Metacognition is defined as the ability to observe, monitor, and make judgments about one’s own cognitive status. Judgments of learning (JOLs) and retrospective confidence judgments (RCJs) are two elements of metacognition related to memory, or metamemory. JOLs refer to one’s assumptions of their memory performance prior to completing a memory task, while RCJs describe one’s subjective assessment of their memory performance after they have completed the task. Traumatic brain injury (TBI) is known to negatively impact general metacognitive functioning. However, the nuanced effects of TBI on constituent metacognitive subprocesses like JOLs and RCJs remain unclear. This study aimed to characterize patterns of brain activity that occur when individuals with TBI render JOLs and RCJs during a meta-memory task. Differences between JOL- and RCJ-related patterns of activation were also explored.

20 participants with moderate-to-severe TBI completed a metacognition task while undergoing functional magnetic resonance imaging (fMRI). Participants were first exposed to target slides with a set of polygons placed in specific locations, then asked to identify the target slides within a set of distractors. Before identifying the target slides, participants rated how well they believed they would remember the polygons’ shape and location (JOL). After answering, they rated how confident they were that the answer they provided was correct (RCJ). First-level time series analyses of fMRI data were conducted for each participant using FSL FEAT. Higher-level random effects modeling was then performed to assess average activation across all participants. Finally, contrasts were applied to examine and compare JOL- and RCJ-specific patterns of activation.

JOLs were associated with activation of the left frontal gyri, bilateral anterior cingulate, left insula, and right putamen (p < 0.01). RCJs were associated with activation of the bilateral frontal gyri, bilateral posterior and anterior cingulate, left insula, right putamen, and left thalamus (p < 0.01). Compared to RCJs, JOLs demonstrated greater left insula activation (p < 0.01). Compared to JOLs, RCJs demonstrated greater activation of the left superior frontal gyrus, bilateral middle frontal gyrus, and bilateral anterior cingulate (p < 0.01).

The areas of activation found in this study were consistent with structures previously identified in the broader metacognition literature. Overall, RCJs produced activity in a greater number of regions that was more bilaterally distributed compared to JOLs. Moreover, several regions that were active during both metacognitive subprocesses tended to be even more active during RCJs. A hypothesis for this observation suggests that, unlike JOLs, the additional involvement of reflecting on one’s immediate memory of completing the task during RCJs may require greater recruitment of resources compared to JOLs. Importantly, these findings suggest that, while different metacognitive subprocesses may recruit similar brain circuitry, some subprocesses may require more potent and widespread activation of this circuitry than others. As such, subprocesses with greater activational needs and complexity, such as RCJs, may be more susceptible to damage caused by TBI. Future research should aim to compare patterns of activation associated with certain metacognitive subprocesses between survivors of TBI and healthy controls.

It has been well established that sustaining a head injury can result in cognitive impairments, but there is little research on the impact of head injuries within middle-aged and older adult samples. Given the two most common samples for head trauma research are athletes and military service members, most of this literature presents findings of individuals under 35 years old. It is important to study head injury outcomes in older samples because greater lengths of time may have passed since the injuries occurred, which may influence findings. Additionally, research indicates that head injuries can lead to measurable executive functioning difficulties - a cognitive domain previously established as susceptible to cognitive ageing-related decline. Therefore, the current investigation seeks to assess the connection between history of head injury and executive functioning performance in middle-aged and older adult participants.

The current study examined 1150 participants from the 2nd wave of the Midlife in the United States cohort (MIDUS) and 801 participants of the MIDUS refresher panel. As a part of the biomarkers study, participants indicated how many head injuries they experienced (up to three) along with whether they were hospitalized and the year the injury occurred. As a part of the cognitive study, participants completed a battery of measures that were combined into a single Z-scored executive functioning measure. Regression was used to evaluate the association between self-reported head trauma and executive functioning, controlling for age and gender. Post hoc analyses examined hospitalization and recency of head injury.

Of the 1951 included participants, 70.7% reported zero head injuries, 20.8% reported one head injury, 5.8% reported two head injuries, and 2.7% reported at least three head injuries. History of head trauma was not associated with lower levels of executive functioning (F[3,1945]=2.68, p=.38). Furthermore, executive functioning performance was not associated with hospitalization for head injury (b=-.04, p=.31) or recent head injuries (b=-.04, p=.70).

The current results do not provide evidence of decreased executive functioning performance linked to history of head injury in middle-aged and older adults. These findings are inconsistent with earlier literature suggesting that executive dysfunction is associated with prior head trauma. It is important to consider, however, that the operationalization of executive functioning as a cognitive domain is controversial and produces significant debate. Therefore, the present results solely indicate a lack of connection between previous head trauma and executive functioning, specifically as assessed by the current definition and measures. The present analyses were limited by the broad inclusion of all head injuries rather than a narrowed scope of specifically concussions or mild traumatic brain injuries. However, the study had the advantage of being adequately powered via a large sample size. The current results suggest that additional research is needed within middle-aged and older adult samples to investigate possible connections between head trauma and executive functioning performance using alternate definitions and assessments.

To characterize reasons for rehospitalization of Veterans and Service Members with mild, moderate, and severe traumatic brain injury (TBI) who received inpatient rehabilitation at a Veterans Affairs (VA) Polytrauma Rehabilitation Center (PRC) up to 10 years postinjury. TBI is a chronic condition, and a subset of TBI survivors experience rehospitalization after discharge from inpatient rehabilitation. Extant literature focuses primarily on persons with moderate-to-severe TBI and utilizes broad categories when determining readmission reasons. The present study aimed to delineate with greater specificity the reasons for rehospitalization up to 10 years postinjury across the TBI severity spectrum.

Participants were drawn from the VA TBI Model Systems multicenter longitudinal study for a cross-sectional analysis. Eligibility criteria included TBI diagnosis per case definition; age > 16 years at TBI; admitted for inpatient rehabilitation at one of the five VA PRCs; and informed consent by the participant or legally authorized representative. At follow up interviews 1, 2, 5, and 10 years post-TBI, participants were asked whether they were rehospitalized within the past year (up to five admissions). Rehospitalizations were classified according to the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project classification (18 categories). In the present analyses, TBI severity was classified by duration of posttraumatic amnesia (PTA; 0-1 days=mild, 2+ days=moderate-severe). Statistical analyses were conducted in SPSS.

