Neuronal Activity In Motor Cortex Research Articles

Brain-machine interface learning is facilitated by specific patterning of distributed cortical feedback.

Neuroprosthetics offer great hope for motor-impaired patients. One obstacle is that fine motor control requires near-instantaneous, rich somatosensory feedback. Such distributed feedback may be recreated in a brain-machine interface using distributed artificial stimulation across the cortical surface. Here, we hypothesized that neuronal stimulation must be contiguous in its spatiotemporal dynamics to be efficiently integrated by sensorimotor circuits. Using a closed-loop brain-machine interface, we trained head-fixed mice to control a virtual cursor by modulating the activity of motor cortex neurons. We provided artificial feedback in real time with distributed optogenetic stimulation patterns in the primary somatosensory cortex. Mice developed a specific motor strategy and succeeded to learn the task only when the optogenetic feedback pattern was spatially and temporally contiguous while it moved across the topography of the somatosensory cortex. These results reveal spatiotemporal properties of the sensorimotor cortical integration that set constraints on the design of neuroprosthetics.

Differential Effects of Astrocyte Manipulations on Learned Motor Behavior and Neuronal Ensembles in the Motor Cortex.

Although motor cortex is crucial for learning precise and reliable movements, whether and how astrocytes contribute to its plasticity and function during motor learning is unknown. Here, we report that astrocyte-specific manipulations in primary motor cortex (M1) during a lever push task alter motor learning and execution, as well as the underlying neuronal population coding. Mice that express decreased levels of the astrocyte glutamate transporter 1 (GLT1) show impaired and variable movement trajectories, whereas mice with increased astrocyte Gq signaling show decreased performance rates, delayed response times, and impaired trajectories. In both groups, which include male and female mice, M1 neurons have altered interneuronal correlations and impaired population representations of task parameters, including response time and movement trajectories. RNA sequencing further supports a role for M1 astrocytes in motor learning and shows changes in astrocytic expression of glutamate transporter genes, GABA transporter genes, and extracellular matrix protein genes in mice that have acquired this learned behavior. Thus, astrocytes coordinate M1 neuronal activity during motor learning, and our results suggest that this contributes to learned movement execution and dexterity through mechanisms that include regulation of neurotransmitter transport and calcium signaling.SIGNIFICANCE STATEMENT We demonstrate for the first time that in the M1 of mice, astrocyte function is critical for coordinating neuronal population activity during motor learning. We demonstrate that knockdown of astrocyte glutamate transporter GLT1 affects specific components of learning, such as smooth trajectory formation. Altering astrocyte calcium signaling by activation of Gq-DREADD upregulates GLT1 and affects other components of learning, such as response rates and reaction times as well as trajectory smoothness. In both manipulations, neuronal activity in motor cortex is dysregulated, but in different ways. Thus, astrocytes have a crucial role in motor learning via their influence on motor cortex neurons, and they do so by mechanisms that include regulation of glutamate transport and calcium signals.

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.

Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice

Perturbed neuronal Ca2+ homeostasis is implicated in Alzheimer's disease, which has primarily been demonstrated in mice with amyloid-β deposits but to a lesser and more variable extent in tauopathy models.In this study, we injected AAV to express Ca2+ indicator in layer II/III motor cortex neurons and measured neuronal Ca2+ activity by two photon imaging in awake transgenic JNPL3 tauopathy and wild-type mice. Various biochemical measurements were conducted in postmortem mouse brains for mechanistic insight and a group of animals received two intravenous injections of a tau monoclonal antibody spaced by four days to test whether the Ca2+ dyshomeostasis was related to pathological tau protein.Under running conditions, we found abnormal neuronal Ca2+ activity in tauopathy mice compared to age-matched wild-type mice with higher frequency of Ca2+ transients, lower amplitude of peak Ca2+ transients and lower total Ca2+ activity in layer II/III motor cortex neurons. While at resting conditions, only Ca2+ frequency was increased. Brain levels of soluble pathological tau correlated better than insoluble tau levels with the degree of Ca2+ dysfunction in tauopathy mice. Furthermore, tau monoclonal antibody 4E6 partially rescued Ca2+ activity abnormalities in tauopathy mice after two intravenous injections and decreased soluble pathological tau protein within the brain. This correlation and antibody effects strongly suggest that the neuronal Ca2+ dyshomeostasis is causally linked to pathological tau protein.These findings also reveal more pronounced neuronal Ca2+ dysregulation in tauopathy mice than previously reported by two-photon imaging that can be partially corrected with an acute tau antibody treatment.

