RESUMEN
Correlated activity of neurons can lead to long-term strengthening or weakening of the connections between them. In addition, the behavioral context, imparted by execution of physical movements or the presence of a reward, can modulate the plasticity induced by Hebbian mechanisms. In the present study, we have combined behavior and induced neuronal correlations to strengthen connections in the motor cortex of adult behaving monkeys. Correlated activity was induced using an electrical-conditioning protocol in which stimuli gated by voluntary movements were used to produce coactivation of neurons at motor-cortical sites involved in those movements. Delivery of movement-dependent stimulation resulted in small increases in the strength of associated cortical connections immediately after conditioning. Remarkably, when paired with further repetition of the movements that gated the conditioning stimuli, there were substantially larger gains in the strength of cortical connections, which occurred in a use-dependent manner, without delivery of additional conditioning stimulation. In the absence of such movements, little change was observed in the strength of motor-cortical connections. Performance of the motor behavior in the absence of conditioning also did not produce any changes in connectivity. Our results show that combining movement-gated stimulation with further natural use of the "conditioned" pathways after stimulation ends can produce use-dependent strengthening of connections in adult primates, highlighting an important role for behavior in cortical plasticity. Our data also provide strong support for combining movement-gated stimulation with use-dependent physical rehabilitation for strengthening connections weakened by a stroke or spinal cord injury.
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Corteza Motora , Plasticidad Neuronal , Volición , Animales , Estimulación Eléctrica , Haplorrinos , Corteza Motora/fisiología , Movimiento/fisiología , Plasticidad Neuronal/fisiología , Volición/fisiologíaRESUMEN
Classic in vitro studies have described spike-timing-dependent plasticity (STDP) at a synapse: the connection from neuron A to neuron B is strengthened (or weakened) when A fires before (or after) B within an optimal time window. Accordingly, more recent in vivo works have demonstrated behavioral effects consistent with an STDP mechanism; however, many relied on single-unit recordings. The ability to modify cortical connections becomes useful in the context of injury, when connectivity and associated behavior are compromised. To avoid the need for long-term, stable isolation of single units, one could control timed activation of two cortical sites with paired electrical stimulation. We tested the hypothesis that STDP could be induced via prolonged paired stimulation as quantified by cortical evoked potentials (EPs) in the sensorimotor cortex of awake, behaving monkeys. Paired simulation between two interconnected sites produced robust effects in EPs consistent with STDP, but only at 2/15 tested pairs. The stimulation protocol often produced increases in global network excitability or depression of the conditioned pair. Together, these results suggest that paired stimulation in vivo is a viable method to induce STDP between cortical populations, but that factors beyond activation timing must be considered to produce conditioning effects.SIGNIFICANCE STATEMENT Plasticity of neural connections is important for development, learning, memory, and recovery from injury. Cellular mechanisms underlying spike-timing-dependent plasticity have been studied extensively in vitro Recent in vivo work has demonstrated results consistent with the previously defined cellular mechanisms; however, the output measure in these studies was typically an indirect assessment of plasticity at the neural level. Here, we show direct plasticity in recordings of neuronal populations in awake, behaving nonhuman primates induced by paired electrical stimulation. In contrast to in vitro studies, we found that plastic effects were only produced between specific cortical areas. These findings suggest that similar mechanisms drive plasticity in vitro and in vivo, but that cortical architecture may contribute significantly to site-dependent effects.
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Potenciales de Acción/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Corteza Sensoriomotora/citología , Animales , Biofisica , Mapeo Encefálico , Estimulación Eléctrica , Electrodos Implantados , Macaca nemestrina , Masculino , Red Nerviosa/fisiología , Tiempo de Reacción/fisiología , Corteza Sensoriomotora/fisiología , Estadísticas no Paramétricas , Factores de Tiempo , VigiliaRESUMEN
Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity.
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Interfaces Cerebro-Computador , Retroalimentación Fisiológica/fisiología , Modelos Neurológicos , Modelos Estadísticos , Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Simulación por Computador , Humanos , Neurorretroalimentación/fisiología , Estadística como AsuntoRESUMEN
Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1-3 min separated by 3-10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust.NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI.
