Neurons In Primary Motor Cortex Research Articles

Neurons in Primary Motor Cortex Encode Hand Orientation in a Reach-to-Grasp Task

It is disputed whether those neurons in the primary motor cortex (M1) that encode hand orientation constitute an independent channel for orientation control in reach-to-grasp behaviors. Here, we trained two monkeys to reach forward and grasp objects positioned in the frontal plane at different orientation angles, and simultaneously recorded the activity of M1 neurons. Among the 2235 neurons recorded in M1, we found that 18.7% had a high correlation exclusively with hand orientation, 15.9% with movement direction, and 29.5% with both movement direction and hand orientation. The distributions of neurons encoding hand orientation and those encoding movement direction were not uniform but coexisted in the same region. The trajectory of hand rotation was reproduced by the firing patterns of the orientation-related neurons independent of the hand reaching direction. These results suggest that hand orientation is an independent component for the control of reaching and grasping activity.

A novel role for the DNA repair gene Rad51 in Netrin-1 signalling

Mutations in RAD51 have recently been linked to human Congenital Mirror Movements (CMM), a developmental disorder of the motor system. The only gene previously linked to CMM encodes the Netrin-1 receptor DCC, which is important for formation of corticospinal and callosal axon tracts. Thus, we hypothesised that Rad51 has a novel role in Netrin-1-mediated axon development. In mouse primary motor cortex neurons, Rad51 protein was redistributed distally down the axon in response to Netrin-1, further suggesting a functional link between the two. We next manipulated Rad51 expression, and assessed Netrin-1 responsiveness. Rad51 siRNA knockdown exaggerated Netrin-1-mediated neurite branching and filopodia formation. RAD51 overexpression inhibited these responses, whereas overexpression of the CMM-linked R250Q mutation, a predicted loss-of-function, had no effect. Thus, Rad51 appears to negatively regulate Netrin-1 signalling. Finally, we examined whether Rad51 might operate by modulating the expression of the Unc5 family, known negative regulators of Netrin-1-responsiveness. Unc5b and Unc5c transcripts were downregulated in response to Rad51 knockdown, and upregulated with RAD51 overexpression, but not R250Q. Thus, Rad51 negatively regulates Netrin-1 signalling, at least in part, by modulating the expression of Unc5s. Imbalance of positive and negative influences is likely to lead to aberrant motor system development resulting in CMMs.

Spatiotemporal Distribution of Location and Object Effects in Primary Motor Cortex Neurons during Reach-to-Grasp.

Reaching and grasping typically are viewed as processes that proceed concurrently in the arm and hand, respectively. The arm region in the primary motor cortex (M1) is assumed to control reaching, while the hand region controls grasping. During naturalistic reach-grasp-manipulate movements, we found, however, that neuron activity proceeds largely in two sequential phases, each spanning both arm and hand representations in M1. The first phase is related predominantly to the reach location, and the second is related to the object about to be grasped. Our findings indicate that reaching and grasping are successive aspects of a single movement. Initially the arm and the hand both are projected toward the object's location, and later both are shaped to grasp and manipulate.

Primary motor cortex neurons classified in a postural task predict muscle activation patterns in a reaching task.

Primary motor cortex (M1) activity correlates with many motor variables, making it difficult to demonstrate how it participates in motor control. We developed a two-stage process to separate the process of classifying the motor field of M1 neurons from the process of predicting the spatiotemporal patterns of its motor field during reaching. We tested our approach with a neural network model that controlled a two-joint arm to show the statistical relationship between network connectivity and neural activity across different motor tasks. In rhesus monkeys, M1 neurons classified by this method showed preferred reaching directions similar to their associated muscle groups. Importantly, the neural population signals predicted the spatiotemporal dynamics of their associated muscle groups, although a subgroup of atypical neurons reversed their directional preference, suggesting a selective role in antagonist control. These results highlight that M1 provides important details on the spatiotemporal patterns of muscle activity during motor skills such as reaching.

Modulation of Premotor and Primary Motor Cortical Activity during Volitional Adjustments of Speed-Accuracy Trade-Offs.

