Inhibitory and facilitatory connectivity from ventral premotor to primary motor cortex in healthy humans at rest - A bifocal TMS study

Objective:In macaques, intracortical electrical stimulation of ventral premotor cortex (PMv) can modu-late ipsilateral primary motor cortex (M1) excitability at short interstimulus intervals (ISIs).Methods:Adopting the same conditioning-test approach, we used bifocal transcranial magnetic stimula-tion (TMS) to examine intrahemispheric connectivity between left PMv and M1 in humans. A condition-ing stimulus (CS) was applied to PMv at intensities of 80% and 90% of active motor threshold (AMT) and90% and 110% of resting motor threshold (RMT). A supra-threshold test stimulus (TS) was given 2, 4, 6, 8and 10 ms after the CS and the amplitude of the motor evoked potential (MEP) was measured to probecorticospinal excitability.Results:The CS facilitated corticospinal excitability in ipsilateral M1 when PMv was stimulated with 80%AMT 4 or 6 ms before the TS. At the same ISIs, the CS suppressed corticospinal excitability when the stim-ulus intensity was increased to 90% RMT. Conditioning effects were site-specific because conditioning thedorsal premotor cortex (PMd) at three different sites produced different effects. Using neuronavigatedTMS the PMv site where applied CS produced changes in ipsilateral M1 excitability was located at theborder between ventral Brodmann area (BA) 6 and BA 44, the human homologue of monkey’s PMv (areaF5).Conclusion:We infer that the corticospinal motor output from M1 to contralateral hand muscles can befacilitated or inhibited by a CS over ipsilateral PMv.Significance:The fact that conditioning effects following PMd stimulation differ from those after PMvstimulation supports the concept that inputs from premotor cortices to M1 are functionally segregated