PEO-CYTOP Fluoropolymer Nanosheets as a Novel Open-Skull Window for Imaging of the Living Mouse Brain.

SummaryIn vivo two-photon deep imaging with a broad field of view has revealed functional connectivity among brain regions. Here, we developed a novel observation method that utilizes a polyethylene-oxide-coated CYTOP (PEO-CYTOP) nanosheet with a thickness of ∼130 nm that exhibited a water retention effect and a hydrophilized adhesive surface. PEO-CYTOP nanosheets firmly adhered to brain surfaces, which suppressed bleeding from superficial veins. By taking advantage of the excellent optical properties of PEO-CYTOP nanosheets, we performed in vivo deep imaging in mouse brains at high resolution. Moreover, PEO-CYTOP nanosheets enabled to prepare large cranial windows, achieving in vivo imaging of neural structure and Ca2+ elevation in a large field of view. Furthermore, the PEO-CYTOP nanosheets functioned as a sealing material, even after the removal of the dura. These results indicate that this method would be suitable for the investigation of neural functions that are composed of interactions among multiple regions.

Contribution of the ventrolateral thalamus to the locomotion-related activity of motor cortex.

The activity of motor cortex is necessary for accurate stepping on a complex terrain. How this activity is generated remains unclear. The goal of this study was to clarify the contribution of signals from the ventrolateral thalamus (VL) to formation of locomotion-related activity of motor cortex during vision-independent and vision-dependent locomotion. In two cats, we recorded the activity of neurons in layer V of motor cortex as cats walked on a flat surface and a horizontal ladder. We reversibly inactivated ~10% of the VL unilaterally with the glutamatergic transmission antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and analyzed how this affected the activity of motor cortex neurons. We examined neuronal subpopulations with somatosensory receptive fields on different segments of the forelimb and pyramidal tract projecting neurons (PTNs). We found that the VL contribution to the locomotion-related activity of motor cortex is very powerful and has both excitatory and inhibitory components. The magnitudes of both the excitatory and inhibitory contributions fluctuate over the step cycle and depend on locomotion task. On a flat surface, the VL contributes more excitation to the shoulder- and elbow-related neurons than the wrist/paw-related cells. The VL excites the shoulder-related group the most during the transition from stance to swing phase, while most intensively exciting the elbow-related group during the transition from swing to stance. The VL contributes more excitation for the fast- than slow-conducting PTNs. Upon transition to vision-dependent locomotion on the ladder, the VL contribution increases more for the wrist/paw-related neurons and slow-conducting PTNs.NEW & NOTEWORTHY How the activity of motor cortex is generated and the roles that different inputs to motor cortex play in formation of response properties of motor cortex neurons during movements remain unclear. This is the first study to characterize the contribution of the input from the ventrolateral thalamus (VL), the main subcortical input to motor cortex, to the activity of motor cortex neurons during vision-independent and vision-dependent locomotion.

Altered Recruitment of Motor Cortex Neuronal Activity During the Grasping Phase of Skilled Reaching in a Chronic Rat Model of Unilateral Parkinsonism.

