Alterations in cerebral blood flow (CBF) are associated with risk of cognitive decline and Alzheimer’s disease (AD). Although apolipoprotein E (APOE) ε4 and greater vascular risk burden have both been linked to reduced CBF in older adults, less is known about how APOE ε4 status and vascular risk may interact to influence CBF. We aimed to determine whether the effect of vascular risk on CBF varies by gene dose of APOE ε4 alleles (i.e., number of e4 alleles) in older adults without dementia.

144 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent arterial spin labeling (ASL) and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure assessment. Vascular risk was assessed using pulse pressure (systolic blood pressure -diastolic blood pressure), which is thought to be a proxy for arterial stiffening. Participants were classified by number of APOE ε4 alleles (n0 alleles = 87, m allele = 46, n2 alleles = 11). CBF in six FreeSurfer-derived a priori regions of interest (ROIs) vulnerable to AD were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regression models tested the interaction between categorical APOE ε4 dose (0, 1, or 2 alleles) and continuous pulse pressure on CBF in each ROI, adjusting for age, sex, cognitive diagnosis (cognitively unimpaired vs. mild cognitive impairment), antihypertensive medication use, cerebral metabolism (FDG-PET composite), reference CBF region (precentral gyrus), and AD biomarker positivity defined using the ADNI-optimized phosphorylated tau/ß-amyloid ratio cut-off of > 0.0251 pg/ml.

A significant pulse pressure X APOE ε4 dose interaction was found on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex (ps < .005). Among participants with two e4 alleles, higher pulse pressure was significantly associated with lower CBF (ps < .001). However, among participants with zero or one ε4 allele, there was no significant association between pulse pressure and CBF (ps > .234). No significant pulse pressure X APOE ε4 dose interaction was found in the inferior temporal cortex, rostral middle frontal gyrus, or medial orbitofrontal cortex (ps > .109). Results remained unchanged when additionally controlling for general vascular risk assessed via the modified Hachinski Ischemic Scale.

These findings demonstrate that the cross-sectional association between pulse pressure and region-specific CBF differs by APOE ε4 dose. In particular, a detrimental effect of elevated pulse pressure on CBF in AD-vulnerable regions was found only among participants with the e4/e4 genotype. Our findings suggest that pulse pressure may play a mechanistic role in neurovascular unit dysregulation for those genetically at greater risk for AD. Given that pulse pressure is just one of many potentially modifiable vascular risk factors for AD, future studies should seek to examine how these other factors (e.g., diabetes, high cholesterol) may interact with APOE genotype to affect cerebrovascular dysfunction.

Cognitive dysfunction is a common non-motor symptom of Parkinson’s disease (PD). Cognitive decline in PD is likely associated with dysfunction in the cholinergic system, which is affected by synuclein pathology early in the disease course. Recent studies have shown an association between reduced integrity of the basal forebrain (BF), which provides cholinergic innervation to most of cortex, and diminished cognitive functioning in PD. Specifically, those with PD and reduced cholinergic innervation also have higher rates of cognitive impairment. However, no study has directly investigated the relationship between basal forebrain integrity and cortical cholinergic levels. In the present study, we examined this relationship through measures of basal forebrain microstructural integrity and cholinergic nerve terminal density in cortical and subcortical gray matter.

Participants included 92 non-demented individuals with idiopathic PD (M:F=64:28; Age=67.0±7.1 yrs) who underwent structural MRI, diffusion MRI, and [18F] fluoroethoxybenzovesamicol (FEOBV) cholinergic PET imaging. We used a basal forebrain and region of interest defined by AssemblyNet, which uses ensembles of pretrained convolutional neural networks to create a full brain segmentation. Bilateral putamen from this atlas was also included as a control region. We measured microstructural integrity using free water fraction (FWF), a diffusion MRI-derived metric of extracellular water that associates with cellular density and neuroinflammation. For PET data, we computed the distribution volume ratio (DVR) by regions as defined by FreeSurfer. A factor analysis of DVR in all 88 FreeSurfer ROIs resulted in seven clusters of ROIs covering 1) widespread bilateral cortical regions (PC1); 2) subcortical and limbic regions (PC2); 3) bilateral cingulate regions (PC3); 4) left frontal regions (PC4); 5) right frontal and temporal regions (PC5); 6) cerebellum (PC6); and 7) bilateral entorhinal cortex and left temporal cortex (PC7). We performed seven separate regression analyses per ROI (controlling for age and disease duration) to evaluate the association between BF FWF and cholinergic levels in these regions. To determine if these ROIs showed unique associations with BF FWF, we then entered ROIs with a significant association with BF FWF as independent variables in a stepwise regression with forward selection with BF FWF as the dependent variable.

BF FWF was significantly and negatively associated with cholinergic levels in PC1 (AR2=.042, ß=-0.208, p=.04), PC3 (AR2=.044, ß=-0.206, p=.03), PC4 (AR2=.056, ß=-0.239, p=.02), and PC7 (ß=-0.215, p=.04). BF FWF trended towards a negative association with cholinergic levels in PC5 (AR2=.045, ß=-0.168, p=.09) and PC6 (ß=-0.188, p=.09). Putamen FWF did not significantly associate with any of the ROIs. In the follow-up stepwise regression, only PC4 contributed significantly to the overall model (AR2=.061, ß=-0.261, p=.02).

Basal forebrain FWF was inversely related to cholinergic levels in regions that are directly innervated by the basal forebrain (e.g., cingulate cortex, left frontal cortex, and bilateral entorhinal cortex). Future research should directly investigate the relationship between basal forebrain integrity, cortical cholinergic levels, and cognition. Separating the basal forebrain into specific nuclei would also be beneficial, as different nuclei may have differing associations with specific hemispheric cholinergic pathways and cognition.

