The Effects of Previous Concussions on the Physiological Complexity of Motor Output During a Continuous Isometric Visual-Motor Tracking Task

The majority of clinical impairments following a concussion resolve within 7-10 days. However, there is limited clarity as to long-term impact of this injury on neurocognitive function, motor control, and particularly integration of these domains. While repetitive head trauma is associated with numerous neurological disorders, the link is not well described. Visual-motor tracking tasks have been used to identify differences in visual processing, error detection, and fine motor control in aging and numerous pathologies. Examining the complexity of motor output from visual-motor tracking provides insight into multiple cognitive and motor function domains, and into fine motor control used for daily living, work, and sport. The purpose of this dissertation was, therefore, to: (1) use multiple regression to determine the extent to which concussion history and symptoms (loss of consciousness and amnesia) influence visual-motor task performance multiscale complexity, and (2) determine whether task performance complexity can distinguish, through logistic regression and prediction, between individuals with and without a history of concussion. In study 1, individuals with (n = 35) and without (n = 15) a history of concussion performed a visual-motor tracking task. Men and women exhibited linear decreases in task performance complexity, as well as midand high-frequency task performance components, with increasing numbers of concussions. However, men and women exhibited differing patterns, as did those with and without a history of concussion-related loss of consciousness. Finally, trial-to-trial complexity variability increased with increasing numbers of concussions. Findings indicate (1) a cumulative reduction in the way in which previously concussed individuals process and integrate visual information to guide behavior and (2) gender is an important consideration in concussion-related visual-motor outcomes. In Study 2, individuals with (n = 85) and without (n = 42) a history of concussion performed a visualmotor tracking task. Linear and nonlinear measures of task performance were used to build gender-specific logistic classification models using 10-fold cross-validation. When ensuring 80% sensitivity, the best models were 75-80% accurate in predicting a history of concussion. Such discrimination has clinical value in identifying individuals who merit further evaluation and observation over time for conditions related to repetitive head traumas

The Role of Prefrontal Cortical Surface Area and Volume in Preclinical Suicidal Ideation in a Non-Clinical Sample

Suicidal ideation (SUI) can occur in the absence of concomitant psychiatric diagnoses, and even normal levels can be problematic among individuals experiencing excess stress or lack of social support. The objective of this study was to investigate the neuroanatomical basis of SUI in non-clinical human populations who are within the normal limits of SUI, after accounting for elevated stress and perceived lack of social support. Neuroanatomical data were collected from 55 healthy individuals (mean age 30.9 +/- 8.1 years, 27 females) whose depression severity levels were below the Diagnostic and Statistical Manual of Mental Disorders criteria. Measures of SUI, aggression, stress, non-support, and treatment rejection were collected from the treatment-consideration scales (TCS) of the Personality Assessment Inventory (PAI). Correlations between standardized SUI scores and three brain morphometry measures, including vertex wise cortical thickness (CT), cortical surface area (CSA), and cortical volume (CV), were estimated for each participant, controlling for age, sex, intracranial volume, and the remaining TCS measures. We observed a significant negative association between scores on SUI and both CSA and CV (cluster-forming threshold of p < 0.005, clusterwise threshold of p < 0.05, FOR corrected for multiple comparisons) within the left rostral middle frontal gyrus. Our findings suggest that greater CSA and CV within the dorsolateral prefrontal cortex are associated with reduced SUI in a non-clinical population with mild levels of stress and perceived lack of social support. Because the dorsolateral prefrontal cortex has been broadly linked to cognitive reappraisal, self-critical thoughts, and emotional regulation, greater CSA and CV within these regions may lead to better mental health by protecting healthy individuals from engaging in SUI during periods of stress and perceived insufficient social support. As our data consisted of only healthy individuals with non-clinical levels of SUI, further investigation will be necessary to explore the neural basis of SUI in populations who may be at greater risk of future suicidal behavior.U.S. Army Medical Research and Materiel Command [W81XWH-09-1-0730]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Ability-Based Emotional Intelligence Is Associated With Greater Cardiac Vagal Control and Reactivity

