Damage to the corticospinal tract is a leading cause of motor disability, for example in stroke or spinal cord injury. Some function usually recovers, but whether plasticity of undamaged ipsilaterally descending corticospinal axons and/or brainstem pathways such as the reticulospinal tract contributes to recovery is unknown. Here, we examined the connectivity in these pathways to motor neurons after recovery from corticospinal lesions. Extensive unilateral lesions of the medullary corticospinal fibres in the pyramidal tract were made in three adult macaque monkeys. After an initial contralateral flaccid paralysis, motor function rapidly recovered, after which all animals were capable of climbing and supporting their weight by gripping the cage bars with the contralesional hand. In one animal where experimental testing was carried out, there was (as expected) no recovery of fine independent finger movements. Around 6 months post-lesion, intracellular recordings were made from 167 motor neurons innervating hand and forearm muscles. Synaptic responses evoked by stimulating the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus were recorded and compared with control responses in 207 motor neurons from six unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak in both lesioned and control animals, suggesting a limited role for this pathway in functional recovery. In contrast, mono- and disynaptic excitatory post-synaptic potentials elicited from the medial longitudinal fasciculus significantly increased in average size after recovery, but only in motor neurons innervating forearm flexor and intrinsic hand muscles, not in forearm extensor motor neurons. We conclude that reticulospinal systems sub-serve some of the functional recovery after corticospinal lesions. The imbalanced strengthening of connections to flexor, but not extensor, motor neurons mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors.

We studied the synchronization of single units in macaque deep cerebellar nuclei (DCN) with local field potentials (LFPs) in primary motor cortex (M1) bilaterally during performance of a precision grip task. Analysis was restricted to periods of steady holding, during which M1 oscillations are known to be strongest. Significant coherence between DCN units and M1 LFP oscillations bilaterally was seen at approximately 10-40 Hz (contralateral M1: 25/87 units; ipsilateral: 9/87 units). Averaged coherence between DCN units and contralateral M1 LFP showed a prominent approximately 17-Hz coherence peak and an average phase of approximately -pi/2 radians, implying that the DCN units fired around the time of maximal depolarization of M1 cells. The lack of a time delay between DCN and M1 activity suggests that the cerebellum and cortex may form a pair of phase coupled oscillators. Although coherence values were low (mean peak coherence, 0.018), we used a computational model to show that this probably resulted from the nonlinearity of spike generating mechanisms within the DCN. DCN unit discharge and DCN LFPs also showed significant coherence at approximately 10-40 Hz, with similarly low magnitude (mean peak coherence, 0.012). The average coherence phase was -2.5 radians for the 6- to 14-Hz range and -1.1 radians for the 17- to 41-Hz range, suggesting different frequency-specific underlying mechanisms. Finally, 4/40 pairs of simultaneously recorded DCN units showed a significant cross-correlation peak, and 16/40 pairs showed significant unit-unit coherence. The extensive oscillatory synchronization observed between cerebellum and motor cortex may have functional importance in sensorimotor processing.

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Strong experimental evidence implicates the corticospinal tract in voluntary control of the contralateral forelimb. Its potential role in controlling the ipsilateral forelimb is less well understood, although anatomical projections to ipsilateral spinal circuits are identified. We investigated inputs to motoneurons innervating hand and forearm muscles from the ipsilateral corticospinal tract using multiple methods. Intracellular recordings from 62 motoneurons in three anesthetized monkeys revealed no monosynaptic and only one weak oligosynaptic EPSP after stimulation of the ipsilateral corticospinal tract. Single stimulus intracortical microstimulation of the primary motor cortex (M1) in awake animals failed to produce any responses in ipsilateral muscles. Strong stimulation (Ͼ500 A, single stimulus) of the majority of corticospinal axons at the medullary pyramids revealed only weak suppressions in ipsilateral muscles at longer latencies than the robust facilitations seen contralaterally. Spike-triggered averaging of ipsilateral muscle activity from M1 neural discharge (184 cells) did not reveal any postspike effects consistent with monosynaptic corticomotoneuronal connections. We also examined the activity of 191 M1 neurons during ipsilateral or contralateral "reach to precision grip" movements. Many cells (67%) modulated their activity during ipsilateral limb movement trials (compared with 90% with contralateral trials), but the timing of this activity was best correlated with weak muscle activity in the contralateral nonmoving arm. We conclude that, in normal adults, any inputs to forelimb motoneurons from the ipsilateral corticospinal tract are weak and indirect and that modulation of M1 cell firing seems to be related primarily to control of the contralateral limb.