Recent work suggests that while animals decide between reaching actions, neurons in dorsal premotor (PMd) and primary motor (M1) cortex reflect a dynamic competition between motor plans and determine when commitment to a choice is made. This competition is biased by at least two sources of information: the changing sensory evidence for one choice versus another, and an urgency signal that grows over time. Here, we test the hypothesis that the urgency signal adjusts the trade-off between speed and accuracy during both decision-making and movement execution. Two monkeys performed a reaching decision task in which sensory evidence continuously evolves over the course of each trial. In different blocks, task timing parameters encouraged monkeys to voluntarily adapt their behavior to be either hasty or conservative. Consistent with our hypothesis, during the deliberation process the baseline and gain of neural activity in decision-related PMd (29%) and M1 cells (45%) was higher when monkeys applied a hasty policy than when they behaved conservatively, but at the time of commitment the population activity was similar across blocks. Other cells (30% in PMd, 30% in M1) showed activity that increased or decreased with elapsing time until the moment of commitment. Movement-related neurons were also more active after longer decisions, as if they were influenced by the same urgency signal controlling the gain of decision-related activity. Together, these results suggest that the arm motor system receives an urgency/vigor signal that adjusts the speed-accuracy trade-off for decision-making and movement execution. Significance statement: This work addresses the neural mechanisms that control the speed-accuracy trade-off in both decisions and movements, in the kinds of dynamic situations that are typical of natural animal behavior. We found that many "decision-related" premotor and motor neurons are modulated in a time-dependent manner compatible with an "urgency" signal that changes between hasty and conservative decision policies. We also found that such modulation influenced cells related to the speed of the reaching movements executed by the animals to report their decisions. These results suggest that a unified mechanism determines speed-accuracy trade-off adjustments during decision-making and movement execution, potentially influencing both the cognitive and motor aspects of reward-oriented behavior.

Motor cortex neurons: from experiment to model via evolutionary algorithms

There are several types of neurons in primary motor cortex, with differences in ion channels, dynamics, morphology, as well as differences in synaptic input localization and axonal projections. To constrain computer models of cortical neurons, it is necessary to record from these different types of neurons. Model parameters can then be optimized, to minimize the difference between the model and experimental data. We have performed experiments recording from 2 classes of layer 5 pyramidal neurons in mouse motor cortex: corticospinal (SPI) and corticostriatal (STR). These neurons exhibit differences in synaptic inputs, axonal projections, and intrinsic membrane properties. Somatic whole-cell recordings were performed in both classes and current steps were injected (-0.2 to 0.6 nanoamperes) to produce different dynamical behaviors, including hyperpolarization-induced sag, alterations in firing rate and spike timing. We have developed multiple computer models of the different neuronal classes, each with varying complexity, and all constrained by experimental data. Two optimization methods were used: 1. evolutionary algorithms, 2. NEURON's principal axis (praxis) error minimization algorithm. We optimized model parameters with multiple fitness functions, first independently, and then in different combinations. The fitness functions quantified differences between experimental and simulated data, for firing frequency, resting membrane potential (RMP), action potential shape, interspike interval voltage trajectory, spike timing, hyperpolarization-induced sag, and voltage responses to onset/offset of current injections. We assessed optimized performance of different classes of neuronal compartmental models, with varying levels of morphological complexity, across the fitness functions. The models included a 5-compartment pyramidal neuron (with soma, basal dendrite, and three apical dendritic segments), and a ~904-compartment pyramidal neuron with detailed dendritic and axonal geometry reconstructed from our experiments. All model neurons included the same set of ion channels: INa and IKdr for action potential generation; IKa for rapid repolarization following an action potential; IKm and IKd for afterhyperpolarization; Ih for resonance, sag, excitability, and contribution to RMP; calcium channels (L, N, T-type) for bursting, excitability modulation, and contribution to backpropagating action potentials; calcium-activated potassium channels for regulating excitability after depolarization-induced calcium influx. We performed optimization in two phases: 1. optimize passive properties and compartmental geometry; 2. optimize maximal conductance and kinetics of each ion channel. The distribution of ion channels were constrained by patterns from experimental literature. For example, Ih increased exponentially with distance from the soma, while somatic and axonal compartments had higher densities of Na and K channels to allow action potential generation. This also reduced free parameters for optimization. Across the different models, the firing frequency, sag, and RMP had nearly perfect fits to the experimental data, while using a spike timing fitness function reduced spike time errors to within 1-10 ms. Due to the high dimensionality of parameter space, different subsets of fitness functions tended to improve independently, while others were correlated. We assessed which parameter values and ion channels had the largest impact on each fitness function using a post-optimization sensitivity analysis. Our methods were effective in optimizing both SPI and STR neurons and will likely generalize to other cell types.

