Summarizing, we have presented evidence in humans for two "negative motor areas" which we had speculated play a significant role in the planning of voluntary motor movements. A review of the more recent experimental literature shows that histological, physiological, and electrical stimulation studies in animals reveal the existence of two frontal regions that from the experimental data also seem to play an essential role in the preparation (as opposed to execution) of voluntary movements. Current available evidence suggests that these two areas (areas F5 and F6 of Rizzolatti et al.) correspond to the negative motor areas we have described in human studies. Also of interest is that Broca's area in the dominant hemisphere overlaps the corresponding negative motor area. This observation suggests that Broca's area has evolved from area F5 of monkeys specializing in the planning of fine movements necessary for speech production. We feel that current evidence suggests the existence of three mechanisms by which cortical stimulation (by electrical stimulation or by epileptic activation) can generate negative motor phenomena: 1. The "silent period," which is consistently contralateral, has a somatotopic distribution, and tends to affect predominantly muscles involved in fine movements. It is of relatively short duration and seems to be generated by the activation of cortical areas in the primary sensorimotor region. The H-reflex is not inhibited during the silent period, suggesting that the silent period is generated by a decrease in the excitatory input through direct corticospinal neurons on the spinal alpha motoneurons. It is possible that in normal individuals this system is used for fine tuning of fine distal movements. The negative myoclonus seen in some patients with focal cortical epilepsy is probably generated by this mechanism. The primary and supplementary "negative motor areas" described in this chapter. This effect also has a somatotopic distribution but can affect muscle bilaterally even if there is a clear predominance contralaterally. The negative motor effect does not influence postural tone and can be prolonged. The negative motor effect is probably produced by activation of agranular cortex immediately in front of the primary and supplementary face motor area. These cortical areas are probably used for organization and integration of fine motor movement. Activation of these areas would produce an apraxia of fine movements. Focal atonic seizures are probably generated by this mechanism. 3. The fast-conducting corticoreticulospinal pathways, which by activation of the brainstem inhibitory centers (NRPo, n.r. magnocellularis dorsal beta, and NRGc), tend to produce bilateral atonia of axial, postural muscles. This system probably does not depend on the presence of the direct corticospinal pathways. By analogy with cataplexy, which is probably produced by activation of similar brainstem inhibitory systems, we would expect the H-reflex to be markedly diminished or even to disappear during the atomic phase (64). This pathway would be used normally for postural adjustments and locomotion. The bilateral massive atonic seizures, seen most frequently in patients with severe and diffuse cortical lesions, are probably produced by this mechanism. However, the bilateral atonic seizures occasionally seen in patients with focal cortical lesions may also be produced by a similar mechanism.