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Cerebellum (London, England) Feb 2022Interactions between cerebellum (CB) and primary motor cortex (M1) are critical for effective motor function. Although the associated neurophysiological processes are... (Review)
Review
Interactions between cerebellum (CB) and primary motor cortex (M1) are critical for effective motor function. Although the associated neurophysiological processes are yet to be fully characterised, a growing body of work using non-invasive brain stimulation (NIBS) techniques has significantly progressed our current understanding. In particular, recent developments with both transcranial magnetic (TMS) and direct current (tDCS) stimulation suggest that CB modulates the activity of local excitatory interneuronal circuits within M1. These circuits are known to be important both physiologically and functionally, and understanding the nature of their connectivity with CB therefore has the potential to provide important insight for NIBS applications. Consequently, this mini-review provides an overview of the emerging literature that has investigated interactions between CB and the intracortical excitatory circuits of M1.
Topics: Cerebellum; Evoked Potentials, Motor; Motor Cortex; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 33978934
DOI: 10.1007/s12311-021-01278-z -
The Journal of Physiology Jul 2023Transcranial magnetic stimulation (TMS) is a non-invasive technique that is increasingly used to study the human brain. One of the principal outcome measures is the... (Review)
Review
Transcranial magnetic stimulation (TMS) is a non-invasive technique that is increasingly used to study the human brain. One of the principal outcome measures is the motor-evoked potential (MEP) elicited in a muscle following TMS over the primary motor cortex (M1), where it is used to estimate changes in corticospinal excitability. However, multiple elements play a role in MEP generation, so even apparently simple measures such as peak-to-peak amplitude have a complex interpretation. Here, we summarize what is currently known regarding the neural pathways and circuits that contribute to the MEP and discuss the factors that should be considered when interpreting MEP amplitude measured at rest in the context of motor processing and patients with neurological conditions. In the last part of this work, we also discuss how emerging technological approaches can be combined with TMS to improve our understanding of neural substrates that can influence MEPs. Overall, this review aims to highlight the capabilities and limitations of TMS that are important to recognize when attempting to disentangle sources that contribute to the physiological state-related changes in corticomotor excitability.
Topics: Humans; Transcranial Magnetic Stimulation; Motor Cortex; Muscle, Skeletal; Evoked Potentials, Motor; Brain; Electromyography
PubMed: 37254441
DOI: 10.1113/JP281885 -
The Journal of Neuroscience : the... Apr 2021It is generally supposed that primary motor cortex (M1) receives somatosensory input predominantly via primary somatosensory cortex (S1). However, a growing body of...
It is generally supposed that primary motor cortex (M1) receives somatosensory input predominantly via primary somatosensory cortex (S1). However, a growing body of evidence indicates that M1 also receives direct sensory input from the thalamus, independent of S1; such direct input is particularly evident at early ages before M1 contributes to motor control. Here, recording extracellularly from the forelimb regions of S1 and M1 in unanesthetized rats at postnatal day (P)8 and P12, we compared S1 and M1 responses to self-generated (i.e., reafferent) forelimb movements during active sleep and wake, and to other-generated (i.e., exafferent) forelimb movements. At both ages, reafferent responses were processed in parallel by S1 and M1; in contrast, exafferent responses were processed in parallel at P8 but serially, from S1 to M1, at P12. To further assess this developmental difference in processing, we compared exafferent responses to proprioceptive and tactile stimulation. At both P8 and P12, proprioceptive stimulation evoked parallel responses in S1 and M1, whereas tactile stimulation evoked parallel responses at P8 and serial responses at P12. Independent of the submodality of exafferent stimulation, pairs of S1-M1 units exhibited greater coactivation during active sleep than wake. These results indicate that S1 and M1 independently develop somatotopy before establishing the interactive relationship that typifies their functionality in adults. Learning any new motor task depends on the ability to use sensory information to update motor outflow. Thus, to understand motor learning, we must also understand how animals process sensory input. Primary somatosensory cortex (S1) and primary motor cortex (M1) are two interdependent structures that process sensory input throughout life. In adults, the functional relationship between S1 and M1 is well established; however, little is known about how S1 and M1 begin to transmit or process sensory information in early life. In this study, we investigate the early development of S1 and M1 as a sensory processing unit. Our findings provide new insights into the fundamental principles of sensory processing and the development of functional connectivity between these important sensorimotor structures.
Topics: Animals; Female; Forelimb; Male; Motor Cortex; Movement; Rats; Rats, Sprague-Dawley; Sleep; Somatosensory Cortex; Touch Perception; Wakefulness
PubMed: 33622773
DOI: 10.1523/JNEUROSCI.2614-20.2021 -
Scientific Reports Aug 2021The eyelid motor system has been used for years as an experimental model for studying the neuronal mechanisms underlying motor and cognitive learning, mainly with...
