Distal forelimb representations in primary motor cortex are redistributed after forelimb restriction: a longitudinal study in adult squirrel monkeys

Primary motor cortex (M1) movement representations reflect acquired motor skills. Representations of muscles and joints used in a skilled task expand. However, it is unknown whether motor restriction in healthy individuals results in complementary reductions in M1 representations. With the use of intracortical microstimulation techniques in squirrel monkeys, detailed maps of movement representations in M1 were derived before and up to 35 wk after restriction of the preferred distal forelimb (DFL) by use of a soft cast. Although total DFL area and movement threshold remained constant, casting resulted in a redistribution of digit and wrist/forearm representations. Digit representations progressively decreased, whereas wrist/forearm representations progressively increased in areal extent. In three of four monkeys, hand preference returned to normal by the end of the postcast recovery period, and postrecovery maps demonstrated reversal of restriction-induced changes. However, in one monkey, a chronic motor impairment occurred in the casted limb. Rehabilitation via a forced-use paradigm resulted in recovery in use and skill of the impaired limb, as well as restoration of normal motor maps. These results demonstrate that plasticity in motor representations can be induced by training or restricting movements of the limb. Physiological changes induced by restriction appear to be reversible, even in the case of adverse motor outcomes. The respective contributions of both disuse and lost motor skills are discussed. These results have relevance for clinical conditions requiring forelimb casting as well as interpreting the differential effects of injury and disuse that are necessarily intertwined after cortical injury, as occurs in stroke.

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Neurophysiological correlates of hand preference in primary motor cortex of adult squirrel monkeys

Journal of Neuroscience ◽

10.1523/jneurosci.12-08-02918.1992 ◽

1992 ◽

Vol 12 (8) ◽

pp. 2918-2947 ◽

Cited By ~ 181

Author(s):

RJ Nudo ◽

WM Jenkins ◽

MM Merzenich ◽

T Prejean ◽

R Grenda

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Hand Preference ◽

Squirrel Monkeys

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Corticospinal Tract Microstructure Correlates With Beta Oscillatory Activity in the Primary Motor Cortex After Stroke

Stroke ◽

10.1161/strokeaha.121.034344 ◽

2021 ◽

Author(s):

Robert Schulz ◽

Marlene Bönstrup ◽

Stephanie Guder ◽

Jingchun Liu ◽

Benedikt Frey ◽

...

Keyword(s):

Motor Cortex ◽

Fractional Anisotropy ◽

Primary Motor Cortex ◽

Supplementary Motor Area ◽

Premotor Cortex ◽

Motor Impairment ◽

Motor Area ◽

Oscillatory Activity ◽

Premotor Area ◽

Beta Power

Background and Purpose: Cortical beta oscillations are reported to serve as robust measures of the integrity of the human motor system. Their alterations after stroke, such as reduced movement-related beta desynchronization in the primary motor cortex, have been repeatedly related to the level of impairment. However, there is only little data whether such measures of brain function might directly relate to structural brain changes after stroke. Methods: This multimodal study investigated 18 well-recovered patients with stroke (mean age 65 years, 12 males) by means of task-related EEG and diffusion-weighted structural MRI 3 months after stroke. Beta power at rest and movement-related beta desynchronization was assessed in 3 key motor areas of the ipsilesional hemisphere that are the primary motor cortex (M1), the ventral premotor area and the supplementary motor area. Template trajectories of corticospinal tracts (CST) originating from M1, premotor cortex, and supplementary motor area were used to quantify the microstructural state of CST subcomponents. Linear mixed-effects analyses were used to relate tract-related mean fractional anisotropy to EEG measures. Results: In the present cohort, we detected statistically significant reductions in ipsilesional CST fractional anisotropy but no alterations in EEG measures when compared with healthy controls. However, in patients with stroke, there was a significant association between both beta power at rest ( P =0.002) and movement-related beta desynchronization ( P =0.003) in M1 and fractional anisotropy of the CST specifically originating from M1. Similar structure-function relationships were neither evident for ventral premotor area and supplementary motor area, particularly with respect to their CST subcomponents originating from premotor cortex and supplementary motor area, in patients with stroke nor in controls. Conclusions: These data suggest there might be a link connecting microstructure of the CST originating from M1 pyramidal neurons and beta oscillatory activity, measures which have already been related to motor impairment in patients with stroke by previous reports.

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The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study

Neurorehabilitation and Neural Repair ◽

10.1177/1545968319826052 ◽

2019 ◽

Vol 33 (2) ◽

pp. 130-140 ◽

Cited By ~ 4

Author(s):

Ronan A. Mooney ◽

Suzanne J. Ackerley ◽

Deshan K. Rajeswaran ◽

John Cirillo ◽

P. Alan Barber ◽

...

