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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.

Aim Heightened craving among individuals with alcohol use disorder (AUD) has been attributed to a hypersensitivity to alcohol cues in attentional brain networks. Active mindfulness training has been shown to help improve attentional control. Here, we examined alcohol cue-related hypersensitivity among individuals with AUD who received rolling group mindfulness-based relapse prevention (MBRP) in combination with transcranial direct current stimulation (tDCS), over right inferior frontal gyrus. Methods Participants (n = 68) viewed a series of emotionally negative, emotionally neutral and alcohol-related images. Following image presentation, participants were asked to rate their level of craving for the alcohol cues, and their level of negative affect evoked by neutral and negative cues. During the task, electroencephalogram (EEG) was recorded to capture an event-related component shown to relate to emotionally salient stimuli: the late positive potential (LPP). Participants who completed a follow-up EEG (n = 37) performed the task a second time after up to eight sessions of MBRP coupled with active or sham tDCS. Results We found that both craving ratings and the LPP significantly decreased in response to alcohol cues from pre- to post-treatment, but not for other image cues. The magnitude of alcohol image craving reductions was associated with the number of MBRP group sessions attended. Active tDCS was not associated with craving ratings, but it was associated with greater LPP amplitudes across image types. Conclusions Taken together, these results suggest that disruption of alcohol-cue hypersensitivity in people with AUD may be a target mechanism of MBRP.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI (n = 44), chronic mild-to-moderate TBI (n = 26), and nonbrain-injured control participants (CTRL; n = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for “clinically significant apathy,” finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.

Background: Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment. Pseudocontinuous arterial spin labeling (pCASL) has been used in multiple studies to explore changes in cerebral blood flow (CBF) that may result in acute and chronic TBI, and is a promising neuroimaging modality for assessing response to therapies. Methods: Twenty-four subjects with chronic mild-moderate TBI (mmTBI) were enrolled in a pilot study of 10 days of computerized executive function training combined with active or sham anodal transcranial direct current stimulation (tDCS) for treatment of cognitive PPS. Behavioral surveys, neuropsychological testing, and magnetic resonance imaging (MRI) with pCASL sequences to assess global and regional CBF were obtained before and after the training protocol. Results: Robust improvements in depression, anxiety, complex attention, and executive function were seen in both active and sham groups between the baseline and post-treatment visits. Global CBF decreased over time, with differences in regional CBF noted in the right inferior frontal gyrus (IFG). Active stimulation was associated with static or increased CBF in the right IFG, whereas sham was associated with reduced CBF. Neuropsychological performance and behavioral symptoms were not associated with changes in CBF. Discussion: The current study suggests a complex picture between mmTBI, cerebral perfusion, and recovery. Changes in CBF may result from physiologic effect of the intervention, compensatory neural mechanisms, or confounding factors. Limitations include a small sample size and heterogenous injury sample, but these findings suggest promising directions for future studies of cognitive training paradigms in mmTBI.