Several distinct models of emotional intelligence (EI) have been developed over the past two decades. The ability model conceptualizes EI as a narrow set of interconnected, objectively measured, cognitive-emotional abilities, including the ability to perceive, manage, facilitate, and understand the emotions of the self and others. By contrast, trait or mixed models focus on subjective ratings of emotional/social competencies. Theoretically, EI is associated with neurobiological processes involved in emotional regulation and reactivity. The neurovisceral integration (NVI) model proposes a positive relationship between cardiac vagal control (CVC) and cognitive-emotional abilities similar to those encompassed by EI. The current study examined the association between CVC and EI. Because ability EI is directly tied to actual performance on emotional tasks, we hypothesized that individuals with higher ability-based EI scores would show greater levels of CVC at rest, and in response to a stressful task. Because mixedmodels of EI are not linked directly to observable emotional behavior, we predicted no association with CVC. Consistent with expectations, individuals with higher levels of ability EI, but not mixed EI, had higher levels of CVC. We also found that individuals with greater levels of CVC who demonstrated reactivity to a stress induction had significantly higher EI compared to individuals that did not respond to the stress induction. Our findings support the theoretically expected overlap between constructs within the NVI model and ability EI model, however, the observed effect size was small, and the associations between EI and CVC should not be taken to indicate a causal connection. Results suggest that variance in the ability to understand emotional processes in oneself and to reason about one's visceral experience may facilitate better CVC. Future work manipulating either CVC or EI may prove informative in teasing apart the causal role driving their observed relationship.Joint Warfighter Medical Research Program [W81XWH-16-1-0062]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Rested-Baseline Responsivity of the Ventral Striatum Is Associated With Caloric and Macronutrient Intake During One Night of Sleep Deprivation

Background: Sleep loss contributes to obesity through a variety of mechanisms, including neuroendocrine functioning, increased hunger, and increased food intake. Additionally, sleep loss alters functional activation within brain regions associated with reward and behavioral control. However, it remains unknown whether individual differences in baseline neural functioning can predict eating behaviors during total sleep deprivation (TSD). We used functional magnetic resonance imaging (fMRI) to test the hypothesis that individuals with increased baseline responsiveness within reward regions are more vulnerable to TSD-induced overeating. Methods:N = 45 subjects completed several fMRI scans during a single pre-TSD session that included performance on the Multi-Source Interference Task (MSIT) and the n-back task. Subjects returned to the laboratory for an overnight TSD session, during which they were given ad libitum access to 10,900 kcal of food. Leftover food and packaging were collected every 6 h (00:00, 06:00, and 12:00) to measure total food consumption. Subjects reported sleepiness every hour and performed a food rating task every 3 h. Results: Functional activation within the ventral striatum during the MSIT and n-back positively correlated with total caloric and carbohydrate intake during the final 6 h (06:00-12:00) of TSD. Activation within the middle and superior temporal gyri during the MSIT also correlated with total carbohydrates consumed. Food consumption did not correlate with subjective sleepiness, hunger, or food desire. Conclusions: Individual differences in neural activity of reward processing areas (i.e., nucleus accumbens) prior to sleep deprivation are associated with an individual's propensity to overeat during subsequent sleep deprivation. This suggests that individual differences within reward processing pathways are potential key factors in sleep loss related overeating. Sleep loss and obesity are tightly linked. Both phenomena have been associated with increased neural activation in regions associated with reward, inhibitory control, and disrupted dopamine signaling. Elevated baseline reward sensitivity in the ventral striatum appears to be further compounded by sleep deprivation induced dysfunction in the reward neurocircuitry, increasing the likelihood of overeating. Our findings suggest that large individual differences in baseline responsiveness of hedonic reward pathways may modulate the association between sleep loss and obesity.Defense Advanced Research Projects Agency (DARPA), DARPA Young Faculty Award [D12AP00241]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Insomnia and daytime sleepiness: risk factors for sports-related concussion

