Browsing by Author "Nicolelis, Miguel AL"

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    A Brain to Spine Interface for Transferring Artificial Sensory Information.
    (Scientific reports, 2020-01-21) Yadav, Amol P; Li, Daniel; Nicolelis, Miguel AL
    Lack of sensory feedback is a major obstacle in the rapid absorption of prosthetic devices by the brain. While electrical stimulation of cortical and subcortical structures provides unique means to deliver sensory information to higher brain structures, these approaches require highly invasive surgery and are dependent on accurate targeting of brain structures. Here, we propose a semi-invasive method, Dorsal Column Stimulation (DCS) as a tool for transferring sensory information to the brain. Using this new approach, we show that rats can learn to discriminate artificial sensations generated by DCS and that DCS-induced learning results in corticostriatal plasticity. We also demonstrate a proof of concept brain-to-spine interface (BTSI), whereby tactile and artificial sensory information are decoded from the brain of an "encoder" rat, transformed into DCS pulses, and delivered to the spinal cord of a second "decoder" rat while the latter performs an analog-to-digital conversion during a sensory discrimination task. These results suggest that DCS can be used as an effective sensory channel to transmit prosthetic information to the brain or between brains, and could be developed as a novel platform for delivering tactile and proprioceptive feedback in clinical applications of brain-machine interfaces.
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    A Closed Loop Brain-machine Interface for Epilepsy Control Using Dorsal Column Electrical Stimulation.
    (Scientific reports, 2016-09-08) Pais-Vieira, Miguel; Yadav, Amol P; Moreira, Derek; Guggenmos, David; Santos, Amílcar; Lebedev, Mikhail; Nicolelis, Miguel AL
    Although electrical neurostimulation has been proposed as an alternative treatment for drug-resistant cases of epilepsy, current procedures such as deep brain stimulation, vagus, and trigeminal nerve stimulation are effective only in a fraction of the patients. Here we demonstrate a closed loop brain-machine interface that delivers electrical stimulation to the dorsal column (DCS) of the spinal cord to suppress epileptic seizures. Rats were implanted with cortical recording microelectrodes and spinal cord stimulating electrodes, and then injected with pentylenetetrazole to induce seizures. Seizures were detected in real time from cortical local field potentials, after which DCS was applied. This method decreased seizure episode frequency by 44% and seizure duration by 38%. We argue that the therapeutic effect of DCS is related to modulation of cortical theta waves, and propose that this closed-loop interface has the potential to become an effective and semi-invasive treatment for refractory epilepsy and other neurological disorders.
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    Building an organic computing device with multiple interconnected brains.
    (Scientific reports, 2015-07-09) Pais-Vieira, Miguel; Chiuffa, Gabriela; Lebedev, Mikhail; Yadav, Amol; Nicolelis, Miguel AL
    Recently, we proposed that Brainets, i.e. networks formed by multiple animal brains, cooperating and exchanging information in real time through direct brain-to-brain interfaces, could provide the core of a new type of computing device: an organic computer. Here, we describe the first experimental demonstration of such a Brainet, built by interconnecting four adult rat brains. Brainets worked by concurrently recording the extracellular electrical activity generated by populations of cortical neurons distributed across multiple rats chronically implanted with multi-electrode arrays. Cortical neuronal activity was recorded and analyzed in real time, and then delivered to the somatosensory cortices of other animals that participated in the Brainet using intracortical microstimulation (ICMS). Using this approach, different Brainet architectures solved a number of useful computational problems, such as discrete classification, image processing, storage and retrieval of tactile information, and even weather forecasting. Brainets consistently performed at the same or higher levels than single rats in these tasks. Based on these findings, we propose that Brainets could be used to investigate animal social behaviors as well as a test bed for exploring the properties and potential applications of organic computers.
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    Chronic spinal cord electrical stimulation protects against 6-hydroxydopamine lesions.
    (Scientific reports, 2014-01-23) Yadav, Amol P; Fuentes, Romulo; Zhang, Hao; Vinholo, Thais; Wang, Chi-Han; Freire, Marco Aurelio M; Nicolelis, Miguel AL
    Although L-dopa continues to be the gold standard for treating motor symptoms of Parkinson's disease (PD), it presents long-term complications. Deep brain stimulation is effective, but only a small percentage of idiopathic PD patients are eligible. Based on results in animal models and a handful of patients, dorsal column stimulation (DCS) has been proposed as a potential therapy for PD. To date, the long-term effects of DCS in animal models have not been quantified. Here, we report that DCS applied twice a week in rats treated with bilateral 6-OHDA striatal infusions led to a significant improvement in symptoms. DCS-treated rats exhibited a higher density of dopaminergic innervation in the striatum and higher neuronal cell count in the substantia nigra pars compacta compared to a control group. These results suggest that DCS has a chronic therapeutical and neuroprotective effect, increasing its potential as a new clinical option for treating PD patients.
