Mapping the Causal Roles of Non-Primary Motor Areas in Human Reach Planning and Execution

Haddadshargh, G.; de Freitas, R. M.; Mak, J.; Boos, A.; Fang, X.; Collinger, J.; McKernan, G.; Zhan, L.; Liu, F.; Wittenberg, G. F.

doi:10.1101/2025.09.11.671853

bioRxiv · 10.1101/2025.09.11.671853

Mapping the Causal Roles of Non-Primary Motor Areas in Human Reach Planning and Execution

Haddadshargh, G.·de Freitas, R. M.·Mak, J.·Boos, A.·Fang, X.·Collinger, J.·McKernan, G.·Zhan, L.·Liu, F.·Wittenberg, G. F.

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Abstract

Non-primary motor areas, including the dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and posterior parietal cortex (PPC), are involved in movement planning, but their precise contributions remain unclear. We used functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and kinematic assessments to explore how these areas influence reaching performance in neurologically intact adults. Participants performed a reaching task using the KINARM exoskeleton robot. Brief TMS pulse trains were initiated before movement onset to perturb cortical activity at subthreshold and suprathreshold intensities targeting bilateral PMd, PMv, and PPC. Subthreshold stimulation of contralateral PMd and PMv reduced reach efficiency and smoothness, while suprathreshold stimulation of contralateral PPC increased deviation error and reduced smoothness. Among ipsilateral targets, PMd showed consistent TMS-induced effects, and was the only target where resting-state connectivity predicted behavioral response. Stronger interhemispheric connectivity in the primary motor cortex and weaker interhemispheric PPC connectivity were associated with greater reductions in straightness and smoothness during subthreshold ipsilateral PMd stimulation. These findings show that perturbation of premotor and parietal areas during early movement execution alters reach trajectories, and differences in network organization explain variability in behavioral response. Identifying contributions of cortical areas and connectivity patterns may help personalize interventions after stroke. This study was registered at ClinicalTrials.gov under ID NCT04286516.

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Haddadshargh, G., de Freitas, R. M., Mak, J., Boos, A., Fang, X., Collinger, J., McKernan, G., Zhan, L., Liu, F., Wittenberg, G. F.. 2025-09-12. Mapping the Causal Roles of Non-Primary Motor Areas in Human Reach Planning and Execution. https://doi.org/10.1101/2025.09.11.671853

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