A structurally informed model for modulating functional connectivity

TL;DR

This paper introduces a predictive model that explains how TMS-induced brain activity changes functional connectivity by incorporating structural connectivity data, aiding the development of targeted neuropsychiatric therapies.

Contribution

The study presents a novel model linking structural and functional brain connectivity to predict TMS effects, validated with neuroimaging data from 29 individuals.

Findings

TMS-induced FC changes are best predicted by white matter fiber connections.

Structural core regions enhance predictability of TMS effects.

Overlap of structural core with functional systems correlates with greater FC change.

Abstract

Functional connectivity (FC) between brain regions tracks symptom severity in many neuropsychiatric disorders. Transcranial magnetic stimulation (TMS) directly alters regional activity and indirectly alters FC. Predicting how FC will change following TMS is difficult, but would allow novel therapies that target FC to improve symptoms. We address this challenge by proposing a predictive model that explains how TMS-induced activation can change the strength of FC. Here, we focus on the FC of the frontoparietal (FPS) and default mode (DMS) systems given the importance of their FC in executive function and affective disorders. We fit this model to neuroimaging data in 29 individuals who received TMS to the frontal cortex and evaluated the FC between the FPS and DMS. For each individual, we measured the TMS-induced change in FC between the FPS and DMS (the FC network), and the structural coupling between the stimulated area and the FPS and DMS (the structural context network (SCN)). We find that TMS-induced FC changes are best predicted when the model accounts for white matter fibers from the stimulated area to the two systems. We find that the correlation between these two networks (structure-function coupling) - and therefore the predictability of the TMS-induced modulation - was highest when the SCN contained a dense core of intraconnected regions, indicating that the stimulated area had ample access to an anatomical module. Further, we found that when the core of the SCN overlapped with the FPS and DMS, we observed the greatest change in the strength of their FC. Broadly, our findings explain how the structural connectivity of a stimulated region modulates TMS-induced changes in the brain's functional network. Efforts to account for such structural connections could improve predictions of TMS response, further informing the development of TMS protocols for clinical translation.