The eyelid motor system has been used for years as an experimental model for studying the neuronal mechanisms underlying motor and cognitive learning, mainly with classical conditioning procedures. Nonetheless, it is not known yet which brain structures, or neuronal mechanisms, are responsible for the acquisition, storage, and expression of these motor responses. Here, we studied the temporal correlation between unitary activities of identified eyelid and vibrissae motor cortex neurons and the electromyographic activity of the orbicularis oculi and vibrissae muscles and magnetically recorded eyelid positions during classical conditioning of eyelid and vibrissae responses, using both delay and trace conditioning paradigms in behaving mice. We also studied the involvement of motor cortex neurons in reflexively evoked eyelid responses and the kinematics and oscillatory properties of eyelid movements evoked by motor cortex microstimulation. Results show the involvement of the motor cortex in the performance of conditioned responses elicited during the classical conditioning task. However, a timing correlation analysis showed that both electromyographic activities preceded the firing of motor cortex neurons, which must therefore be related more with the reinforcement and/or proper performance of the conditioned responses than with their acquisition and storage.
Topics: Animals; Conditioning, Classical; Eyelids; Male; Mice, Inbred C57BL; Motor Cortex; Motor Neurons; Vibrissae; Mice
PubMed: 34404871
DOI: 10.1038/s41598-021-96153-6 -
The Journal of Neuroscience : the... Oct 2023The primary motor cortex (M1) and the dorsal striatum play a critical role in motor learning and the retention of learned behaviors. Motor representations of...
The primary motor cortex (M1) and the dorsal striatum play a critical role in motor learning and the retention of learned behaviors. Motor representations of corticostriatal ensembles emerge during motor learning. In the coordinated reorganization of M1 and the dorsal striatum for motor learning, layer 5a (L5a) which connects M1 to the ipsilateral and contralateral dorsal striatum, should be a key layer. Although M1 L5a neurons represent movement-related activity in the late stage of learning, it is unclear whether the activity is retained as a memory engram. Here, using male transgenic mice, we conducted two-photon calcium imaging of striatum-projecting L5a intratelencephalic (IT) neurons in forelimb M1 during late sessions of a self-initiated lever-pull task and in sessions after 6 d of nontraining following the late sessions. We found that trained male animals exhibited stable motor performance before and after the nontraining days. At the same time, we found that M1 L5a IT neurons strongly represented the well-learned forelimb movement but not uninstructed orofacial movements. A subset of M1 L5a IT neurons consistently coded the well-learned forelimb movement before and after the nontraining days. Inactivation of M1 IT neurons after learning impaired task performance when the lever was made heavier or when the target range of the pull distance was narrowed. These results suggest that a subset of M1 L5a IT neurons continuously represent skilled movement after learning and serve to fine-tune the kinematics of well-learned movement. Motor memory persists even when it is not used for a while. IT neurons in L5a of the M1 gradually come to represent skilled forelimb movements during motor learning. However, it remains to be determined whether these changes persist over a long period and how these neurons contribute to skilled movements. Here, we show that a subset of M1 L5a IT neurons retain information for skilled forelimb movements even after nontraining days. Furthermore, suppressing the activity of these neurons during skilled forelimb movements impaired behavioral stability and adaptability. Our results suggest the importance of M1 L5a IT neurons for tuning skilled forelimb movements over a long period.
Topics: Mice; Animals; Male; Motor Cortex; Movement; Neurons; Learning; Forelimb
PubMed: 37699714
DOI: 10.1523/JNEUROSCI.0428-23.2023 -
Nature Oct 2021Full-length SMART-seq single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform...
Full-length SMART-seq single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform markers for different cell types. Used in conjunction with spatial RNA capture and gene-tagging methods, this enables the inference of spatially resolved isoform expression for different cell types. Here, in a comprehensive analysis of 6,160 mouse primary motor cortex cells assayed with SMART-seq, 280,327 cells assayed with MERFISH and 94,162 cells assayed with 10x Genomics sequencing, we find examples of isoform specificity in cell types-including isoform shifts between cell types that are masked in gene-level analysis-as well as examples of transcriptional regulation. Additionally, we show that isoform specificity helps to refine cell types, and that a multi-platform analysis of single-cell transcriptomic data leveraging multiple measurements provides a comprehensive atlas of transcription in the mouse primary motor cortex that improves on the possibilities offered by any single technology.
Topics: Animals; Atlases as Topic; Female; GABAergic Neurons; Gene Expression Profiling; Glutamates; In Situ Hybridization, Fluorescence; Male; Mice; Mice, Inbred C57BL; Motor Cortex; Neurons; Organ Specificity; Sequence Analysis; Single-Cell Analysis; Transcriptome
PubMed: 34616073
DOI: 10.1038/s41586-021-03969-3 -
Human Brain Mapping May 2022Sensorimotor coordination requires orchestrated network activity in the brain, mediated by inter- and intra-hemispheric interactions that may be affected by...