Participants (N=1101; n=338 0-1 days PTA, n=513 2+ days PTA, n=250 no PTA data) ranged in age from 17 years to 91 years at the time of interview. Participants across all follow up timepoints reported 317 rehospitalizations in the past year. 19.45% of Year 1 participants, 24.37% of Year 2 participants, 16.19% of Year 5 participants, and 16.25% of Year 10 participants reported 1+ rehospitalizations in the past year. When controlling for age, participants with at least 2 days of PTA were more likely to be rehospitalized at least once compared to those with 0-1 days of PTA at Year 2 (OR=4.05, p<0.001) and Year 5 (OR=2.39, p=0.03) post-TBI. The three most common reasons for rehospitalization across all timepoints were injury and poisoning (17.3%), mental illness (16.7%), and diseases of the nervous system and sense organs (9.1%). Mental illness was the modal reason for rehospitalization at Years 2, 5, and 10, frequently due to substance- or alcohol-related disorders and suicide/intentional self-inflicted injury.

Compared to prior research, rates of rehospitalization were lower in this sample across follow-up time points. The inclusion of mild TBI in this analysis may partially explain the discrepancy. Importantly, two of the top three rehospitalization reasons are potentially preventable, and strategies to reduce risk of re-injury and minimize escalation of psychiatric distress should therefore be explored. Psychoeducation, supervision, and mental health support during the transition from hospital to community should be considered in order mitigate preventable causes of rehospitalization among long-term TBI survivors.

Poststroke depression is common in those with stroke and is associated with worse functional outcomes, recurrence of stroke, and increased mortality. Poststroke depression has been most commonly associated with lesions of the frontal lobe and anterior regions of the brain, in addition to lesions in subcortical structures. Yet, there is also evidence that indicates the presence of depressive symptoms in those with infratentorial (including brainstem, pontine, and cerebellar) stroke, which may be mediated by alternative pathophysiologic mechanisms. Patients undergoing acute inpatient stroke rehabilitation may present with depressive symptoms that go unassessed or untreated throughout their recovery, including those with infratentorial stroke. The current objective was to evaluate the degree of depressive symptoms in patients with infratentorial stroke compared to those with supratentorial stroke.

Participants were admitted to an acute inpatient rehabilitation unit for stroke rehabilitation. Participants were enrolled in an ongoing clinical trial. Participants with recent infratentorial stroke (N = 7; 4 female; Median age = 69 years; Median education = 16 years) were administered the Patient Health Questionnaire-9 (PHQ-9) to assess symptoms of depression. Severity of depressive symptoms (PHQ-9 total score) in participants with infratentorial stroke was compared to those with supratentorial stroke (N = 19; 10 female; Median age = 69 years; Median education = 15 years) through Mann-Whitney U tests.

Participants with infratentorial stroke endorsed similar levels of depression to those with supratentorial stroke. Participants with infratentorial stroke endorsed overall mild depressive symptoms (Mean PHQ-9 score = 7.29; Median = 7), similar to those with supratentorial stroke (Mean PHQ-9 score = 7.11; Median = 6). Significant differences in depressive symptoms were not observed between participants with infratentorial and supratentorial stroke (p = .785).

Patients with infratentorial and supratentorial stroke may experience a similar degree of poststroke depression. Despite differences in suspected pathophysiologic mechanisms, infratentorial and supratentorial stroke appear to influence depressive symptoms to a similar extent. While future analyses with larger sample sizes are indicated, the current study indicates that patients with infratentorial and supratentorial stroke should be evaluated for depressive symptoms during the acute phases of recovery to inform treatment and potentially improve outcomes.

Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.

41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.

In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).

Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.

Alexithymia is characterized by difficulty identifying and describing one’s emotions. Alexithymia is more prevalent and severe after acquired brain injury (ABI; Fynn et al., 2021). Additionally, studies have shown frequent impairment of affect recognition after ABI (Neumann et. al, 2014). Research examining the relationship between the subjective experience of alexithymia and the objective ability to recognize emotion in others has been limited, especially among individuals with ABI. Some research indicates that alexithymia is more common following traumatic brain injury (TBI) than non-traumatic brain injury such as stroke; however, no previous research has examined the relationship between alexithymia and affect perception comparing adults with TBI and stroke. Accordingly, this study aimed to fill that gap.

Participants were 218 adults in three groups: healthy adults (HA; n = 99), TBI (n = 63), and stroke (n = 56).

Participants completed a neuropsychological battery that included the Toronto Alexithymia Scale-20 (TAS; Bagby et al., 1994), and a multicultural Face Emotion Perception Test (MFEPT). The MFEPT used images from the Montreal Set of Facial Displays of Emotion (Beaupre et al., 2000) to assess recognition accuracy for anger, sadness, fear, disgust, and neutral expressions. The Recognition Memory Test (RMT; Warrington, 1984) was included to account for variance in facial affect recognition associated with face recognition only.

Analysis of variance indicated a significant difference among the means on TAS (p < .001, n2 = .09. Tukey post hoc tests indicated lower TAS among HA than Stroke (d = -0.73, p = .001) and TBI (d = -0.56, p = .002) groups; however, TBI and Stroke did not differ significantly (d = -0.15, p = .667). Chi-square tests indicated that the percent of HA with clinically-elevated alexithymia (7.1%) was lower than Stroke (21.4%, p = .009) and TBI (25.8%, p = .001), who did not differ significantly (p = .610). Pearson correlations indicated medium inverse correlations between alexithymia and affect recognition for Stroke (r = -.39, p = .002) and TBI (r = -.36, p = .002). For HA, who showed low alexithymia, the relationship was not significant (r = -.15, p = .070). Examination of the TAS subscales indicated that TAS-Total correlations with MFEPT were driven primarily by Difficulty Identifying Feelings (DIF), as compared to Difficulty Describing Feelings or Externally-oriented Thinking. Partial correlations between TAS-DIF and MFEPT accounting for RMT remained significant for both TBI (rp = -.23, p = .036) and Stroke (rp = -.39 p = .002).

