Activity In Motor Cortex Research Articles

Decoding the Spike-Band Subthreshold Motor Cortical Activity

Intracortical Brain-Computer Interfaces (iBCI) use single-unit activity (SUA), multiunit activity (MUA) and local field potentials (LFP) to control neuroprosthetic devices. SUA and MUA are usually extracted from the bandpassed recording through amplitude thresholding, while subthreshold data are ignored. Here, we show that subthreshold data can actually be decoded to determine behavioral variables with test set accuracy of up to 100%. Although the utility of SUA, MUA and LFP for decoding behavioral variables has been explored previously, this study investigates the utility of spike-band subthreshold activity exclusively. We provide evidence suggesting that this activity can be used to keep decoding performance at acceptable levels even when SUA quality is reduced over time. To the best of our knowledge, the signals that we derive from the subthreshold activity may be the weakest neural signals that have ever been extracted from extracellular neural recordings, while still being decodable with test set accuracy of up to 100%. These results are relevant for the development of fully data-driven and automated methods for amplitude thresholding spike-band extracellular neural recordings in iBCIs containing thousands of electrodes.

Ageing attenuates exercise-enhanced motor cortical plasticity.

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean±SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean±SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults.

The Influence of Different Inter-Trial Intervals on the Quantification of Intracortical Facilitation in the Primary Motor Cortex.

Intracortical facilitation (ICF) is a paired-pulse transcranial magnetic stimulation (TMS) measurement used to quantify interneuron activity in the primary motor cortex (M1) in healthy populations and motor disorders. Due to the prevalence of the technique, most of the stimulation parameters to optimize ICF quantification have been established. However, the underappreciated methodological issue of the time between ICF trials (inter-trial interval; ITI) has been unstandardized, and different ITIs have never been compared in a paired-pulse TMS study. This is important because single-pulse TMS studies have found motor evoked potential (MEP) amplitude reductions over time during TMS trial blocks for short, but not long ITIs. The primary purpose was to determine the influence of different ITIs on the measurement of ICF. Twenty adults completed one experimental session that involved 4 separate ICF trial blocks with each utilizing a different ITI (4, 6, 8, and 10 s). Two-way ANOVAs indicated no significant ITI main effects for test MEP amplitudes, condition-test MEP amplitudes, and therefore ICF. Accordingly, all ITIs studied provided nearly identical ICF values when averaged over entire trial blocks. Therefore, it is recommended that ITIs of 4-6 s be utilized for ICF quantification to optimize participant comfort and experiment time efficiency.

Investigating Cerebellar Modulation of Premovement Beta-Band Activity during Motor Adaptation.

Enhancing cerebellar activity influences motor cortical activity and contributes to motor adaptation, though it is unclear which neurophysiological mechanisms contributing to adaptation are influenced by the cerebellum. Pre-movement beta event-related desynchronization (β-ERD), which reflects a release of inhibitory control in the premotor cortex during movement planning, is one mechanism that may be modulated by the cerebellum through cerebellar-premotor connections. We hypothesized that enhancing cerebellar activity with intermittent theta burst stimulation (iTBS) would improve adaptation rates and increase β-ERD during motor adaptation. Thirty-four participants were randomly assigned to an active (A-iTBS) or sham cerebellar iTBS (S-iTBS) group. Participants performed a visuomotor task, using a joystick to move a cursor to targets, prior to receiving A-iTBS or S-iTBS, following which they completed training with a 45° rotation to the cursor movement. Behavioural adaptation was assessed using the angular error of the cursor path relative to the ideal trajectory. The results showed a greater adaptation rate following A-iTBS and an increase in β-ERD, specific to the high β range (20-30 Hz) during motor planning, compared to S-iTBS, indicative of cerebellar modulation of the motor cortical inhibitory control network. The enhanced release of inhibitory activity persisted throughout training, which suggests that the cerebellar influence over the premotor cortex extends beyond adaptation to other stages of motor learning. The results from this study further understanding of cerebellum-motor connections as they relate to acquiring motor skills and may inform future skill training and rehabilitation protocols.

The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes.

Association between activity in the ventral premotor cortex and spinal cord activation during force generation-A combined cortico-spinal fMRI study.

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is associated with the activity in the cerebral primary motor and premotor areas is poorly understood. Here, we conducted combined cortico-spinal functional magnetic resonance imaging during a simple visually guided isometric force generation task in 20 healthy young subjects. Activation was localized in the right cervical spinal cord and left primary motor and premotor areas. The main finding is that spinal activation was negatively correlated with ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation, while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding that extends our understanding of human motor function beyond the animal literature.

