Anatomical characterization of premotor-motor connectivity in humans by paired intraoperative direct cortical stimulation

The human motor cortex represents the major source of corticospinal output and receives input from a constellation of sensorimotor regions in the surrounding cerebral cortex and subcortical regions. Here we tested cortico-cortical connections by means of direct cortical stimulation in intraoperative settings. We used short trains of 3 pulses (0.2 ms duration, 2ms ISI) as test stimuli to the motor cortex and as conditioning stimuli to the premotor cortex in 14 human patients undergoing brain surgery for tumour resection under general anaesthesia with intraoperative neurophysiological monitoring. We observed that short-latency inhibitory conditioning effects clustered in two distinct regions within the precentral sulcus: a dorsal premotor cluster was centred around the mean coordinates (MNI) of x=±23.5; y=-9.4; z=73.9 and a ventral premotor cluster around the x=±55.5; y=9.1; z=40.8 coordinates. A third cluster, with excitatory effects was found along the convexity of the superior frontal gyrus (SFG), around the mean coordinates of x=±19.7; y=12.8; z=70. The earliest effective ISIs were: 4 ms for the dorsal and ventral precentral clusters, compatibly with direct cortico-cortical connections. The SFG cluster exerted conditioning effect on M1 at shortest ISI of 8 ms, compatible with either direct or indirect connections to M1. We show that intraoperative neurophysiology can assess premotor-motor connections with a Conditioning-Test stimulus technique. The two inhibitory precentral foci are compatible with human equivalents of dorsal and ventral premotor cortices in non-human primates. The SFG cluster may be related to flexible control of upper limb movements.