Consistent with prior research, alexithymia was more prevalent and severe among adults with TBI and stroke as compared to healthy adults. Adults with TBI and stroke showed similar levels of alexithymia, and the pattern of associations is consistent with the theory that alexithymia disrupts recognition of emotion displayed by others. This link may partly explain the robust findings of diminished and impaired social and interpersonal outcomes after ABI. Future research should test these links directly, to support the development of interventions to maximize social and interpersonal well-being after ABI.

Apathy, or loss of motivation and interest, is a common sequela of moderate to severe traumatic brain injury (msTBI) and has been associated with frontal lesions and with executive dysfunction in a sample an average of one year post injury (Andersson & Bergdalen, 2002). In older adults sustaining msTBI in particular, the appearance of apathy is more likely to be comorbid with depression when compared to injury in younger adults (Kant et al., 1998). However, studies have consistently shown an important dissociation between apathy and depression, despite overlapping symptoms, with apathy in particular associated with frontal lobe damage (Worthington & Wood, 2018). The present study holds two primary goals. First, to examine the relationship between current apathy ratings and cognition after controlling for ratings of depression and perceived changes in apathy, to account for the unique relationship of injury-related apathy on cognition. Second, to examine the potential variable role of APOE4 carrier status on depression and apathy ratings.

110 older adults with a lifetime history of msTBI (M=9.5 years post-injury) were included as part of a cross-sectional study. Apathy was measured using the Frontal Systems and Behaviors Scale (FrSBe) for both current apathy ratings and perceived change in apathy from pre- to post-injury. Depression was measured using the depression subscale of the Brief Symptom Inventory (BSI). Outcome measures included normed scores for learning (HVLT-R total recall), retention (HVLT-R percent retention), processing speed (Trails A), set-shifting and working memory (Trails B, Digit Span Backwards), and phonemic and category fluency (D-KEFS letter and category fluency). The main independent variable of interest was current apathy ratings. Depression and perceived apathy change were included as control variables for all analyses. Vif scores were calculated for all analyses to ensure that variables were not multicollinear. Finally, we ran an ANOVA to examine the relationship between apathy, depression, and APOE4 carrier status.

When controlling for depression and perceived changes in apathy, current apathy ratings were associated with poorer performance on learning (p=.04, n2=.04), processing speed (p=.001, n2=.10), set-shifting (p=.02, n2=.05), attention (p=.04, n2=.04), phonemic fluency (p=.001, n2=.09), category fluency (p=.001, n2=.10). Current apathy ratings were not associated with retention or working memory. Apathy was significantly associated with depression (p <.001), but was not associated with APOE4 carrier status or the interaction between depression and carrier status.

Despite overlap between depressive symptoms and apathy questionnaires (i.e., loss of interest/pleasure), by controlling for depressive symptoms and perceived changes following injury, we demonstrate the significant independent association of apathy and cognition in an older sample with chronic msTBI. Further, although previous work has shown strong associations between depression and APOE4 carrier status in chronic msTBI samples (Vervoordt et al., 2021), there was no significant relation with apathy directly in our sample, providing further evidence that these are neurobiologically distinct syndromes.

An acquired brain injury (ABI) is a neurological pathology that generates a physical injury in the brain. These include cerebrovascular accidents (CVA) and traumatic brain injuries (TBI). Brain injuries can cause cognitive, emotional, and social problems, which have the potential to severely alter a person’s independence and quality of life. Loneliness, thesubjective experience of social isolation, has been shown to be the best predictor of mental health problems and poorquality of life in patients with ABI. This study aimed to explore the relationship between cognitive, emotional, and social determinants and loneliness in Puerto Ricans with ABI in the chronic phase.

Cross-sectional, exploratory, and correlational methods were implemented. Assessments included the Frontal Systems Behavioral Scale - Spanish version (FrSBe-SP), Perth Emotional Reactivity Scale -Spanish version (PERS), Anticipated Stigma and Concealment (ASC), and the University of California Los Angeles - Loneliness Scale (UCLA-LS).

A total of seventeen participated (n=17). Twenty-nine percent of participants were female. Forty-seven percent had history of previous CVA and fifty-two percent had history of TBI. Correlational analyses suggest a positive and significant relationship between executive dysfunction (FrSBe-SP) and feelings of loneliness (UCLA-LS) (p=.601), as well as a positive and significant relationship between neuroticism-negative emotional reactivity (PERS) and feelings of loneliness (UCLA-LS) (p=.736). Correlational analysis suggests there is no significant relationship between anticipated stigma (ASC) and feelings of loneliness (UCLA-LS) (p=.282).

Our findings suggest that there is a significant relationship between cognitive determinants (executive functions) and emotional determinants (neuroticism) with feelings of loneliness in people with a history of ABI. These results support the connection between executive dysfunction, the tendency to experience negative emotions, and the subjective experience of loneliness, consistent with previous studies. However, our study did not find any significant relationship between interactional determinants, such as stigma and concealment, and loneliness. Understanding the role of cognition, emotions, and social variables in reported feelings of loneliness is important for clinical neuropsychological assessment and rehabilitation interventions.

Numerous survivors of Intimate Partner Violence (IPV) experience physical violence to the head and neck areas, placing them at high risk of sustaining a brain injury (BI). Studies report that the prevalence of traumatic BI among IPV survivors ranges from 35% to as much as 80%. IPV-related BIs can have debilitating long-term consequences on survivors’ quality of life and overall functioning. One important factor impacting quality of life following TBI is verbal memory abilities. Given the link between verbal memory abilities and functional status, identifying predictors of verbal memory performance has important implications for directing support and rehabilitative efforts for survivors of IPV-related BIs. The current aim of the study was to investigate predictors of verbal memory performance following TBI among survivors of IPV.

A modified HELPS Brain Injury (BI) screener was administered to women receiving services for IPV through community organizations and shelters in two urban, Midwestern cities. Women who screened positive for IPV-related BI (n=32) were invited to complete a comprehensive neuropsychological evaluation including the Rey Auditory Verbal Learning Test. The delayed recall score of the RAVLT was used as a measure of verbal memory performance. BI history and characteristics were based on survivors’ responses to the modified HELPS screener. Multiple regression was used to determine significant predictors of verbal performance with RAVLT-Delayed Recall scores serving as the criterion, and education, age, number of reported injuries, number of injuries that left participants feeling dazed/confused, following provider recommendations, and childhood history of injury all entered as predictors.

