Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia.

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Cortical Involvement in the Generation of Essential Tremor

Journal of Neurophysiology ◽

10.1152/jn.00477.2006 ◽

2007 ◽

Vol 97 (5) ◽

pp. 3219-3228 ◽

Cited By ~ 96

Author(s):

Jan Raethjen ◽

R. B. Govindan ◽

Florian Kopper ◽

M. Muthuraman ◽

Günther Deuschl

Keyword(s):

Essential Tremor ◽

Hot Spot ◽

Power Spectra ◽

Emg Activity ◽

Cortical Circuits ◽

Coherent Signals ◽

Cortical Motor ◽

Tremor Frequency ◽

Cortical Involvement

Conflicting results on the existence of tremor-related cortical activity in essential tremor (ET) have raised questions on the role of the cortex in tremor generation. Here we attempt to address these issues. We recorded 64 channel surface EEGs and EMGs from forearm muscles in 15 patients with definite ET. EEG and EMG power spectra, relative power of the rhythmic EMG activity, relative EEG power at the tremor frequency, and EEG–EMG and EEG–EEG coherence were calculated and their dynamics over time explored. Corticomuscular delay was studied using a new method for narrow-band coherent signals. Corticomuscular coherence in the contralateral central region at the tremor frequency was present in all patients in recordings with a relative tremor EMG power exceeding a certain level. However, the coherence was lost intermittently even with tremors far above this level. Physiological 15- to 30-Hz coherence was found consistently in 11 patients with significantly weaker EMG activity in this frequency range. A more frontal (mesial) hot spot was also intermittently coupled with the tremor and the central hot spot in five patients. Corticomuscular delays were compatible with transmission in fast corticospinal pathways and feedback of the tremor signal. Thus the tremor rhythm is intermittently relayed only in different cortical motor areas. We hypothesize that tremor oscillations build up in different subcortical and subcortico-cortical circuits only temporarily entraining each other.

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Neural Plasticity as a Basis for Motor Learning and Neurorehabilitation

Brain Impairment ◽

10.1375/brim.9.2.103 ◽

2008 ◽

Vol 9 (2) ◽

pp. 103-113 ◽

Cited By ~ 2

Author(s):

Rüdiger J. Seitz ◽

Thomas A. Matyas ◽

Leeanne M. Carey

Keyword(s):

Motor Learning ◽

Neural Plasticity ◽

Cortical Excitability ◽

Premotor Cortex ◽

Experimental Studies ◽

Brain Structures ◽

Transient Phenomena ◽

Cortical Motor ◽

Before And After ◽

Motor Representations

AbstractSkilled action is the end-product of learning processes that can improve several aspects of motor control such as strategic movement organisation, perceptual–motor associations, or muscle commands for basic components of sequentially evolving, complex movements. Experimental studies in healthy participants using functional imaging and transcranial magnetic stimulation have identified separable processes that form cortical motor representations and that assist this formation of representations. These processes capitalise on use-dependent plasticity and changes in cortical excitability before and after practice. In terms of neural circuits, motor learning manifests measurably via structures that support transient phenomena, such as attentive error monitoring, or through continued activation of brain structures that support control processes still adapting. Specifically, movement guidance engages the dorsal premotor and parietal cortex along the intraparietal sulcus in addition to the supplementary motor area and the anterior cerebellum. Movement conception based on explicit experience of the movement task involves the inferior premotor cortex. Evidence in patients recovering from brain lesions such as stroke, suggests that similar principles hold for neurorehabilitation as well. The challenging issue is to what degree altered motor strategies afford improvement in function through relearning and neural plasticity.

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Reliability in the location of hindlimb motor representations in Fischer-344 rats

Journal of Neurosurgery Spine ◽

10.3171/2013.4.spine12961 ◽

2013 ◽

Vol 19 (2) ◽

pp. 248-255 ◽

Cited By ~ 11

Author(s):

Shawn B. Frost ◽

Maria Iliakova ◽

Caleb Dunham ◽

Scott Barbay ◽

Paul Arnold ◽

...