Parkinson’s disease (PD) is associated with metabolic disorders such as insulin resistance. Pharmacological intervention used to treat insulin resistance, like GLP-1 agonists, may have auspicious results in the treatment for PD. The objective of this clinical trial was to assess the therapeutic effect of liraglutide on non-motor symptoms, such as, but not limited to, cognitive function and emotional well-being, and quality of life for individuals with PD.

In a single-center, randomized, double-blind, placebo-controlled trial, PD patients self-administered liraglutide injections once-daily (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptom scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2). Secondary outcomes included quality of life scores (Parkinson Disease Questionnaire, PDQ-39) and other neuropsychological tests, including Delis-Kaplan Executive Function System (DKEFS), Geriatric Depression Scale (GDS), and Parkinson’s Anxiety Scale (PAS) scores.

Sixty-three subjects were enrolled and randomized to liraglutide (n=42) or placebo (n=21). Mean age in years was 63.5 (9.8) and 64.2 (6.4) for liraglutide and placebo cohorts, respectively (p=0.78), and mean age at symptom onset was 58.9 (10.5) and 59.3 (7.5) for liraglutide and placebo cohorts, respectively (p=0.86). At 54 weeks, NMSS scores had improved by 6.6 points in the liraglutide group and worsened by 6.5 points in the placebo group, a 13.1 point adjusted mean difference (p<0.05). Further analysis showed all nine NMSS sub-domain changes favoring the liraglutide group, with one (attention/memory) reaching statistical significance (p<0.05). Secondary outcome analyses revealed a significant improvement of PDQ-39 (p<0.001) and Parkinson’s Anxiety Scale - Avoidance Behavior scores (p<0.05) in the treatment group. MDRS-2 sub-scores did not further differentiate study groups, while DKEFS letter fluency scores favored placebo group (p<0.05).

Treatment with liraglutide improved self-reported non-motor symptoms of PD, activities of daily living, and quality of life. These results validate similar outcomes reported with other GLP-1 agonists implicating consideration for novel treatment opportunities for individuals with PD. Notably, the absence of significant performance-based cognitive changes over the duration of the trial for the participants in this study has several plausible explanations given participant-related baseline demographic and clinical factors. Implications for neuropsychologists will be discussed.

Autonomic dysfunction is an important non-motor symptom of Parkinson’s disease (PD), with point prevalence estimates of approximately 50-70%. Common presentations include cardiovascular dysregulation, gastrointestinal dysfunction, impaired thermoregulation, and sexual dysfunction. In the present study, we sought to examine whether autonomic symptoms would predict trajectories of change in depression and anxiety over a 5-year period in newly diagnosed individuals with PD. Given that alterations in autonomic nervous system functioning (e.g., reduced heart rate variability, lower autonomic arousal) are frequently observed in individuals who have anxiety and depression, as well as the negative influence these symptoms can have on quality of life/functioning, we predicted that greater autonomic symptoms would be related to increased mood symptoms over time.

Participants included 414 individuals from the Parkinson’s Progression Markers Initiative, a prospective study of newly diagnosed and untreated individuals with PD. The PD participants (mean age=61.6+9.7, mean education=15.6+3.0, 92.5% non-Hispanic White) were followed annually for up to five years. Self-reported autonomic symptoms were measured using the Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction (SCOPA-AUT), which consists of a total score and 6 subdomain scores (gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, sexual). Mood measures included the Geriatric Depression Scale (GDS) and State-Trait Anxiety Inventory (STAI). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III. Bootstrapped linear regressions were performed to evaluate the relationship between autonomic symptoms (subdomains) and mood using data from the last visit (year 5). For longitudinal analyses, bootstrapped multilevel modeling was used to examine a) changes in SCOPA-AUT total over time (unconditional growth model only) and b) the relationship between mood and SCOPA-AUT total score over time, controlling for age/sex and motor severity.

Autonomic symptoms explained 28.2% of the total variance in trait anxiety, with unique predictors of gastrointestinal (/3=.266, p<.001) and thermoregulatory (ß=.202, p=.004) symptoms. For depression, autonomic symptoms explained 27.9% of the total variance, with unique predictors of gastrointestinal (ß=.225, p=.012), thermoregulatory (ß=.178, p=.013), and cardiovascular (ß=.154, p=.012) symptoms. There was a gradual linear increase in total autonomic symptoms over time (b=0.86, p<.001). Greater total autonomic symptoms were associated with higher average trait anxiety (b=0.54, p<.001), slightly greater increase in trait anxiety over time (b=0.04, p<.05), and occasion-to-occasion fluctuations in trait anxiety (b=0.24, p<.001). Similarly, increased total autonomic symptoms were associated with higher average depressive symptoms (b=0.14, p<.001), minimally greater increase in depressive symptoms over time (b=0.01, p<.05), and occasion-to-occasion fluctuations in depressive symptoms (b=0.08, p<.001). Motor severity did not explain individual differences or trajectories of change in depression or trait anxiety.

Autonomic symptoms, particularly gastrointestinal, cardiovascular, and thermoregulatory dysfunction, were related to increased mood symptoms in PD patients and predicted increases in depression/anxiety over time. Our findings do not distinguish between two theoretical possibilities - whether autonomic symptoms lead to depression/anxiety versus involvement of co-occurring neural systems underlying both. Regardless, our study highlights the importance of treating autonomic dysfunction in early PD, and future work should incorporate additional measures of autonomic dysfunction (e.g., physiological probes).