Dynamic reorganization of neural activity in motor cortex during new sequence production.

Although previous studies have shown that primary motor cortex (M1) neurons are modulated during the performance of a sequence of movements, it is not known how this neural activity in the M1 reorganizes during new learning of sequence-dependent motor skills. Here we trained monkeys to move to each of four spatial targets to produce multiple distinct sequences of movements in which the spatial organization of the targets determined uniquely the serial order of the movements. After the monkeys memorized the sequences, we changed one element of these over-practised sequences and the subjects were required to learn the new sequence through trial and error. When one element in an over-learned four-element sequence was changed, the sequence-specific neural activity was totally disrupted, but relatively minor changes in the direction-specific activity were observed. The data suggest that sequential motor skills are represented within M1 in the context of the complete sequential behavior rather than as a series of single consecutive movements; and sequence-specific neurons in the M1 are involved in new learning of sequence by using memorized knowledge to acquire complex motor skill efficiently.

Modulation of the Intracortical LFP during Action Execution and Observation

The activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter. Upper limb EMGs were recorded to control for covert muscle activity during observation.The movement-related potential (MRP), investigated as intracortical low-frequency LFP activity (<9 Hz), was modulated in both M1 and PMv, not only during action execution but also during action observation. Moreover, the temporal LFP modulations during execution and observation were highly correlated in both cortical areas. Beta power in both PMv and M1 was clearly modulated in both conditions. Although the MRP was detected only during dynamic periods of the task (reach/grasp/release), beta decreased during dynamic and increased during static periods (hold).Comparison of LFPs for different grasps provided evidence for partially nonoverlapping networks being active during execution and observation, which might be related to different inputs to motor areas during these conditions. We found substantial information about grasp in the MRP corroborating its suitability for brain-machine interfaces, although information about grasp was generally low during action observation.

Neurons in red nucleus and primary motor cortex exhibit similar responses to mechanical perturbations applied to the upper-limb during posture.

Primary motor cortex (M1) and red nucleus (RN) are brain regions involved in limb motor control. Both structures are highly interconnected with the cerebellum and project directly to the spinal cord, although the contribution of RN is smaller than M1. It remains uncertain whether RN and M1 serve similar or distinct roles during posture and movement. Many neurons in M1 respond rapidly to mechanical disturbances of the limb, but it remains unclear whether RN neurons also respond to such limb perturbations. We have compared discharges of single neurons in RN (n = 49) and M1 (n = 109) of one monkey during a postural perturbation task. Neural responses to whole-limb perturbations were examined by transiently applying (300 ms) flexor or extensor torques to the shoulder and/or elbow while the monkeys attempted to maintain a static hand posture. Relative to baseline discharges before perturbation onset, perturbations evoked rapid (<100 ms) changes of neural discharges in many RN (28 of 49, 57%) and M1 (43 of 109, 39%) neurons. In addition to exhibiting a greater proportion of perturbation-related neurons, RN neurons also tended to exhibit higher peak discharge frequencies in response to perturbations than M1 neurons. Importantly, neurons in both structures exhibited similar response latencies and tuning properties (preferred torque directions and tuning widths) in joint-torque space. Proximal arm muscles also displayed similar tuning properties in joint-torque space. These results suggest that RN is more sensitive than M1 to mechanical perturbations applied during postural control but both structures may play a similar role in feedback control of posture.

Arm and hand movement: current knowledge and future perspective.

