The role of white matter variability in TMS neuromodulatory effects

Background

Transcranial Magnetic Stimulation (TMS) is a widely used tool to explore the causal role of focal brain regions in cognitive processing. TMS effects over attentional processes are consistent and replicable, while at the same time subjected to individual variability. This individual variability needs to be understood to better comprehend TMS effects, and most importantly, its clinical applications.

Objective

This study aimed to explore the role of white matter variability in TMS neuromodulatory effects on behavior in healthy participants (N = 50).

Methods

Participants completed an attentional task in which orienting and alerting cues preceded near-threshold targets. Continuous Theta Burst Stimulation (cTBS) was applied over the left frontal eye field (FEF) or an active vertex condition. White matter was explored with diffusion-weighted imaging tractography and Tract-Based Spatial Statistics (TBSS).

Results

Behaviorally, TMS over the left FEF slowed down reaction times (especially in the alerting task), impaired accuracy in the objective task, and reduced the proportion of seen targets (as compared to the vertex condition). Attentional effects increased, overall, when TMS was applied to the left FEF as compared to the vertex condition. Correlations between white matter and TMS effects showed i) reduced TMS effects associated with the microstructural properties of long-range white matter pathways such as the superior longitudinal fasciculus (SLF), and interhemispheric fibers of the corpus callosum (CC), and ii) increased TMS effects in participants with high integrity of the CC connecting the stimulated region with the opposite hemisphere. Additionally, variability in attentional effects was also related to white matter, showing iii) increased alerting effects in participants with low integrity of association, commissural, and projection fibers, and iv) increased orienting effects in participants with high integrity of the right SLF III.

Conclusion

All these observations highlight the importance of taking into account individual variability in white matter for the understanding of cognitive processing and brain neuromodulation effects.