Apathy is a primary lack of motivation that is frequently reported in Parkinson’s disease (PD) and often misdiagnosed as depression. In PD, apathy worsens over time with motor symptom progression. Evidence over the past 15 years has documented that use of selective serotonin reuptake inhibitors (SSRIs) is associated with increased apathy in patients with depression, including individuals with PD. In PD, this appears to be related to downregulation of dopaminergic systems by serotonin. Despite increasing evidence, SSRIs continue to be heavily prescribed in individuals with PD— potentially worsening apathy and decreasing quality of life for these individuals. This study is an update, re-examining the relationship between apathy and the use of SSRIs and other antidepressants in a large cohort of individuals with PD.

Participants included a convenience sample of 387 nondemented individuals with idiopathic PD who were in their mid-60's (mean age=64.9+8.72 years), well-educated (mean=14.95+2.78 years), predominantly male (72.4%), non-Hispanic white (94.5%), and in mid-stage of disease severity (on medication Unified Parkinson Disease Rating Scale motor score=25.3+10.1). All scored above clinical cutoff for dementia on a cognitive screener (Dementia Rating Scale-2 (DRS) > 125). Medications, cognitive, mood, and clinical data were extracted from chart review. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped into SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs) and other. Analyses included bootstrapped Pearson’s correlations, Pearson’s chi-square, and linear regressions

Among 387 individuals with PD, 41.3% (N=160) were taking antidepressant medications. Of these 160, 61.3% were on SSRIs, 24.4% on SNRIs, and the remainder on other antidepressants. Approximately 36.9% of the 387 PD patients exceeded recommended clinical cutoffs for apathy (AS >14) and 23.5% for depression (BDI-II >14) (Starkstein et al., 1992; Beck et al., 1996). Individuals taking SSRIs (N=98, x2=5.14, p=0.023) or SNRIs (N=39; x2=5.43, p=0.020) were more likely to be clinically apathetic than those taking other depression medications (N=23; x2=1.28, p=0.26). Results of a multiple regression with age, education, disease duration, motor severity, DRS-2, BDI-II, and all psychotropic medications (anti-depressants, anti-anxiety, anti-psychotics) as independent variables explained 42.8% of the variance in total apathy scores (F[17,285]=12.550, p<0.001). SSRIs were the only medication to significantly predict greater AS scores (ß=0.110, p=0.020) in this model. Less education (ß=-0.119, p=0.017) worse cognition (ß=-0.128, p=0.009), and greater depressive symptoms (ß=0.561, p<0.001) were also significant predictors of apathy.

These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy as a potential adverse effect when determining which anti-depressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative anti-depressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study. Longitudinal studies are also needed to elucidate the relationship of apathy and anti-depressant use over time, specifically to determine potential causality of this observed association. Funding: T32-NS082168

While Parkinson’s disease (PD) is traditionally known as a movement disorder, cognitive decline is one of the most debilitating and common non-motor symptoms. Cognitive profiles of individuals with PD are notably heterogeneous (Goldman et al., 2018). While this variability may arise from the disease itself, other factors might play a role. Greater anticholinergic medication use has been linked to worse cognition in those with PD (Fox et al., 2011, Shah et al., 2013). However, past studies on this topic had small sample sizes, limited ranges of disease duration, and only used cognitive screeners. Thus, this study aimed to examine this question within a large, clinical sample, using a more comprehensive neuropsychological battery. We hypothesized that higher anticholinergic medication usage would relate to worse cognitive performance, particularly memory.

Participants included 491 nondemented individuals with PD (m=64.7, SD=9.04 years old; education m=15.01, SD=2.79; 71.9% male; 94.3% non-Hispanics white) who underwent a comprehensive neuropsychological assessment at the UF Fixel Institute’s movement disorders program. Medications at the time of the neuropsychological evaluation were identified from chart review and scored based on anticholinergic properties using the Magellan Anticholinergic Risk Scale (Rudolph J.L., et al, 2008); each medication was scored from 0 (no load) to 3 (high load). The neuropsychological battery included measures across 5 cognitive domains: (1) executive function (Trails B, Stroop Interference, Letter Fluency), (2) verbal delayed memory (WMS-III Logical Memory and Hopkin’s Verbal Learning Test-Revised delayed recalls), (3) language (Boston Naming Test-II, Animal Fluency), (4) visuospatial skills (Judgment of Line Orientation, Face Recognition Test), and (5) attention/working memory (WAIS-III Digit Span Forward and Backward). The published normative scores for each task were converted into z-scores and averaged into a domain composite. Due to non-normality of Magellan scores, Spearman correlations examined the relationship between each cognitive domain composite score and Magellan scores.

As predicted, higher Magellan scores were significantly associated with worse memory (r=-0.11, p=0.016), with a small effect size. There were no significant relationships between Magellan scores and the remaining cognitive domains (EF, language, visuospatial, attention).

We found that greater anticholinergic burden was associated with worse performance on memory, but not other neuropsychological domains, in a large cohort of nondemented individuals with PD who underwent comprehensive assessment. This finding corresponds to previous literature in smaller PD cohorts. Though the effect size was low, this finding highlights the importance of monitoring anticholinergic burden in PD patients in order to minimize detrimental effects of medications on memory function. Future work should examine whether greater anticholinergic burden predicts future progression of memory decline.

Acknowledgement: Supported in part by the NIH, T32-NS082168

Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.

We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.

At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).

Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.

Community reintegration and participation have been shown to be significantly correlated to improved Quality of Life (QoL) following moderate to severe traumatic brain injury (msTBI), yet these models often come with significant levels of unaccounted variability (Pierce and Hanks, 2006). Measures for community participation frequently employ objective measures of participation, such as number of outings in a week or current employment status (Migliorini et al., 2016), which may not adequately account for lifestyle differences, especially in aging populations. Less often integrated are subjective measures of an individual’s own belongingness and autonomy within the community (Heineman et al., 2011), also referred to as their participation enfranchisement (PE). The present study examines three questions pertinent to the potential clinical value of PE. First, do measures of objective participation significantly predict an individual’s PE ratings? Second, are both types of measures equally successful predictors of QoL for aging individuals with chronic-stage msTBI. Finally, would controlling for either objective or subjective integration ratings enable neurocognitive assessments to better predict QoL post injury?