Keyword(s):

Motor Cortex ◽

Upper Limb ◽

Primary Motor Cortex ◽

Motor Impairment ◽

Intracortical Inhibition ◽

Chronic Stroke ◽

Stroke Patients ◽

Gaba Concentration ◽

Chronic Stage ◽

And Function

Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. Results. Short-interval intracortical inhibition was similar between patients and controls ( P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls ( P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function ( P = .002 and P = .017). GABA concentration was lower within ipsilesional ( P = .009) and contralesional ( P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

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Dopamine D2 receptors modulate intrinsic properties and synaptic transmission of parvalbumin interneurons in the mouse primary motor cortex

10.1101/802140 ◽

2019 ◽

Author(s):

Jérémy Cousineau ◽

Léa Lescouzères ◽

Anne Taupignon ◽

Lorena Delgado-Zabalza ◽

Emmanuel Valjent ◽

...

Keyword(s):

Motor Cortex ◽

Synaptic Transmission ◽

Motor Skills ◽

Primary Motor Cortex ◽

Pyramidal Neurons ◽

D2 Receptors ◽

Receptor Subtypes ◽

Parvalbumin Interneurons ◽

Layer V ◽

Gabaergic Synaptic Transmission

AbstractDopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate how DA, through the activation of D2 receptors (D2R), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in layer V of M1. Our data reveal a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.Significance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.

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Neural Substrates of Practice Structure That Support Future Off-Line Learning

Journal of Neurophysiology ◽

10.1152/jn.00315.2009 ◽

2009 ◽

Vol 102 (4) ◽

pp. 2462-2476 ◽

Cited By ~ 33

Author(s):

Nicholas F. Wymbs ◽

Scott T. Grafton

Keyword(s):

Motor Cortex ◽

Motor Skills ◽

Primary Motor Cortex ◽

Neural Substrates ◽

Skill Learning ◽

Opposite Pattern ◽

Practice Schedule ◽

Random Schedule ◽

Subcortical Regions ◽

Equivalent Motor

Off-line learning is facilitated when motor skills are acquired under a random practice schedule and retention suffers when a similar set of motor skills are practiced under a blocked schedule. The current study identified the neural correlates of a random training schedule while participants learned a set of four-element finger sequences using their nondominant hand during functional magnetic resonance imaging. A go/no go task was used to separately probe brain areas supporting sequence preparation and production. By the end of training, the random practice schedule, relative to the block schedule, recruited a broad premotor–parietal network as well as sensorimotor and subcortical regions during both preparation and production trials, despite equivalent motor performance. Longitudinal analysis demonstrated that preparation-related activity under a random schedule remained stable or increased over time. The blocked schedule showed the opposite pattern. Across individual subjects, successful skill retention was correlated with greater activity at the end of training in the ipsilateral left motor cortex, for both preparation and production. This is consistent with recent evidence that attributes off-line learning to training-related processing within primary motor cortex. These results reflect the importance of an overlooked aspect of motor skill learning. Specifically, how trials are organized during training—with a random schedule—provides an effective basis for the formation of enduring motor memories, through enhanced engagement of core regions involved in the active preparation and implementation of motor programs.

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Inducing Homeostatic-Like Plasticity in Human Motor Cortex Through Converging Corticocortical Inputs

Journal of Neurophysiology ◽

10.1152/jn.91046.2008 ◽

2009 ◽

Vol 102 (6) ◽

pp. 3180-3190 ◽

Cited By ~ 40

Author(s):

Monika Pötter-Nerger ◽

Sarah Fischer ◽

Claudia Mastroeni ◽

Sergiu Groppa ◽

Günther Deuschl ◽

...

Keyword(s):

Motor Cortex ◽

Median Nerve ◽

Primary Motor Cortex ◽

Premotor Cortex ◽

Long Term Potentiation ◽

Corticospinal Excitability ◽

Human Motor Cortex ◽

Induced Changes ◽

Homeostatic Response

Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1HAND) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression (LTD)–like or long-term potentiation (LTP)–like plasticity in left M1HAND through different afferents. We hypothesized that the left M1HAND would integrate LTP- and LTD-like plasticity in a homeostatic fashion. In ten healthy volunteers, low-intensity repetitive transcranial magnetic stimulation (rTMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1HAND via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve and left M1HAND to induce spike-time–dependent plasticity in sensory-to-motor inputs to left M1HAND. We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PASN20+2ms) or an LTD-like decrease (PASN20−5ms) in corticospinal excitability. The amplitude of motor-evoked potentials was recorded from intrinsic hand muscles to assess stimulation-induced changes in corticospinal excitability. Premotor-to-motor preconditioning triggered a homeostatic response to subsequent sensory-to-motor PAS. After facilitatory 5 Hz rTMS, “facilitatory” PASN20+2ms suppressed corticospinal excitability. Likewise, “inhibitory” PASN20−5ms facilitated corticospinal excitability after “inhibitory” 1 Hz rTMS. There was a negative linear relationship between the excitability changes induced by PMD rTMS and those elicited by subsequent PAS. Excitability changes were not paralleled by changes in performance during a finger-tapping task. These results provide evidence for a homeostatic response pattern in the human M1HAND that integrates acute plastic changes evoked through different “input channels.”