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Condicionamiento Operante/fisiología , Corteza Motora/fisiología , Neuronas/fisiología , Núcleo Accumbens/fisiología , Refuerzo en Psicología , Potenciales de Acción , Animales , Estimulación Eléctrica , Electromiografía , Macaca nemestrina , Masculino , Recompensa , Extremidad Superior/fisiologíaRESUMEN
A motor cortex-based brain-computer interface (BCI) creates a novel real world output directly from cortical activity. Use of a BCI has been demonstrated to be a learned skill that involves recruitment of neural populations that are directly linked to BCI control as well as those that are not. The nature of interactions between these populations, however, remains largely unknown. Here, we employed a data-driven approach to assess the interaction between both local and remote cortical areas during the use of an electrocorticographic BCI, a method which allows direct sampling of cortical surface potentials. Comparing the area controlling the BCI with remote areas, we evaluated relationships between the amplitude envelopes of band limited powers as well as non-linear phase-phase interactions. We found amplitude-amplitude interactions in the high gamma (HG, 70-150 Hz) range that were primarily located in the posterior portion of the frontal lobe, near the controlling site, and non-linear phase-phase interactions involving multiple frequencies (cross-frequency coupling between 8-11 Hz and 70-90 Hz) taking place over larger cortical distances. Further, strength of the amplitude-amplitude interactions decreased with time, whereas the phase-phase interactions did not. These findings suggest multiple modes of cortical communication taking place during BCI use that are specialized for function and depend on interaction distance.
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Interfaces Cerebro-Computador , Aprendizaje/fisiología , Corteza Motora/fisiología , Adolescente , Adulto , Niño , Biología Computacional , Electrocorticografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Red Nerviosa/fisiología , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
The majority of subjects who attempt to learn control of a brain-computer interface (BCI) can do so with adequate training. Much like when one learns to type or ride a bicycle, BCI users report transitioning from a deliberate, cognitively focused mindset to near automatic control as training progresses. What are the neural correlates of this process of BCI skill acquisition? Seven subjects were implanted with electrocorticography (ECoG) electrodes and had multiple opportunities to practice a 1D BCI task. As subjects became proficient, strong initial task-related activation was followed by lessening of activation in prefrontal cortex, premotor cortex, and posterior parietal cortex, areas that have previously been implicated in the cognitive phase of motor sequence learning and abstract task learning. These results demonstrate that, although the use of a BCI only requires modulation of a local population of neurons, a distributed network of cortical areas is involved in the acquisition of BCI proficiency.
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Interfaces Cerebro-Computador/psicología , Corteza Cerebral/fisiología , Aprendizaje/fisiología , Adaptación Fisiológica , Adolescente , Adulto , Corteza Cerebral/anatomía & histología , Fenómenos Electrofisiológicos , Femenino , Humanos , Masculino , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Adulto JovenRESUMEN
The motor system is capable of adapting to changed conditions such as amputations or lesions by reorganizing cortical representations of peripheral musculature. To investigate the underlying mechanisms we induced targeted reorganization of motor output effects by establishing an artificial recurrent connection between a forelimb muscle and an unrelated site in the primary motor cortex (M1) of macaques. A head-fixed computer transformed forelimb electromyographic activity into proportional subthreshold intracortical microstimulation (ICMS) during hours of unrestrained volitional behavior. This conditioning paradigm stimulated the cortical site for a particular muscle in proportion to activation of another muscle and induced robust site- and input-specific reorganization of M1 output effects. Reorganization was observed within 25 min and could be maintained with intermittent conditioning for successive days. Control stimulation that was independent of muscle activity, termed "pseudoconditioning," failed to produce reorganization. Preconditioning output effects were gradually restored during volitional behaviors following the end of conditioning. The ease of changing the relationship between cortical sites and associated muscle responses suggests that under normal conditions these relations are maintained through physiological feedback loops. These findings demonstrate that motor cortex outputs may be reorganized in a targeted and sustainable manner through artificial afferent feedback triggered from controllable and readily recorded muscle activity. Such cortical reorganization has implications for therapeutic treatment of neurological injuries.
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Retroalimentación Fisiológica/fisiología , Actividad Motora/fisiología , Corteza Motora/citología , Corteza Motora/fisiología , Músculo Esquelético/inervación , Plasticidad Neuronal/fisiología , Animales , Condicionamiento Psicológico/fisiología , Vías Eferentes/citología , Vías Eferentes/fisiología , Estimulación Eléctrica , Electromiografía , Miembro Anterior/inervación , Miembro Anterior/fisiología , Macaca nemestrina , Masculino , Contracción Muscular/fisiología , Desnervación Muscular/métodos , Músculo Esquelético/fisiología , Músculo Esquelético/cirugía , TorqueRESUMEN
A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms, and paralysed muscles have been activated by functional electrical stimulation. Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain-machine interfaces. Monkeys learned to use 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 paralysed limbs.
