Neurons In Motor Cortex Research Articles

Refinement of Active and Passive Membrane Properties of Layer V Pyramidal Neurons in Rat Primary Motor Cortex During Postnatal Development.

Achieving the distinctive complex behaviors of adult mammals requires the development of a great variety of specialized neural circuits. Although the development of these circuits begins during the embryonic stage, they remain immature at birth, requiring a postnatal maturation process to achieve these complex tasks. Understanding how the neuronal membrane properties and circuits change during development is the first step to understand their transition into efficient ones. Thus, using whole cell patch clamp recordings, we have studied the changes in the electrophysiological properties of layer V pyramidal neurons of the rat primary motor cortex during postnatal development. Among all the parameters studied, only the voltage threshold was established at birth and, although some of the changes occurred mainly during the second postnatal week, other properties such as membrane potential, capacitance, duration of the post-hyperpolarization phase or the maximum firing rate were not defined until the beginning of adulthood. Those modifications lead to a decrease in neuronal excitability and to an increase in the working range in young adult neurons, allowing more sensitive and accurate responses. This maturation process, that involves an increase in neuronal size and changes in ionic conductances, seems to be influenced by the neuronal type and by the task that neurons perform as inferred from the comparison with other pyramidal and motor neuron populations.

Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control

The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display robust high-frequency firing, ultra-narrow spike waveforms, superfast Na+ current inactivation kinetics, and large resurgent Na+ currents (INaR). These properties of songbird pallial motor neurons closely resemble those of specialized large pyramidal neurons in mammalian primary motor cortex. They emerge during the early phases of song development in males, but not females, coinciding with a complete switch of Na+ channel subunit expression from Navβ3 to Navβ4. Dynamic clamping and dialysis of Navβ4’s C-terminal peptide into juvenile RA neurons provide evidence that Navβ4, and its associated INaR, promote neuronal excitability. We thus propose that INaR modulates the excitability of upper motor neurons that are required for the execution of fine motor skills.

Short-interval intracortical inhibition and facilitation targeting upper and lower limb muscles

Transcranial magnetic stimulation (TMS) can be used to study excitability of corticospinal neurons in human motor cortex. It is currently not fully elucidated if corticospinal neurons in the hand vs. leg representation show the same or different regulation of their excitability by GABAAergic and glutamatergic interneuronal circuitry. Using a paired-pulse TMS protocol we tested short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in 18 healthy participants. Motor evoked potentials were evoked in one hand (abductor digiti minimi) and one leg muscle (tibialis anterior), with systematic variation of the intensities of the first (S1) and second (S2) pulse between 60 and 140% resting motor threshold (RMT) in 10% steps, at two interstimulus intervals of 1.5 and 2.1 ms. For the hand and leg motor representations and for both interstimulus intervals, SICI occurred if the intensities of S1 < RMT and S2 > RMT, while SICF predominated if S1 = S2 ≤ RMT, or S1 > RMT and S2 < RMT. Findings confirm and extend previous evidence that the regulation of excitability of corticospinal neurons of the hand versus leg representation in human primary cortex through GABAAergic and glutamatergic interneuronal circuits is highly similar, and that corticospinal neurons of both representations are activated by TMS transsynaptically in largely identical ways.

The role of neurophysiological assessments during the combined treatment of patients with malignant brain tumors

Introduction. Dynamic monitoring and evaluation of the results of therapy of patients with malignant brain diseases is a complex and urgent problem in modern medicine. The aim of the study was to assess the reliability of the transcranial magnetic stimulation technique as a tool for neurophysiological monitoring in patients with malignant brain tumors. Material and methods. Two groups of patients were formed: adults with large focal solitary lesions of the central nervous system (glioma) (n=20), who underwent radiotherapy, and a control comparison group (n=16). All patients underwent diagnostic transcranial magnetic stimulation before and after treatment. Results. In the main group the application of transcranial magnetic stimulation in dynamics allowed to reveal reliable improvement of conduction along the central motor pathways (increase in amplitude of the evoked motor response). The obtained data of neurophysiological examination correlated with clinical improvement in the patient group. Discussion. Some parameters of the motor evoked response (MEP) changed reliably, as after the radiation treatment performed. Obtained changes (amplitude of MEP and, especially, its threshold) to the greatest extent reflect functional state of cortical motoneurons, as well as their anatomical preservation in case of organic changes. Before therapy in all cases there was a reliable tendency to a smaller amplitude and a higher threshold of cortical MEPs, which reflects a decrease in the functional activity of motor cortex neurons; a slower central motor conduction time also draws attention. These changes had a universal character and were registered in all patients. Conclusion. Diagnostic transcranial magnetic stimulation, taking into account age limitations inherent to it as a technique, is a valuable additional neurophysiological technique. It is safe, inexpensive and does not require expensive consumables, and is applicable to a wide range of diseases.