41 older-adults (M= 65.32; SD= 7.51) with a history of msTBI were included (M= 12.59 years post-injury;SD= 8.29) for analysis. Subjective community integration was measured through the Participation Enfranchisement Survey. The Participation Assessment with Recombined Tools-Objective (PART-O) provided the objective measurement of participation. Quality of life was assessed through the Quality of Life after Brain Injury (QOLIBRI). An estimate of neurocognitive performance was created through the Brief Test of Adult Cognition by Telephone (BTACT), which includes six domains including: verbal-learning and memory (immediate and delayed recall), working memory (digit-span backwards), reasoning (number sequencing), semantic fluency (category fluency), and processing speed (backwards counting). Performance on the BTACT, PE ratings, and PART-O scores were included as the dependent variables in stepwise, linear regression models predicting QoL ratings to assess the differential contribution of the dependent variables and potential interaction effects.

While both the PART-O (f(1,39)=5.52;p=.024,n2=.124) and the PE survey (f(1,39)=14.31 ;p<.001,n2=.268) significantly predicted QoL, the addition of PE in the PART-O model resulted in significant (20.9%) reduction in unaccounted variance. Further in the model controlling for PE, PART-O no longer provides a significant (p=.15) contribution to the model estimating QoL (f(2,38)=8.41; p=.001). Performance on the BTACT correlated with PART-O (p<.0001), but not PE (p=.13) ratings. Finally, across two models controlling for BTACT performance, PE (p=.002,partial n2=.23), but not PART-O (p=.28,partial n2=.031) contributed significantly to QoL predictions. No significant interactions between PART-O, PE, and/or BTACT were observed when added to any model.

MsTBI impacts nearly every facet of an individual’s life, and as such, improving QoL post-injury requires a broad, yet well-considered approach. The objective ratings of participation, subjective PE, BTACT performance, all independently predicted quality of life in this sample. However, after controlling for neurocognitive assessment performance, PE was shown to independently contribute to quality of life, while the PART-O ratings no longer provided significant contribution. While community integration is a vital factor to consider for long-term rehabilitation, tailoring what “integration” means to the patient may hold significant potential to improve long-term quality of life.

It has been posited that alcohol use may confound the association between greater concussion history and poorer neurobehavioral functioning. However, while greater alcohol use is positively correlated with neurobehavioral difficulties, the association between alcohol use and concussion history is not well understood. Therefore, this study investigated the cross-sectional and longitudinal associations between cumulative concussion history, years of contact sport participation, and health-related/psychological factors with alcohol use in former professional football players across multiple decades.

Former professional American football players completed general health questionnaires in 2001 and 2019, including demographic information, football history, concussion/medical history, and health-related/psychological functioning. Alcohol use frequency and amount was reported for three timepoints: during professional career (collected retrospectively in 2001), 2001, and 2019. During professional career and 2001 alcohol use frequency included none, 1-2, 3-4, 5-7 days/week, while amount included none, 12, 3-5, 6-7, 8+ drinks/occasion. For 2019, frequency included never, monthly or less, 2-4 times/month, 2-3 times/week, >4 times/week, while amount included none, 1-2, 3-4, 5-6, 7-9, 10+ drinks/occasion. Scores on a screening measure for Alcohol Use Disorder (CAGE) were also available at during professional career and 2001 timepoints. Concussion history was recorded in 2001 and binned into five groups: 0, 1-2, 3-5, 6-9, 10+. Depression and pain interference were assessed via PROMIS measures at all timepoints. Sleep disturbance was assessed in 2001 via separate instrument and with PROMIS Sleep Disturbance in 2019. Spearman’s rho correlations tested associations between concussion history and years of sport participation with alcohol use across timepoints, and whether poor health functioning (depression, pain interference, sleep disturbance) in 2001 and 2019 were associated with alcohol use both within and between timepoints.

Among the 351 participants (Mage=47.86[SD=10.18] in 2001), there were no significant associations between concussion history or years of contact sport participation with CAGE scores or alcohol use frequency/amount during professional career, 2001, or 2019 (rhos=-.072-.067, ps>.05). In 2001, greater depressive symptomology and sleep disturbance were related to higher CAGE scores (rho=.209, p<.001; rho=.176, p<.001, respectively), while greater depressive symptomology, pain interference, and sleep disturbance were related to higher alcohol use frequency (rho=.176, p=.002; rho=.109, p=.045; rho=.132, p=.013, respectively) and amount/occasion (rho=.215, p<.001; rho=.127, p=.020; rho=.153, p=.004, respectively). In 2019, depressive symptomology, pain interference, and sleep disturbance were not related to alcohol use (rhos=-.047-.087, ps>.05). Between timepoints, more sleep disturbance in 2001 was associated with higher alcohol amount/occasion in 2019 (rho=.115, p=.036).

Increased alcohol intake has been theorized to be a consequence of greater concussion history, and as such, thought to confound associations between concussion history and neurobehavioral function later in life. Our findings indicate concussion history and years of contact sport participation were not significantly associated with alcohol use cross-sectionally or longitudinally, regardless of alcohol use characterization. While higher levels of depression, pain interference, and sleep disturbance in 2001 were related to greater alcohol use in 2001, they were not associated cross-sectionally in 2019. Results support the need to concurrently address health-related and psychological factors in the implementation of alcohol use interventions for former NFL players, particularly earlier in the sport discontinuation timeline.