Premotor cortex is hypoactive during sustained vowel production in individuals with Parkinson's disease and hypophonia.

Hypophonia is a common feature of Parkinson's disease (PD); however, the contribution of motor cortical activity to reduced phonatory scaling in PD is still not clear. In this study, we employed a sustained vowel production task during functional magnetic resonance imaging to compare brain activity between individuals with PD and hypophonia and an older healthy control (OHC) group. When comparing vowel production versus rest, the PD group showed fewer regions with significant BOLD activity compared to OHCs. Within the motor cortices, both OHC and PD groups showed bilateral activation of the laryngeal/phonatory area (LPA) of the primary motor cortex as well as activation of the supplementary motor area. The OHC group also recruited additional activity in the bilateral trunk motor area and right dorsal premotor cortex (PMd). A voxel-wise comparison of PD and HC groups showed that activity in right PMd was significantly lower in the PD group compared to OHC (p < 0.001, uncorrected). Right PMd activity was positively correlated with maximum phonation time in the PD group and negatively correlated with perceptual severity ratings of loudness and pitch. Our findings suggest that hypoactivation of PMd may be associated with abnormal phonatory control in PD.

Tuned to Tremor: Increased Sensitivity of Cortico-Basal Ganglia Neurons to Tremor Frequency in the MPTP Nonhuman Primate Model of Parkinson's Disease.

Rest tremor is one of the most prominent clinical features of Parkinson's disease (PD). Here, we hypothesized that cortico-basal ganglia neurons tend to fire in a pattern that matches PD tremor frequency, suggesting a resonance phenomenon. We recorded spiking activity in the primary motor cortex (M1) and globus pallidus external segment of 2 female nonhuman primates, before and after parkinsonian state induction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The arm of nonhuman primates was passively rotated at seven different frequencies surrounding and overlapping PD tremor frequency. We found entrainment of the spiking activity to arm rotation and a significant sharpening of the tuning curves in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine state, with a peak response at frequencies that matched the frequency of PD tremor. These results reveal increased sensitivity of the cortico-basal ganglia network to tremor frequency and could indicate that this network acts not only as a tremor switch but is involved in setting its frequency.SIGNIFICANCE STATEMENT Tremor is a prominent clinical feature of Parkinson's disease; however, its underlying pathophysiology is still poorly understood. Using electrophysiological recordings of single cortico-basal ganglia neurons before and after the induction of a parkinsonian state, and in response to passive arm rotation, this study reports increased sensitivity to tremor frequency in Parkinson's disease. We found sharpening of the population tuning to the midrange of the tested frequencies (1-13.3 Hz) in the healthy state that further increased in the parkinsonian state. These results hint at the increased frequency-tuned sensitivity of cortico-basal ganglia neurons and suggest that they tend to resonate with the tremor.

Voluntary muscle activation in people with Multiple Sclerosis is reduced across a wide range of forces following maximal effort fatiguing contractions.

Although Multiple Sclerosis (MS) is frequently associated with motor impairment, little is known about how muscle activation is affected with MS. The aim of this study was to use transcranial magnetic stimulation (TMS) and motor nerve stimulation to investigate voluntary muscle activation in people with MS across a range of contraction forces. Ten people with MS (39 ± 7 years) and 10 healthy controls (40 ± 5 years) performed elbow flexions at target contraction forces of 25%, 50%, 75%, 90%, and 100% maximal voluntary contraction (MVC) while electromyography (EMG) of the biceps brachii was recorded. Sustained elbow flexion MVCs were then performed until force declined to 60% of baseline MVC, where the target contraction forces were again examined but after the sustained MVC. Following the sustained MVC there was a reduction in biceps EMG amplitude (P < 0.01) and motor cortical voluntary activation (P < 0.01) for the MS group across all contraction intensities. There was also an increase in the rate of torque development for motor nerve resting twitches in the MS group following the sustained MVC (P = 0.03). Despite the MS group reporting higher Fatigue Severity Scale scores (P < 0.01), disease duration was a better predictor of muscle activation for the MS group (r = -0.757, P = 0.01). These findings indicate that voluntary muscle activation is compromised in people with MS following maximal effort contractions, which may be associated with disease duration rather than self-reports of fatigue.

Connecting the dots: harnessing dual-site transcranial magnetic stimulation to quantify the causal influence of medial frontal areas on the motor cortex.

