Neuromodulation of Cognitive Control Neurocircuits for Stroke Rehabilitation

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Nearly 70% of chronic stroke patients have impairment in at least one cognitive domain. Many of these deficits are subtle, not directly assessed by therapists, and yet are barriers to achieving optimal recovery. While cognitive deficits can be parsed into unique subdomains (e.g., working memory, response inhibition, set shifting), diverse processes are supported by a common neural network: the Multiple Demand Network (MDN). The MDN consists of ‘core’ nodes: bilateral dorsolateral (dlPFC) and ventrolateral prefrontal cortex, intraparietal sulcus, pre-supplementary motor area (preSMA), dorsal anterior cingulate and bilateral insula. The left dlPFC node includes the site typically targeted with therapeutic repetitive transcranial magnetic stimulation (rTMS) for depression. Thus, it is not surprising that cognitive improvements have been a reported outcome of therapeutic rTMS to left dlPFC among neuropsychiatric disorders and a wide range of neurological conditions including mild to moderate cognitive impairment, dementia, and Alzheimer’s and Parkinson’s diseases. Targeting this cognitive network with rTMS may be a fruitful and innovative therapeutic adjuvant for cognitive rehabilitation in chronic stroke. Additionally, the preSMA, which also is a node in this network, is easily accessible to TMS. Since it is integrally involved in motor control, it could be an especially promising target for remediating deficits as it may affect both cognitive and motor control. Before proceeding to a clinical trial of MDN-guided rTMS as a therapeutic tool for stroke patients, it is critical to determine the functional integrity of the MDN in chronic stroke patients. Aim 1 is to test whether chronic stroke patients engage the MDN in a manner similar to control participants for endogenous cognitive tasks, specifically working memory and response inhibition. While these tasks both engage the MDN, response inhibition preferentially activates the preSMA. Furthermore, response inhibition represents the intersection of cognitive and motor control, underscoring its relevance in functional recovery in chronic stroke. Assessing both tasks will provide information on MDN functional integrity across task domains, as well as whether preSMA deficits are particularly prominent. Aim 2 is to determine which of these two nodes of the MDN (dlPFC versus preSMA) shows stronger activation of the MDN. This will be achieved by applying a series of TMS pulses to each location while the participant is in the MRI scanner, i.e., concurrent TMS-fMRI, a unique tool that was first developed here at the Medical University of South Carolina. The results from these endogenous and exogenous probes will be used to determine which site is a more promising target for cognitive improvement via rTMS.