Keyword(s):

Fischer 344 Rats ◽

Motor Representation ◽

Fischer 344 ◽

Computer Interfaces ◽

Cortical Motor ◽

Center Location ◽

Cord Injury ◽

Rat Strain ◽

Cortical Localization ◽

Motor Representations

Object The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for reliably locating cortical motor representations of the hindlimb. Methods Intracortical microstimulation techniques were used to derive detailed maps of the hindlimb motor representations in 6 adult Fischer-344 rats. Results The organization of the hindlimb movement representation, while variable across individual rats in topographic detail, displayed several commonalities. The hindlimb representation was positioned posterior to the forelimb motor representation and posterolateral to the motor trunk representation. The areal extent of the hindlimb representation across the cortical surface averaged 2.00 ± 0.50 mm2. Superimposing individual maps revealed an overlapping area measuring 0.35 mm2, indicating that the location of the hindlimb representation can be predicted reliably based on stereotactic coordinates. Across the sample of rats, the hindlimb representation was found 1.25–3.75 mm posterior to the bregma, with an average center location approximately 2.6 mm posterior to the bregma. Likewise, the hindlimb representation was found 1–3.25 mm lateral to the midline, with an average center location approximately 2 mm lateral to the midline. Conclusions The location of the cortical hindlimb motor representation in Fischer-344 rats can be reliably located based on its stereotactic position posterior to the bregma and lateral to the longitudinal skull suture at midline. The ability to accurately predict the cortical localization of functional hindlimb territories in a rodent model is important, as such animal models are being increasingly used in the development of brain-computer interfaces for restoration of function after spinal cord injury.

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Local activation of α2 adrenergic receptors is required for vagus nerve stimulation induced motor cortical plasticity

Scientific Reports ◽

10.1038/s41598-021-00976-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ching-Tzu Tseng ◽

Solomon J. Gaulding ◽

Canice Lei E. Dancel ◽

Catherine A. Thorn

Keyword(s):

Motor Cortex ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Cortical Plasticity ◽

Cortical Reorganization ◽

Cortical Motor ◽

The Central Nervous System ◽

Motor Cortical ◽

Recovery Of Motor Function

AbstractVagus nerve stimulation (VNS) paired with rehabilitation training is emerging as a potential treatment for improving recovery of motor function following stroke. In rats, VNS paired with skilled forelimb training results in significant reorganization of the somatotopic cortical motor map; however, the mechanisms underlying this form of VNS-dependent plasticity remain unclear. Recent studies have shown that VNS-driven cortical plasticity is dependent on noradrenergic innervation of the neocortex. In the central nervous system, noradrenergic α2 receptors (α2-ARs) are widely expressed in the motor cortex and have been critically implicated in synaptic communication and plasticity. In current study, we examined whether activation of cortical α2-ARs is necessary for VNS-driven motor cortical reorganization to occur. Consistent with previous studies, we found that VNS paired with motor training enlarges the map representation of task-relevant musculature in the motor cortex. Infusion of α2-AR antagonists into M1 blocked VNS-driven motor map reorganization from occurring. Our results suggest that local α2-AR activation is required for VNS-induced cortical reorganization to occur, providing insight into the mechanisms that may underlie the neuroplastic effects of VNS therapy.

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The Cortical Motor Areas and the Emergence of Motor Skills: A Neuroanatomical Perspective

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-070918-050216 ◽

2021 ◽

Vol 44 (1) ◽

Author(s):

Peter L. Strick ◽

Richard P. Dum ◽

Jean-Alban Rathelot

Keyword(s):

Motor Skills ◽

Primary Motor Cortex ◽

Annual Review ◽

Publication Date ◽

Motor Tasks ◽

Motor Behaviors ◽

Cortical Motor ◽

Neural Substrate ◽

Spatiotemporal Coordination ◽

Motor Areas

What changes in neural architecture account for the emergence and expansion of dexterity in primates? Dexterity, or skill in performing motor tasks, depends on the ability to generate highly fractionated patterns of muscle activity. It also involves the spatiotemporal coordination of activity in proximal and distal muscles across multiple joints. Many motor skills require the generation of complex movement sequences that are only acquired and refined through extensive practice. Improvements in dexterity have enabled primates to manufacture and use tools and humans to engage in skilled motor behaviors such as typing, dance, musical performance, and sports. Our analysis leads to the following synthesis: The neural substrate that endows primates with their enhanced motor capabilities is due, in part, to ( a) major organizational changes in the primary motor cortex and ( b) the proliferation of output pathways from other areas of the cerebral cortex, especially from the motor areas on the medial wall of the hemisphere. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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P062 Modulation of dorsolateral prefrontal cortex (DLPFC) through repetitive transcranial magnetic stimulation (rTMS) during capsaicin induced pain: effects on nociceptive control and motor cortical circuits

Clinical Neurophysiology ◽

10.1016/s1388-2457(08)60333-8 ◽

2008 ◽

Vol 119 ◽

pp. S87

Author(s):

Filippo Brighina ◽

Marina De Tommaso ◽

Antonio Palermo ◽

Francesca Giglia ◽

Maristella Panetta ◽

...

