Recovery of neurophysiological measures in post-COVID fatigue: a 12-month longitudinal follow-up study.

One of the major consequences of the COVID-19 pandemic has been the significant incidence of persistent fatigue following resolution of an acute infection (i.e. post-COVID fatigue).

Neural dysregulation in post-COVID fatigue.

Following infection with SARS-CoV-2, a substantial minority of people develop lingering after-effects known as 'long COVID'. Fatigue is a common complaint with a substantial impact on daily life, but the neural mechanisms behind post-COVID fatigue remain unclear. We recruited 37 volunteers with self-reported fatigue after a mild COVID infection and carried out a battery of behavioural and neurophysiological tests assessing the central, peripheral and autonomic nervous systems.

Long-latency Responses to a Mechanical Perturbation of the Index Finger Have a Spinal Component.

In an uncertain external environment, the motor system may need to respond rapidly to an unexpected stimulus. Limb displacement causes muscle stretch; the corrective response has multiple activity bursts, which are suggested to originate from different parts of the neuraxis. The earliest response is so fast, it can only be produced by spinal circuits; this is followed by slower components thought to arise from primary motor cortex (M1) and other supraspinal areas.

Postural control of arm and fingers through integration of movement commands.

Every movement ends in a period of stillness. Current models assume that commands that hold the limb at a target location do not depend on the commands that moved the limb to that location. Here, we report a surprising relationship between movement and posture in primates: on a within-trial basis, the commands that hold the arm and finger at a target location depend on the mathematical integration of the commands that moved the limb to that location.

Rapid crossed responses in an intrinsic hand muscle during perturbed bimanual movements.

Mechanical perturbations in one upper limb often elicit corrective responses in both the perturbed as well as its contralateral and unperturbed counterpart. These crossed corrective responses have been shown to be sensitive to the bimanual requirements of the perturbation, but crossed responses (CRs) in hand muscles are far less well studied. Here, we investigate corrective CRs in an intrinsic hand muscle, the first dorsal interosseous (1DI), to clockwise and anticlockwise mechanical perturbations to the contralateral index finger while participants performed a bimanual finger abduction task.

The mammalian spinal commissural system: properties and functions.

Commissural systems are essential components of motor circuits that coordinate left-right activity of the skeletomuscular system. Commissural systems are found at many levels of the neuraxis including the cortex, brainstem, and spinal cord. In this review we will discuss aspects of the mammalian spinal commissural system.

The Corticospinal Discrepancy: Where are all the Slow Pyramidal Tract Neurons?

This feature article focuses on the discrepancy between the distribution of axon diameters within the primate corticospinal tract, determined neuroanatomically, and the distribution of axonal conduction velocities within the same tract, determined electrophysiologically. We point out the importance of resolving this discrepancy for a complete understanding of corticospinal functions, and discuss the various explanations for the mismatch between anatomy and physiology.

Classification of Neurons in the Primate Reticular Formation and Changes after Recovery from Pyramidal Tract Lesion.

The reticular formation is important in primate motor control, both in health and during recovery after brain damage. Little is known about the different neurons present in the reticular nuclei. Here we recorded extracellular spikes from the reticular formation in five healthy female awake behaving monkeys (193 cells), and in two female monkeys 1 year after recovery from a unilateral pyramidal tract lesion (125 cells).

Corticospinal gating during action preparation and movement in the primate motor cortex.

During everyday actions there is a need to be able to withhold movements until the most appropriate time. This motor inhibition is likely to rely on multiple cortical and subcortical areas, but the primary motor cortex (M1) is a critical component of this process. However, the mechanisms behind this inhibition are unclear, particularly the role of the corticospinal system, which is most often associated with driving muscles and movement.

Interhemispheric connectivity during bimanual isometric force generation.

Interhemispheric interactions through the corpus callosum play an important role in the control of bimanual forces. However, the extent to which physiological connections between primary motor cortices are modulated during increasing levels of bimanual force generation in intact humans remains poorly understood. Here we studied coherence between electroencephalographic (EEG) signals and the ipsilateral cortical silent period (iSP), two well-known measures of interhemispheric connectivity between motor cortices, during unilateral and bilateral 10%, 40%, and 70% of maximal isometric voluntary contraction (MVC) into index finger abduction.

Pathways mediating functional recovery.

Following damage to the motor system (e.g., after stroke or spinal cord injury), recovery of upper limb function exploits the multiple pathways which allow motor commands to be sent to the spinal cord.

Spinal commissural connections to motoneurons controlling the primate hand and wrist.

Left-right coordination is essential for locomotor movements and is partly mediated by spinal commissural systems. Such coordination is also essential for reaching and manipulation in primates, but the role of spinal commissural systems here has not been studied. We investigated commissural connectivity to motoneurons innervating forelimb muscles using intracellular recordings in acutely anesthetized macaque monkeys.

Cells in the monkey ponto-medullary reticular formation modulate their activity with slow finger movements.

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.

Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey.

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.

Corticomuscular coherence during bilateral isometric arm voluntary activity in healthy humans.

Bilateral voluntary contractions involve functional changes in both primary motor cortices. We investigated whether a voluntary contraction controlled by one hemisphere can influence oscillatory processes contralaterally. Corticomuscular coherence was calculated between EEG recorded over the motor cortex hand representation and electromyogram from the first dorsal interosseous muscle when the nondominant hand performed a precision grip task.

Lack of evidence for direct corticospinal contributions to control of the ipsilateral forelimb in monkey.

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.

Physiological changes underlying bilateral isometric arm voluntary contractions in healthy humans.

Many bilateral motor tasks engage simultaneous activation of distal and proximal arm muscles, but little is known about their physiological interactions. Here, we used transcranial magnetic stimulation to examine motor-evoked potentials (MEPs), interhemispheric inhibition at a conditioning-test interval of 10 (IHI(10)) and 40 ms (IHI(40)), and short-interval intracortical inhibition (SICI) in the left first dorsal interosseous (FDI) muscle during isometric index finger abduction. The right side remained at rest or performed isometric voluntary contraction with the FDI, biceps or triceps brachii, or the tibialis anterior.

Spinal interneuron circuits reduce approximately 10-Hz movement discontinuities by phase cancellation.

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.

Coherence between motor cortical activity and peripheral discontinuities during slow finger movements.

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.

Quantifying neural coding of event timing.

Single-neuron firing is often analyzed relative to an external event, such as successful task performance or the delivery of a stimulus. The perievent time histogram (PETH) examines how, on average, neural firing modulates before and after the alignment event. However, the PETH contains no information about the single-trial reliability of the neural response, which is important from the perspective of a target neuron.

Bilateral representation in the deep cerebellar nuclei.

The cerebellum is normally assumed to represent ipsilateral movements. We tested this by making microelectrode penetrations into the deep cerebellar nuclei (mainly nucleus interpositus) of monkeys trained to perform a reach and grasp task with either hand. Following weak single electrical stimuli, many sites produced clear bilateral facilitation of multiple forelimb muscles.

Different contributions of the corpus callosum and cerebellum to motor coordination in monkey.

We investigated the different contribution of the corpus callosum (CC) and cerebellum to motor control in two macaque monkeys trained to perform a precision grip task with one or both hands. Recordings were made from antidromically identified CC cells and nearby unidentified neurons (UIDs) in the hand representation of the supplementary motor area (SMA) and compared with cells from the deep cerebellar nuclei (DCN). All cells showed their greatest modulation in activity (rate change locked to particular task event) during the movement epochs of the task (CC, 21.

Cortico-cerebellar coherence during a precision grip task in the monkey.

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).