Some active-duty military service members and veterans experience combinations of persistent traumatic stress, depression, suicidal ideation, anger, aggressive behavior, substance misuse, sleep disturbance, complicated grief, moral injury, headaches and migraines, chronic bodily pain, and cognitive weakness or deficits. The purpose of this study is to describe the clinical outcomes of active-duty service members and veterans who have completed the traumatic brain injury (TBI) and brain health track of a two-week intensive clinical treatment and rehabilitation program.

The sample included 141 participants, with a history of TBI, in the Intensive Clinical Program (ICP). The ICP is a multidisciplinary, two-week treatment and rehabilitation program for active duty service members and veterans with complex psychological, cognitive, and physical health concerns. The program is comprised of daily individual therapy, group psychotherapy, psychoeducation, skills-building groups, and complementary and alternative medicine treatments. Participants in the ICP completed the following measures prior to initiating treatment and immediately following completion of treatment: Neurobehavioral Symptom Inventory (NSI), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Patient Health Questionnaire-9 (PHQ-9), Self-Efficacy for Symptom Management Scale (SE-SMS), and Patient-Reported Outcomes Measurement Information System (PROMIS)-Satisfaction with Participation in Social Roles and Activities-Short Form 8a, version 1.0 (PROMIS-S). Wilcoxon signed ranks tests were used to examine differences in scores on self-report measures from pretreatment to posttreatment for the full sample and within three subgroups stratified by age (in years: 20-34; 35-45; and 46-66). For the NSI, changes in the proportion of participants endorsing moderate or worse levels of individual symptoms from pretreatment to posttreatment were assessed using McNemar’s tests. Alpha levels were set at p<0.05 for all analyses.

Participants reported statistically significant improvements across all of the administered measures (NSI, PCL-5, PHQ-9, PROMIS-S, and SE-SMS) upon conclusion of treatment. Effect sizes ranged from medium to large (d=0.34-1.04) for the full sample. Effect sizes were largely consistent across age subgroups (20-34: d=0.32-1.05; 35-45: d=0.55-0.96; 46-66: d=0.28-1.05). The magnitude of change on the SE-SMS appeared to be less with increasing age (20-34: d=1.05; 35-45: d=0.69; 46-66: d=0.28). Individual item analyses for the NSI revealed statistically significant reductions in the proportion of participants endorsing moderate or greater severity from pretreatment to posttreatment for 18 of 22 symptoms.

Active duty service members and veterans participating in the two-week TBI and brain health intensive clinical program reported considerable symptom reduction at the conclusion of the program. Further research is indicated to assess the durability of symptom reduction.

Return to driving after moderate-to-severe traumatic brain injury (TBI) is often a key step in recovery to regain independence. Survivors are often eager to resume driving and may do so despite having residual cognitive limitations from their injury. A better understanding is needed of how cognition and self-awareness impact survivors’ driving after injury. This study examined the influence of cognition and self-awareness on driving patterns following moderate-to-severe TBI.

Participants were 350 adults aged 19-87 years (mean age = 46 years; 70% male) with history of moderate-to-severe TBI, who resumed driving and were enrolled in the TBI Model System. Cross-sectional data were obtained ranging 1-30 years post injury, including questions on driving practices, the Brief Test of Adult Cognition by Telephone (BTACT), and the Functional Independence Measure (FIM). Self-awareness of cognitive function was measured via the discrepancy between dichotomized ratings (intact versus impaired) of objective cognitive testing (BTACT) and self-reported cognitive function (FIM Cognition subscale). Driving patterns included frequency (driving 'more than once a week’ versus 'once a week or less') and restricted driving behavior (total number of driving situations the survivor described as restricted, ranging 0-15). Regression analyses were conducted to examine the relationships between cognition, self-awareness, and each driving outcome (frequency and restriction), followed by causal mediation analyses to examine the mediating effect of self-awareness. Demographics (age, sex, education), injury characteristics (time since injury, injury severity, history of seizures in past year), and medical/social factors (family income, motor function, urban-rural classification) were included in the models as covariates.

Thirty-nine percent of survivors had impaired self-awareness, 88% of survivors drove numerous times per week, and the average survivor reported limited driving in 6 situations (out of 15 total situations). Cognition was inversely related to impaired self-awareness (OR = 0.03, p < 0.001) and inversely related to restricted driving behavior (b = -0.79, p < 0.001). Motor function was positively related to impaired self-awareness (OR = 1.28, p < 0.01). Cognition was not related to driving frequency, and self-awareness did not mediate the relationships between cognition and driving patterns (all p > 0.05).

Most survivors who drive after their injury are driving frequently, but the situations they drive in differ based on their cognitive ability. Impaired self-awareness of cognitive deficits is common after TBI, and self-awareness of cognitive function does not affect driving patterns. Future research needs to focus on how cognition affects nuanced aspects of driving behavior after injury (i.e., types of situations survivors drive in).

Previous research has shown that positive outcomes are associated with receiving a neuropsychological evaluation (NPE). The current project examined hospitalization outcomes following an NPE in a sample of patients who had sustained a traumatic brain injury (TBI). Hospitalization rates were compared between the two years pre- and two years post-evaluation. The role that insurance status plays on these health outcomes was also examined. This project is part of a growing effort to evaluate outcomes of clinical neuropsychological services in order to better characterize the broad health impacts of NPEs.