Dual-site transcranial magnetic stimulation has been widely employed to investigate the influence of cortical structures on the primary motor cortex. Here, we leveraged this technique to probe the causal influence of two key areas of the medial frontal cortex, namely the supplementary motor area and the medial orbitofrontal cortex, on primary motor cortex. We show that supplementary motor area stimulation facilitates primary motor cortex activity across short (6 and 8ms) and long (12ms) inter-stimulation intervals, putatively recruiting cortico-cortical and cortico-subcortico-cortical circuits, respectively. Crucially, magnetic resonance imaging revealed that this facilitatory effect depended on a key morphometric feature of supplementary motor area: individuals with larger supplementary motor area volumes exhibited more facilitation from supplementary motor area to primary motor cortex for both short and long inter-stimulation intervals. Notably, we also provide evidence that the facilitatory effect of supplementary motor area stimulation at short intervals is unlikely to arise from spinal interactions of volleys descending simultaneously from supplementary motor area and primary motor cortex. On the other hand, medial orbitofrontal cortex stimulation moderately suppressed primary motor cortex activity at both short and long intervals, irrespective of medial orbitofrontal cortex volume. These results suggest that dual-site transcranial magnetic stimulation is a fruitful approach to investigate the differential influence of supplementary motor area and medial orbitofrontal cortex on primary motor cortex activity, paving the way for the multimodal assessment of these fronto-motor circuits in health and disease.

Mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation.

The supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse. The aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities. To this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21-67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task. Mean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p < 0.01). Bimanual finger tapping led to a significant increase in taps during stimulation (28.43taps) compared to unimanual tapping (p < 0.01). Compared to baseline, completion time for the NHPT increased significantly during stimulation (baseline: 13.6 s, stimulation: 16.4 s; p < 0.01). No differences between hemispheres were observed. The current study validated and extended a rnTMS based protocol for the mapping of the SMA regarding motor function of upper and lower extremity. This protocol could be beneficial to better understand functional SMA organisation and improve preoperative planning in patients with SMA lesions.

Comparison of virtual reality to physical box and blocks on cortical an neuromuscualar activations in young adults

The purpose of this study was to assess the changes in neural activations when performing the box and block test (BBT) in virtual reality (VR) compared to the physical BBT. Young healthy participants performed three trials of the BBT with their left and right hands in both the VR BBT, using VR hand controllers, and physical BBT conditions. Electromyography sensors were placed on the upper extremity of both arms and functional near-infrared spectroscopy was used to measure motor cortex activations throughout each condition. While a reduction in BBT score and increased wrist extensor neuromuscular activity is exhibited during the VR condition, there is no statistical difference in motor cortex activation between the two BBT conditions. This work provides a basis for exploring cortical and neuromuscular responses to VR in patient populations.

Brain activation associated with low- and high-intensity concentric versus eccentric isokinetic contractions of the biceps brachii: An fNIRS study.

Studies have shown that neural responses following concentric (CON) and eccentric (ECC) muscle contractions are different, which suggests differences in motor control associated with CON and ECC contractions. This study aims to determine brain activation of the left primary motor cortex (M1) and left and right dorsolateral prefrontal cortices (DLPFCs) during ECC and CON of the right bicep brachii (BB) muscle at low- and high-contraction intensities. Eighteen young adults (13M/5F, 21-35 years) were recruited to participate in one familiarization and two testing sessions in a randomized crossover design. During each testing session, participants performed either ECC or CON contractions of the BB (3 sets × 8 reps) at low- (25% of maximum ECC/CON, 45°/s) and high-intensity (75% of maximum ECC/CON, 45°/s) on an isokinetic dynamometer. Eleven-channel functional near-infrared spectroscopy was used to measure changes in oxyhemoglobin (O2 Hb) from the left M1, and left and right DLPFC during ECC and CON contractions. Maximum torque for ECC was higher than CON (43.3 ± 14.1 vs. 46.2 ± 15.7 N m, p = 0.025); however, no differences in O2 Hb were observed between contraction types at low or high intensities in measured brain regions. High-intensity ECC and CON contractions resulted in greater increases in O2 Hb of M1 and bilateral DLPFC compared to low-intensity ECC and CON contractions (p = 0.014). Our findings suggest no differences in O2 Hb responses between contraction types at high and low intensities. High-contraction intensities resulted in greater brain activation of the M1 and bilateral DLPFC, which may have implications for neurorehabilitation to increase central adaptations from exercise.