Parkinson's disease causes prominent difficulties in the generation and execution of voluntary limb movements, including regulation of distal muscles and coordination of proximal and distal movement components to achieve accurate grasping. Difficulties with manual dexterity have a major impact on activities of daily living. We used extracellular single neuron recordings to investigate the neural underpinnings of parkinsonian movement deficits in the motor cortex of chronic unilateral 6-hydroxydopamine lesion male rats performing a skilled reach-to-grasp task the. Both normal movements and parkinsonian deficits in this task have striking homology to human performance. In lesioned animals there were several differences in the activity of cortical neurons during reaches by the affected limb compared with control rats. These included an increase in proportions of neurons showing rate decreases, along with increased amplitude of their average rate-decrease response at specific times during the reach, suggesting a shift in the balance of net excitation and inhibition of cortical neurons; a significant increase in the duration of rate-increase responses, which could result from reduced coupling of cortical activity to specific movement components; and changes in the timing and incidence of neurons with pure rate-increase or biphasic responses, particularly at the end of reach when grasping would normally be occurring. The changes in cortical activity may account for the deficits that occur in skilled distal motor control following dopamine depletion, and highlight the need for treatment strategies targeted toward modulating cortical mechanisms for fine distal motor control in patients.SIGNIFICANCE STATEMENT We show for the first time in a chronic lesion rat model of Parkinson's disease movement deficits that there are specific changes in motor cortex neuron activity associated with the grasping phase of a skilled motor task. Such changes provide a possible mechanism underpinning the problems with manual dexterity seen in Parkinson's patients and highlight the need for treatment strategies targeted toward distal motor control.

Altered Primary Motor Cortex Neuronal Activity in a Rat Model of Harmaline-Induced Tremor During Thalamic Deep Brain Stimulation.

Although deep brain stimulation (DBS) is a clinically effective surgical treatment for essential tremor (ET), and its neurophysiological mechanisms are not fully understood. As the motor thalamus is the most popular DBS target for ET, and it is known that the thalamic nucleus plays a key role in relaying information about the external environment to the cerebral cortex, it is important to investigate mechanisms of thalamic DBS in the context of the cerebello-thalamo-cortical neuronal network. To examine this, we measured single-unit neuronal activities in the resting state in M1 during VL thalamic DBS in harmaline-induced tremor rats and analyzed neuronal activity patterns in the thalamo-cortical circuit. Four activity patterns – including oscillatory burst, oscillatory non-burst, irregular burst, and irregular non-burst – were identified by harmaline administration; and those firing patterns were differentially affected by VL thalamic DBS, which seems to drive pathologic cortical signals to signals in normal status. As specific neuronal firing patterns like oscillation or burst are considered important for information processing, our results suggest that VL thalamic DBS may modify pathophysiologic relay information rather than simply inhibit the information transmission.

Effect of pulsed transcranial ultrasound stimulation at different number of tone-burst on cortico-muscular coupling

BackgroundPulsed transcranial ultrasound stimulation (pTUS) can modulate the neuronal activity of motor cortex and elicit muscle contractions. Cortico-muscular coupling (CMC) can serve as a tool to identify interaction between the oscillatory activity of the motor cortex and effector muscle. This research aims to explore the neuromodulatory effect of low-intensity, pTUS with different number of tone burst to neural circuit of motor-control system by analyzing the coupling relationship between motor cortex and tail muscle in mouse. The motor cortex of mice was stimulated by pulsed transcranial ultrasound with different number of tone bursts (NTB = 100 150 200 250 300). The local field potentials (LFPs) in tail motor cortex and electromyography (EMG) in tail muscles were recorded simultaneously during pTUS. The change of integral coupling strength between cortex and muscle was evaluated by mutual information (MI). The directional information interaction between them were analyzed by transfer entropy (TE).ResultsAlmost all of the MI and TE values were significantly increased by pTUS. The results of MI showed that the CMC was significantly enhanced with the increase of NTB. The TE results showed the coupling strength of CMC in descending direction (from LFPs to EMG) was significantly higher than that in ascending direction (from EMG to LFPs) after stimulation. Furthermore, compared to NTB = 100, the CMC in ascending direction were significantly enhanced when NTB = 250, 300, and CMC in descending direction were significantly enhanced when NTB = 200, 250, 300.ConclusionThese results confirm that the CMC between motor cortex and the tail muscles in mouse could be altered by pTUS. And by increasing the NTB (i.e. sonication duration), the coupling strength within the cortico-muscular circuit could be increased, which might further influence the motor function of mice. It demonstrates that, using MI and TE method, the CMC could be used for quantitatively evaluating the effect of pTUS with different NTBs, which might provide a new insight into the effect of pTUS neuromodulation in motor cortex.

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks

Two-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2–5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.

Predominance of Movement Speed Over Direction in Neuronal Population Signals of Motor Cortex: Intracranial EEG Data and A Simple Explanatory Model.

