Claire L. Witham

Contributions of descending and ascending pathways to corticomuscular coherence in humans

Non‐technical summary Neural activity in parts of the cerebral cortex related to movement oscillates at frequencies around 20 Hz. These oscillations are correlated with similar rhythms in contracting muscles on the opposite side of the body. In this work, we used an analysis method called directed coherence to investigate the direction of oscillatory coupling. We find that oscillations travel not only from cortex to muscle (as expected for a motor command), but also back from muscle to cortex (reflecting sensory input). This oscillatory loop may allow the cortex to measure features of the limb state, integrating sensory inflow with the motor command.

Corticomuscular Coherence Between Motor Cortex, Somatosensory Areas and Forearm Muscles in the Monkey

Corticomuscular coherence has previously been reported between primary motor cortex (M1) and contralateral muscles. We examined whether such coherence could also be seen from somatosensory areas. Local field potentials (LFPs) were recorded from primary somatosensory cortex (S1; areas 3a and 2) and posterior parietal cortex (PPC; area 5) simultaneously with M1 LFP and forearm EMG activity in two monkeys during an index finger flexion task. Significant beta-band (∼20 Hz) corticomuscular coherence was found in all areas investigated. Directed coherence (Granger causality) analysis was used to investigate the direction of effects. Surprisingly, the strongest beta-band directed coherence was in the direction from S1/PPC to muscle; it was much weaker in the ascending direction. Examination of the phase of directed coherence provided estimates of the time delay from cortex to muscle. Delays were longer from M1 (∼62 ms for the first dorsal interosseous muscle) than from S1/PPC (∼36 ms). We then looked at coherence and directed coherence between M1 and S1 for clues to this discrepancy. Directed coherence showed large beta-band effects from S1/PPC to M1, with smaller directed coherence in the reverse direction. The directed coherence phase suggested a delay of ∼40 ms from M1 to S1. Corticomuscular coherence from S1/PPC could involve multiple pathways; the most important is probably common input from M1 to S1/PPC and muscles. If correct, this implies that somatosensory cortex receives oscillatory efference copy information from M1 about the motor command. This could allow sensory inflow to be interpreted in the light of its motor context.

Corticospinal Inputs to Primate Motoneurons Innervating the Forelimb from Two Divisions of Primary Motor Cortex and Area 3a

Previous anatomical work in primates has suggested that only corticospinal axons originating in caudal primary motor cortex (“new M1”) and area 3a make monosynaptic cortico-motoneuronal connections with limb motoneurons. By contrast, the more rostral “old M1” is proposed to control motoneurons disynaptically via spinal interneurons. In six macaque monkeys, we examined the effects from focal stimulation within old and new M1 and area 3a on 135 antidromically identified motoneurons projecting to the upper limb. EPSPs with segmental latency shorter than 1.2 ms were classified as definitively monosynaptic; these were seen only after stimulation within new M1 or at the new M1/3a border (incidence 6.6% and 1.3%, respectively; total n = 27). However, most responses had longer latencies. Using measures of the response facilitation after a second stimulus compared with the first, and the reduction in response latency after a third stimulus compared with the first, we classified these late responses as likely mediated by either long-latency monosynaptic (n = 108) or non-monosynaptic linkages (n = 108). Both old and new M1 generated putative long-latency monosynaptic and non-monosynaptic effects; the majority of responses from area 3a were non-monosynaptic. Both types of responses from new M1 had significantly greater amplitude than those from old M1. We suggest that slowly conducting corticospinal fibers from old M1 generate weak late monosynaptic effects in motoneurons. These may represent a stage in control of primate motoneurons by the cortex intermediate between disynaptic output via an interposed interneuron seen in nonprimates and the fast direct monosynaptic connections present in new M1. SIGNIFICANCE STATEMENT The corticospinal tract in Old World primates makes monosynaptic connections to motoneurons; previous anatomical work suggests that these connections come only from corticospinal tract (CST) neurons in the subdivision of primary motor cortex within the central sulcus (“new M1”) and area 3a. Here, we show using electrophysiology that cortico-motoneuronal connections from fast conducting CST fibers are indeed made exclusively from new M1 and its border with 3a. However, we also show that all parts of M1 and 3a have cortico-motoneuronal connections over more slowly conducting CST axons, as well as exert disynaptic effects on motoneurons via interposed interneurons. Differences between old and new M1 are thus more subtle than previously thought.

