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Background: Persistent posttraumatic symptoms (PPS) may manifest after a mild-moderate traumatic brain injury (mmTBI) even when standard brain imaging appears normal. Transcranial direct current stimulation (tDCS) represents a promising treatment that may ameliorate pathophysiological processes contributing to PPS.Objective/Hypothesis: We hypothesized that in a mmTBI population, active tDCS combined with training would result in greater improvement in executive functions and post-TBI cognitive symptoms and increased resting state connectivity of the stimulated region, i.e., left dorsolateral prefrontal cortex (DLPFC) compared to control tDCS.Methods: Thirty-four subjects with mmTBI underwent baseline assessments of demographics, symptoms, and cognitive function as well as resting state functional magnetic resonance imaging (rsfMRI) in a subset of patients (n = 24). Primary outcome measures included NIH EXAMINER composite scores, and the Neurobehavioral Symptom Inventory (NSI). All participants received 10 daily sessions of 30 min of executive function training coupled with active or control tDCS (2 mA, anode F3, cathode right deltoid). Imaging and assessments were re-obtained after the final training session, and assessments were repeated after 1 month. Mixed-models linear regression and repeated measures analyses of variance were calculated for main effects and interactions.Results: Both active and control groups demonstrated improvements in executive function (EXAMINER composite: p < 0.001) and posttraumatic symptoms (NSI cognitive: p = 0.01) from baseline to 1 month. Active anodal tDCS was associated with greater improvements in working memory reaction time compared to control (p = 0.007). Reaction time improvement correlated significantly with the degree of connectivity change between the right DLPFC and the left anterior insula (p = 0.02).Conclusion: Anodal tDCS improved reaction time on an online working memory task in a mmTBI population, and decreased connectivity between executive network and salience network nodes. These findings generate important hypotheses for the mechanism of recovery from PPS after mild-moderate TBI.

Abstract. Depression is a pervasive psychiatric problem following mild traumatic brain injury (mTBI). However, the onset and course of symptom expression following mTBI can differ from that of spontaneous episodes of depression. Here, we aimed to assess a physiological metric closely linked to depression: respiratory sinus arrhythmia (RSA), a measure of high frequency heart rate variability. RSA is reduced during depressive episodes, and higher resting RSA has been shown to predict future recovery from depression. In this study, we investigated if these patterns were observed throughout the typical timeframe of sub-acute mTBI recovery. Although RSA did not differ between mTBI ( n = 50) and control ( n = 27) groups, depressive symptoms were reliably correlated with RSA only in the mTBI group. This pattern was consistent 2 weeks, 2 months, and 4 months post-injury. Furthermore, resting RSA shortly following injury predicted the trajectory of depressive symptoms 2 months later. These findings generalize the connection between RSA and depression to a clinical population where depressive symptoms are common but often difficult to parse from other post-trauma consequences.

Delayed memory deficits are common for patients with mild traumatic brain injury (mTBI), according to a recent systematic review of meta-analyses (Karr et al., 2014). However, there has been little work to identify different cognitive processes that may be underpinning these delayed memory deficits for mTBI. Frontal cortex is important for delayed memory, and is implicated in the pathophysiology of mTBI; moreover, frontal lobes are typically considered the locus of executive abilities. To further explore these relationships, we sought to partly explain delayed memory deficits after mTBI by examining behavioral indicators of executive function. Results showed that sub-acute as well as chronic mTBI patients performed worse than controls on the delayed memory trial of the Hopkins Verbal Learning Test-Revised (Brandt & Benedict, 2001), recalling approximately 18% and 15% fewer words, respectively. Furthermore, worse delayed memory performance was associated with less use of the cognitive strategy of semantic clustering, and with lower scores for the executive function composite from a standardized neuropsychological battery (NIH EXAMINER; Kramer et al., 2014). In contrast, serial clustering, a memory organizational strategy thought to be less dependent on executive function, did not show strong relationships to clinical status or delayed memory performance. This exploratory work suggests novel hypotheses to be tested in future, confirmatory studies, including that general executive functions and/or semantic clustering will mediate delayed memory deficits following mTBI.

Objective: This study assessed the convergent validity of the NIHTB-CB in a sample of children and adolescents with CCM-1 and non-affected relatives. Method: Twenty-two participants with CCM-1 and 7 non-affected relatives completed the NIHTB-CB and traditional neuropsychological measures. The following domains were assessed: memory (NIHTB-CB Picture Sequencing Memory and Child and Adolescent Memory Profile- Screening Index), word reading (NIHTB-CB Oral Reading and Wide Range Achievement Test-4th Word Reading [WRAT-4 WR]), processing speed (NIHTB-CB Pattern Comparison and Symbol Digit Modalities Test), and attention/working memory (NIHTB-CB List Sorting and Digit Span). Results: The non-affected group scored higher than the CCM-1 group on WRAT-4 WR (t = 2.68, p = .02) and NIHTB-CB Oral Reading (t = 2.18, p = .05). The groups did not differ on the other measures (p > .05). Pearson’s correlations ranged from .45 for memory to .81 for word reading, demonstrating adequate construct validity for memory, processing speed, and attention/ working memory and good to very good for word reading. The NIHTB-CB was more likely to identify participants as impaired for memory (17.2% vs 6.9%) and processing speed (62.1% vs. 3.4%). The traditional attention/working memory measure was more likely to identify participants as impaired (27.6% vs 3.4%). Impairment rates were similar for the word reading measures. Conclusions: Of the domains considered, convergent validity was best established for word reading. Although correlations were adequate, rates of impairment differed for memory, processing speed, and attention/ working memory, suggesting that caution is warranted when comparing the NIHTB-CB to traditional measures in these areas.

Objective: CCM1 is a rare condition that confers risk for negative neurological sequelae, including hemorrhage, seizures, and chronic headache. This study examines cognitive and psychosocial functioning in pediatric patients with CCM1 and describes emerging clinical care guidelines. Method: Twenty-two children and adolescents with CCM-1 and 7 non-affected relatives participated in this cross-sectional pilot study. Cognitive testing and behavior and emotion questionnaires were completed. A subset of participants with CCM1 (n = 11) had repeat brain MRI (average 4.89 years between scans). Results: Patients with CCM1 and their non-affected relatives did not differ on the NIH Toolbox Fluid and Crystallized composites (p > 0.05). Processing speed also did not significantly differ, although both group means were below average normatively (NIH Toolbox Pattern Comparison T-score; CCM1 = 31.50 [12.02], non-affected relatives = 37.57 [14.58]). In the subgroup with repeat imaging, slower processing speed was associated with an increase in large lesions (p = 0.03) and with younger age at CCM1 diagnosis (p = 0.04). Self- and parent-reported internalizing problems and parent-reported externalizing problems did not differ between groups (p > 05). In the CCM1 group, patient-reported disengaged coping was associated with more internalizing problems (p = 0.03). Conclusions: Neuropsychological evaluation is an important component of long-term, multi-disciplinary care for pediatric patients with CCM1, particularly if lesions are progressive. The pilot sample was overall well-adjusted behaviorally and emotionally. The use of disengaged coping strategies was associated with more internalizing symptoms and coping may be a key modifiable risk factor in this population. Psychosocial monitoring may therefore be warranted.