Understanding sex differences among persons with moderate-to-severe traumatic brain injury (TBI) is critical to addressing the unique needs of both males and females from acute care through to rehabilitation. Epidemiological studies suggest that 7 of every 10 persons with moderate-to-severe TBI are male, with females representing about 30%–33%.

To examine the proportion of female and male individuals included in randomized controlled trials (RCTs) of interventions for moderate-to-severe TBI.

A systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up to and including December 2022 using MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO databases. Studies were included if they met the following criteria: (1) human participants with a mean age ≥18 years, (2) ≥50% of the sample had moderate-to-severe TBI and (3) the study design was a RCT. Data extracted included author, year, country, sample size, number of female/male participants and time post-injury.

595 RCTs met the criteria for inclusion, published between 1978 and 2022, totaling 86,662 participants. The average proportion of female participants was 23.14%, and the percentage increased a small but significant amount over time. There was a significantly lower percentage of female participants in RCTs initiated in the acute phase (≤ 1 month) when compared with RCTs conducted in the chronic phase (≥ 6 months) post-injury (p < 0.001).

Female participants are underrepresented in RCTs of moderate-to-severe TBI. Addressing this underrepresentation is critical to establish effective treatments for all persons with TBI.

Traumatic brain injury (TBI)-induced anxiety is a common but under-investigated disorder, for which neuroinflammation is a significant contributor. Here we aim to investigate the protective effects of genistein, a plant-derived anti-inflammatory drug, against TBI-induced anxiety, and the underlying mechanisms.

A rat model of TBI was constructed using the lateral fluid percussion injury method. Genistein at the doses of 5, 10, and 20 mg/kg were used to treat rats at 30 min, 12 h, 24 h, 48 h, and 72 h up to 14 days after TBI. The evaluation of neurological deficit was performed preoperatively, on days 1, 3, 7, and 14 after TBI. The elevated plus maze test was carried out to assess anxiety and explorative behaviours, and the open field test was performed to assess locomotive activities. Brain injury was assessed by measuring brain water content and TdT-mediated dUTP Nick-End Labeling staining. Inflammatory responses were examined using enzyme-linked immunosorbent assay. The mRNA and protein expression were analysed using real-time polymerase chain reaction and Western blot, respectively.

In the behavioural level, genistein treatment alleviated TBI-induced anxiety behaviours and neurological deficit in rats. In the meanwhile, brain oedema was also reduced by genistein treatment, showing alleviating effects of genistein at the pathological level. TUNEL staining also showed reduced apoptosis in rats treated with genistein. Genistein also inhibited Nlrp3/caspase-1 signalling, unveiling the effects of genistein in altering molecular pathways in brains with TBI.

Genistein alleviates anxiety-like behaviours in TBI rats, which may be mediated via inhibiting Nlrp/caspase-1 signalling pathway.

Neuropsychiatric symptoms are common after traumatic brain injury (TBI) and often resolve within 3 months post-injury. However, the degree to which individual patients follow this course is unknown. We characterized trajectories of neuropsychiatric symptoms over 12 months post-TBI. We hypothesized that a substantial proportion of individuals would display trajectories distinct from the group-average course, with some exhibiting less favorable courses.

Participants were level 1 trauma center patients with TBI (n = 1943), orthopedic trauma controls (n = 257), and non-injured friend controls (n = 300). Trajectories of six symptom dimensions (Depression, Anxiety, Fear, Sleep, Physical, and Pain) were identified using growth mixture modeling from 2 weeks to 12 months post-injury.

Depression, Anxiety, Fear, and Physical symptoms displayed three trajectories: Stable-Low (86.2–88.6%), Worsening (5.6–10.9%), and Improving (2.6–6.4%). Among symptomatic trajectories (Worsening, Improving), lower-severity TBI was associated with higher prevalence of elevated symptoms at 2 weeks that steadily resolved over 12 months compared to all other groups, whereas higher-severity TBI was associated with higher prevalence of symptoms that gradually worsened from 3–12 months. Sleep and Pain displayed more variable recovery courses, and the most common trajectory entailed an average level of problems that remained stable over time (Stable-Average; 46.7–82.6%). Symptomatic Sleep and Pain trajectories (Stable-Average, Improving) were more common in traumatically injured groups.