Participants for the current study come from the Optum® de-identified Electronic Health Record dataset. The final sample included 245 patients who completed at least one NPE and were diagnosed with a TBI, according to ICD codes associated with their healthcare records. Patients were aged 21-87 (M = 51.55, SD = 16.74) with an average Charleston Comorbidity Index of 1.77 (SD = 2.41). The sample consisted of 124 females (50.6%), 121 males (49.4%). The majority of the sample identified as non-Hispanic white (N = 213; 86.9%), while 8.6% identified as another race or ethnicity. Regarding insurance, the most common insurance type was commercial (61.6%), followed by Medicare (13.5%), Medicaid (9.4%), and uninsured (6.5%). Those with unknown insurance status, race, or ethnicity were excluded from analyses of those variables.

Hospitalization incidence for the sample was significantly lower in the two years following a NPE, X2(1, N = 245) = 26.98, p < .001, compared to the two years prior. The mean number of hospitalizations were also lower following a NPE (t(244) = 4.83, p < .001). Insurance status did not show a significant main effect or interaction on mean number of hospitalizations over time. Regarding demographic variables, there was no significant main effects of race/ethnicity group or interaction between race/ethnicity and hospitalization rate change over time. However, there was a significant interaction between hospitalization rate change over time and gender (F(242) = 4.74, p = 0.030). A significant decrease in hospitalizations over time was seen for males (p < .001), while females showed a trend-level decrease that approached significance (p = .06).

Consistent with previous research, significant reductions in hospitalization incidence and mean number of hospitalizations were seen following a NPE. This finding did not vary based on insurance status. However, hospitalization outcomes varied as a function of gender. These findings suggest that completing a NPE following a traumatic brain injury may contribute to improved hospitalization outcomes, but it does not appear that this benefit is seen equally for all patients. Insurance status may play a role in accessibility to care and hospitalization outcomes in this population, but that relationship is likely influenced by other factors, including racial identity, gender, and income. Future research is needed to investigate the extent that NPEs impact hospitalization rates in the broader context of insurance, demographic factors, and socioeconomic status.

To assess the impact of injury severity on disease specific quality of life after Traumatic Brain Injury

The study was carried out in Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India after obtaining ethical clearance from Institute Ethics Committee. Sixty consecutive patients aged 18 and above with moderate to severe TBI (GCS score of 3-12 at admission) attending the Outpatient Department of Neurosurgery Specialty were screened. Out of 60 participants, 40 had moderate TBI (GCS 9-12) and 20 patients had severe TBI (GCS 3-8). The participants having any pre-existing major psychiatric disorders, intellectual disability, current or past history of substance abuse, degenerative and/or progressive condition, terminal illness and past history of TBI were excluded. Written informed consent was obtained from each participant. Socio-demographic details and information about clinical status at the time of admission and discharge were obtained from participant and hospital records. Disease specific quality of life was measured by QOLIBRI (Quality of life after brain injury). It is a self-reported measure comprising of 37 items. The first part assesses the subjects’ satisfaction with his HRQL in 4 domains (cognition, self, daily life and autonomy, and social relationships). The second part measures how much the subject is bothered after TBI in 2 domains (emotions and physical problems). The other tools administered were Glasgow Outcome Scale and Barthel’s Index of Activities of Daily Living (functional status); Mini Mental State Examination (cognitive status): Hospital Anxiety and Depression Scale (anxiety and depression).

The data was analyzed using statistical package for social sciences software version 21 (SPSS). There were no significant differences between both groups with regard to age, gender, education status, marital status, family type and place of residence. Both groups were similar with regard to mode of injury and duration of injury. With regard to treatment during admission both group had significant differences. Among severe TBI group 90% underwent surgical intervention whereas among moderate TBI group only 45% underwent surgical intervention. Significant difference was present in GCS score at discharge between both the groups. After 6 months of injury both group had no significant difference with regard to functional status, global cognitive functioning, anxiety and depression. With regard to quality of life significant difference emerged between the groups on QOLIBRI total score. On various subscales of QOLIBRI - significant differences were noted only in the domains of social relationship and emotions. There were no differences between them on domains of cognition, self, daily life and physical problems.

After 6 months of TBI, the participants in both groups (Moderate TBI and severe TBI) had similar functioning with regard to daily activities and psychological functioning. With regard to quality of life both groups emerged to be significantly different on overall quality of life and domains of social relationship and emotions.

Metacognitive deficits are common following traumatic brain injury (TBI), and this has important implications for recovery, social relationships, and rehabilitative outcomes (Chiou et al., 2011; Flashman & McAllister, 2002; Ownsworth & Fleming, 2005). Metacognitive deficits have historically been measured using self-report (Allen & Ruff, 1990; Newman et al., 2000; Sherer et al., 1995; Sherer et al., 1998), which is problematic as individuals with an awareness of deficit cannot accurately reflect on their own condition (Akturk & Sahin, 2011). In the past two decades, studies have transitioned to using more objective measures to assess metacognition, including error monitoring tasks (McAvinue et al., 2005; Yeung & Summerfield, 2012) and tasks using retrospective confidence judgments (RCJs) (Busey et al., 2000). Importantly, both tasks are used to study “metacognition,” but clear distinctions as to what domains these tasks measure has not been elucidated. Additionally, both tasks have been linked to executive functioning broadly, but error detection tasks are uniquely associated with measures of attention and self-reported anxiety (Hoerold et al., 2008; O’Keefe et al., 2007), indicating that there may be distinct processes that comprise metacognition. It is a goal to determine what domains these tasks represent so proper assessments of metacognitive ability can be conducted in this population.

Participants included 23 older adults with moderate-severe TBI and 16 age, sex, and education matched healthy control (HC) individuals ages 53-80. All participants received identical neuropsychological test batteries, including two tasks of metacognition (error monitoring task, RCJ task), neurocognitive tasks of attention (Digit Span - Forward, Trail Making Test A) and executive functioning (Digit Span - Backward, Trail Making Test B), and a self-report measure of anxiety (Brief Symptom Inventory - Anxiety subscale). To determine overlapping constructs measured by the two metacognitive tasks, these tasks were correlated with each other and with an attention composite, executive functioning (EF) composite, and anxiety measure in the TBI and HC groups.

