Responses of single corticospinal neurons to intracortical stimulation of primary 1 motor and premotor cortex in the anesthetized macaque monkey . 2 3

30 The responses of individual primate corticospinal neurons to localized electrical stimulation 31 of primary motor (M1) and of ventral premotor cortex (area F5) are poorly documented. To 32 rectify this and to study interactions between responses from these areas, we recorded 33 corticospinal axons, identified by pyramidal tract stimulation, in the cervical spinal cord of 34 three chloralose-anesthetized macaque monkeys. Single stimuli (≤ 400 μA) were delivered 35 to the hand area of M1 or F5 through intracortical microwire arrays. Only 14/112 (13%) 36 axons showed responses to M1 stimuli indicating direct intracortical activation of 37 corticospinal neurons (D-responses); no D-responses were seen from F5. In contrast, sixty38 two axons (55%) exhibited consistent later responses to M1 stimulation corresponding to 39 indirect activation (I-responses), showing that single-pulse intracortical stimulation of motor 40 areas can result in trans-synaptic activation of a high proportion of the corticospinal output. A 41 combined latency histogram of all axon responses was non-periodic, clearly different from 42 the periodic surface-recorded corticospinal volleys. This was readily explained by correcting 43 for conduction velocities of individual axons. D-responding axons, taken as originating in 44 neurons close to the M1 stimulating electrodes, showed more I-responses from M1 than 45 those without a D-response, and 8/10 of these axons also responded to F5 stimulation. 46 Altogether, 33% of tested axons responded to F5 stimulation, most of which also showed I47 responses from M1. These excitatory effects are in keeping with facilitation of hand muscles 48 evoked from F5 being relayed via M1, and this was further demonstrated by facilitation of 49 test responses from M1 by conditioning F5 stimuli. 50 51 52