How neuronal activity of motor cortex is related to movement is a central topic in motor neuroscience. Motor-cortical single neurons are more closely related to hand movement velocity than speed, that is, the magnitude of the (directional) velocity vector. Recently, there is also increasing interest in the representation of movement parameters in neuronal population activity, such as reflected in the intracranial EEG (iEEG). We show that in iEEG, contrasting to what has been previously found on the single neuron level, speed predominates over velocity. The predominant speed representation was present in nearly all iEEG signal features, up to the 600–1000 Hz range. Using a model of motor-cortical signals arising from neuronal populations with realistic single neuron tuning properties, we show how this reversal can be understood as a consequence of increasing population size. Our findings demonstrate that the information profile in large population signals may systematically differ from the single neuron level, a principle that may be helpful in the interpretation of neuronal population signals in general, including, for example, EEG and functional magnetic resonance imaging. Taking advantage of the robust speed population signal may help in developing brain–machine interfaces exploiting population signals.

Phase-dependent modulation as a novel approach for therapeutic brain stimulation.

Closed-loop paradigms provide us with the opportunity to optimize stimulation protocols for perturbation of pathological oscillatory activity in brain-related disorders. In this vein, spiking activity of motor cortex neurons and beta activity of local field potentials in the subthalamic nucleus have both been used independently of each other as neuronal signals to trigger deep brain stimulation for alleviating Parkinsonism. These approaches were superior to the standard continuous high-frequency stimulation protocols used in daily practice. However, they achieved their effects by bursts of stimulation that were applied at high-frequency as well, i.e., independent of the phase information in the stimulated region. In this context, we propose that, by timing stimulation pulses relative to the ongoing oscillation, an alternative approach, namely the targeted perturbation of pathological rhythms, could be obtained. In this modeling study, we first captured the underlying dynamics of neuronal oscillations in the human subthalamic nucleus by phased coupled neuronal oscillators. We then quantified the nature of the interaction between these coupled oscillators by obtaining a physiologically informed phase response curve from local field potentials. Reconstruction of the phase response curve predicted the sensitivity of the phase oscillator to external stimuli, revealing phase intervals that optimally maximized the degree of perturbation. We conclude that our specifically timed intervention based on the coupled oscillator concept will enable us to identify personalized ways of delivering stimulation pulses in closed-loop paradigms triggered by the phase of pathological oscillations. This will pave the way for novel physiological insights and substantial clinical benefits. In addition, this precisely phased modulation may be capable of modifying the effective interactions between oscillators in an entirely new manner.

Modulation of motor cortex neuronal activity and motor behavior during subthalamic nucleus stimulation in the normal primate.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for advanced Parkinson's disease (PD). An emerging hypothesis is that the therapeutic benefit of DBS is derived from direct modulation of primary motor cortex (M1), yet little is known about the influence of STN DBS on individual neurons in M1. We investigated the effect of STN DBS, delivered at discrete interval intensities (20, 40, 60, 80, and 100%) of corticospinal tract threshold (CSTT), on motor performance and M1 neuronal activity in a naive nonhuman primate. Motor performance during a food reach and retrieval task improved during low-intensity stimulation (20% CSTT) but worsened as intensity approached the threshold for activation of corticospinal fibers (80% and 100% CSTT). To assess cortical effects of STN DBS, spontaneous, extracellular neuronal activity was collected from M1 neurons before, during, and after DBS at the same CSTT stimulus intensities. STN DBS significantly modulated the firing of a majority of M1 neurons; however, the direction of effect varied with stimulus intensity such that, at 20% CSTT, most neurons were suppressed, whereas at the highest stimulus intensities the majority of neurons were activated. At a population level, firing rates increased as stimulus intensity increased. These results show that STN DBS influences both motor performance and M1 neuronal activity systematically according to stimulus intensity. In addition, the unanticipated reduction in reach times suggests that STN DBS, at stimulus intensities lower than typically used for treatment of PD motor signs, can enhance normal motor performance.

Body stability and muscle and motor cortex activity during walking with wide stance.