Hyperexcitability and brain morphological differences in mice lacking the cystine/glutamate antiporter, system xc.

System xc- (Sxc- ) is a heteromeric antiporter (L-cystine/L-glutamate exchanger) expressed predominately on astrocytes in the central nervous system. Its activity contributes importantly to the maintenance of the ambient extracellular glutamate levels, as well as, to cellular redox homeostasis. Since alterations in glutamate levels and redox modifications could cause structural changes, we analyzed gross regional morphology of thionin-stained brain sections and cellular and subcellular morphology of Golgi-Cox stained layer V pyramidal neurons in the primary motor cortex (PM1) of mice naturally null for SLC7A11 (SLC7A11sut/sut )-the gene that encodes the substrate specific light chain (xCT) for Sxc- . Intriguingly, in comparison to age- and sex-matched wild-type (SLC7A11+/+ ) littermate controls, we found morphologic changes-including increased dendritic complexity and mushroom spine area in males and reduced corpus callosum and soma size in females-that have previously been described, in each case, as morphological correlates of excitability. Consistent with this, we found that both male and female SLC7A11sut/sut mice had lower convulsive seizure thresholds and greater seizure severity than their sex-matched wild-type (SLC7A11+/+ ) littermates after acute challenge with two pharmacologically distinct chemoconvulsants: the Glu receptor agonist, kainic acid (KA), or the GABAA receptor antagonist, pentylenetetrazole (PTZ). These results suggest that the loss of Sxc- signaling in males and females perturbs excitatory/inhibitory (E/I) balance in vivo, potentially through its regulation of cellular and subcellular morphology.

Individualized beta-band oscillatory transcranial direct current stimulation over the primary motor cortex enhances corticomuscular coherence and corticospinal excitability in healthy individuals

BackgroundSimultaneously modulating individual neural oscillation and cortical excitability may be important for enhancing communication between the primary motor cortex and spinal motor neurons, which plays a key role in motor control. However, it is unknown whether individualized beta-band oscillatory transcranial direct current stimulation (otDCS) enhances corticospinal oscillation and excitability. ObjectiveThis study investigated the effects of individualized beta-band otDCS on corticomuscular coherence (CMC) and corticospinal excitability in healthy individuals. MethodsIn total, 29 healthy volunteers participated in separate experiments. They received the following stimuli for 10 min on different days: 1) 2-mA otDCS with individualized beta-band frequencies, 2) 2-mA transcranial alternating current stimulation (tACS) with individualized beta-band frequencies, and 3) 2-mA transcranial direct current stimulation (tDCS). The changes in CMC between the vertex and tibialis anterior (TA) muscle and TA muscle motor-evoked potentials (MEPs) were assessed before and after (immediately, 10 min, and 20 min after) stimulation on different days. Additionally, 20-Hz otDCS for 10 min was applied to investigate the effects of a fixed beta-band frequency on CMC. ResultsotDCS significantly increased CMC and MEPs immediately after stimulation, whereas tACS and tDCS had no effects. There was a significant negative correlation between normalized CMC changes in response to 20-Hz otDCS and the numerical difference between the 20-Hz and individualized CMC peak frequency before the stimulation. ConclusionsThese findings suggest that simultaneous modulation of neural oscillation and cortical excitability is critical for enhancing corticospinal communication. Individualized otDCS holds potential as a useful method in the field of neurorehabilitation.

Timescales of Local and Cross-Area Interactions during Neuroprosthetic Learning.