The model indicated that a large percentage of the variability (R2 = .378) in delayed recall performance could be attributed to the combination of predictors in the model (F (6, 25) = 2.828, p = .047). Examination of the regression coefficients indicated that only following provider recommendations (ß = .420, p = .019), and number of injuries that induced disorientation/confusion (ß = -.592, p = .004) were significantly related to delayed recall after controlling for all other variables in the model.

The results of this study suggest that injury severity and adhering to medical recommendations after IPV-related TBI play a significant role in predicting cognitive functioning. Consistent with existing literature, our findings show that injury characteristics of severity and repetition are closely associated with memory functioning. These findings have implications for guiding screening procedures that may be more sensitive to functional outcome in survivors of IPV who are at risk for BI. Furthermore, our findings highlight a need to increase awareness of IPV-related BI in medical professionals, and to support these front-line staff in providing medical care and psychoeducation about BI to IPV survivors.

Assessment of clinical, functional and psychological outcome after 6 months of moderate and severe TBI

Sixty consecutive participants aged 18 and above with moderate to severe TBI (GCS score of 3-12 at admission) attending the Outpatient Department of Neurosurgery Specialty, Post Graduate Institute of Medical Education and Research, Chandigarh, India were recruited. The exclusion criteria were 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. Ethical clearance was obtained from Institute Ethics Committee. Written informed consent was obtained from all participants prior to inclusion in the study. Socio-demographic details (age, sex, marital status, family type, place of residence, education and occupation) and clinical details (mode of injury, injury severity, treatment, status on discharge, any previous co morbidities) were obtained from participant and hospital records. Functional outcome was assessed by Glasgow Outcome Scale and Barthel’s Index of Activities of Daily Living. Mini Mental State Examination (MMSE) was used to assess cognitive status. Hospital Anxiety and Depression Scale was used to assess symptoms of anxiety and depression.

Out of 60 patients, 40 had moderate head injury and 20 patients had suffered from severe head injury. There were 53 male (88.3%) and 7 (11.7%) female and the mean age was 34 years (SD=14.5). The mean duration of TBI was 11 months (SD=6.5). Fifty percent participants were married and majority was living in joint/extended families. Majorities were residing in rural localities 36 (60%). With regard to education level 11.7% were illiterate, 33% were educated up to 10th standard and 21.7% up to 12th standard. With regard to occupation, 11.7% were unemployed, 6.7% were housewives, 11.7% were students, 8.3% were retired and rest (61.6%) was engaged in varied occupations.

The most common mode of injury was road traffic accident (90%). Contusion was the most common CT abnormality noted (37 patients, 61.7%). Regarding treatment, 36 patients (60%) underwent surgical intervention and 24 (40%) were managed conservatively. With regard to surgical intervention, 28 (77.8 %) patients underwent decompressive hemicraniectomy and subsequent cranioplasty and rest 8 (22.2 %) underwent craniotomy and hematoma evacuation. As per Glasgow Outcome Scale, 50 (83%) had low disability and 10 (17%) had moderate to severe disability. The mean Barthel’s Index score was 19.6+1.07 (Range 15-20) which indicated that most of the patients had resumed independence in activities of daily living. Only 25% participants were observed to have cognitive impairment (MMSE). With regard to anxiety and depression 16.7% showed symptoms of anxiety whereas 30% showed symptoms of depression (HADS score >8).

After 6 months of TBI, most participants had resumed independence in activities of daily living but cognitive impairment is persistent in 25% and symptoms of depression in 30% participants.

Extant literature suggests significant heterogeneity in recovery trajectories after experiencing a moderate to severe traumatic brain injury (TBI) during childhood (Moran et al., 2016). The Cognitive and Linguistic Scale (CALS) is a promising non-norm-referenced measure designed for serial monitoring within an inpatient rehabilitation setting that may optimize prediction of acute recovery and long-term neuropsychological functioning. To date, the CALS has primarily been examined in the context of injury characteristics such as severity and etiology (e.g., Slomine et al., 2016), and it is unclear what non-injury factors may be relevant to consider. Using archival data gathered from an inpatient pediatric neurorehabilitation program, this study examined associations between the CALS and select sociodemographic factors to better inform the clinical utility of the measure.

Participants included 56 youth (46% BIPOC, 66% male) aged 2-17 years (M = 12.40, SD = 3.99) who were admitted for moderate to severe TBI to an inpatient rehabilitation program at a regional tertiary care children’s hospital. Data extracted from medical records included demographic information (i.e., age at injury, sex, ethnoracial identity, address, initial Glasgow Coma Scale (GCS) rating, CALS at admission, and full-scale IQ (FSIQ) at discharge. GCS was used as a proxy for injury severity. Residential addresses were geocoded and area-level median income was used as a proxy for familial socioeconomic status (SES). A multiple regression model was utilized to parse the individual contributions of demographic variables) on initial CALS performance while accounting for injury severity. Parallel regression models were used to determine whether patient characteristics moderate the association between initial CALS performance and cognitive functioning at discharge.

Preliminary analyses demonstrated that there were no significant associations between GCS and demographic variables, ps > .05. Patient age at injury was significantly associated with CALS total score at admission above and beyond injury severity and other demographic characteristics, t (31) = 2.55, p = .016, such that older age was associated with higher initial CALS scores. Results of moderator analyses between CALS and patient characteristics showed a significant main effect of injury severity, such that higher GCS was associated with higher FSIQ at discharge across models, ps < .05. No significant interactions were identified.

These findings provide additional evidence for the generalizability of the CALS and further characterize its associations with non-injury factors, which is important for better understanding aspects that contribute to recovery trajectories and outcomes after moderate to severe TBI. Given the longstanding challenges in regard to the validity of neuropsychological assessment for diverse groups, it is critical to explicitly examine cultural context when considering the clinical utility of a measure. A limitation of the current study is the utilization of broad demographic information due to limited availability of sociocultural data. Future research should examine more granular and culturally-specific variables that may impact CALS performance (e.g., educational attainment, linguistic considerations), beyond using broad-based demographic data as a proxy for sociocultural factors. Another important next step is to utilize serial administrations of the CALS to examine the impact of sociocultural factors on recovery trajectories following TBI.