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Macaca nemestrina/fisiología , Corteza Motora/citología , Músculos/inervación , Músculos/fisiología , Neuronas/fisiología , Parálisis/fisiopatología , Animales , Estimulación Eléctrica , Corteza Motora/fisiología , Movimiento , Músculos/fisiopatología , Bloqueo Nervioso , Desempeño Psicomotor , TorqueRESUMEN
All bodily movements stimulate peripheral receptors that activate neurons in the brain and spinal cord through afferent feedback. How these reafferent signals are processed within the CNS during movement is a key question in motor control. We investigated cutaneous sensory-evoked potentials in the spinal cord, primary somatosensory and motor cortex, and premotor cortex in monkeys performing an instructed delay task. Afferent inputs from cutaneous receptors were suppressed at several levels in a task-dependent manner. We found two types of suppression. First, suppression during active limb movement was observed in the spinal cord and all three cortical areas. This suppression was induced by both bottom-up and top-down gating mechanisms. Second, during preparation for upcoming movement, evoked responses were suppressed exclusively in the motor cortical areas and the magnitude of suppression was correlated with the reaction time of the subsequent movement. This suppression could be induced by a top-down gating mechanism to facilitate the preparation and execution of upcoming movement.
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Corteza Cerebral/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Función Ejecutiva/fisiología , Movimiento/fisiología , Filtrado Sensorial/fisiología , Médula Espinal/fisiología , Vías Aferentes , Análisis de Varianza , Animales , Conducta , Fenómenos Biomecánicos , Fenómenos Biofísicos , Estimulación Eléctrica , Macaca fascicularis , Macaca nemestrina , Tiempo de ReacciónRESUMEN
The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.
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Relojes Biológicos , Electroencefalografía/métodos , Potenciales Evocados Motores , Dedos/fisiopatología , Corteza Motora/fisiopatología , Movimiento , Red Nerviosa/fisiopatología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Imagery of motor movement plays an important role in learning of complex motor skills, from learning to serve in tennis to perfecting a pirouette in ballet. What and where are the neural substrates that underlie motor imagery-based learning? We measured electrocorticographic cortical surface potentials in eight human subjects during overt action and kinesthetic imagery of the same movement, focusing on power in "high frequency" (76-100 Hz) and "low frequency" (8-32 Hz) ranges. We quantitatively establish that the spatial distribution of local neuronal population activity during motor imagery mimics the spatial distribution of activity during actual motor movement. By comparing responses to electrocortical stimulation with imagery-induced cortical surface activity, we demonstrate the role of primary motor areas in movement imagery. The magnitude of imagery-induced cortical activity change was approximately 25% of that associated with actual movement. However, when subjects learned to use this imagery to control a computer cursor in a simple feedback task, the imagery-induced activity change was significantly augmented, even exceeding that of overt movement.
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Biorretroalimentación Psicológica , Corteza Cerebral/fisiología , Actividad Motora , Adolescente , Adulto , Niño , Estimulación Eléctrica , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We report the first neural recording during ecstatic meditations called jhanas and test whether a brain reward system plays a role in the joy reported. Jhanas are Altered States of Consciousness (ASC) that imply major brain changes based on subjective reports: (1) external awareness dims, (2) internal verbalizations fade, (3) the sense of personal boundaries is altered, (4) attention is highly focused on the object of meditation, and (5) joy increases to high levels. The fMRI and EEG results from an experienced meditator show changes in brain activity in 11 regions shown to be associated with the subjective reports, and these changes occur promptly after jhana is entered. In particular, the extreme joy is associated not only with activation of cortical processes but also with activation of the nucleus accumbens (NAc) in the dopamine/opioid reward system. We test three mechanisms by which the subject might stimulate his own reward system by external means and reject all three. Taken together, these results demonstrate an apparently novel method of self-stimulating a brain reward system using only internal mental processes in a highly trained subject.