How does the brain integrate signals with different timescales to drive purposeful actions? Brain-machine interfaces (BMIs) offer a powerful tool to causally test how distributed neural networks achieve specific neural patterns. During neuroprosthetic learning, actuator movements are causally linked to primary motor cortex (M1) neurons, i.e., "direct" neurons that project to the decoder and whose firing is required to successfully perform the task. However, it is unknown how such direct M1 neurons interact with both "indirect" local (in M1 but not part of the decoder) and across area neural populations (e.g., in premotor cortex/M2), all of which are embedded in complex biological recurrent networks. Here, we trained male rats to perform a M1-BMI task and simultaneously recorded the activity of indirect neurons in both M2 and M1. We found that both M2 and M1 indirect neuron populations could be used to predict the activity of the direct neurons (i.e., "BMI-potent activity"). Interestingly, compared with M1 indirect activity, M2 neural activity was correlated with BMI-potent activity across a longer set of time lags, and the timescale of population activity patterns evolved more slowly. M2 units also predicted the activity of both M1 direct and indirect neural populations, suggesting that M2 population dynamics provide a continuous modulatory influence on M1 activity as a whole, rather than a moment-by-moment influence solely on neurons most relevant to a task. Together, our results indicate that longer timescale M2 activity provides modulatory influence over extended time lags on shorter-timescale control signals in M1.SIGNIFICANCE STATEMENT A central question in the study of motor control is whether primary motor cortex (M1) and premotor cortex (M2) interact through task-specific subpopulations of neurons, or whether tasks engage broader correlated networks. Brain-machine interfaces (BMIs) are powerful tools to study cross-area interactions. Here, we performed simultaneous recordings of M1 and M2 in a BMI task using a subpopulation of M1 neurons (direct neurons). We found that activity outside of direct neurons in M1 and M2 was predictive of M1-BMI task activity, and that M2 activity evolved at slower timescales than M1. These findings suggest that M2 provides a continuous modulatory influence on M1 as a whole, supporting a model of interactions through broad correlated networks rather than task-specific neural subpopulations.

Neuronal activity reorganization in motor cortex for successful locomotion after a lesion in the ventrolateral thalamus.

Thalamic stroke leads to ataxia if the cerebellum-receiving ventrolateral thalamus (VL) is affected. The compensation mechanisms for this deficit are not well understood, particularly the roles that single neurons and specific neuronal subpopulations outside the thalamus play in recovery. The goal of this study was to clarify neuronal mechanisms of the motor cortex involved in mitigation of ataxia during locomotion when part of the VL is inactivated or lesioned. In freely ambulating cats, we recorded the activity of neurons in layer V of the motor cortex as the cats walked on a flat surface and horizontally placed ladder. We first reversibly inactivated ∼10% of the VL unilaterally using glutamatergic transmission antagonist CNQX and analyzed how the activity of motor cortex reorganized to support successful locomotion. We next lesioned 50%-75% of the VL bilaterally using kainic acid and analyzed how the activity of motor cortex reorganized when locomotion recovered. When a small part of the VL was inactivated, the discharge rates of motor cortex neurons decreased, but otherwise the activity was near normal, and the cats walked fairly well. Individual neurons retained their ability to respond to the demand for accuracy during ladder locomotion; however, most changed their response. When the VL was lesioned, the cat walked normally on the flat surface but was ataxic on the ladder for several days after lesion. When ladder locomotion normalized, neuronal discharge rates on the ladder were normal, and the shoulder-related group was preferentially active during the stride's swing phase.NEW & NOTEWORTHY This is the first analysis of reorganization of the activity of single neurons and subpopulations of neurons related to the shoulder, elbow, or wrist, as well as fast- and slow-conducting pyramidal tract neurons in the motor cortex of animals walking before and after inactivation or lesion in the thalamus. The results offer unique insights into the mechanisms of spontaneous recovery after thalamic stroke, potentially providing guidance for new strategies to alleviate locomotor deficits after stroke.

Neural Encoding of Reaches in a Linear Cortical Model.

To effectively control the arm, motor cortical neurons must produce complex patterns of activation that vary with the position and orientation of the arm and reach direction. In order to better understand how such a finely tuned dynamical system could arise and what its basic organizing principles are, we develop a model of the motor cortex as a linear dynamical system with feedback coupled to a two-joint model of the macaque arm. By optimizing the connections between neural populations with respect to an objective function that penalizes error between hand and target, as well as neural and muscular energy use, we show that certain properties of the motor cortex, such as muscle synergies, can naturally be obtained. We also demonstrate that the optimization process produces a stable neural system in which targets in the physical space are mapped to attracting fixed points in the neural state space. Finally, we show that this optimization process produces neural units with complex spatial and temporal activation patterns.

Comparison between the modelled response of primary motor cortex neurons to pulse-width modulated and conventional TMS stimuli.

In this study, the neural response to pulse-width modulated (PWM) transcranial magnetic stimulation (TMS) is estimated using a computational neural model which simulates the response of cortical neurons to TMS. The recently introduced programmable TMS uses PWM to approximate conventional resonance-based TMS pulses by fast switching between voltage levels. The effect of such stimulation on the six cortical layers is modelled by estimating the activation threshold of the neurons. Modelling results are compared between the novel device and that of conventional TMS stimuli generated by Magstim stimulators. The neural responses to the PWM pulses and the conventional stimuli show a high correlation, which validates the use of pulse-width modulated pulses in TMS.Clinical Relevance- This computational modelling study demonstrates an equivalent effect of PWM and conventional TMS pulses on the nervous system which paves the way to more flexibility in exploring and choosing stimulation parameters for TMS treatment.

