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

Davin K Quinn,Thomas Jones,Claude William Shuttleworth,Rebecca Rieger,Darbi Gill,Violet Fratzke,Andrew R Mayer,J Kevin Wilson,Ronald A Yeo,Michael A Hunter,Joel Upston,Emma Brandt,Jacqueline Story-Remer,Jessica D Richardson,Richard Campbell,Vincent P Clark

doi:10.3389/fneur.2020.545174

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.

Highlights

Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment
One of the more promising hypotheses receiving significant scientific attention is that of abnormal cerebral perfusion, in which traumatic injury causes impaired neurovascular coupling and mismatch between neuronal metabolic demand and cerebral blood flow (CBF) [13,14,15,16]
Global CBF was noted to decrease over time, while increases in mood, attention, and executive function were observed, consistent with a hypothesis of increased cerebral efficiency

Summary

Introduction

Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment. A significant minority of patients with mild traumatic brain injury (mTBI), up to 33%, go on to experience functional impairment a year later [1, 2] These persistent post-traumatic symptoms (PPS) can range from the somatic (dizziness, headaches, light sensitivity) to the cognitive (difficulty focusing, impaired memory) and emotional realms (depression, irritability, anxiety) [3]. Arterial spin-labeling (ASL) and pseudocontinuous ASL (pCASL) magnetic resonance imaging sequences are techniques for measuring cerebral perfusion that have gained traction recently It has permitted quantification of both global and regional CBF without use of injected or inhaled agents [21, 22], based on the premise of magnetically labeling arterial blood protons prior to their flowing into a region of interest to act as an endogenous “tracer.” [21]

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