Keyword(s):

Prefrontal Cortex ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Dorsolateral Prefrontal Cortex ◽

Repetitive Transcranial Magnetic Stimulation ◽

Cortical Circuits ◽

Dorsolateral Prefrontal ◽

Motor Cortical

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Integrated Motor Cortical Control of Task-Related Muscles During Pointing in Humans

Journal of Neurophysiology ◽

10.1152/jn.2002.87.6.3006 ◽

2002 ◽

Vol 87 (6) ◽

pp. 3006-3017 ◽

Cited By ~ 67

Author(s):

Hervé Devanne ◽

Leonardo G. Cohen ◽

Nezha Kouchtir-Devanne ◽

Charles Capaday

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Large Body ◽

Indirect Evidence ◽

Cortical Circuits ◽

Triceps Brachii ◽

Pointing Movement ◽

Co Activation ◽

Motor Cortical ◽

Near Threshold

A large body of compelling but indirect evidence suggests that the motor cortex controls the different forelimb segments as a whole rather than individually. The purpose of this study was to obtain physiological evidence in behaving human subjects on the mode of operation of the primary motor cortex during coordinated movements of the forelimb. We approached this problem by studying a pointing movement involving the shoulder, elbow, wrist, and index finger as follows. Focal transcranial magnetic stimulation (TMS) was used to measure the input-output (I/O) curves—a measure of the corticospinal pathway excitability—of proximal (anterior deltoid, AD, and triceps brachii, TB) and distal muscles (extensor carpi radialis, ECR, and first dorsal interosseus, 1DI) during isolated contraction of one of these muscles or during selective co-activation with other muscles involved in pointing. Compared to an isolated contraction of the ECR, the plateau-level of the ECR sigmoid I/O curve increased markedly during co-activation with the AD while pointing. In contrast, the I/O curve of AD was not influenced by activation of the more distal muscles involved in pointing. Moreover, the 1DI I/O curve was not influenced by activation of the more proximal muscles. Three arguments argue for a cortical site of facilitation of ECR motor potentials. First, ECR motor potentials evoked by a near threshold TMS stimulus were facilitated when the AD and ECR were co-activated during pointing but not those in response to a near threshold anodal electrical stimulus. Second, the ECR H reflex was not found to be task dependent, indicating that the recruitment gain of the ECR α-motoneuron pool did not differ between tasks. Finally, in comparison with an isolated ECR contraction, intracortical inhibition tested at the ECR cortical site was decreased during pointing. These results suggest that activation of shoulder, elbow, and wrist muscles involved in pointing appear to involve, at least in part, common motor cortical circuits. In contrast, at least in the pointing task, the motor cortical circuits involved in activation of the 1DI appear to act independently.

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Handedness, Dexterity, and Motor Cortical Representations

Journal of Neurophysiology ◽

10.1152/jn.00512.2010 ◽

2011 ◽

Vol 105 (1) ◽

pp. 88-99 ◽

Cited By ~ 32

Author(s):

Jessica A. Bernard ◽

Stephan F. Taylor ◽

Rachael D. Seidler

Keyword(s):

Motor Evoked Potentials ◽

Behavioral Measures ◽

Poffenberger Paradigm ◽

First Dorsal Interosseous Muscle ◽

Interhemispheric Transfer Time ◽

Motor Cortical ◽

Motor Representations ◽

Cortical Representations ◽

Contralateral Motor ◽

Dorsal Interosseous Muscle

Motor system organization varies with handedness. However, previous work has focused almost exclusively on direction of handedness (right or left) as opposed to degree of handedness (strength). In the present study, we determined whether measures of interhemispheric interactions and degree of handedness are related to contra- and ipsilateral motor cortical representations. Participants completed a battery of handedness assessments including both handedness preference measures and behavioral measures of intermanual differences in dexterity, a computerized version of the Poffenberger paradigm (PP) to estimate interhemispheric transfer time (IHTT), and they underwent transcranial magnetic stimulation (TMS) mapping of both motor cortices while we recorded muscle activity from the first dorsal interosseous muscle bilaterally. A greater number of ipsilateral motor evoked potentials (iMEPs) were elicited in less lateralized individuals with the number of iMEPs correlated with IHTT. There were no relationships between handedness or lateralization of dexterity and symmetry of contralateral motor representations, although this symmetry was related to IHTT. Finally, IHTT was positively correlated with multiple measures of laterality and handedness. These findings demonstrate that degree of laterality of dexterity is related to the propensity for exhibiting iMEPs and the speed of interhemispheric interactions. However, it is not clear whether iMEPs are directly mediated via ipsilateral corticospinal projections or are transcallosally transmitted.

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