SIMpLE: A Mobile Cloud-Based System for Health Monitoring of People with ALS.

Adopting telemonitoring services during the pandemic for people affected by chronic disease is fundamental to ensure access to health care services avoiding the risk of COVID-19 infection. Among chronic diseases, Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease of adulthood, caused by the loss of spinal, bulbar and cortical motor neurons, which leads to paralysis of the voluntary muscles and, also, involves respiratory ones. Therefore, remote monitoring and teleconsulting are essential services for ALS patients with limited mobility, as the disease progresses, and for those living far from ALS centres and hospitals. In addition, the COVID 19 pandemic has increased the need to remotely provide the best care to patients, avoiding infection during ALS centre visits. The paper illustrates an innovative, secure medical monitoring and teleconsultation mobile cloud-based system for disabled people, such as those with ALS (Amyotrophic Lateral Sclerosis). The design aims to remotely monitor biosignals, such as ECG (electrocardiographic) and EMG (electromyographic) signals of ALS patients in order to prevent complications related to the pathology.

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. Methods: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010–2020. Discussion: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. Conclusion: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study.

Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption

Complex body movements require complex dynamics and coordination among neurons in motor cortex. Conversely, a long-standing theoretical notion supposes that if many neurons in motor cortex become excessively synchronized, they may lack the necessary complexity for healthy motor coding. However, direct experimental support for this idea is rare and underlying mechanisms are unclear. Here we recorded three-dimensional body movements and spiking activity of many single neurons in motor cortex of rats with enhanced synaptic inhibition and a transgenic rat model of Rett syndrome (RTT). For both cases, we found a collapse of complexity in the motor system. Reduced complexity was apparent in lower-dimensional, stereotyped brain-body interactions, neural synchrony, and simpler behavior. Our results demonstrate how imbalanced inhibition can cause excessive synchrony among movement-related neurons and, consequently, a stereotyped motor code. Excessive inhibition and synchrony may underlie abnormal motor function in RTT.

The effect of cathodal transspinal direct current stimulation on tibialis anterior stretch reflex components in humans.

Spinal DC stimulation (tsDCS) shows promise as a technique for the facilitation of functional recovery of motor function following central nervous system (CNS) lesion. However, the network mechanisms that are responsible for the effects of tsDCS are still uncertain. Here, in a series of experiments, we tested the hypothesis that tsDCS increases the excitability of the long-latency stretch reflex, leading to increased excitability of corticospinal neurons in the primary motor cortex. Experiments were performed in 33 adult human subjects (mean age 28 ± 7years/14 females). Subjects were seated in a reclining armchair with the right leg attached to a footplate, which could be quickly plantarflexed (100deg/s; 6deg amplitude) to induce stretch reflexes in the tibialis anterior (TA) muscle at short (45ms) and longer latencies (90-95ms). This setup also enabled measuring motor evoked potentials (MEPs) and cervicomedullary evoked potentials (cMEPs) from TA evoked by transcranial magnetic stimulation (TMS) and electrical stimulation at the cervical junction, respectively. Cathodal tsDCS at 2.5 and 4mA was found to increase the long-latency reflex without any significant effect on the short-latency reflex. Furthermore, TA MEPs, but not cMEPs, were increased following tsDCS. We conclude that cathodal tsDCS over lumbar segments may facilitate proprioceptive transcortical reflexes in the TA muscle, and we suggest that the most likely explanation of this facilitation is an effect on ascending fibers in the dorsal columns.

Electrical stimulation of the common peroneal nerve and its effects on the relationship between corticomuscular coherence and motor control in healthy adults