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Encéfalo/fisiología , Meditación , Recompensa , Concienciación/fisiología , Electroencefalografía , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Different sleep stages have been shown to be vital for a variety of brain functions, including learning, memory, and skill consolidation. However, our understanding of neural dynamics during sleep and the role of prominent LFP frequency bands remain incomplete. To elucidate such dynamics and differences between behavioral states we collected multichannel LFP and spike data in primary motor cortex of unconstrained macaques for up to 24 h using a head-fixed brain-computer interface (Neurochip3). Each 8-s bin of time was classified into awake-moving (Move), awake-resting (Rest), REM sleep (REM), or non-REM sleep (NREM) by using dimensionality reduction and clustering on the average spectral density and the acceleration of the head. LFP power showed high delta during NREM, high theta during REM, and high beta when the animal was awake. Cross-frequency phase-amplitude coupling typically showed higher coupling during NREM between all pairs of frequency bands. Two notable exceptions were high delta-high gamma and theta-high gamma coupling during Move, and high theta-beta coupling during REM. Single units showed decreased firing rate during NREM, though with increased short ISIs compared to other states. Spike-LFP synchrony showed high delta synchrony during Move, and higher coupling with all other frequency bands during NREM. These results altogether reveal potential roles and functions of different LFP bands that have previously been unexplored.
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Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in awake nonhuman primates to stimulation, we recorded single-unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex (M1) of three macaque monkeys. Stimuli between 5 and 50 µA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 ms. ICMS pulses also induced a period of inhibition lasting up to 150 ms that typically followed the initial excitatory response. Higher current amplitudes led to a greater probability of evoking a spike and extended the duration of inhibition. The likelihood of evoking a spike in a neuron was dependent on the spontaneous firing rate as well as the delay between its most recent spike time and stimulus onset. Tonic repetitive stimulation between 2 and 20 Hz often modulated both the probability of evoking spikes and the duration of inhibition; high-frequency stimulation was more likely to change both responses. On a trial-by-trial basis, whether a stimulus evoked a spike did not affect the subsequent inhibitory response; however, their changes over time were often positively or negatively correlated. Our results document the complex dynamics of cortical neural responses to electrical stimulation that need to be considered when using ICMS for scientific and clinical applications.
Asunto(s)
Neuronas , Vigilia , Animales , Neuronas/fisiología , Estimulación Eléctrica/métodos , PrimatesRESUMEN
Intracortical recordings comprise both fast events, action potentials (APs), and slower events, known as local field potentials (LFPs). Although it is believed that LFPs mostly reflect local synaptic activity, it is unclear which of their signal components are most closely related to synaptic potentials and would therefore be causally related to the occurrence of individual APs. This issue is complicated by the significant contribution from AP waveforms, especially at higher LFP frequencies. In recordings of single-cell activity and LFPs from the human temporal cortex, we computed quantitative, nonlinear, causal dynamic models for the prediction of AP timing from LFPs, at millisecond resolution, before and after removing AP contributions to the LFP. In many cases, the timing of a significant number of single APs could be predicted from spike-free LFPs at different frequencies. Not surprisingly, model performance was superior when spikes were not removed. Cells whose activity was predicted by the spike-free LFP models generally fell into one of two groups: in the first group, neuronal spike activity was associated with specific phases of low LFP frequencies, lower spike activity at high LFP frequencies, and a stronger linear component in the spike-LFP model; in the second group, neuronal spike activity was associated with larger amplitude of high LFP frequencies, less frequent phase locking, and a stronger nonlinear model component. Spike timing in the first group was better predicted by the sign and level of the LFP preceding the spike, whereas spike timing in the second group was better predicted by LFP power during a certain time window before the spike.
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Potenciales de Acción/fisiología , Potenciales Evocados/fisiología , Modelos Neurológicos , Neuronas/fisiología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Adulto , Mapeo Encefálico , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Aprendizaje por Asociación de Pares/fisiología , Factores de Tiempo , Aprendizaje VerbalRESUMEN
Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
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Investigación Biomédica , Encefalopatías/fisiopatología , Encefalopatías/terapia , Plasticidad Neuronal/fisiología , Envejecimiento , Animales , Trastornos del Conocimiento/etiología , Humanos , Recuperación de la Función , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapiaRESUMEN
It has been proposed that the efficacy of neuronal connections is strengthened when there is a persistent causal relationship between presynaptic and postsynaptic activity. Such activity-dependent plasticity may underlie the reorganization of cortical representations during learning, although direct in vivo evidence is lacking. Here we show that stable reorganization of motor output can be induced by an artificial connection between two sites in the motor cortex of freely behaving primates. An autonomously operating electronic implant used action potentials recorded on one electrode to trigger electrical stimuli delivered at another location. Over one or more days of continuous operation, the output evoked from the recording site shifted to resemble the output from the corresponding stimulation site, in a manner consistent with the potentiation of synaptic connections between the artificially synchronized populations of neurons. Changes persisted in some cases for more than one week, whereas the output from sites not incorporated in the connection was unaffected. This method for inducing functional reorganization in vivo by using physiologically derived stimulus trains may have practical application in neurorehabilitation after injury.