Research has shown that a small, yet significant minority of individuals with traumatic brain injuries (TBI) experience psychotic symptoms post-TBI. TBI has also been associated with earlier onset schizophrenia in individuals with a genetic risk for psychosis.

The current case presents a 15-year-old female with pre-existing psychotic symptoms (auditory and visual hallucinations [AVH] and delusions) who stopped experiencing AVH a few weeks post-injury. The, at least temporary, cessation of her hallucinations raises several important questions about the neuroanatomy of pediatric psychosis and the impact of TBI on a potentially divergently developing brain.

Patient is a 15-year-old female who identifies as Hispanic (adopted, of Central American origin). Prior to her injury her developmental history was notable probable neglect prior to adoption, and her psychiatric history was notable for major depressive disorder, anxiety, chronic insomnia, and AVH. AVH were religious in nature and involved command hallucinations. AVH had been attributed to her chronic insomnia, per medical records. Participant was in a motorcycle accident with her caregiver and sustained a severe traumatic brain injury (GCS=3-8). Medical workup, including MRI, indicated a right basal ganglia hemorrhage, right thalamic hemorrhage, as well as injury of the brain stem at the pons, resulting in left-sided hemiparesis. She was ultimately diagnosed with traumatic right-sided intracerebral hemorrhage, traumatic subdural hematoma, traumatic hemorrhage of basal ganglia, traumatic encephalopathy, and a left homonymous hemianopia (left visual field cut) from her right temporal parietal injury. She received a neuropsychological evaluation 10 months post-TBI. Testing included: subtests of the WISC-V, measures of sustained attention and executive functioning, tasks of orientation and memory, and questionnaire measures assessing social-emotional, executive, and adaptive functioning. Parent and adolescent clinical interviews were conducted.

Results indicated appropriate orientation, broadly intact intelligence presumed consistent with premorbid functioning, average sustained attention, and deficits in aspects executive functioning, visual-motor processing speed, and fine motor skills. Although she performed well on objective measures of memory, she reported significant long term social memory loss (e.g., difficulties remembering friends and memories of emotional connectedness) during the clinical interview. Interview and questionnaire measures also indicated continued challenges with depression and anxiety, as well as post-traumatic personality changes, tics, and symptoms of trauma. Patient reported that her hallucinations, both visual and auditory, stopped early in her recovery post-TBI; patient’s premorbid delusions were still present post-TBI.

This case raises questions related to the impact of structural or axonal injury to regions or networks in the brain that may be associated with psychosis. It also adds to a minimal literature examining AVH in pediatric TBI. Using the current literature as a framework we will explore 1) the injury to this patient’s thalamus as it relates to both her emotional memory deficits as well as the interruption of her AVH hallucinations, and 2) the relationship between her visual field cut and the interruption of her visual hallucinations. Overall, this case study highlights the unique nature of the developing brain both in terms of the TBI and psychosis.

Executive function (EF) is a self-regulatory construct well-established as a predictor of long-term academic achievement and socioemotional functioning in children (Best et al., 2009; Diamond, 2013; Zelazo & Carlson, 2020). Traumatic brain injury (TBI) in childhood frequently results in EF deficits (Beauchamp & Anderson, 2013; Levin & Hanten, 2005). In comparison to adults (Okonkwo et al., 2013), there is an absence of viable blood biomarkers for pediatric TBI to assist in diagnosis and prognosis. Osteopontin (OPN), an inflammatory cytokine, has recently been identified as a putative pediatric TBI blood biomarker (Gao et al., 2020). However, more work is needed to establish OPN’s utility in predicting functional outcomes. Thus, the present study aimed to test relations between OPN measured during the first 72 hours of hospitalization and EF 6-12 months post injury among a sample of pediatric TBI patients.

Sample consisted of 38 children (age at injury = 4.60-16.67 years, M age = 10.61 years, 65.8% male, lowest Glasgow Coma Scale [GCS] score = 3-15, M gcs = 9.97) with TBI whose parents completed the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2; Gioia et al., 2015) 6-12 months post injury. Plasma OPN was measured at hospital admission, 24 hours after admission, 48 hours after admission, and 72 hours after admission. 7-scores for each BRIEF-2 clinical scale (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task-Monitor, Organization of Materials) and composite index (Behavior Regulation Index, Emotion Regulation Index, Cognitive Regulation Index, Global Executive Composite) were used in analyses.

Correlation analyses revealed large positive associations (rs = .50-.73, ps = <.001.039) between 48-hour OPN and all BRIEF-2 scales/indices except Initiate. OPN at 24 hours positively correlated with Task-Monitor (r = .40, p = .037). Bivariate logistic regression analyses testing whether OPN predicted at least mildly elevated BRIEF-2 t-scores (>60) did not yield significant associations. Additional supplementary analyses testing whether alternative injury markers - glial fibrillary acidic protein (GFAP), ubiquitin C-terminal Hydrolase-L1 (UCH-L1), S100 calcium binding protein B (S100B) - measured at all time points as well as lowest GCS score correlated with EF revealed the following: admission S100B positively correlated with Inhibit (r = .34, p = .045), 48-hour UCH-L1 negatively correlated with Initiate (r = -.49, p = .041) and Cognitive Regulation Index (r = -.48, p = .044), and 72-hour UCH-L1 negatively correlated with Initiate (r = -.47, p = .048).

Findings showed higher OPN at 48 hours post admission was broadly related to worse parent-reported EF 6-12 months later, with 24-hour OPN also showing limited associations. Higher levels of alternative injury markers likewise showed limited associations with EF outcomes. Null logistic regression findings may be due to few participants having elevated BRIEF-2 scores. Disrupted EF development may be more noticeable after longer time periods as children age and self-regulatory demands increase. Overall, OPN was found to more consistently predict EF outcomes than GCS score and other injury markers. This could be because OPN is a marker of inflammation, which may be particularly predictive of TBI cognitive outcomes.

