Cerebral Perfusion Effects of Cognitive Training and Transcranial Direct Current Stimulation in Mild-Moderate TBI

Abstract

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.

Transcranial direct current stimulation modulates working memory and prefrontal-insula connectivity after mild-moderate traumatic brain injury

“…That the finding is located in the right hemisphere, contralateral to the original site of stimulation, compared to the left DLPFC which received the highest presumed electric current density during tDCS but did not demonstrate connectivity change with any other region over time, also argues in favor of a compensation-recovery model, given the theorized role of the right hemisphere in depression, anxiety, and even somatization. Prior work by our group has found right DLPFC CBF reductions are associated with clinical improvement (Quinn et al, 2020) suggesting that recovery from prolonged postconcussive symptoms may be linked to regionally specific physiologic changes in the right prefrontal cortex characterized by both decreased connectivity and decreased perfusion. More work is needed to determine how functional connectivity between large-scale networks may underly chronic symptomatic states, compensation, and recovery after TBI, and to determine the strength of effects, optimal stimulation parameters, and mechanistic underpinnings of tDCS for mmTBI.…”

Transcranial Direct Current Stimulation as a Treatment Tool for Mild Traumatic Brain Injury

“…Quinn, et al [ 71 ] investigated whether anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) plus cognitive training altered cerebral blood flow (CBF) on pseudocontinuous arterial spin-labeling (pCASL) sequences in mTBI patients. Twenty-four subjects (15 male) with chronic mTBI with cognitive persistent post-traumatic symptoms were enrolled in the study.…”

“…The frontal poles [ 64 ], DLFPC [ 71 ], and M1 [ 93 ] were the tDCS brain targets in the reviewed studies and the choice of the tDCS target brain target should coincide with the study outcomes and be relevant to the studied population. For example, the DLPFC is the important role that this site exerts in cognitive function and some studies have shown that DLPFC is associated with attention and working memory function [ 45 , 95 ].…”

“…Thus, the results obtained from tDCS may vary substantially and would be reflected in brain activity changes that might be assessed via neuroimaging and neuropsychological tests. Furthermore, in the two extracted human studies [ 64 , 71 ], the target patients were identified based on symptoms of cognitive impairment post-TBI as opposed to being categorized by objective measures, such as conventional brain imaging or known brain lesion, which may not be possible in this population [ 19 , 20 ]. Understandably, from the standpoint of rehabilitating the entire population, it may not be appropriate not to select patients based on their known lesions.…”

Effects of Transcranial Direct Current Stimulation (tDCS) on Cognitive Performance and Cerebral Oxygen Hemodynamics: A Systematic Review

“…In addition to neuro-cognitive modulation, tDCS may invoke cerebroperfusional modulation associated with cortical hemodynamic functions (Zheng et al, 2011 ; Takai et al, 2016 ; Quinn et al, 2020 ). However, the interaction between tDCS induced effects on cognition and cerebral perfusion across aging remains widely unknown.…”