BackgroundSensory input via neuromuscular electrical stimulation (NMES) may contribute to synchronization between motor cortex and spinal motor neurons and motor performance improvement in healthy adults and stroke patients. However, the optimal NMES parameters used to enhance physiological activity and motor performance remain unclear. In this study, we focused on sensory feedback induced by a beta-band frequency NMES (β-NMES) based on corticomuscular coherence (CMC) and investigated the effects of β-NMES on CMC and steady-state of isometric ankle dorsiflexion in healthy volunteers. Twenty-four participants received β-NMES at the peak beta-band CMC or fixed NMES (f-NMES) at 100 Hz on different days. NMES was applied to the right part of the common peroneal nerve for 20 min. The stimulation intensity was 95% of the motor threshold with a pulse width of 1 ms. The beta-band CMC and the coefficient of variation of force (Force CV) were assessed during isometric ankle dorsiflexion for 2 min. In the complementary experiment, we applied β-NMES to 14 participants and assessed beta-band CMC and motor evoked potentials (MEPs) with transcranial magnetic stimulation.ResultsNo significant changes in the means of beta-band CMC, Force CV, and MEPs were observed before and after NMES conditions. Changes in beta-band CMC were correlated to (a) changes in Force CV immediately, at 10 min, and at 20 min after β-NMES (all cases, p < 0.05) and (b) changes in MEPs immediately after β-NMES (p = 0.01). No correlations were found after f-NMES.ConclusionsOur results suggest that the sensory input via NMES was inadequate to change the beta-band CMC, corticospinal excitability, and voluntary motor output. Whereas, the β-NMES affects the relationship between changes in beta-band CMC, Force CV, and MEPs. These findings may provide the information to develop NMES parameters for neurorehabilitation in patients with motor dysfunction.

Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH

A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification of cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain1,2. Single-cell epigenomic profiling3,4 further provides information on gene-regulatory signatures of different cell types. Understanding how different cell types contribute to brain function, however, requires knowledge of their spatial organization and connectivity, which is not preserved in sequencing-based methods that involve cell dissociation. Here we used a single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH)5, to generate a molecularly defined and spatially resolved cell atlas of the mouse primary motor cortex. We profiled approximately 300,000 cells in the mouse primary motor cortex and its adjacent areas, identified 95 neuronal and non-neuronal cell clusters, and revealed a complex spatial map in which not only excitatory but also most inhibitory neuronal clusters adopted laminar organizations. Intratelencephalic neurons formed a largely continuous gradient along the cortical depth axis, in which the gene expression of individual cells correlated with their cortical depths. Furthermore, we integrated MERFISH with retrograde labelling to probe projection targets of neurons of the mouse primary motor cortex and found that their cortical projections formed a complex network in which individual neuronal clusters project to multiple target regions and individual target regions receive inputs from multiple neuronal clusters.

Neurons in Primary Motor Cortex Encode External Perturbations during an Orientation Reaching Task

When confronting an abrupt external perturbation force during movement, subjects continuously adjust their behaviors to adapt to changes. Such adaptation is of great importance for realizing flexible motor control in varied environments, but the potential cortical neuronal mechanisms behind it have not yet been elucidated. Aiming to reveal potential neural control system compensation for external disturbances, we applied an external orientation perturbation while monkeys performed an orientation reaching task and simultaneously recorded the neural activity in the primary motor cortex (M1). We found that a subpopulation of neurons in the primary motor cortex specially created a time-locked activity in response to a “go” signal in the adaptation phase of the impending orientation perturbation and did not react to a “go” signal under the normal task condition without perturbation. Such neuronal activity was amplified as the alteration was processed and retained in the extinction phase; then, the activity gradually faded out. The increases in activity during the adaptation to the orientation perturbation may prepare the system for the impending response. Our work provides important evidence for understanding how the motor cortex responds to external perturbations and should advance research about the neurophysiological mechanisms underlying motor learning and adaptation.

Neurons of rat motor cortex become active during both grasping execution and grasping observation

In non-human primates, a subset of frontoparietal neurons (mirror neurons) respond both when an individual executes an action and when it observes another individual performing a similar action.1-8 Mirror neurons constitute an observation and execution matching system likely involved in others' actions processing3,5,9 and in a large set of complex cognitive functions.10,11 Here, we show that the forelimb motor cortex of rats contains neurons presenting mirror properties analogous to those observed in macaques. We provide this evidence by event-related potentials acquired by microelectrocorticography and intracortical single-neuron activity, recorded from the same cortical region during grasping execution and observation. Mirror responses are highly specific, because grasping-related neurons do not respond to the observation of either grooming actions or graspable food alone. These results demonstrate that mirror neurons are present already in species phylogenetically distant from primates, suggesting for them a fundamental, albeit basic, role not necessarily related to higher cognitive functions. Moreover, because murine models have long been valued for their superior experimental accessibility and rapid life cycle, the present finding opens an avenue to new empirical studies tackling questions such as the innate or acquired origin of sensorimotor representations and the effects of social and environmental deprivation on sensorimotor development and recovery.

Role of the motor cortex in the generation of classically conditioned eyelid and vibrissae responses

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.

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study

ObjectiveTo test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1). MethodsIn a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects. ResultsThe facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS. ConclusionsThe results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations. SignificanceThese observations can be used to optimize iTBS investigational and therapeutic applications.