Alpha frequency tACS and pain avoidance learning in chronic pain patients

About This Grant

PROJECT SUMMARY/ABSTRACT The overarching goal of this project is to gain mechanistic insights into the brain-behavior relationship underlying pain avoidance and its modulation using alpha-frequency transcranial alternating current stimulation (tACS) targeting the dorsomedial prefrontal cortex (dmPFC). While adaptive avoidance of pain aids in survival, maladaptive pain avoidance plays a key role in the development and maintenance of chronic pain hampering physical therapy and rehabilitation, especially in conditions like complex regional pain syndrome (CRPS) with a high burden of psychopathology. An emerging perspective characterizes chronic pain as a learning impairment - an inability to differentiate between situations predicting threat vs. safety - resulting in fear and avoidance spreading to potentially safe activities. Although much of the impairment is attributed to the dysfunction and disinhibition involving the prefrontal networks, the underlying neurophysiology and its causal relationship with pain avoidance behavior is yet to be determined. We take a multimodal approach to study how behavior, brain neurophysiology and autonomic nervous system (ANS) responses are modulated by enhancing the alpha oscillatory power in the dmPFC. Given the alpha oscillations in the dmPFC facilitate inhibitory processes required for decision making and learning, we hypothesize that enhancing alpha power via tACS will promote adaptive pain avoidance behavior in CRPS patients. In Aim 1 will use an instrumental pain avoidance task in conjunction with a computational reinforcement learning model to quantify the effects of tACS on threat and safety learning behaviors. The task will be performed while we collect magnetoencephalography (MEG), a state-of-the-art brain imaging device. Aim 2 will examine both pain avoidance task-related and resting-state MEG activity to quantify the effects of tACS on brain neurophysiology in terms of alpha oscillatory power and connectivity. Aim 3 will evaluate the effects of tACS on ANS responses in terms of heart rate variability – a parasympathetic measure from EKG – and fear arousal – a sympathetic measure from galvanic skin conductance responses. The data from this project will clarify the spectral specificity with which pain avoidance behavior is represented in the dmPFC and ability to directly modulate them. This project is the first of its kind to investigate affective- motivational dimensions of chronic pain using tACS and will establish the foundation for future augmented protocols combining tACS with rehabilitation.