Modulation and transmission of peripheral inputs in monkey cuneate and external cuneate nuclei

Somatosensory signals undergo substantial modulation in the dorsal column nuclei. We examined transmission of signals from forelimb afferents in primate cuneate and external cuneate nuclei. In anesthetized macaque monkeys, the median, ulnar, deep radial, and superficial radial nerves were electrically stimulated at 1.5–2× motor threshold with independent Poisson trains whereas extracellular recordings were made from 317 cells. Responses to peripheral stimulation included instances of both brief facilitation and long lasting suppression. A high proportion of cells (87%) responded to stimulation of two or more peripheral nerves, suggesting a large amount of convergence. Facilitated cells showed coherence with the peripheral stimulation across a broad frequency range; coherence was especially high in cells that responded with a burst of action potentials. Cells that responded with suppression also showed significant coherence, but this fell rapidly for frequencies above 25 Hz. Similar results were seen in both the main and external cuneate. When stimulation of one nerve was conditioned by a preceding nerve stimulus, the response to the second stimulus was attenuated for around 40 ms. This occurred independently of whether the first stimulus produced an initial facilitation or suppression or whether the same or a different nerve served as a conditioning stimulus. Mechanical stimulation of a receptive field suppressed responses to a second identical mechanical stimulus over a similar timescale. We conclude that the primate cuneate nucleus is capable of transmitting temporal information about stimuli with high fidelity; stimuli interact both temporally and spatially to modulate the onward transmission of information.

Coding of digit displacement by cell spiking and network oscillations in the monkey sensorimotor cortex

β-Band oscillations occur in motor and somatosensory cortices and muscle activity. Oscillations appear most strongly after movements, suggesting that they may represent or probe the limbs final sensory state. We tested this idea by training two macaque monkeys to perform a finger flexion to one of four displacements, which was then held for 2 s without visual feedback of absolute displacement. Local field potential (LFP) and single unit spiking were recorded from the rostral and caudal primary motor cortex and parietal areas 3a, 3b, 2, and 5. Information theoretic analysis determined how well unit firing rate or the power of LFP oscillations coded finger displacement. All areas encoded significant information about finger displacement after the movement into target, both in β-band (∼20 Hz) oscillatory activity and unit firing rate. On average, the information carried by unit firing was greater (0.07 bits) and peaked earlier (0.73 s after peak velocity) than that by LFP β-oscillations (0.05 bits and 0.95 s). However, there was considerable heterogeneity among units: some cells did not encode maximal information until midway through the holding phase. In 30% of cells, information in rate lagged information in LFP oscillations recorded at the same site. Finger displacement may be represented in the cortex in multiple ways. Coding the digit configuration immediately after a movement probably relies on nonoscillatory feedback, or efference copy. With increasing delay after movement cessation, oscillatory processing may also play a part.

Automated face recognition of rhesus macaques

Graphical abstract

Information theoretic analysis of proprioceptive encoding during finger flexion in the monkey sensorimotor system

There is considerable debate over whether the brain codes information using neural firing rate or the fine-grained structure of spike timing. We investigated this issue in spike discharge recorded from single units in the sensorimotor cortex, deep cerebellar nuclei, and dorsal root ganglia in macaque monkeys trained to perform a finger flexion task. The task required flexion to four different displacements against two opposing torques; the eight possible conditions were randomly interleaved. We used information theory to assess coding of task condition in spike rate, discharge irregularity, and spectral power in the 15- to 25-Hz band during the period of steady holding. All three measures coded task information in all areas tested. Information coding was most often independent between irregularity and 15–25 Hz power (60% of units), moderately redundant between spike rate and irregularity (56% of units redundant), and highly redundant between spike rate and power (93%). Most simultaneously recorded unit pairs coded using the same measure independently (86%). Knowledge of two measures often provided extra information about task, compared with knowledge of only one alone. We conclude that sensorimotor systems use both rate and temporal codes to represent information about a finger movement task. As well as offering insights into neural coding, this work suggests that incorporating spike irregularity into algorithms used for brain-machine interfaces could improve decoding accuracy.

A protocol for training group-housed rhesus macaques (Macaca mulatta) to cooperate with husbandry and research procedures using positive reinforcement

Highlights • We present a protocol for station-training adult rhesus macaques in social groups of 2–9 adults.• 61/65 monkeys successfully trained to sit by individual targets.• All males trained in 2 × 15 min training sessions.• High rank females trained in 6 × 15 min sessions; low rank females: 11 × 15 min.• Dominance rank was the only predictor of time taken to train.

Reply from C. L. Witham and S. N. Baker.

We thank Drs Schouten and Campfens for their interest in our paper. We are more optimistic about the practical capabilities of directed coherence than the position they adopt in their letter, but we would also emphasise the need for caution in using these methods.