Motor cortex contribution to dynamic force regulation in the index finger revealed by TMS interference

Lifting a paper cup without crushing it, and releasing it not too early when placing it on the table, demand precise force regulation in flexor and extensor muscles, throughout the grasping act. In healthy humans, such fine control is thought to be mediated primarily by the contralateral corticospinal tract (CST), whose main origin is the primary motor cortex (M1).  However, the specific cortical mechanisms underlying graded force modulation and directional control in human’s hand and fingers’ muscles remain unclear. Understanding these nuances is not only of theoretical interest but has practical significance, especially in the context of neurological injury.  In case of damage to the contralateral CST (e.g. due to stroke), it was suggested that non-crossing descending pathways from the ipsilateral (intact) hemisphere, i.e., the ipsilateral M1, or cortico-reticulospinal tract (CReST; comprising the cortico-reticular tract [CRT] and reticulospinal tract [RST]) may act as a functional bypass to spinal motor neurons. Recognizing that direction- and force-dependent control mechanisms may be at play, offers a path to more refined and personalized rehabilitation strategies, depending on the specific motor function injured in the patient. To address these open questions, we applied online repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt cortical activity at the stimulated site (TMS-interference), during a continuous isometric index-finger force-tracking task. Eleven healthy adults performed a dynamic controlled increase and decrease of isometric force with the index finger, at low (0-20% of maximal voluntary contraction, MVC) and high (0-60% MVC) levels, interrupted by short episodes (2 seconds) of TMS interference (10Hz rTMS) over the contralateral and the ipsilateral primary motor cortices (clM1, ilM1; location defined by maximal amplitude of evoked potentials recruited from the first dorsal interosseus muscle upon single-pulse TMS) and a midline control site (Pz). Performance was quantified by accuracy (root mean square error, RMSE), smoothness (total variation, TV), and consistency (standard deviation of absolute error, SDAE) metrics of the generated force. We found that rTMS over clM1 produced greater interference than rTMS over ilM1 (RMSE p<0.009; TV p<0.001; SDAE p<0.003). Performance metrics did not differ under conditions of TMS interference applied over ilM1, Pz and no stimulation. Interestingly, interactions in the TV measure revealed stronger interference during the force decrement phase of the task (controlled release) compared to the force increment phase (condition×direction p=0.00018) and at low compared with high force (condition×force p=0.0023). These findings provide direct causal evidence that ongoing activity in clM1 is essential for maintenance of dynamic force regulation during the grasping act, particularly for delicate grasping employing low-forces, and during controlled release of objects. Relative resilience to TMS interference at higher forces may point to a greater contribution from other descending motor tracts when a strong grip is needed.

M.Sc. student under the supervision of Prof. Firas Mawase.