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Dendritic Spine Density and Dynamics of Layer 5 Pyramidal Neurons of the Primary Motor Cortex Are Elevated With Aging

Cerebral Cortex ◽

10.1093/cercor/bhz124 ◽

2019 ◽

Vol 30 (2) ◽

pp. 767-777 ◽

Cited By ~ 3

Author(s):

A M Davidson ◽

H Mejía-Gómez ◽

M Jacobowitz ◽

R Mostany

Keyword(s):

Motor Cortex ◽

Dendritic Spine ◽

Healthy Aging ◽

Primary Motor Cortex ◽

Cortical Cell ◽

Motor Impairment ◽

Fine Motor ◽

Aged Mouse ◽

Spine Density ◽

Dendritic Spine Density

AbstractIt is well established that motor impairment often occurs alongside healthy aging, leading to problems with fine motor skills and coordination. Although previously thought to be caused by neuronal death accumulating across the lifespan, it is now believed that the source of this impairment instead stems from more subtle changes in neural connectivity. The dendritic spine is a prime target for exploration of this problem because it is the postsynaptic partner of most excitatory synapses received by the pyramidal neuron, a cortical cell that carries much of the information processing load in the cerebral cortex. We repeatedly imaged the same dendrites in young adult and aged mouse motor cortex over the course of 1 month to look for differences in the baseline state of the dendritic spine population. These experiments reveal increased dendritic spine density, without obvious changes in spine clustering, occurring at the aged dendrite. Additionally, aged dendrites exhibit elevated spine turnover and stabilization alongside decreased long-term spine survival. These results suggest that at baseline the aged motor cortex may exist in a perpetual state of relative instability and attempts at compensation. This phenotype of aging may provide clues for future targets of aging-related motor impairment remediation.

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Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20908356 ◽

2020 ◽

Vol 41 (1) ◽

pp. 182-193 ◽

Cited By ~ 1

Author(s):

Kathryn L West ◽

Dinesh K Sivakolundu ◽

Mark D Zuppichini ◽

Monroe P Turner ◽

Jeffrey S Spence ◽

...

Keyword(s):

Multiple Sclerosis ◽

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Motor Cortex ◽

Healthy Volunteers ◽

Primary Motor Cortex ◽

Motor Impairment ◽

Oxygen Metabolism ◽

Button Press

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural–vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (ΔCBF), cerebral metabolic rate of oxygen (ΔCMRO2), and flow–metabolism coupling (ΔCBF/ΔCMRO2), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant ΔCBF and ΔCMRO2 increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow–metabolism coupling (ΔCBF/ΔCMRO2) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in ΔCBF and ΔCMRO2 in MSP with motor impairment. Additionally, ΔCBF and ΔCMRO2 responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural–vascular coupling.

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Acquisition of motor memory determines the interindividual variability of learning-induced plasticity in the primary motor cortex

Journal of Applied Physiology ◽

10.1152/japplphysiol.00470.2018 ◽

2018 ◽

Vol 125 (4) ◽

pp. 990-998

Author(s):

Masato Hirano ◽

Shinji Kubota ◽

Yoshiki Koizume ◽

Kozo Funase

Keyword(s):

Motor Cortex ◽

Motor Skills ◽

Primary Motor Cortex ◽

Interindividual Variability ◽

Motor Evoked Potentials ◽

Plantar Flexion ◽

Skill Learning ◽

Tracking Task ◽

Motor Memory ◽

Visuomotor Tracking

Acquisition of new motor skills induces plastic reorganization in the primary motor cortex (M1). Previous studies have demonstrated the increases in the M1 excitability through motor skill learning. However, this M1 reorganization is highly variable between individuals even though they improve their skill performance through the same training protocol. To reveal the source of this interindividual variability, we examined the relationship between an acquisition of memory-guided feedforward movements and the learning-induced increases in the M1 excitability. Twenty-eight subjects participated in experiment 1. We asked subjects to learn a visuomotor tracking task. The subjects controlled a cursor on a PC monitor to pursue a target line by performing ankle dorsiflexion and plantar flexion. In experiment 1, we removed the online visual feedback provided by the cursor movement once every six trials, which enabled us to assess whether the subjects could perform accurate memory-guided movements. Motor-evoked potentials (MEP) were elicited in the tibialis anterior muscle by transcranial magnetic stimulation of the relevant M1 before and after the learning of the visuomotor tracking task and after half the trials. We found that the MEP amplitude was increased along with the improvement in memory-guided movements. In experiment 2 ( n = 10), we confirmed this relationship by examining whether the improvement in memory-guided movements induces increases in MEP amplitude. The results of this study indicate that the plastic reorganization of the M1 induced by the learning of a visuomotor skill is associated with the acquisition of memory-guided movements. NEW & NOTEWORTHY Acquisition of novel motor skills increases excitability of the primary motor cortex (M1). We recently reported that the amount of increases in the M1 excitability is highly variable between individuals even though they learned the same skill to the similar extent, yet the sources of this interindividual variability still remain unclear. The present study revealed that this interindividual variability is associated with whether individuals acquire a motor memory, which enables them to produce accurate memory-guided movements.

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