In the TBI group, the metacognitive tasks were significantly correlated with each other (r=-0.47, p=0.022). The RCJ task was associated with EF (r=0.47, p=0.025), but not with attention (r=0.20, p=0.358) or anxiety (r=0.25, p=0.248). The error detection task was associated with EF (r=-0.48, p=0.021) and attention (r=-0.46, p=0.026), but not with anxiety (r=-0.19, p=0.383). In the HC group, there were no significant associations between the metacognitive tasks, or between either metacognitive task and EF, attention, or anxiety.

For older adults sustaining TBI, tasks of error detection and tasks using retrospective confidence judgments measured an overlapping construct, with both having an association with executive functioning and only the error detection task being associated with attention. Interestingly, these associations were not found in a healthy control sample of older adults. Both metacognitive tasks have been used in the literature to measure errors of awareness, but this study provides insight that these tasks are measuring different domains of metacognitive ability in older individuals with TBI. Use of multiple tasks of metacognitive ability in this population can help to describe where the deficits of awareness occur following TBI.

Traumatic brain injury (TBI), very common in the United States (US) and occurring at highest rates in older adulthood, is a documented risk factor for cognitive impairment and dementia. However, the full scope of the problem is unknown, as comparative incidence of TBI among older adults is poorly characterized. Moreover, the effect of demographics (race/ethnicity, sex) and cognitive and medical status, as well as education, socioeconomic status, and other social determinants of health (SDOH) on TBI risk is not well understood. We aimed to explore the impact of demographics, cognitive and medical status, and SDOH on vulnerability to new TBIs among older adults.

Enrollees 65 and older in the nationally representative Health and Retirement Study (HRS) who consented to have their survey data linked to Medicare claims and had not experienced a head injury prior to HRS enrollment were studied. We used claims data 2000-2018 to obtain incident TBI diagnoses and harnessed the detailed demographic, cognitive, medical, and SDOH information available in the HRS. Incident TBI was defined using inpatient and outpatient International Classification of Disease (ICD 9 and 10) codes received the same day as an emergency room (ER) visit code and a computed tomography (CT) scan code, occurring after the enrollee’s baseline HRS interview. We calculated descriptive statistics and bivariate associations for TBI status with demographic and SDOH characteristics measured at baseline using sample weights to account for the complex survey design.

Of respondents meeting inclusion criteria (n=9273) during the study follow-up period of 18 years, 8.9% received emergency room treatment for a TBI. Older adults who experienced TBI during the study period were more likely to be female (p=0.0006), and white (p=0.0001), to have normal cognition (vs. cognitive impairment or dementia, p=0.0011), higher education (p<0.0001), and higher income (p=0.01). Having lung disease (p=0.0003) or functional impairment (p=0.03) at baseline were protective against experiencing a TBI.

Our results suggest that almost 9% of US older adults received ER treatment for a new TBI during the 18-year study period, and that race, sex, and SDOH factors may increase risk for, or be protective against, TBI. This novel investigation into the impact of demographics and SDOH on incident TBI suggests access to care may impact who gets treatment for TBI. Further study is indicated and may lead to opportunities for both targeted intervention (e.g., primary TBI prevention) to groups most at risk as well as identification and mollification of the most relevant structural and contextual factors (e.g., access to care) to reduce risk of TBI among older adults.

To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).

Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.

pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).

Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.

There are many common beliefs within the general public about Chronic Traumatic Encephalopathy (CTE) that contradict research findings and scientific evidence. Therefore, the goal of this study was to examine the accuracy of CTE knowledge across three diverse samples.

The three groups included in the sample were 333 college students (54%), 196 individuals from the public (32%), and 90 psychology trainees/clinicians (54%) for a total of 619 participants. Online surveys were used to collect the CTE knowledge accuracy (i.e., the number correct divided by the total number of questions) of the sample. The questions about CTE were adapted from Merz et al. (2017) and from the Sports Neuropsychology Society’s “CTE: A Q and A Fact Sheet.”

Overall, CTE knowledge accuracy was 52% (M = 51%, SD = .24). Regarding inaccurate beliefs, two-thirds of the sample believed that CTE was related to sports participation alone even if a head injury did not occur, and most participants believed that CTE could be caused by a single injury. Additionally, confidence in CTE knowledge was positively correlated with willingness to allow their child to play a high contact sport despite overall low CTE knowledge accuracy. Last, many participants reported education (67%) and health care providers (61%) as their main sources of CTE information while only 18% of participants cited television/movies. However, when asked to provide additional details about their CTE information source, many participants cited ESPN specials and the movie “Concussion” as the main reason they learned of the condition and sought out additional information.

The results of this study are consistent with previous research on CTE knowledge accuracy. This further supports the need for clinicians and researchers to address misconceptions by providing information and scientific facts.

Individuals who have experienced traumatic brain injury (TBI) are at an elevated risk for worsened physical and psychological outcomes. Increased rates of anxiety and depression, along with cognitive issues, are common post-TBI. While there is some evidence that anxiety and depression may affect objective cognitive performance, less is known about their effect on other factors that are associated with the individual’s capacity to complete the task, such as perceived workload of the cognitive task. Workload represents an individual’s perception of task difficulty and serves as a proxy for the magnitude of mental demands a given task places on an individual. Preliminary findings in the literature suggest that individuals with TBI commonly report greater workload when completing cognitive tasks compared to neurotypical peers, but the influence of anxiety and depression on survivors’ workload remains unclear. Considering the elevated rates of psychological and cognitive problems in individuals with TBI, the present study examined the moderating role of anxiety and depression on TBI survivor workload perception of a stress-inducing working memory task.