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    Cortical neurons multiplex reward-related signals along with sensory and motor information.
    (Proc Natl Acad Sci U S A, 2017-06-13) Ramakrishnan, Arjun; Byun, Yoon Woo; Rand, Kyle; Pedersen, Christian E; Lebedev, Mikhail A; Nicolelis, Miguel AL
    Rewards are known to influence neural activity associated with both motor preparation and execution. This influence can be exerted directly upon the primary motor (M1) and somatosensory (S1) cortical areas via the projections from reward-sensitive dopaminergic neurons of the midbrain ventral tegmental areas. However, the neurophysiological manifestation of reward-related signals in M1 and S1 are not well understood. Particularly, it is unclear how the neurons in these cortical areas multiplex their traditional functions related to the control of spatial and temporal characteristics of movements with the representation of rewards. To clarify this issue, we trained rhesus monkeys to perform a center-out task in which arm movement direction, reward timing, and magnitude were manipulated independently. Activity of several hundred cortical neurons was simultaneously recorded using chronically implanted microelectrode arrays. Many neurons (9-27%) in both M1 and S1 exhibited activity related to reward anticipation. Additionally, neurons in these areas responded to a mismatch between the reward amount given to the monkeys and the amount they expected: A lower-than-expected reward caused a transient increase in firing rate in 60-80% of the total neuronal sample, whereas a larger-than-expected reward resulted in a decreased firing rate in 20-35% of the neurons. Moreover, responses of M1 and S1 neurons to reward omission depended on the direction of movements that led to those rewards. These observations suggest that sensorimotor cortical neurons corepresent rewards and movement-related activity, presumably to enable reward-based learning.
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    Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's disease.
    (Movement disorders : official journal of the Movement Disorder Society, 2017-06) Yadav, Amol P; Nicolelis, Miguel AL
    Spinal cord stimulation has been used for the treatment of chronic pain for decades. In 2009, our laboratory proposed, based on studies in rodents, that electrical stimulation of the dorsal columns of the spinal cord could become an effective treatment for motor symptoms associated with Parkinson's disease (PD). Since our initial report in rodents and a more recent study in primates, several clinical studies have now described beneficial effects of dorsal column stimulation in parkinsonian patients. In primates, we have shown that dorsal column stimulation activates multiple structures along the somatosensory pathway and desynchronizes the pathological cortico-striatal oscillations responsible for the manifestation of PD symptoms. Based on recent evidence, we argue that neurological disorders such as PD can be broadly classified as diseases emerging from abnormal neuronal timing, leading to pathological brain states, and that the spinal cord could be used as a "channel" to transmit therapeutic electrical signals to disrupt these abnormalities. © 2017 International Parkinson and Movement Disorder Society.
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    Spike avalanches exhibit universal dynamics across the sleep-wake cycle.
    (PLoS One, 2010-11-30) Ribeiro, Tiago L; Copelli, Mauro; Caixeta, Fábio; Belchior, Hindiael; Chialvo, Dante R; Nicolelis, Miguel AL; Ribeiro, Sidarta
    BACKGROUND: Scale-invariant neuronal avalanches have been observed in cell cultures and slices as well as anesthetized and awake brains, suggesting that the brain operates near criticality, i.e. within a narrow margin between avalanche propagation and extinction. In theory, criticality provides many desirable features for the behaving brain, optimizing computational capabilities, information transmission, sensitivity to sensory stimuli and size of memory repertoires. However, a thorough characterization of neuronal avalanches in freely-behaving (FB) animals is still missing, thus raising doubts about their relevance for brain function. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we employed chronically implanted multielectrode arrays (MEA) to record avalanches of action potentials (spikes) from the cerebral cortex and hippocampus of 14 rats, as they spontaneously traversed the wake-sleep cycle, explored novel objects or were subjected to anesthesia (AN). We then modeled spike avalanches to evaluate the impact of sparse MEA sampling on their statistics. We found that the size distribution of spike avalanches are well fit by lognormal distributions in FB animals, and by truncated power laws in the AN group. FB data surrogation markedly decreases the tail of the distribution, i.e. spike shuffling destroys the largest avalanches. The FB data are also characterized by multiple key features compatible with criticality in the temporal domain, such as 1/f spectra and long-term correlations as measured by detrended fluctuation analysis. These signatures are very stable across waking, slow-wave sleep and rapid-eye-movement sleep, but collapse during anesthesia. Likewise, waiting time distributions obey a single scaling function during all natural behavioral states, but not during anesthesia. Results are equivalent for neuronal ensembles recorded from visual and tactile areas of the cerebral cortex, as well as the hippocampus. CONCLUSIONS/SIGNIFICANCE: Altogether, the data provide a comprehensive link between behavior and brain criticality, revealing a unique scale-invariant regime of spike avalanches across all major behaviors.