Pediatric traumatic brain injury (TBI) is the leading cause of disability in children under the age of 15, often resulting in executive function deficits and poor behavioral outcomes. Damage to white matter tracts may be a driving force behind these difficulties. We examined if whether 1) greater TBI severity was associated with worse neurobehavioral outcome, 2) greater TBI severity was associated with tract-based white matter microstructure, and 3) worse neurobehavioral outcome was associated with white matter microstructure.

Twelve children with complicated-mild TBI (cmTBI; Mage=12.59, nmale=9), 17 with moderate-to-severe TBI (msTBI; Mage =11.50, nmale=11), and 21 with orthopedic injury (OI; Mage =11.60, nmale=16), 3.94 years post injury on average, were recruited from a large midwestern children’s hospital with a Level 1 Trauma Center. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL) while children completed 64-direction diffusion tensor imaging in a Siemens 3T scanner. White matter microstructure was quantified with FMRIB’s Diffusion Toolbox (FSLv6.0.4). Tract-Based Spatial Statistics computed fractional anisotropy (FA) and mean diffusivity (MD) for the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF), bilaterally.

Group differences were assessed using one-way ANOVA. Children with msTBI were rated as having worse Sluggish Cognitive Tempo on the CBCL than children with cmTBI and OI (p=.02, eta2=.143); no other parent-rated differences reached significance. Group differences were found in left SLF FA (p=.031; msTBI<cmTBI=OI) and approached significance in left UF FA (p=.062, eta2=.114; msTBI<OI). Group differences were also found in right IFOF MD (p=.048; msTBI>OI) and left SLF MD (p=.013; msTBI>cmTBI=OI). Bivariate correlations assessed cross-domain associations. Higher left IFOF FA was associated with better BRIEF Metacognitive Skills (r=-.301, p=.030) and CBCL School Competence (r=.280; p=.049). Higher left SLF FA was associated with better BRIEF Behavioral Regulation and Metacognitive Skills (r=-.331, p=.017 and r=-.291, p=.036, respectively), and CBCL School Competence and Attention Problems (r=.398, p=.004 and r=-.435, p=.001, respectively). Similarly, higher right UF FA was broadly associated with better neurobehavioral outcomes, including Behavioral Regulation and Metacognitive Skills (r=-.324, p=.019 and r=-.359, p=.009, respectively), and School Competence, Attention Problems, and Sluggish Cognitive Tempo (r=.328, p=.020, r=-.398, p=.003, and r=-.356, p=.010, respectively). Higher right CB MD was associated with worse Behavioral Regulation (r=.327, p=.018) and more Attention Problems (r=.278, p=.046); higher left and right SLF MD was associated with Sluggish Cognitive Tempo (r=.363, p=.008, r=.408, p=.003, respectively).

Children with TBI, particularly msTBI, were rated as having cognitive slowing; while other anticipated group differences in neurobehavioral outcomes were not found, this appears driven by milder difficulties in cmTBI and OI groups. In fact, across CBCL and BRIEF subscales, children with msTBI were rated as approaching or exceeding a full standard deviation deficit based on normative data. TBI severity was also associated with white matter microstructure and cross-domain associations linked microstructure with observable neurobehavioral morbidities, suggesting a possible mechanism post-injury. Future longitudinal studies would be useful to examine the temporal evolution of deficits.

The Coma Recovery Scale-Revised (CRS-R) is the gold standard assessment of adults with disorders of consciousness (DoC); however few studies have examined the psychometric properties of the CRS-R in pediatric populations. This study aimed to demonstrate preliminary intra-rater and inter-rater reliability of the CRS-R in children with acquired brain injury (ABI).

Participants included 3 individuals (ages 10, 15, and 17 years) previously admitted to an inpatient pediatric neurorehabilitation unit with DoC after ABI who were followed in an outpatient brain injury clinic due to ongoing severe disability. ABI etiology included traumatic brain injury (TBI; n=2) and encephalitis (n=1). Study participation took place on average 4.6 years after injury (range 2-9). The Glasgow Outcome Scale-Extended, Pediatric Version (GOS-E Peds), a measure of outcome after pediatric brain injury, was administered as part of screening. Two participants were placed in the GOS-E Peds “lower severe disability” category (i.e., score of 6) and one was placed in the “upper severe disability” category (i.e., score of 5). The CRS-R includes 6 subscales measuring responsivity including Auditory (range 0-4), Visual (range 05), Motor (range 0-6), Oromotor/Verbal (range 03), Communication (range 0-2), and Arousal (range 0-3) with higher scores indicating higherlevel function. Subscales are totaled for a CRS-R Total score. Behaviors shown during the CRS-R are used to determine state of DoC [Vegetative State (VS), Minimally Conscious State (MCS) or emergence from a minimally conscious state (eMCS)] based on 2002 Aspen Guidelines. Participants were administered the CRS-R three consecutive times on the same day. Administrations were completed by two raters in this order: Rater 1 (1A), Rater 1 (1B) and Rater 2. Intra-rater reliability was deemed by percent agreement across the 6 subscales between Rater 1A and 1B. Inter-rater reliability was deemed by percent agreement across the 6 subscales between 1A and 2.

Mean CRS-R Total score for Rater 1A was 22 (SD=1.73, range 20-23), Rater 1B was 22 (SD=1.73, range 20-23), and Rater 2 was 21.33 (SD=2.08, range 19-23). Intra-rater reliability was 100% and inter-rater reliability was 94% across all subscales. All participants were deemed eMCS at all 3 ratings.

Data from this very small sample of children suggests that the CRS-R demonstrates both intra-rater and inter-rater reliability in patients with a history of DoC after ABI. Given that all children were at the high end of the scale (eMCS), further research is needed with a larger sample of children with a range of states of DoC.

Integration of neuropsychological services into multidisciplinary clinics for pediatric patients requiring neurocritical care has previously been shown to improve access to care and promote connection to vital services for children recovering from traumatic brain injuries or other serious insults or infections impacting the brain. As such, the objective of this study is two-fold. First, to explore the unique model of care provided by a neuropsychological inpatient service at the Medical College of Wisconsin/Children’s Wisconsin. Secondly, to describe the benefit of neuropsychology in the Brain Recovery Assessment and Interdisciplinary Needs Clinic (BRAIN) a neurocritical care outpatient follow-up multidisciplinary clinic.