Findings illustrate the nature and rates of distinct neuropsychiatric symptom trajectories and their relationship to traumatic injuries. Providers may use these results as a referent for gauging typical v. atypical recovery in the first 12 months post-injury.

Hemodynamic collapse in multi-trauma patients with severe traumatic brain injury (TBI) poses both a diagnostic and therapeutic challenge for prehospital clinicians. Brain injury associated shock (BIAS), likely resulting from catecholamine storm, can cause both ventricular dysfunction and vasoplegia but may present clinically in a manner similar to hemorrhagic shock. Despite different treatment strategies, few studies exist describing this phenomenon in the early post-injury phase. This retrospective observational study aimed to describe the frequency of shock in isolated TBI in prehospital trauma patients and to compare their clinical characteristics to those patients with hemorrhagic shock and TBI without shock.

All prehospital trauma patients intubated by prehospital medical teams from New South Wales Ambulance Aeromedical Operations (NSWA-AO) with an initial Glasgow Coma Scale (GCS) of 12 or less were investigated. Shock was defined as a pre-intubation systolic blood pressure under 90mmHg and the administration of blood products or vasopressors. Injuries were classified from in-hospital computed tomography (CT) reports. From this, three study groups were derived: BIAS, hemorrhagic shock, and isolated TBI without shock. Descriptive statistics were then produced for clinical and treatment variables.

Of 1,292 intubated patients, 423 had an initial GCS of 12 or less, 24 patients (5.7% of the original cohort) had shock with an isolated TBI, and 39 patients had hemorrhagic shock. The hemodynamic parameters were similar amongst these groups, including values of tachycardia, hypotension, and elevated shock index. Prehospital clinical interventions including blood transfusion and total fluids administered were also similar, suggesting they were indistinguishable to prehospital clinicians.

Hemodynamic compromise in the setting of isolated severe TBI is a rare clinical entity. Current prehospital physiological data available to clinicians do not allow for easy delineation between these patients from those with hemorrhagic shock.

Prognosticating outcomes for traumatic brain injury (TBI) patients is challenging due to the required specialized skills and variability among clinicians. Recent attempts to standardize TBI prognosis have leveraged machine learning (ML) methodologies. This study evaluates the necessity and influence of ML-assisted TBI prognostication through healthcare professionals’ perspectives via focus group discussions.

Two virtual focus groups included ten key TBI care stakeholders (one neurosurgeon, two emergency clinicians, one internist, two radiologists, one registered nurse, two researchers in ML and healthcare and one patient representative). They answered six open-ended questions about their perceptions and potential ML use in TBI prognostication. Transcribed focus group discussions were thematically analyzed using qualitative data analysis software.

The study captured diverse perceptions and interests in TBI prognostication across clinical specialties. Notably, certain clinicians who currently do not prognosticate expressed an interest in doing so independently provided they had access to ML support. Concerns included ML’s accuracy and the need for proficient ML researchers in clinical settings. The consensus suggested using ML as a secondary consultation tool and promoting collaboration with internal or external research resources. Participants believed ML prognostication could enhance disposition planning and standardize care regardless of clinician expertise or injury severity. There was no evidence of perceived bias or interference during the discussions.

Our findings revealed an overall positive attitude toward ML-based prognostication. Despite raising multiple concerns, the focus group discussions were particularly valuable in underscoring the potential of ML in democratizing and standardizing TBI prognosis practices.

Neuropsychiatric symptoms in major neurocognitive disorders have been strongly associated with suicidality.

The objectives were to explore suicide rates in degenerative neurocognitive disorders (DNDs), alcohol-related neurocognitive disorders (ARNDs), and traumatic brain injuries (TBIs). Patients who received these diagnoses between 1998 and 2015 (N = 231,817) were identified from nationwide registers, and their mortality was followed up until December 31, 2018. We calculated incidences of suicides per 100,000 person-years, types of suicides, and suicide rates compared with the general population (standardized mortality ratio [SMR]).