Reaching with the arm and grasping with the hand and fingers is a complex behavior that appears in utero, is elaborated over the first few years of life, and serves useful everyday functions throughout the course of human life. Several neurological conditions can impair the ability to produce arm and hand movements and so greatly impact on the quality of life and well-being of the affected individuals. Given the fundamental role that arm and hand movements play in everyday life, deficits related to arm and hand function are one of the most debilitating motor conditions. Neurological conditions that can affect arm and hand movements include autism spectrum disorder, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, cerebral palsy, and stroke-related motor cortex damage as well as spinal cord injury at cervical levels. While arm and hand movement has received considerable attention from both clinicians and researchers from diverse scientific backgrounds, there are a number of broad research questions that still need to be addressed in this research field. The present Research Topic is entirely devoted to arm and hand movement in health as well as in disease. It is a compilation of original research papers and reviews, clinical case studies, hypothesis and theory articles, opinions, commentaries, and methods articles that cover important aspects of the topic from different perspectives. In this volume, de Bruin et al. (1) present data that describe how healthy adults use space while performing a visually guided grasping task. A model for understanding hand functioning in children with cerebral palsy is proposed by Arnould et al. (2) while Johansson et al. (3) explore the effect of timing training on upper limb movement in three children with diplegic cerebral palsy. Parma et al. (4) compare the kinematics of the reach-to grasp movement in patients with vascular and idiopathic Parkinson’s disease whereas Aluru et al. (5) evaluate the effect of auditory constraints on motor performance at different stages after a stroke. Lawrence et al. (6) measure dexterous manipulation in a cross-sectional study comparing gender, age, and absence and presence of disease. Kirsh et al. (7) provide evidence to support the view that neurons outside the primary motor cortex – such as those populating the pontomedullary reticular formation and the spinal cord-drive movement and muscle synergies that primary motor cortex neurons then break up to create individual wrist and finger movements. Sacrey et al. (8) summarize current knowledge related to reaching and grasping in autism spectrum disorder. On the other hand, Whitwell et al. (9) reinstate patient DF’s amazing ability to use information regarding form and orientation of objects to guide skilled reaching actions despite her visual agnosia. In an opinion article, Moore (10) argues that nerve transfer is increasingly popular and is becoming the best treatment strategy for most brachial plexus damage as well as for patients with spinal cord injury at cervical levels. Vicario (11) provides a personal commentary on a paper from Hayashi et al. (12) and, in a review article, Karl and Whishaw (13) summarize the evidence that show that reaching and grasping are from distinct neural and evolutionary origins. Irvine et al. (14) contribute a methods article that assesses the reliability of the Irvine, Beatties, and Bresnahan (IBB) forelimb recovery scale. Fouad et al. (15) demonstrate that continuous viral-mediated brain-derived neurotrophic factor (BDNF) over-expression promotes spasticity in rats with spinal cord hemisections at cervical levels. Alstermark and Pettersson (16) bring evidence to show that lesions to the corticospinal tract that spare the cortico-reticulospinal pathway in the rat have no deleterious effects on skilled reaching and grasping. Finally, Tosolini et al. (17) describe how targeting the full length of the motor endplate region in the mouse forelimb with Fluoro-Gold increases the uptake of this neuroanatomical retrograde tracer in corresponding motor neurons. We are delighted to present “Arm and Hand Movement: Current Knowledge and Future Perspective” as a Research Topic in Frontiers in Neurology. We feel that this wide-ranging compilation of articles by leading experts in upperlimb/forelimb movement and working either in clinical or basic research settings has offered fresh perspectives on the topic. We are thankful for the support of all the scientists who have contributed to this Research Topic and have shared with us their expertise and point of views. Their contributions have deepened our appreciation of the challenge that restoring arm and hand function in different pathologies represents. We invite the readers to experience the diversity in methodological approaches and experimental designs that together have led to broaden our understanding of this particularly wide field of research.