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

BackgroundExcessive heat exposure can lead to hyperthermia in humans, which impairs physical performance and disrupts cognitive function. While heat is a known physiological stressor, it is unclear how severe heat stress affects brain physiology and function. MethodsEleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures (Tre) attained 39.5°C, inducing exertional or passive hyperthermia, respectively. In a separate trial, blended ice was ingested before and during exercise as a cooling strategy. Data were compared to a control condition with seated rest (normothermic). Brain temperature (Tbr), cerebral perfusion, and task-based brain activity were assessed using magnetic resonance imaging techniques. ResultsTbr in motor cortex was found to be tightly regulated at rest (37.3°C ± 0.4°C (mean ± SD)) despite fluctuations in Tre. With the development of hyperthermia, Tbr increases and dovetails with the rising Tre. Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks, implying a reduced central motor drive in hyperthermic participants (Tre = 38.5°C ± 0.1°C). Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia. Executive function was poorer under a passive hyperthermic state, and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex. Conversely, ingestion of blended ice before and during exercise alleviated the rise in both Tre and Tbr and mitigated heat-related neural perturbations. ConclusionSevere heat exposure elevates Tbr, disrupts motor cortical activity and executive function, and this can lead to impairment of physical and cognitive performance.

Bias in Prestimulus Motor Cortical Activity Determines Decision-making Error in Rodents.

Decision-making is a complex process that involves the integration and interpretation of sensory information to guide actions. The rodent motor cortex, which is generally involved in motor planning and execution, also plays a critical role in decision-making processes. In perceptual delayed-response tasks, the rodent motor cortex can represent sensory cues, as well as the decision of where to move. However, it remains unclear whether erroneous decisions arise from incorrect encoding of sensory information or improper utilization of the collected sensory information in the motor cortex. In this study, we analyzed the rodent anterior lateral motor cortex (ALM) while the mice performed perceptual delayed-response tasks. We divided population activities into sensory and choice signals to separately examine the encoding and utilization of sensory information. We found that the encoding of sensory information in the error trials was similar to that in the hit trials, whereas choice signals evolved differently between the error and hit trials. In error trials, choice signals displayed an offset in the opposite direction of instructed licking even before stimulus presentation, and this tendency gradually increased after stimulus onset, leading to incorrect licking. These findings suggest that decision errors are caused by biases in choice-related activities rather than by incorrect sensory encoding. Our study elaborates on the understanding of decision-making processes by providing neural substrates for erroneous decisions.

Neuronal Plasticity and Age-Related Functional Decline in the Motor Cortex.

Physiological aging causes a decline of motor function due to impairment of motor cortex function, losses of motor neurons and neuromuscular junctions, sarcopenia, and frailty. There is increasing evidence suggesting that the changes in motor function start earlier in the middle-aged stage. The mechanism underlining the middle-aged decline in motor function seems to relate to the central nervous system rather than the peripheral neuromuscular system. The motor cortex is one of the responsible central nervous systems for coordinating and learning motor functions. The neuronal circuits in the motor cortex show plasticity in response to motor learning, including LTP. This motor cortex plasticity seems important for the intervention method mechanisms that revert the age-related decline of motor function. This review will focus on recent findings on the role of plasticity in the motor cortex for motor function and age-related changes. The review will also introduce our recent identification of an age-related decline of neuronal activity in the primary motor cortex of middle-aged mice using electrophysiological recordings of brain slices.

Enhancing Prediction of Forelimb Movement Trajectory through a Calibrating-Feedback Paradigm Incorporating RAT Primary Motor and Agranular Cortical Ensemble Activity in the Goal-Directed Reaching Task.

Complete reaching movements involve target sensing, motor planning, and arm movement execution, and this process requires the integration and communication of various brain regions. Previously, reaching movements have been decoded successfully from the motor cortex (M1) and applied to prosthetic control. However, most studies attempted to decode neural activities from a single brain region, resulting in reduced decoding accuracy during visually guided reaching motions. To enhance the decoding accuracy of visually guided forelimb reaching movements, we propose a parallel computing neural network using both M1 and medial agranular cortex (AGm) neural activities of rats to predict forelimb-reaching movements. The proposed network decodes M1 neural activities into the primary components of the forelimb movement and decodes AGm neural activities into internal feedforward information to calibrate the forelimb movement in a goal-reaching movement. We demonstrate that using AGm neural activity to calibrate M1 predicted forelimb movement can improve decoding performance significantly compared to neural decoders without calibration. We also show that the M1 and AGm neural activities contribute to controlling forelimb movement during goal-reaching movements, and we report an increase in the power of the local field potential (LFP) in beta and gamma bands over AGm in response to a change in the target distance, which may involve sensorimotor transformation and communication between the visual cortex and AGm when preparing for an upcoming reaching movement. The proposed parallel computing neural network with the internal feedback model improves prediction accuracy for goal-reaching movements.

