RT Journal Article SR Electronic T1 Regional and age-dependent Effects of Cortical Magnetic Stimulation on Unconstrained Reaching Behavior JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.14.422725 DO 10.1101/2020.12.14.422725 A1 M.A. Urbin A1 Jing Tian A1 Gina P. McKernan A1 Nick Kortzorg A1 Lore Wyers A1 Florian van Halewijck A1 Matthieu P. Boisgontier A1 Oron Levin A1 Stephan P. Swinnen A1 Ilse Jonkers A1 George F. Wittenberg YR 2020 UL http://biorxiv.org/content/early/2020/12/15/2020.12.14.422725.abstract AB Background The specific and dynamic contributions of premotor and supplementary motor areas to reaching movements in aging humans are not well understood.Objective To better understand the role of cortical motor regions and age on the control of unconstrained reaches against gravity by neurologically intact, younger and older adults.Methods Double pulse transcranial magnetic stimulation (TMS) was applied at locations targeting primary motor cortex (M1), dorsal premotor area (PMA), supplementary motor area (SMA), or dorsolateral prefrontal cortex (DLPFC). Paired stimuli were delivered before or after a visual cue was presented to initiate self-paced right-handed reaches to one of three, vertically oriented target locations.Results Regional stimulation effects on movement amplitude were observed both early and late in the reach. PMA stimulation increased reach distance to a greater extent than M1, SMA, and DLPFC stimulation. M1 and PMA stimulation increased deviation from the straight-line path around the time of peak velocity to an extent that was greater than SMA and DLPFC stimulation. Cortical stimulation increased the time that elapsed after, but not before, peak velocity. Despite stronger effects of stimulation on reaches in the younger group, this group had shorter times to reach the target after reaching peak velocity.Conclusion These results provide support for a role of PMA in visually guided movement after movement initiation. For older subjects, the increased time to arrive at the target after peak velocity despite weaker stimulation effects suggests an age-related reduction in sensorimotor processing flexibility for online control of unconstrained reaching.HighlightsDorsal premotor area stimulation at any time during the reaction-time period and early reaching affected early reach kinematics at least as much as stimulation of primary motor cortex.Older individuals had more stimulation-related interference in the late components of reaching despite having less early effect of stimulation, suggesting a reduction in flexibility of dynamic motor control due to aging.The antigravity component of unconstrained reaching did not have special aspects for regional cortical effects of stimulation.Competing Interest StatementThe authors have declared no competing interest.