Participants include N =298 pediatric inpatients from a Level 1 Pediatric Trauma center referred to the neuropsychological inpatient consultation service from February 2020 to July 2022. Qualitative methods were used to describe the flow and number of patients initially referred to the neuropsychological inpatient service and then those who followed up in outpatient neuropsychological care prior to and after the implementation of a multi-disciplinary clinic for children admitted to the Neurocritical Care Unit. Rates of follow-up with neuropsychological care were compared pre- and post-establishment of the multidisciplinary clinic. Additional analyses were conducted to explore factors known to impact follow-up with care post-hospitalization (e.g., socioeconomic status, race, ethnicity).

Prior to the establishment of the BRAIN clinic, approximately 60 to 70% of patients were referred for outpatient neuropsychological follow-up. Approximately 30% of patients referred to the inpatient neuropsychological service following the establishment of the BRAIN clinic were referred for multidisciplinary care, while 20% did not require additional intervention and 50% were referred for outpatient neuropsychological follow-up. Analyses indicated increased follow-up rates with neuropsychological care following the establishment of the BRAIN clinic.

Integration of neuropsychology into inpatient care and subsequent multidisciplinary settings for pediatric patients with traumatic brain injuries or other serious insults and CNS infections increased access to neuropsychological care. Additional clinical implications will be discussed.

Inflicted traumatic brain injury (TBI) is one of the leading causes of childhood injury and death. Studies have consistently demonstrated worse outcomes for children with inflicted TBIs compared to accidental TBIs. Out of home placement, a known developmental risk factor, is a frequent occurrence in inflicted TBI, which may also contribute to worse outcomes for children. Little is known about what injury, child, and family factors predict out-of-home versus in-home placements. We hypothesize that injury severity, child, and family risk factors will be predictive of out-of-home placement after hospital discharge from an inflicted TBI.

Participants included 175 children with inflicted head injuries ages who received care at a large children’s hospital from 2012 to 2021. 88% of children were alive at discharge and were included in the study. The total sample included 154 children. Ages ranged from 0.2 to 76 months (M = 11.81, SD = 14.50) and 64.9 % were male. Race/Ethnicity distribution was as follows: 66.9% White, 29.9% Latinx or Hispanic, 4.6% Black, 3.3% American Indian or Alaskan, and 22.5% identified another race or ethnicity or identified as multiracial. Measures included injury severity (e.g., days spent in the PICU, post-resuscitation GCS), child (e.g., race/ethnicity, gender), and family factors (e.g., prior history of domestic violence, type of insurance). Individual logistic regressions were run to assess the effect of each injury severity, child, and family factor on placement after hospital discharge.

Results indicated that having a caregiver with a history of mental health difficulties and/or a history of substance abuse increased the likelihood of an out-of-home placement for the child after an inflicted TBI. Results also demonstrated that the more caregiver psychosocial concerns reported, the higher the risk of an out-of-home placement for the child after discharge from the hospital. Finally, results indicated that having public insurance significantly increased the risk of an out-of-home placement for the child after discharge from the hospital. Post-hoc analyses were conducted to assess the effect of insurance type on out-of-home placement, while controlling for psychosocial concerns. Results indicated that, even when taking total psychosocial concerns into account, having public insurance significantly increased the risk of an out-of-home placement. Logistic regressions were carried out to assess the effect of injury severity, child, and every other family factor (e.g., prior criminal history) on placement after hospital discharge and the overall models were not significant.

One explanation for these findings is that families with public insurance have less of a social safety net and, thus, are unable to meet the needs of a child with an inflicted TBI. However, we cannot rule out the effect of bias in child welfare practices. Similarly, caregivers with histories of mental health difficulties and substance abuse are likely to have a harder time meeting their child’s needs and providing a stable household, increasing the likelihood of an out-of-home placement. Despite expectations, child and injury severity factors did not play a role in placement decisions after an inflicted TBI, indicating that placement decisions rely more heavily on caregivers’ abilities to meet the child’s needs rather than the child’s medical complexity or the severity of the inflicted TBI.

Evidence-based consensus in children and adolescents following uncomplicated mTBI indicates acute cognitive symptoms resolve over time with minimal long-term impact. However, traditional paper-and-pencil neuropsychological measures used in many studies have been criticized for lacking sensitivity to subtle changes in attention and executive functions. The National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) is a computerized tool assessing overall cognition, fluid cognition, and crystallized cognition with few studies in pediatric mTBI. The aim of this study is to continue to explore the utility of the NIHTB-CB in adolescents recovering from mTBI compared to orthopedic injuries (OI) and healthy controls (HC).

The current pilot study utilized a prospective cohort design with longitudinal follow-up in three cohorts of high school student-athletes aged 14-18 (N= 52). Participants with mTBI (n= 17) or OI (n= 15) sustained during sport were recruited within 10 days of injury from a quaternary care setting. An age- and gender-matched cohort of healthy controls (HC) in an active sport season was included for community comparison (n= 20). The NIHTB-CB was administered as part of a neuropsychological screening battery at enrollment and one month after medical clearance (mTBI and OI) or eight weeks after enrollment (HC).

Results of a 3(group) x 2(time) ANOVA revealed a main effect of time (p < .001), but not group (p = .06), on the overall Fluid Cognition Composite. The mTBI group showed significantly lower performance on a measure of attention/inhibitory control (Flanker) compared to healthy controls acutely post-injury (p = .04; d = 0.72) and following clinical recovery (p < .01; d = 0.98), with no decline observed in the magnitude of group differences over time. The mTBI and OI groups exhibited deficits in performance on a measure of cognitive flexibility (Dimensional Change Card Sort) compared to the HC group acutely post-injury (both p < .01; d = 1.09-0.93). The magnitude of group differences between the OI and HC groups declined over time (p > .05; d = 0.68), whereas the mTBI group continued to show significantly lower performance following clinical recovery compared to the HC group (p = .02; d = 0.81). The mTBI, OI, and HC groups did not exhibit significant differences in working memory, explicit memory, or processing speed acutely post-injury and following clinical recovery (all p > .05; all d = 0.52 - 0.05). No significant effects of group (p = .16), time (p = .67), or the interaction (p = .45) were found on the Crystalized Cognition Composite.

