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.

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.

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