Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: Possible pathways for antinociception

Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, delta-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Putting an "end" to the motor cortex representations of action words

Language processing is an example of implicit learning of multiple statistical cues that provide probabilistic information regarding word structure and use. Much of the current debate about language embodiment is devoted to how action words are represented in the brain, with motor cortex activity evoked by these words assumed to selectively reflect conceptual content and/or its simulation. We investigated whether motor cortex activity evoked by manual action words (e.g., caress) might reflect sensitivity to probabilistic orthographic-phonological cues to grammatical category embedded within individual words. We first review neuroimaging data demonstrating that nonwords evoke activity much more reliably than action words along the entire motor strip, encompassing regions proposed to be action category specific. Using fMRI, we found that disyllabic words denoting manual actions evoked increased motor cortex activity compared with non-body-part-related words (e.g., canyon), activity which overlaps that evoked by observing and executing hand movements. This result is typically interpreted in support of language embodiment. Crucially, we also found that disyllabic nonwords containing endings with probabilistic cues predictive of verb status (e.g., -eve) evoked increased activity compared with nonwords with endings predictive of noun status (e.g., -age) in the identical motor area. Thus, motor cortex responses to action words cannot be assumed to selectively reflect conceptual content and/or its simulation. Our results clearly demonstrate motor cortex activity reflects implicit processing of ortho-phonological statistical regularities that help to distinguish a word's grammatical class.

Rhythm generation in monkey motor cortex explored using pyramidal tract stimulation.

We investigated whether stimulation of the pyramidal tract (PT) could reset the phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We recorded local field potentials (LFPs) and multiple single-unit activity from two conscious macaque monkeys performing a precision grip task. EMG activity was also recorded from the second animal. Single PT stimuli were delivered during the hold period of the task, when oscillations in the LFP were most prominent. Stimulus-triggered averaging of the LFP showed a phase-locked oscillatory response to PT stimulation. Frequency domain analysis revealed two components within the response: a 15-30 Hz component, which represented resetting of on-going beta rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be observed in the EMG activity, at stronger stimulus intensities than were required for resetting the cortical rhythm. Stimulation of the PT during movement elicited a greatly reduced oscillatory response. Analysis of single-unit discharge confirmed that PT stimulation was capable of resetting periodic activity in motor cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified neurones exhibited successive cycles of suppression and facilitation, time locked to the stimulus. We conclude that PTN activity directly influences the generation of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles, contributing to corticomuscular coherence at this same frequency. Since the earliest oscillatory effect observed following stimulation was a suppression of firing, we speculate that inhibitory feedback may be the key mechanism generating such oscillations in the motor cortex.

The role of the primary motor cortex during skill acquisition on a two-degrees-of-freedom movement task

One can partially eliminate motor skills acquired through practice in the hours immediately following practice by applying repetitive transcranial stimulation (rTMS) over the primary motor cortex. The disruption of acquired levels of performance has been demonstrated on tasks that are ballistic in nature. The authors investigated whether motor recall on a discrete aiming task is degraded following a disruption of the primary motor cortex induced via rTMS. Participants (N = 16) maintained acquired performance levels and patterns of muscle activity following the application of rTMS. despite a reduction in corticospinal excitability. Disruption of the primary motor cortex during a consolidation period did not influence the retention of acquired skill in this type of discrete visuomotor task.