Adolescents with mTBI demonstrated deficits on the NIHTB-CB measures of attention and executive functions acutely post-injury and extending beyond clinical recovery compared with healthy controls in this study. These subtle yet persistent deficits in cognitive performance lend support to the growing body of literature suggesting that alterations in neurotransmission may persist beyond resolution of clinical symptoms of mTBI. Further work is needed in larger samples to better understand trends in cognitive deficits and to identify clinical correlates persisting beyond clinical recovery from mTBI.

Recent studies have begun to explore the role of psychological resilience in pediatric mTBI recovery, with findings associating higher levels of resilience with shorter recovery and lower levels of resilience mediated by pre-injury anxiety and depression associated with persistent symptoms. The purpose of this study is to extend the current literature by further exploring the relationship between resilience, post-injury emotional changes, and length of recovery from pediatric mTBI. Based upon previous literature, we predicted that resilience would explain a unique portion of the variance in length of recovery above and beyond acute post-injury emotional symptoms in adolescents recovering from mTBI compared with orthopedic injured (OI) controls.

The current study pulled data from a larger project utilizing a prospective cohort design in two cohorts of high school student-athletes aged 14-18 (N = 32). Participants with mTBI (n = 17) or OI (n = 15) sustained during sport were recruited within 10 days of injury from a quaternary care setting. Participants completed a neuropsychological screening evaluation within one week of enrollment, including self-report rating scales of resilience (Connor-Davidson Resilience Scale-10; CD-RISC) and self- and parent-reported post-concussion symptoms (Post-Concussion Symptom Inventory, Second Edition; PCSI-2). Hierarchical regression analysis was performed with days from injury to recovery as the dependent variable. Predictors were entered in three steps: (1) group (mTBI/OI) and sex, (2) PCSI self- and parent-reported post-injury change in emotional symptoms, and (3) CD-RISC raw score. Bonferroni correction was utilized to control for multiple comparisons.

Group and sex did not provide significant prediction when entered into the first block of the model (p= .61). Introducing PCSI emotional ratings in the second block showed statistically significant improvement, F (2,26) = 5.12, p< .01), accounting for 31% of the variance in recovery length. Addition of the CD-RISC in the third block was not statistically significant (p=.59). Post hoc testing indicated parent ratings on the PCSI were significantly associated with recovery length t(32) = 3.16, p < .01, while self-reported ratings were not (p=.54).

Findings indicated that psychological resilience did not explain a unique portion of the variance in length of recovery above and beyond acute parent report of postinjury emotional symptoms in adolescents recovering from mTBI compared with orthopedic injured (OI) controls. Interestingly, sex, group (mTBI vs. OI), and self-reported acute postinjury emotional symptoms were not significant predictors of recovery length in this sample. Results highlight the significant role of acute changes in emotional symptoms in adolescents recovering from mTBI and OI in predicting length of recovery, as well as the importance of obtaining separate caregiver report. A more robust understanding of factors contributing to recovery from injury can help inform and improve preventive measures and treatment plants for those at risk or impacted; however, psychological resilience may not uniquely contribute to predicting length of recovery in acutely injured adolescents, limiting value added to the clinical exam. Future studies should explore the relationship between type of injury and recovery time in larger samples.

Many Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans have sustained a mild traumatic brain injury (mTBI) during their military service and a substantial “miserable minority” frequently report significant cognitive complaints long after injury. Although existing studies have shown associations between genetic factors (e.g., apolipoprotein E [APOE] and brain-derived neurotrophic factor [BDNF]) and cognitive performance in this vulnerable population, the TBI-genetics literature has generally been varied and inconsistent. Although past findings suggest that individuals who possess APOE £4 and BDNF Met alleles have worse cognitive outcomes after mTBI, this has not been consistently reported. Additionally, the influence of any gene-by-gene interactions on cognition has not been sufficiently explored and therefore remains a critical area of interest. Thus, we examined relationships between APOE and BDNF genotypes on neuropsychological function in a well-characterized sample of younger Veterans with mTBI histories.

Participants included Veterans with a history of mTBI who adequately completed performance validity testing. In total, 78 Veterans (84.6% male; age: M=32.95, SD=7.00; race/ethnicity: 51.3% White, 28.2% Hispanic/Latino, and 20.5% Another Race/Ethnicity) completed a structured clinical interview to collect detailed information on TBI history and underwent a comprehensive neuropsychological exam. A buccal swab was also collected to determine APOE and BDNF allele status for each participant. Three cognitive composite scores were computed reflecting memory (8 items), attention/processing speed (7 items), and executive functioning (10 items). Two-way analyses of covariance (ANCOVAs) adjusting for age, sex, and race/ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning (ε4+/Met-: n=12, ε4+/Met+: n=8, £4-/Met-: n=35, and ε4-/Met+: n=23).

ANCOVAs revealed no significant main effects for APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE x BDNF genotype interaction for all three cognitive composites (memory: p=.026, np2=.068; attention/processing speed: p=.045, np2=.055; and executive functioning: p=.031, np2=.064). Specifically, the interaction was such that Veterans in the ε4+/Met+ group demonstrated the poorest cognitive functioning relative to all other allele group combinations (ε4+/Met-, ε4-/Met+, ε4-/Met-).

The results of this preliminary study demonstrate that, compared to the other genetic subgroups in the TBI sample, Veterans with APOE £4 and BDNF Met alleles demonstrated the poorest cognitive functioning across several domains known to be negatively affected in the context of head injury (i.e., memory, attention/processing speed, and executive functioning). These findings are the first to show an APOE x BDNF interaction in Veterans with histories of mTBI. Further

research is necessary to replicate and extend this study in larger samples. Moreover, future work should incorporate neuroimaging variables to better interrogate structural and functional correlates of these observed genetic polymorphism associations in Veterans with mTBI histories.