The assessment of interhemispheric imbalance using functional near-infrared spectroscopic and transcranial magnetic stimulation for predicting motor outcome after stroke.

To investigate changes in interhemispheric imbalance of cortical excitability during motor recovery after stroke and to clarify the relationship between motor function recovery and alterations in interhemispheric imbalance, with the aim to establish more effective neuromodulation strategies. Thirty-one patients underwent assessments of resting motor threshold (RMT) using transcranial magnetic stimulation (TMS); the cortical activity of the primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA) using functional near-infrared spectroscopy (fNIRS); as well as motor function using upper extremity Fugl-Meyer (FMA-UE). The laterality index (LI) of RMT and fNIRS were also calculated. All indicators were measured at baseline(T1) and 1 month later(T2). Correlations between motor function outcome and TMS and fNIRS metrics at baseline were analyzed using bivariate correlation. All the motor function (FMA-UE1, FMA-UE2, FMA-d2) and LI-RMT (LI-RMT1 and LI-RMT2) had a moderate negative correlation. The higher the corticospinal excitability of the affected hemisphere, the better the motor outcome of the upper extremity, especially in the distal upper extremity (r = -0.366, p = 0.043; r = -0.393, p = 0.029). The greater the activation of the SMA of the unaffected hemisphere, the better the motor outcome, especially in the distal upper extremity (r = -0.356, p = 0.049; r = -0.367, p = 0.042). There was a significant moderate positive correlation observed between LI-RMT2 and LI-SMA1 (r = 0.422, p = 0.018). The improvement in motor function was most significant when both LI-RMT1 and LI-SMA1 were lower. Besides, in patients dominated by unaffected hemisphere corticospinal excitability during motor recovery, LI-(M1 + SMA + PMC)2 exhibited a significant moderate positive association with the proximal upper extremity function 1 month later (r = 0.642, p = 0.007). The combination of both TMS and fNIRS can infer the prognosis of motor function to some extent. Which can infer the role of both hemispheres in recovery and may contribute to the development of effective individualized neuromodulation strategies.

Human upper extremity motor cortex activity shows distinct oscillatory signatures for stereotyped arm and leg movements.

Stepping and arm swing are stereotyped movements that require coordination across multiple muscle groups. It is not known whether the encoding of these stereotyped movements in the human primary motor cortex is confined to the limbs' respective somatotopy. We recorded subdural electrocorticography activities from the hand/arm area in the primary motor cortex of 6 subjects undergoing deep brain stimulation surgery for essential tremor and Parkinson's disease who performed stepping (all patients) and arm swing (n = 3 patients) tasks. We show stepping-related low frequency oscillations over the arm area. Furthermore, we show that this oscillatory activity is separable, both in frequency and spatial domains, from gamma band activity changes that occur during arm swing. Our study contributes to the growing body of evidence that lower extremity movement may be more broadly represented in the motor cortex, and suggest that it may represent a way to coordinate stereotyped movements across the upper and lower extremities.

Altered Thalamocortical Signaling in a Mouse Model of Parkinson's Disease.

Activation of the primary motor cortex (M1) is important for the execution of skilled movements and motor learning, and its dysfunction contributes to the pathophysiology of Parkinson's disease (PD). A well-accepted idea in PD research, albeit not tested experimentally, is that the loss of midbrain dopamine leads to decreased activation of M1 by the motor thalamus. Here, we report that midbrain dopamine loss altered motor thalamus input in a laminar- and cell type-specific fashion and induced laminar-specific changes in intracortical synaptic transmission. Frequency-dependent changes in synaptic dynamics were also observed. Our results demonstrate that loss of midbrain dopaminergic neurons alters thalamocortical activation of M1 in both male and female mice, and provide novel insights into circuit mechanisms for motor cortex dysfunction in a mouse model of PD.SIGNIFICANCE STATEMENT Loss of midbrain dopamine neurons increases inhibition from the basal ganglia to the motor thalamus, suggesting that it may ultimately lead to reduced activation of primary motor cortex (M1). In contrast with this line of thinking, analysis of M1 activity in patients and animal models of Parkinson's disease report hyperactivation of this region. Our results are the first report that midbrain dopamine loss alters the input-output function of M1 through laminar and cell type specific effects. These findings support and expand on the idea that loss of midbrain dopamine reduces motor cortex activation and provide experimental evidence that reconciles reduced thalamocortical input with reports of altered activation of motor cortex in patients with Parkinson's disease.