Objective/Background: Poor quality and inadequate sleep are associated with impaired cognitive, motor, and behavioral components of sport performance and increased injury risk. While prior work identifies sports-related concussions as predisposing factors for poor sleep, the role of sleep as a sports-related concussion risk factor is unknown. The purpose of this study was to quantify the effect of poor sleep quality and insomnia symptoms on future sports-related concussion risk. Patients/Methods: In this study, 190 NCAA Division-1 athletes completed a survey battery, including the Insomnia Severity Index (ISI) and National Health and Nutrition Examination Survey (NHANES) Sleep module. Univariate risk ratios for future sports-related concussions were computed with ISI and NHANES sleepiness scores as independent predictors. An additional multiple logistic regression model including sport, sports-related concussion history, and significant univariate predictors jointly assessed the odds of sustaining a concussion. Results: Clinically moderate-to-severe insomnia severity (RR = 3.13, 95% CI: 1.320-7.424, p = 0.015) and excessive daytime sleepiness two or more times per month (RR = 2.856, 95% CI: 0.681-11.977, p = 0.037) increased concussion risk. These variables remained significant and comparable in magnitude in a multivariate model adjusted for sport participation. Conclusion: Insomnia and daytime sleepiness are independently associated with increased sports-related concussion risk. More completely identifying bidirectional relationships between concussions and sleep requires further research. Clinicians and athletes should be cognizant of this relationship and take proactive measures - including assessing and treating sleep-disordered breathing, limiting insomnia risk factors, improving sleep hygiene, and developing daytime sleepiness management strategies e to reduce sports-related concussion risk and support overall athletic performance. (C) 2019 Elsevier B.V. All rights reserved.Innovations grant from the National Collegiate Athletic Association; US Army Medical Research and Materiel Command grant [W81XWH14-1-0571]; [R01 MD011600]12 month embargo; published online: 25 March 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Daily Morning Blue Light Therapy for Post-mTBI Sleep Disruption: Effects on Brain Structure and Function

Background: Mild traumatic brain injuries (mTBIs) are associated with novel or worsened sleep disruption. Several studies indicate that daily morning blue light therapy (BLT) is effective for reducing post-mTBI daytime sleepiness and fatigue. Studies demonstrating changes in brain structure and function following BLT are limited. The present study's purpose is to identify the effect of daily morning BLT on brain structure and functional connectivity and the association between these changes and self-reported change in post-mTBI daytime sleepiness. Methods: A total of 62 individuals recovering from a mTBI were recruited from two US cities to participate in a double-blind placebo-controlled trial. Eligible individuals were randomly assigned to undergo 6 weeks of 30 min daily morning blue or placebo amber light therapy (ALT). Prior to and following treatment all individuals completed a comprehensive battery that included the Epworth Sleepiness Scale as a measure of self-reported daytime sleepiness. All individuals underwent a multimodal neuroimaging battery that included anatomical and resting-state functional magnetic resonance imaging. Atlas-based regional change in gray matter volume (GMV) and region-to-region functional connectivity from baseline to post-treatment were the primary endpoints for this study. Results: After adjusting for pre-treatment GMV, individuals receiving BLT had greater GMV than those receiving amber light in 15 regions of interest, including the right thalamus and bilateral prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with greater GMV in 74 ROIs, covering many of the same general regions. Likewise, BLT was associated with increased functional connectivity between the thalamus and both prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with increased functional connectivity between attention and cognitive control networks as well as decreased connectivity between visual, motor, and attention networks (all FDR corrected p < 0.05). Conclusions: Following daily morning BLT, moderate to large increases in both gray matter volume and functional connectivity were observed in areas and networks previously associated with both sleep regulation and daytime cognitive function, alertness, and attention. Additionally, these findings were associated with improvements in self-reported daytime sleepiness. Further work is needed to identify the personal characteristics that may selectively identify individuals recovering from a mTBI for whom BLT may be optimally beneficial.Medical Research and Materiel CommandOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Exploratory imaging outcomes of a phase 1b/2a clinical trial of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: Structural effects and functional connectivity outcomes