Recent work has shown that the primate reticulospinal tract can influence spinal interneurons and motoneurons involved in control of the hand. However, demonstrating connectivity does not reveal whether reticular outputs are modulated during the control of different types of hand movement. Here, we investigated how single unit discharge in the pontomedullary reticular formation (PMRF) modulated during performance of a slow finger movement task in macaque monkeys. Two animals performed an index finger flexion–extension task to track a target presented on a computer screen; single units were recorded both from ipsilateral PMRF (115 cells) and contralateral primary motor cortex (M1, 210 cells). Cells in both areas modulated their activity with the task (M1: 87%, PMRF: 86%). Some cells (18/115 in PMRF; 96/210 in M1) received sensory input from the hand, showing a short-latency modulation in their discharge following a rapid passive extension movement of the index finger. Effects in ipsilateral electromyogram to trains of stimuli were recorded at 45 sites in the PMRF. These responses involved muscles controlling the digits in 13/45 sites (including intrinsic hand muscles, 5/45 sites). We conclude that PMRF may contribute to the control of fine finger movements, in addition to its established role in control of more proximal limb and trunk movements. This finding may be especially important in understanding functional recovery after brain lesions such as stroke.

Tremor imposes an important limit to the accuracy of fine movements in healthy individuals and can be a disabling feature of neurological disease. Voluntary slow finger movements are not smooth but are characterized by large discontinuities (i.e., steps) in the tremor frequency range (approximately 10 Hz). Previous studies have shown that these discontinuities are coherent with activity in the primary motor cortex (M1), but that other brain areas are probably also involved. We investigated the contribution of three important subcortical areas in two macaque monkeys trained to perform slow finger movements. Local field potential and singleunit activity were recorded from the deep cerebellar nuclei (DCN), medial pontomedullary reticular formation, and the intermediate zone of the spinal cord (SC). Coherence between LFP and acceleration was significant at 6 to 13 Hz for all areas, confirming the highly distributed nature of the central network responsible for this activity. The coherence phase at 6 to 13 Hz for DCN and pontomedullary reticular formation was similar to our previous results in M1. By contrast, for SC the phase differed from M1 by approximately π rad. Examination of single-unit discharge confirmed that this was a genuine difference in neural spiking and could not be explained by different properties of the local field potential. Convergence of antiphase oscillations from the SC with cortical and subcortical descending inputs will lead to cancellation of approximately 10 Hz oscillations at the motoneuronal level. This could appreciably limit drive to muscle at this frequency, thereby reducing tremor and improving movement precision.T remor is a key limitation to human fine motor performance.However, in tremor research, the puzzle is not so much why our hands shake, but why they often do not. Numerous mechanisms can contribute to unstable contraction: motoneurons are recruited at a fixed frequency, limb segments have mechanical resonance, the monosynaptic stretch reflex arc can produce feedback oscillations, and there are a plethora of central neural oscillators. These factors often converge to produce mechanical oscillations at approximately 10 Hz, the dominant frequency of physiological tremor. Yet despite these multiple sources of instability, in most people, most of the time, tremor is small enough not to impact daily life. We have hypothesized that a specific neural system might have evolved to reduce tremor (1), with clear survival advantages.Slow finger movements in man are characterized by steps or discontinuities that occur at approximately 10 Hz (2). These discontinuities provide a good model for studying tremor, as even though they occur within the same frequency range, they are an order of magnitude bigger (2), facilitating quantitative analysis. Work on both physiological tremor and slow finger movement discontinuities has shown that there is an approximately 10

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Williams ER, Soteropoulos DS, Baker SN. Coherence between motor cortical activity and peripheral discontinuities during slow finger movements. J Neurophysiol 102: 1296J Neurophysiol 102: -1309J Neurophysiol 102: , 2009 doi:10.1152/jn.90996.2008. Slow finger movements in man are not smooth, but are characterized by 8-to 12-Hz discontinuities in finger acceleration thought to have a central source. We trained two macaque monkeys to track a moving target by performing index finger flexion/extension movements and recorded local field potentials (LFPs) and spike activity from the primary motor cortex (M1); some cells were identified as pyramidal tract neurons by antidromic activation or as corticomotoneuronal cells by spike-triggered averaging. There was significant coherence between finger acceleration in the approximately 10-Hz range and both LFPs and spikes. LFP-acceleration coherence was similar for flexion and extension movements (0.094 at 9.8 Hz and 0.11 at 6.8 Hz, respectively), but substantially smaller during steady holding (0.0067 at 9.35 Hz). The coherence phase showed a significant linear relationship with frequency over the 6-to 13-Hz range, as expected for a constant conduction delay, but the slope indicated that LFP lagged acceleration by 18 Ϯ 14 or 36 Ϯ 8 ms for flexion and extension movements, respectively. Directed coherence analysis supported the conclusion that the dominant interaction was in the acceleration to LFP (i.e., sensory) direction. The phase relationships between finger acceleration and both LFPs and spikes shifted by about radians in flexion compared with extension trials. However, for a given trial type the phase relationship with acceleration was similar for cells that increased their firing during flexion or during extension trials. We conclude that movement discontinuities during slow finger movements arise from a reciprocally coupled network, which includes M1 and the periphery.