Effects of Transcranial Magnetic Stimulation on Individual Functional Brain Networks

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2022-12-01T06:00:00.000

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Abstract

Transcranial magnetic stimulation (TMS) has long been utilized as a tool to non-invasively study the association between brain function and cognition and is increasingly being used as a therapeutic intervention to modify brain function in an effort to treat disease. Towards these goals, recent efforts have strived to target and modify large-scale functional brain networks. This work is predicated on observations that the organization of the human functional brain network is related to behavioral performance among individuals across the lifespan, and cognitive decline that has been observed in health aging and in disease states. Large-scale brain networks consist of nodes (brain areas) that vary in their functional characteristics. Nodes belong to distinct subnetworks that represent functional brain systems related to cognition and sensory-motor function. Functional brain network organization has been observed to differ in specific topography and localization across individuals, which motivates efforts towards identifying individual-specific stimulation targets to reduce group-level bias and inaccuracies. This dissertation project utilized resting-state functional correlations (RSFC) to map the functional brain networks of individuals and identify specific stimulation targets in a group of healthy young adult participants (N = 17[9F], 18-30y). RSFC MRI was collected at baseline and 24 hours after completing a 5-day high-frequency rTMS protocol. For each individual participant, two cortical stimulation targets with distinct functional and topological properties were identified: the left angular gyrus (L. Ang.) and left middle frontal gyrus (L. MFG), with each target serving as an active control condition for the other target. On-target stimulation of each cortical target resulted in RSFC changes between the respective target node and its connections in the network, whereas RSFC changes were less evident following off-target (control-site) stimulation. RSFC changes were demonstrated to be related to the baseline RSFC strength and Euclidean distance between each target and their respective network connections, and was also related to on-target stimulation, demonstrating distal impacts of TMS that are mediated by both functional and anatomical features of functionally connected brain regions. On-target TMS to the L. Ang. decreased RSFC within the default-mode system (DMN) and on-target TMS to the L. MFG decreased RSFC within the frontoparietal control system (FPN) as well as in the default- mode system; off-target control stimulation had no impact on RSFC within the DMN. While node-level and system-level correlations were modified as a result of TMS, system segregation, an overall measure quantifying brain network organization was not impacted by TMS, highlighting the potential resiliency of a segregated brain network in the face of TMS perturbation. Notably, measures of episodic memory performance (but also fluid ability and working memory) were not impacted by TMS and were not related to observed changes in RSFC, despite previous reports that have provided evidence for these effects. This dissertation provides evidence that individualized on-target TMS modifies RSFC in a target-specific manner and is related to functional properties of the stimulated node within the brain network.

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