Ten participants with moderate to severe TBI and eight neurologically healthy controls performed the Paced Auditory Serial Addition Task (PASAT). After completing the PASAT, participants reported their subjective workload using the NASA task load index (NASA-TLX). Participants also completed measures of psychological functioning, including the Chicago Multiscale Depression Inventory (CMDI) and the State-Trait Anxiety Inventory (STAI). Relationships between workload and depression and trait anxiety were examined using linear regression.

Linear regression was employed for both the TBI and the healthy control groups to assess the influence of trait anxiety and depression on perceived workload. There was no significant difference between the TBI and HC NASA perceived workload scores. Within the TBI group, there was a significant anxiety by depression interaction (b = -.015, p < .001). Simple slopes analyses revealed that for TBI participants reporting low depression, perceived workload increased with increased anxiety (b = .093, p < .001). For TBI participants reporting high depression, perceived workload decreased as anxiety increased (b = -.38, p = .03). While there was also significant anxiety by depression interaction in the healthy control group (b = .033, p = .04), simple slopes analyses revealed that there were no significant associations for healthy controls.

These results demonstrate that in TBI, level of depression moderates the relationship between anxiety and workload perception. The pattern observed in the TBI group was unique from controls. The present findings suggest that post-TBI, higher depression may temper the influence of anxiety on stressful cognitive task performance and workload rating. The tempering effect of high depression in TBI may represent a biased reporting style or impaired assessment of task difficulty, which may ultimately affect the individual’s capacity to accomplish a task well.

Mobile phone reminding apps can be used by people with acquired brain injury (ABI) to compensate for their memory impairments. However off-the-shelf apps may be difficult to use. ApplTree has been developed to be accessible to this group, compared to off-the-shelf reminding apps such as Google Calendar. This pilot feasibility trial aimed to establish the feasibility of running (and issues that should be addressed to complete) a randomised controlled trial comparing ApplTree to Google Calendar in an ABI community treatment setting.

Adults with self or other reported memory difficulty after an ABI were enrolled (n=39). Those who completed the baseline phase were randomised (n=29) and randomly allocated to the Google Calendar or ApplTree intervention. They were shown a 30 minute video tutorial of the app and an assessment on their ability to use it. Timely completion of everyday memory tasks were measured for a 3 week pre-intervention baseline and 3 week post-intervention follow-up phase. Participants also completed neuropsychological tests assessing memory, attention and executive function and gave qualitative feedback on the app and their experience in the trial.

Recruitment rate was 58% of the target (29 were randomised, n=50 was the target in 2 years). Retention rate was 65.5% and adherence rate was 57.9%. While the feasibility trial was not powered to calculate efficacy, there was a 13% increase in everyday memory tasks completed on time for those in the ApplTree group (n=10) compared to baseline and no change for the Google Calendar group (n=9). Feasibility results indicate 72 participants would need to fully complete a trial to detect the minimum clinically important difference (12.5% increase in successful performance of everyday memory tasks) in the efficacy of ApplTree compared to Google Calendar, should such a difference exist.

The challenges with recruitment of people receiving community care for ABI are highlighted in this trial and discussed along with the impact of the Covid-19 pandemic. Methodological considerations for researchers or clinicians looking to measure everyday memory ability are discussed. The majority (19 of 21) of participants who were given an app were capable of learning to use it during an hour-long session. This indicates it is a feasible intervention that community ABI services could offer. Participant feedback highlighted the merits of design features implemented in ApplTree that can improve the uptake and utility of reminding apps.

Semantic verbal fluency (SVF) has traditionally been correlated with activity in the left anterior temporal lobe. Damage to the anterior temporal lobe, such as from a traumatic brain injury (TBI) or neurodegenerative disease, can result in impairments in semantic fluency and language expression. Although the orbitofrontal cortex (OFC) is not well studied as being correlated to this process, its functional connectivity to language-related brain regions, such as the inferior frontal gyrus (Broca’s area), suggests it may also play a role in SVF. In fact, preliminary research has shown that lesions in the OFC are associated with semantic fluency deficits (Almairac et al. 2015). As such, the goal of this study was to investigate whether OFC volume correlates with SVF in a population of Veterans with a prior TBI.

Thirty-five Veterans who sustained TBIs were included in this study (11% female, age M = 41.77, SD = 11.27; years of education M =14.94, SD = 1.62). All participants underwent a magnetic resonance imaging (MRI) and regional normative volumes were standardized to account for differences in brain size (volume of brain area/total brain volume). Participants were given the Delis Kaplan Executive Function System (D-KEFS) verbal fluency subtest to measure verbal generativity. A Pearson correlation was conducted to investigate the relationship between OFC volume and SVF performance. Post hoc analysis was conducted with Veterans who met the criteria for a TBI sustained by a blast to the head (n = 25).

A significant positive correlation emerged between left OFC volume and semantic fluency (category subtest; p = .03, r = .35). Additional analyses with Veterans with blast-related TBIs indicated a significant correlation between the volume of the OFC and performance on the category (p = .02, r = .45), and switching (p = .02, r = .43) subtests of the D-KEFS verbal fluency test.

These findings demonstrate a correlation between the volume of the left OFC and SVF performance. Specifically, Veterans with TBIs had decreased volume of the OFC which correlated with deficits on a SVF task. Among Veterans with blast-related TBIs, both category and category switching subtests correlated with OFC volume. Given the functional connectivity between the OFC and language areas of the brain, this study highlights the importance of analyzing associated cortical regions beyond the anterior temporal lobe when studying SVF performance.