Neurovascular Coupling: A Unifying Theory for Post-Concussion Syndrome Treatment and Functional Neuroimaging

Abstract

Post-concussion syndrome (PCS) occurs in a significant percentage of concussion patients and is defined as having a history of traumatic brain injury with persistence of three or more symptoms. Standard structural clinical neuroimaging studies show no abnormal findings for the majority of PCS patients as opposed to functional MRI, which often reveals irregularities in the blood-oxygen level dependent (BOLD) signal. This suggests that dysregulation of neurovascular coupling, which causes abnormal BOLD signals, plays a significant role in PCS pathology. However, compared to the pathophysiologic mechanisms occurring in acute concussion, the underlying neuropathophysiology of chronic concussive sequelaeor PCS is less understood, though becoming clearer with emerging research. We present a treatment approach grounded in the physiological theory presented here called Enhanced Performance in Cognition (EPIC), which has shown strong clinical success. Dysregulation of neurovascular coupling (NVC), along with disruptions in cerebrovascular reactivity (CVR) and autonomic nervous system (ANS) dysregulation are the targets of EPIC treatment. Success of the approach itself tentatively supports the hypothesis that these three features figure prominently in the neuropathophysiology of PCS. The aim of this report is to provide a theory of the underlying mechanisms of PCS pathology and its treatment that is in accord with the current corpus of research and explains the recent therapeutic success seen in PCS patient using the EPIC treatment. We propose a novel theory concerning the mechanisms by which NVC dysregulation is normalized. This includes focused, intense and repetitive neurocognitive challenges during post-exercise cognitive boost and the avoidance of intracerebral steal in the setting of restored and re-regulated CVR and ANS. It is intended that both the theory and treatment approach are presented explicitly enough to generate empirical studies with clear hypothetical predictions from the theory as well as clinical innovations with significant relevance to improve current practices.