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Macaca nemestrina/fisiología , Corteza Motora/fisiología , Plasticidad Neuronal/fisiología , Potenciales de Acción , Animales , Estimulación Eléctrica , Electrodos Implantados , Masculino , Movimiento/fisiología , Factores de Tiempo , TorqueRESUMEN
Cortical stimulation (CS) of the motor cortex can cause excitability changes in both hemispheres, showing potential to be a technique for clinical rehabilitation of motor function. However, previous studies that have investigated the effects of delivering CS during movement typically focus on a single hemisphere. On the other hand, studies exploring interhemispheric interactions typically deliver CS at rest. We sought to bridge these two approaches by documenting the consequences of delivering CS to a single motor cortex during different phases of contralateral and ipsilateral limb movement, and simultaneously assessing changes in interactions within and between the hemispheres via local field potential (LFP) recordings. Three macaques were trained in a unimanual reaction time (RT) task and implanted with epidural or intracortical electrodes over bilateral motor cortices. During a given session CS was delivered to one hemisphere with respect to movements of either the contralateral or ipsilateral limb. Stimulation delivered before contralateral limb movement onset shortened the contralateral limb RT. In contrast, stimulation delivered after the end of contralateral movement increased contralateral RT but decreased ipsilateral RT. Stimulation delivered before ipsilateral limb movement decreased ipsilateral RT. All other stimulus conditions as well as random stimulation and periodic stimulation did not have consistently significant effects on either limb. Simultaneous LFP recordings from one animal revealed correlations between changes in interhemispheric alpha band coherence and changes in RT, suggesting that alpha activity may be indicative of interhemispheric communication. These results show that changes caused by CS to the functional coupling within and between precentral cortices is contingent on the timing of CS relative to movement.
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Toward addressing many neuroprosthetic applications, the Neurochip3 (NC3) is a multichannel bidirectional brain-computer interface that operates autonomously and can support closed-loop activity-dependent stimulation. It consists of four circuit boards populated with off-the-shelf components and is sufficiently compact to be carried on the head of a non-human primate (NHP). NC3 has six main components: (1) an analog front-end with an Intan biophysical signal amplifier (16 differential or 32 single-ended channels) and a 3-axis accelerometer, (2) a digital control system comprised of a Cyclone V FPGA and Atmel SAM4 MCU, (3) a micro SD Card for 128 GB or more storage, (4) a 6-channel differential stimulator with ±60 V compliance, (5) a rechargeable battery pack supporting autonomous operation for up to 24 h and, (6) infrared transceiver and serial ports for communication. The NC3 and earlier versions have been successfully deployed in many closed-loop operations to induce synaptic plasticity and bridge lost biological connections, as well as deliver activity-dependent intracranial reinforcement. These paradigms to strengthen or replace impaired connections have many applications in neuroprosthetics and neurorehabilitation.
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Designing brain-computer interfaces (BCIs) that can be used in conjunction with ongoing motor behavior requires an understanding of how neural activity co-opted for brain control interacts with existing neural circuits. For example, BCIs may be used to regain lost motor function after stroke. This requires that neural activity controlling unaffected limbs is dissociated from activity controlling the BCI. In this study we investigated how primary motor cortex accomplishes simultaneous BCI control and motor control in a task that explicitly required both activities to be driven from the same brain region (i.e. a dual-control task). Single-unit activity was recorded from intracortical, multi-electrode arrays while a non-human primate performed this dual-control task. Compared to activity observed during naturalistic motor control, we found that both units used to drive the BCI directly (control units) and units that did not directly control the BCI (non-control units) significantly changed their tuning to wrist torque. Using a measure of effective connectivity, we observed that control units decrease their connectivity. Through an analysis of variance we found that the intrinsic variability of the control units has a significant effect on task proficiency. When this variance is accounted for, motor cortical activity is flexible enough to perform novel BCI tasks that require active decoupling of natural associations to wrist motion. This study provides insight into the neural activity that enables a dual-control brain-computer interface.