Biomechanical and neural mechanisms of balance control during walking are still poorly understood. In this study, we examined the body dynamic stability, activity of limb muscles, and activity of motor cortex neurons [primarily pyramidal tract neurons (PTNs)] in the cat during unconstrained walking and walking with a wide base of support (wide-stance walking). By recording three-dimensional full-body kinematics we found for the first time that during unconstrained walking the cat is dynamically unstable in the forward direction during stride phases when only two diagonal limbs support the body. In contrast to standing, an increased lateral between-paw distance during walking dramatically decreased the cat's body dynamic stability in double-support phases and prompted the cat to spend more time in three-legged support phases. Muscles contributing to abduction-adduction actions had higher activity during stance, while flexor muscles had higher activity during swing of wide-stance walking. The overwhelming majority of neurons in layer V of the motor cortex, 82% and 83% in the forelimb and hindlimb representation areas, respectively, were active differently during wide-stance walking compared with unconstrained condition, most often by having a different depth of stride-related frequency modulation along with a different mean discharge rate and/or preferred activity phase. Upon transition from unconstrained to wide-stance walking, proximal limb-related neuronal groups subtly but statistically significantly shifted their activity toward the swing phase, the stride phase where most of body instability occurs during this task. The data suggest that the motor cortex participates in maintenance of body dynamic stability during locomotion.

Effect of light on the activity of motor cortex neurons during locomotion

The motor cortex plays a critical role in accurate visually guided movements such as reaching and target stepping. However, the manner in which vision influences the movement-related activity of neurons in the motor cortex is not well understood. In this study we have investigated how the locomotion-related activity of neurons in the motor cortex is modified when subjects switch between walking in the darkness and in light.Three adult cats were trained to walk through corridors of an experimental chamber for a food reward. On randomly selected trials, lights were extinguished for approximately 4s when the cat was in a straight portion of the chamber's corridor. Discharges of 146 neurons from layer V of the motor cortex, including 51 pyramidal tract cells (PTNs), were recorded and compared between light and dark conditions. It was found that while cats’ movements during locomotion in light and darkness were similar (as judged from the analysis of three-dimensional limb kinematics and the activity of limb muscles), the firing behavior of 49% (71/146) of neurons was different between the two walking conditions. This included differences in the mean discharge rate (19%, 28/146 of neurons), depth of stride-related frequency modulation (24%, 32/131), duration of the period of elevated firing ([PEF], 19%, 25/131), and number of PEFs among stride-related neurons (26%, 34/131). 20% of responding neurons exhibited more than one type of change.We conclude that visual input plays a very significant role in determining neuronal activity in the motor cortex during locomotion by altering one, or occasionally multiple, parameters of locomotion-related discharges of its neurons.

Evolution of the dynamic properties of the cortex–basal ganglia network after dopaminergic depletion in rats

It is well established that parkinsonian syndrome is associated with alterations of neuronal activity temporal pattern basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in Parkinson's disease patients as well as animal models such as 6-hydroxydopamine treated rats. We recently demonstrated that this increase in oscillatory synchronization is present during high-voltage spindles (HVS) probably underpinned by the disorganization of cortex–BG interactions. Here we investigated the time course of both oscillatory and motor alterations. For that purpose we performed daily simultaneous recordings of neuronal activity in motor cortex, striatum and substantia nigra pars reticulata (SNr), before and after 6-hydroxydopamine lesion in awake rats. After a brief non-dopamine-specific desynchronization, oscillatory activity first increased during HVS followed by progressive motor impairment and the shortening of SNr activation delay. While the oscillatory firing increase reflects dopaminergic depletion, response alteration in SNr neurons is closely related to motor symptom.