During the follow-up, 0.3% (95% confidence interval [95% CI]: 0.2–0.5) of patients with DNDs, 1.1% (0.7–1.8) with ARNDs, and 1.0% (0.7–1.3) with TBIs committed suicide. Suicide mortality rate was higher in men (58.9, 51.3, to 67.4 per 100,000) than in women (9.8, 7.5, to 12.5 per 100,000). The highest suicide rate was in ARNDs (98.8, 65.1, to 143.8 per 100,000), followed by TBIs (82.0, 62.4, to 105.8 per 100,000), and DNDs (21.2, 18.3, to 24.5 per 100,000). The SMRs (95% CI) were 3.69 (2.53–5.38), 2.99 (2.31–3.86), and 1.31 (1.13–1.51), respectively, and no sex difference emerged. The most common cause of death was self-inflicted injury by hanging or drowning (12.4, 10.3, to 14.8 per 100,000).

Suicide rates were higher in all three patient groups than the general population. Suicide risk remained elevated for more than 10 years after diagnosis. The suicide methods were mostly violent.

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.

Following a traumatic brain injury (TBI), the majority of patients report difficulties with prospective memory (PM). However, there is not always a significant relationship between subjective and objective PM measures. Several variables may influence the degree of severity of perceived difficulties, including the severity of the injury and psychoemotional status. The aim of this study was to determine whether the severity of the TBI and anxiety and depressive symptoms were related to objective and subjective difficulties of PM.

50 patients (mean age = 31,3 years old) with a TBI (20 mild and 30 moderate/severe) in the post-acute phase of recovery and 15 matched healthy control participants (mean age = 32,3 years old) were recruited. They completed inventories assessing the presence of anxiety (BAI) and depressive (BDI) symptoms and performed the Ecological test of prospective memory (TEMP), an objective measure of PM. The Comprehensive Assessment of PM (CAPM), a subjective measure of PM, was also filled out by participants and their relatives.

In patients with moderate/severe TBI, significant correlations were found between the CAPM and the BDI (r =.601, p<.001) and the BAI (r =.507, p=.004). A negative correlation was also observed between the relatives’ CAPM scores and the performance of the patients on the TEMP (r= -.374, p=.042). In patients with mild TBI, there was only a strong significant correlation between the CAPM and the BAI scores (r =.574, p=.008). However, no other correlation was significant between this group of patients and their relatives. Additionally, results on the TEMP were not significantly correlated with the CAMP completed by healthy control participants or their relatives. A linear regression conducted in the group of participants with TBI showed that BAI and BDI scores are the only significant predictors of the results on the CAPM (31% of the variance), while TBI severity is the only significant predictor of the results on the TEMP (37% of the variance).

The perception of PM difficulties in patients with a TBI does not seem to be related to their objective performance. Anxiety and depressive symptoms appear to influence their perception more than their objective performance. As suggested by their relatives, a decrease in self-awareness could explain the lack of relationship between subjective PM difficulties of patients with moderate/severe TBI and their objective performance. On the other hand, TBI severity is more strongly related to objective performance on PM tests. These results highlight the importance of using different measures to accurately assess PM and the various factors influencing this construct.

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.

To determine the effects of the non-classic psychedelic, ibogaine, on cognitive functioning. Ibogaine is an indole alkaloid derived from the Tabernanthe Iboga plant family, indigenous to Africa, and traditionally used in spiritual and healing ceremonies. Ibogaine has primarily been studied with respect to its clinical efficacy in reducing substance addiction. There are, however, indications that it also may enhance recovery from traumatic experiences. Ibogaine is a Schedule 1 substance in the USA.

Participants were U.S. Special Operations Veterans who had independently and voluntarily referred themselves for an ibogaine retreat at a specialized clinic outside the USA prior to learning about this observational study. After meeting rigorous screening requirements, 30 participants were enrolled, all endorsing histories of combat and repeated blast exposure, as well as traumatic brain injury. Participants were seen in person pre-treatment, post-treatment, and one-month post-treatment for neuropsychological testing, neuroimaging, and collection of clinical outcome measures. All 30 participants were seen pre- and post-treatment, of whom 27 were also able to return one-month post-treatment.

The neuropsychological battery included the the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test - Revised (BVMT-R), the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Working Memory Index (Digit Span and Arithmetic) and Processing Speed Index (Symbol Search and Coding), and the Delis-Kaplan Executive Function System (D-KEFS) tests of Verbal Fluency (VF), Trail Making (TMT), Color Word (CW), and Tower Test (TT). For repeated measures, alternate forms were used whenever possible.

