods: Secondary analysis was conducted on data from a sample...
What are we learning about how to treat Posttraumatic Stress Disorder?
PTSD.Why do some people experience
PTSD, but not others? And what are we learning about how to treat it?MPR News host Kerri Miller spoke with the
BSC's Brian Engdahl, a neuroscience professor at the University of Minnesota, and the Anderson Chair in
PTSDResearch at the University of Minnesota Medical School
Brain function in Gulf War Illness and associated mental health comorbidities
Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex
Gulf War Illness as a neuroimmune disease
permalinkExperimental Brain Research - 2017-10-01Georgopoulos AP, James L, Carpenter A, Engdahl B, Leuthold A, Lewis S10.1007/s00221-017-5050-0GWI is a chronic disease characterized by the involvement of several organs, including the brain (Christova et al., Exp Brain Res doi: 10.1007/s00221-017-5010-8, 2017). In a previous study (Georgopoulos et al., J Neural Eng 4:349-355, 2015), we identified six protective alleles from Class II
HLAgenes, and more recently, we investigated the brain correlates of this protection (James et al., EBioMedicine 13:72-79, 2016). Those and other studies (Israeli, Lupus, 21:190-194, 2012) suggested an involvement of the immune system in
GWI. In a recent study (Engdahl et al., EBioMedicine doi: 10.1016/j.ebiom.2016.08.030, 2016), we showed that the brain pattern of
SNI; Georgopoulos et al., J Neural Eng 4:349-355, 2007) in
GWIis distinctly different from that in healthy controls. Here we focused on the
SNIitself, as a basic measure of neural communication (irrespective of specific connections) and compared it between
American Legion Brain Sciences presents Scholarship Awards Winners
permalink2017-10-01The American Legion Brain Sciences Foundation presented two recipients with Scholarships at the 2017 American Legion Family awards ceremony. The recipients were (from left to right) Jasmine Joseph and Matt Green.
Subcortical brain atrophy in Gulf War Illness
permalinkExperimental Brain Research - 2017-09-01Christova P, James L, Engdahl B, Lewis S, Carpenter A, Georgopoulos AP10.1007/s00221-017-5010-8GWI 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
GWIhas 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
GWIcomprising 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...