Activity of motor cortex neurons during backward locomotion

Forward walking (FW) and backward walking (BW) are two important forms of locomotion in quadrupeds. Participation of the motor cortex in the control of FW has been intensively studied, whereas cortical activity during BW has never been investigated. The aim of this study was to analyze locomotion-related activity of the motor cortex during BW and compare it with that during FW. For this purpose, we recorded activity of individual neurons in the cat during BW and FW. We found that the discharge frequency in almost all neurons was modulated in the rhythm of stepping during both FW and BW. However, the modulation patterns during BW and FW were different in 80% of neurons. To determine the source of modulating influences (forelimb controllers vs. hindlimb controllers), the neurons were recorded not only during quadrupedal locomotion but also during bipedal locomotion (with either forelimbs or hindlimbs walking), and their modulation patterns were compared. We found that during BW (like during FW), modulation in some neurons was determined by inputs from limb controllers of only one girdle, whereas the other neurons received inputs from both girdles. The combinations of inputs could depend on the direction of locomotion. Most often (in 51% of forelimb-related neurons and in 34% of the hindlimb-related neurons), the neurons received inputs only from their own girdle when this girdle was leading and from both girdles when this girdle was trailing. This reconfiguration of inputs suggests flexibility of the functional roles of individual cortical neurons during different forms of locomotion.

A Wireless Brain-Machine Interface for Real-Time Speech Synthesis

BackgroundBrain-machine interfaces (BMIs) involving electrodes implanted into the human cerebral cortex have recently been developed in an attempt to restore function to profoundly paralyzed individuals. Current BMIs for restoring communication can provide important capabilities via a typing process, but unfortunately they are only capable of slow communication rates. In the current study we use a novel approach to speech restoration in which we decode continuous auditory parameters for a real-time speech synthesizer from neuronal activity in motor cortex during attempted speech.Methodology/Principal FindingsNeural signals recorded by a Neurotrophic Electrode implanted in a speech-related region of the left precentral gyrus of a human volunteer suffering from locked-in syndrome, characterized by near-total paralysis with spared cognition, were transmitted wirelessly across the scalp and used to drive a speech synthesizer. A Kalman filter-based decoder translated the neural signals generated during attempted speech into continuous parameters for controlling a synthesizer that provided immediate (within 50 ms) auditory feedback of the decoded sound. Accuracy of the volunteer's vowel productions with the synthesizer improved quickly with practice, with a 25% improvement in average hit rate (from 45% to 70%) and 46% decrease in average endpoint error from the first to the last block of a three-vowel task.Conclusions/SignificanceOur results support the feasibility of neural prostheses that may have the potential to provide near-conversational synthetic speech output for individuals with severely impaired speech motor control. They also provide an initial glimpse into the functional properties of neurons in speech motor cortical areas.

Altered neuronal activities in the motor cortex with impaired motor performance in adult rats observed after infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients

Although definite evidences are available to state that, neuronal activity is a prime determinant of animal behavior, the specific relationship between local field potentials of the motor cortex after intervention with CSF from human patients and animal behavior have remained opaque. The present study has investigated whether cerebrospinal fluid from sporadic amyotrophic lateral sclerosis (sALS) patients could disrupt neuronal activity of the motor cortex, which could be associated with disturbances in the motor performance of adult rats. CSF from ALS patients (ALS-CSF) was infused into the lateral ventricle of Wistar rats. After 24 h, the impact of ALS-CSF on the local field potentials (LFPs) of the motor cortex and on the motor behavior of animals were examined. The results indicate that ALS-CSF produced a bivariate distribution on the relative power values of the LFPs of the motor cortex 24 h following infusion. However, the behavioral results did not show bimodality, instead showed consistent decrease in motor performance: on rotarod and grip strength meter. The neuronal activity of the motor cortex negatively correlated with the duration of ALS symptoms at the time of lumbar puncture. Although the effect of ALS-CSF was more pronounced at 24 h following infusion, the changes observed in LFPs and motor performance appeared to revert to baseline values at later time points of testing. In the current study, we have shown that, ALS-CSF has the potential to perturb neuronal activity of the rat motor cortex which was associated with poor performance on motor function tests.

Direct control of paralysed muscles by cortical neurons

A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury via artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralyzed limbs1–3. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms4–10, and paralyzed muscles have been activated by functional electrical stimulation (FES)11–13. Here we show that monkeys can directly control stimulation of muscles using the activity of neurons in motor cortex, thereby restoring goal-directed movements to a transiently paralyzed arm. Moreover, neurons could control functional stimulation equally well regardless of any prior association to movement, a finding that significantly expands the source of control signals for brain-machine interfaces. Monkeys learned to utilize these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralyzed limbs.