Repeated-measures ANOVA revealed significant effects of time, with post-treatment improvements across multiple measures including processing speed (WAIS-IV PSI; F(2,25) = 26.957, p < .001), executive functions (CW Conditions 3 and 4: F(1.445,25) = 11.383, p < .001 and F(1.381,25) = 7.687, p = .004, respectively), verbal fluency (VF Condition 3 correct and accuracy: F(2,25) = 6.419, p = .003 and F(2,25) = 153.076, p < .001, respectively), and verbal learning (HVLT Total Recall (alternate forms used at each time point): F(1.563,23) = 6.958, p = .004). Score progression graphs are presented. Performance on all other cognitive measures did not significantly change following treatment.

To our knowledge, this is the first prospective study examining neuropsychological test performance following ibogaine use at post-treatment and one-month post-treatment time points. Our results indicated that several cognitive domains improved either post-treatment or one-month post-ibogaine treatment, suggesting ibogaine’s therapeutic potential for cognition in the context of traumatic brain injury and mood disorders. Potential explanations include neuroplastic changes, reduction of PTSD and mood-related effects on cognitive functioning, and practice effects. While we found no evidence of negative cognitive consequences for up to one-month post-single-ibogaine treatment, further study of this substance is necessary to clarify its clinical utility and safety parameters.

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.

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.

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.

Limitations of traditional neuropsychological assessment include testing in a highly controlled environment designed to minimize distraction. While informative, it may not fully capture real-world cognitive functioning. This may be particularly important for individuals with mild traumatic brain injury (mTBI), a subset of whom report subtle challenges with complex cognitive functioning that are not consistently captured by neuropsychological assessment. The objective of this study was to extend previous work examining cognitive correlates of performance on functional assessment tool, the Goal Processing Sale (GPS), in a larger sample of Veterans with mTBI.

46 Veterans with chronic mTBI completed GPS and neuropsychological measures (mean age = 43.5; education = 15 years; 89% male). 93% of participants had clinically significant PTSD (PCL-M > 31). The GPS is an ecologically valid assessment in which participants plan and execute a complex task following specified rules under a time constraint. Performance is rated on a 0 (not able) to 10 (absolutely not a problem) scale in 8 domains: 1) Planning, 2) Initiation, 3) Self-Monitoring, 4) Maintenance of Attention, 5) Sequencing and Switching of Attention, 6) Flexible Problem Solving, 7) Task Execution, and 8) Learning and Memory. The GPS Overall Performance is average of 8 domain scores. Neuropsychological assessment data were scored using standardized norms and transformed into z-scores. Scores were averaged into 2 domains: 1) Overall Attention/Executive Function (4 subdomains: Working Memory [Auditory Consonant Trigrams, WAIS-III Letter Number Sequencing], Sustained Attention [Digit Vigilance Test], Inhibition [D-KEFS Stroop Inhibition], Mental Flexibility [Trail Making Test B, D-KEFS Stroop Inhibition Switching, Design Fluency Switching, Verbal Fluency Switching]) and 2) Overall Memory (2 subdomains: Total Recall [HVLT-R, BVMT-R], and Delayed Recall [HVLT-R, BVMT-R]).

Pearson correlation coefficients were used to determine relation between overall GPS and overall executive function performance, as well as 8 GPS subdomain and 8 neuropsychological domain/subdomain scores. To adjust for multiple comparisons, p < .01 was used.

Overall GPS performance was statistically significantly related to Overall Attention/Executive Functioning and Overall Memory. Investigating further, multiple significant subdomain relations emerged. GPS Planning was related to Inhibition. GPS Self-Monitoring and GPS Task Execution were related to Mental Flexibility. GPS Maintenance of Attention and GPS Flexible Problem Solving were related to Mental Flexibility and Inhibition. GPS Sequencing and Switching of Attention was related to Mental Flexibility and Total Recall.

GPS Learning and Memory was related to Working Memory, Mental Flexibility, and Inhibition. GPS Initiation was not related to neuropsychological measures.

Current findings build upon prior work establishing validity of GPS functional assessment measure (Novakovic-Agopian et al., 2012). Seven of 8 GPS subdomains were related to at least one aspect of executive functioning assessed with neuropsychological measures, with the majority related to mental flexibility. Taken together, findings suggest that the GPS converges with traditional measures, offering a method to capture multiple aspects of executive functioning applied together. Further, it may also be useful tool capturing aspects of executive functioning in complex, ecologically-valid settings often not captured with traditional neuropsychological assessment.