Cell based therapy in Amyotrophic Lateral Sclerosis

AIM: To review recent accomplishments in cell transplant treatment for ALS and future options with iPSC technology. OBJECTIVE: To learn about different stem cell therapies in amyotrophic lateral sclerosis disease. BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease, characterized by the predominant loss of motor neurons (MNs) in primary motor cortex, the brainstem, and the spinal cord. Amyotrophic lateral sclerosis is a multifactorial progressive neurodegenerative disorder leading to severe disability due to skeletal muscle paralysis and death within 3-5 years of diagnosis. Cell-based therapy has been proposed as an ultimate source for regeneration of MNs. Since direct replacement or restoring of motor neurons using various stem cells is challenging, enrichment of healthy donor-derived astrocytes appears to be a more realistic and beneficial approach. Autologous somatic stem cell-based human trials are now in track to reveal the outcome of the ongoing trials. Recent accomplishments in cell transplant treatment for ALS and future options with iPSC technology is discussed. REASON: Furthermore, Induced pluripotent stem cell (IPSC)-based ALS disease drug screen and autologous cell transplant options will broaden therapeutic options.

Motor cortex single-neuron and population contributions to compensation for multiple dynamic force fields.

To elucidate how primary motor cortex (M1) neurons contribute to the performance of a broad range of different and even incompatible motor skills, we trained two monkeys to perform single-degree-of-freedom elbow flexion/extension movements that could be perturbed by a variety of externally generated force fields. Fields were presented in a pseudorandom sequence of trial blocks. Different computer monitor background colors signaled the nature of the force field throughout each block. There were five different force fields: null field without perturbing torque, assistive and resistive viscous fields proportional to velocity, a resistive elastic force field proportional to position and a resistive viscoelastic field that was the linear combination of the resistive viscous and elastic force fields. After the monkeys were extensively trained in the five field conditions, neural recordings were subsequently made in M1 contralateral to the trained arm. Many caudal M1 neurons altered their activity systematically across most or all of the force fields in a manner that was appropriate to contribute to the compensation for each of the fields. The net activity of the entire sample population likewise provided a predictive signal about the differences in the time course of the external forces encountered during the movements across all force conditions. The neurons showed a broad range of sensitivities to the different fields, and there was little evidence of a modular structure by which subsets of M1 neurons were preferentially activated during movements in specific fields or combinations of fields.

Illuminating brain stimulation therapy

Biomedicine Stroke, the disruption in blood supply to the brain, affects approximately 15 million people worldwide each year. With few treatment options, strokes leave one third of their sufferers permanently disabled. Magnetic stimulation of the brain is one promising therapy,but it is relatively non-specific. To determine which cell types may promote recovery; Cheng et al. engineered mice to express light-activated protein receptors in their neurons. They then used light to activate specific neurons and found that while stimulating neurons in the ipsilesional primary motor cortex had no effect on healthy mice, it did help mice recover after stroke. Stimulating neurons in a targeted manner may be a promising therapy for stroke patients and cause fewer side effects. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1404109111 (2014).

Amyotrophic lateral sclerosis - cell based therapy and novel therapeutic development.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized by the predominant loss of motor neurons (MNs) in primary motor cortex, the brainstem, and the spinal cord, causing premature death in most cases. Minimal delay of pathological development by available medicine has prompted the search for novel therapeutic treatments to cure ALS. Cell-based therapy has been proposed as an ultimate source for regeneration of MNs. Recent completion of non-autologous fetal spinal stem cell transplant to ALS patients brought renewed hope for further human trials to cure the disease. Autologous somatic stem cell-based human trials are now in track to reveal the outcome of the ongoing trials. Furthermore, induced pluripotent stem cell (iPSC)-based ALS disease drug screen and autologous cell transplant options will broaden therapeutic options. In this review paper, we discuss recent accomplishments in cell transplant treatment for ALS and future options with iPSC technology.

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

BackgroundLower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural “intent”. A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of “intent” may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements.MethodsWe hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called “Motolink”, which detects these neural patterns and triggers a “spinal” stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for “Motolink” hardware.ResultsWe identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the “Motolink” system to detect the neural “intent” of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements.ConclusionWe present a direct cortical “intent”-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

Rapid acquisition of novel interface control by small ensembles of arbitrarily selected primary motor cortex neurons.