Sensorimotor coordination requires orchestrated network activity in the brain, mediated by inter- and intra-hemispheric interactions that may be affected by aging-related changes. We adopted a theoretical model, according to which intra-hemispheric inhibition from premotor to primary motor cortex is mandatory to compensate for inter-hemispheric excitation through the corpus callosum. To test this as a function of age we acquired electroencephalography (EEG) simultaneously with functional magnetic resonance imaging (fMRI) in two groups of healthy adults (younger N = 13: 20-25 year and older N = 14: 59-70 year) while learning a unimanual motor task. On average, quality of performance of older participants stayed significantly below that of the younger ones. Accompanying decreases in motor-event-related EEG β-activity were lateralized toward contralateral motor regions, albeit more so in younger participants. In this younger group, the mean β-power during motor task execution was significantly higher in bilateral premotor areas compared to the older adults. In both groups, fMRI blood oxygen level dependent (BOLD) signals were positively correlated with source-reconstructed β-amplitudes: positive in primary motor and negative in premotor cortex. This suggests that β-amplitude modulation is associated with primary motor cortex "activation" (positive BOLD response) and premotor "deactivation" (negative BOLD response). Although the latter results did not discriminate between age groups, they underscore that enhanced modulation in primary motor cortex may be explained by a β-associated excitatory crosstalk between hemispheres.
Topics: Aged; Aging; Cohort Studies; Electroencephalography; Humans; Magnetic Resonance Imaging; Motor Cortex
PubMed: 35133058
DOI: 10.1002/hbm.25791 -
Proceedings of the National Academy of... Apr 2023Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with...
Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.
Topics: Humans; Corpus Striatum; Sensorimotor Cortex; Neostriatum; Motor Cortex; Transcranial Magnetic Stimulation; Magnetic Resonance Imaging
PubMed: 37023134
DOI: 10.1073/pnas.2219693120 -
Molecular and Cellular Neurosciences Sep 2023There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). Mucuna pruriens has been used in the treatment of humans with PD....
Recovery of motor function is associated with rescue of glutamate biomarkers in the striatum and motor cortex following treatment with Mucuna pruriens in a murine model of Parkinsons disease.
There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). Mucuna pruriens has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of Mucuna pruriens, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase (TH) protein expression in the nigrostriatal pathway, or glutamate biomarkers in both the striatum and motor cortex. Following MPTP administration, resulting in an 80 % loss of striatal TH, treatment with Mucuna pruriens failed to rescue either striatal TH or the dopamine transporter back to the control levels, but there was restoration of gait/motor function. There was an MPTP-induced loss of TH-labeled neurons in the substantia nigra pars compacta and in the number of striatal dendritic spines, both of which failed to be recovered following treatment with Mucuna pruriens. This Mucuna pruriens-induced locomotor recovery following MPTP was associated with restoration of two striatal glutamate transporter proteins, GLAST (EAAT1) and EAAC1 (EAAT3), and the vesicular glutamate transporter 2 (Vglut2) within the motor cortex. Post-MPTP treatment with Mucuna pruriens, results in locomotor improvement that is associated with recovery of striatal and motor cortex glutamate transporters but is independent of nigrostriatal TH restoration.
Topics: Parkinson Disease; Glutamic Acid; Biomarkers; Motor Cortex; Mucuna; Plant Extracts; Gait; Pars Compacta; Basal Ganglia; Animals; Mice
PubMed: 37527694
DOI: 10.1016/j.mcn.2023.103883 -
Journal of Neurophysiology Feb 2021The mammalian motor cortex is topographically organized into representations of discrete body parts (motor maps). Studies in adult rats using long-duration intracortical...
The mammalian motor cortex is topographically organized into representations of discrete body parts (motor maps). Studies in adult rats using long-duration intracortical microstimulation (LD-ICMS) reveal that forelimb motor cortex is functionally organized into several spatially distinct areas encoding complex, multijoint movement sequences: elevate, advance, grasp, and retract. The topographical arrangement of complex movements during development and the influence of skilled learning are unknown. Here, we determined the emergence and topography of complex forelimb movement representations in rats between () and . We further investigated the expression of the maps for complex movements under conditions of reduced cortical inhibition and whether skilled forelimb motor training could alter their developing topography. We report that simple forelimb movements are first evoked at and are confined to the caudal forelimb area (CFA), whereas complex movements first reliably appear at and are observed in both the caudal and rostral forelimb areas (RFA). During development, the topography of complex movement representations undergoes reorganization with "grasp" and "elevate" movements predominantly observed in the RFA and all four complex movements observed in CFA. Under reduced cortical inhibition, simple and complex movements were first observed in the CFA on and , respectively, and the topography is altered relative to a saline control. Further, skilled motor learning was associated with increases in "grasp" and "retract" representations specific to the trained limb. Our results demonstrate that early-life motor experience during development can modify the topography of complex forelimb movement representations. The motor cortex is topographically organized into maps of different body parts. We used to think that the function of motor cortex was to drive individual muscles, but more recently we have learned that it is also organized to make complex movements. However, the development and plasticity of those complex movements is completely unknown. In this paper, the emergence and topography of complex movement representation, as well as their plasticity during development, is detailed.
Topics: Animals; Evoked Potentials, Motor; Forelimb; Male; Motor Cortex; Motor Skills; Neural Inhibition; Neurogenesis; Neuronal Plasticity; Rats; Rats, Long-Evans
PubMed: 33471611
DOI: 10.1152/jn.00531.2020