Abstract Introduction Allopregnanolone (ALLO), an endogenous neurosteroid, promoted neurogenesis and oligogenesis and restored cognitive function in animal models of Alzheimer's disease (AD). Based on these discovery research findings, we conducted a randomized‐controlled phase 1b/2a multiple ascending dose trial of ALLO in persons with early AD (NCT02221622) to assess safety, tolerability, and pharmacokinetics. Exploratory imaging outcomes to determine whether ALLO impacted hippocampal structure, white matter integrity, and functional connectivity are reported. Methods Twenty‐four individuals participated in the trial (n = 6 placebo; n = 18 ALLO) and underwent brain magnetic resonance imaging (MRI) before and after 12 weeks of treatment. Hippocampal atrophy rate was determined from volumetric MRI, computed as rate of change, and qualitatively assessed between ALLO and placebo sex, apolipoprotein E (APOE) ε4 allele, and ALLO dose subgroups. White matter microstructural integrity was compared between placebo and ALLO using fractional and quantitative anisotropy (QA). Changes in local, inter‐regional, and network‐level functional connectivity were also compared between groups using resting‐state functional MRI. Results Rate of decline in hippocampal volume was slowed, and in some cases reversed, in the ALLO group compared to placebo. Gain of hippocampal volume was evident in APOE ε4 carriers (range: 0.6% to 7.8% increased hippocampal volume). Multiple measures of white matter integrity indicated evidence of preserved or improved integrity. ALLO significantly increased fractional anisotropy (FA) in 690 of 690 and QA in 1416 of 1888 fiber tracts, located primarily in the corpus callosum, bilateral thalamic radiations, and bilateral corticospinal tracts. Consistent with structural changes, ALLO strengthened local, inter‐regional, and network level functional connectivity in AD‐vulnerable regions, including the precuneus and posterior cingulate, and network connections between the default mode network and limbic system. Discussion Indicators of regeneration from previous preclinical studies and these exploratory MRI‐based outcomes from this phase 1b/2a clinical cohort support advancement to a phase 2 proof‐of‐concept efficacy clinical trial of ALLO as a regenerative therapeutic for mild AD (REGEN‐BRAIN study; NCT04838301)

Elevated Aggression and Reduced White Matter Integrity in Mild Traumatic Brain Injury: A DTI Study

Mild traumatic brain injury (mTBI) remains the most commonly reported head injury in the United States, and is associated with a wide range of post-concussive symptoms including physical, cognitive and affective impairments. Elevated aggression has been documented in mTBI; however, the neural mechanisms associated with aggression at the chronic stage of recovery remain poorly understood. In the present study, we investigated the association between white matter integrity and aggression in mTBI using diffusion tensor imaging (DTI). Twenty-six age-matched adults participated in the study, including 16 healthy controls (HCs) and 10 individuals in the chronic stage of recovery (either 6-months or 12 months post-mTBI). Psychological measures of aggression included the Buss-Perry Aggression Questionnaire and the Personality Assessment Inventory (PAI). Axonal pathways implicated in affective processing were studied, including the corpus callosum, anterior thalamic radiation, cingulum and uncinate fasciculus, and measures of white matter integrity included fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). We found that adults with mTBI in the chronic stage of recovery had higher levels aggression. Individuals with mTBI also had greater RD in the corpus callosum compared to HCs, indicating reduced fiber integrity. Furthermore, we observed a significant association between reduced white matter integrity in the corpus callosum and greater aggression. Our findings provide additional evidence for underlying neuroanatomical mechanisms of aggression, although future research will be necessary to characterize the specific relationship between aggression and the white matter pathways we identified.Office of the Assistant Secretary of Defense for Health Affairs; Defense Health Agency J9, Research and Development Directorate, through the US Army Medical Research and Materiel Command (USAMRMC) [W81XWH-12-0386]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]