Pioneering studies demonstrated that novel degrees of freedom could be controlled individually by directly encoding the firing rate of single motor cortex neurons, without regard to each neuron's role in controlling movement of the native limb. In contrast, recent brain-computer interface work has emphasized decoding outputs from large ensembles that include substantially more neurons than the number of degrees of freedom being controlled. To bridge the gap between direct encoding by single neurons and decoding output from large ensembles, we studied monkeys controlling one degree of freedom by comodulating up to four arbitrarily selected motor cortex neurons. Performance typically exceeded random quite early in single sessions and then continued to improve to different degrees in different sessions. We therefore examined factors that might affect performance. Performance improved with larger ensembles. In contrast, other factors that might have reflected preexisting synaptic architecture-such as the similarity of preferred directions-had little if any effect on performance. Patterns of comodulation among ensemble neurons became more consistent across trials as performance improved over single sessions. Compared with the ensemble neurons, other simultaneously recorded neurons showed less modulation. Patterns of voluntarily comodulated firing among small numbers of arbitrarily selected primary motor cortex (M1) neurons thus can be found and improved rapidly, with little constraint based on the normal relationships of the individual neurons to native limb movement. This rapid flexibility in relationships among M1 neurons may in part underlie our ability to learn new movements and improve motor skill.

Primary Motor Cortex Neurons during Individuated Finger and Wrist Movements: Correlation of Spike Firing Rates with the Motion of Individual Digits versus Their Principal Components.

The joints of the hand provide 24 mechanical degrees of freedom. Yet 2–7 principal components (PCs) account for 80–95% of the variance in hand joint motion during tasks that vary from grasping to finger spelling. Such findings have led to the hypothesis that the brain may simplify operation of the hand by preferentially controlling PCs. We tested this hypothesis using data recorded from the primary motor cortex (M1) during individuated finger and wrist movements. Principal component analysis (PCA) of the simultaneous position of the five digits and the wrist showed relatively consistent kinematic synergies across recording sessions in two monkeys. The first three PCs typically accounted for 85% of the variance. Cross-correlations then were calculated between the firing rate of single neurons and the simultaneous flexion/extension motion of each of the five digits and the wrist, as well as with each of their six PCs. For each neuron, we then compared the maximal absolute value of the cross-correlations (MAXC) achieved with the motion of any digit or the wrist to the MAXC achieved with motion along any PC axis. The MAXC with a digit and the MAXC with a PC were themselves highly correlated across neurons. A minority of neurons correlated more strongly with a PC than with any digit. But for the populations of neurons sampled from each of two subjects, MAXCs with digits were slightly but significantly higher than those with PCs. We therefore reject the hypothesis that M1 neurons preferentially control PCs of hand motion. We cannot exclude the possibility that M1 neurons might control kinematic synergies identified using linear or non-linear methods other than PCA. We consider it more likely, however, that neurons in other centers of the motor system – such as the pontomedullary reticular formation and the spinal gray matter – drive synergies of movement and/or muscles, which M1 neurons act to fractionate in producing individuated finger and wrist movements.

Crouching tiger, hidden dimensions

A study finds that, during movement preparation, when motor cortex is active, but elicits no muscle output, firing of individual neurons in dorsal premotor and primary motor cortex cancels out at the level of population activity.

The roles of monkey M1 neuron classes in movement preparation and execution

The motor cortices exhibit substantial activity while preparing movements, yet the arm remains still during preparation. We investigated whether a subpopulation of presumed inhibitory neurons in primary motor cortex (M1) might be involved in “gating” motor output during preparation, while permitting output during movement. This hypothesis predicts a release of inhibition just before movement onset. In data from M1 of two monkeys, we did not find evidence for this hypothesis: few neurons exhibited a clear pause during movement, and these were at the tail end of a broad distribution. We then identified a subpopulation likely to be enriched for inhibitory interneurons, using their waveform shapes. We found that the firing rates of this subpopulation tended to increase during movement instead of decreasing as predicted by the M1 gating model. No clear subset that might implement an inhibitory gate was observed. Together with previous evidence against upstream inhibitory mechanisms in premotor cortex, this provides evidence against an inhibitory “gate” for motor output in cortex. Instead, it appears that some other mechanism must likely exist.

Somatosensory responses in a human motor cortex

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications.