Biology subjects

Patil, P. G.

Publications and source records attributed to Patil, P. G..

12 recordsLinked to original sources

bioRxiv2024

Sparse neural networks enable low-power, implantable neural interfaces

Recent advances in brain-machine interfaces (BMIs) using neural network decoders and increased channel count have improved the restoration of speech and motor function, but at the cost of higher power consumption. For wireless, implantable BMIs to be clinically viable, power consumption must be limited to prevent thermal tissue damage and enable long use without frequent charging. Here, we show how neural network "pruning" creates sparse decoders that require fewer computations and active channels for reduced power consumption. Across multiple movement decoding tasks using brain and muscle signals, recurrent neural network decoders can be compressed by over 100x while maintaining strong performance, enabling decoding on the implant with <1% power increase compared to decoding externally. Pruning also allows for deactivating up to 89% of channels, reducing BMI power by up to 5x. Counterintuitively, our findings suggest that BMIs employing a subset of a larger number of channels may achieve lower power consumption than BMIs with fewer channels, for a given performance level. These results suggest a path toward power-efficient, implantable BMIs suitable for long-term clinical use.

bioengineering↗

bioRxiv2024

Functional Electrical Stimulation and Brain-Machine Interfaces for Simultaneous Control of Wrist and Finger Flexion

Brain-machine interface (BMI) controlled functional electrical stimulation (FES) is a promising treatment to restore hand movements to people with cervical spinal cord injury. Recent intracortical BMIs have shown unprecedented successes in decoding user intentions, however the hand movements restored by FES have largely been limited to predetermined grasps. Restoring dexterous hand movements will require continuous control of many biomechanically linked degrees-of-freedom in the hand, such as wrist and finger flexion, that would form the basis of those movements. Here we investigate the ability to restore simultaneous wrist and finger flexion, which would enable grasping with a controlled hand posture and assist in manipulating objects once grasped. We demonstrate that intramuscular FES can enable monkeys with temporarily paralyzed hands to move their fingers and wrist across a functional range of motion, spanning an average 88.6 degrees at the metacarpophalangeal joint flexion and 71.3 degrees of wrist flexion, and intramuscular FES can control both joints simultaneously in a real-time task. Additionally, we demonstrate a monkey using an intracortical BMI to control the wrist and finger flexion in a virtual hand, both before and after the hand is temporarily paralyzed, even achieving success rates and acquisition times equivalent to able-bodied control with BMI control after temporary paralysis in two sessions. Together, this outlines a method using an artificial brain-to-body interface that could restore continuous wrist and finger movements after spinal cord injury. One Sentence SummaryWe show in non-human primates that intramuscular functional electrical stimulation can flex the wrist and fingers through a functional range of movement, can be controlled precisely, and that a brain-machine interface can determine command signals for intended finger and wrist flexion.

neuroscience↗

bioRxiv2024

Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by decoding neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks. TeaserA neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.

neuroscience↗

bioRxiv2023

Balancing Memorization and Generalization in RNNsfor High Performance Brain-Machine Interfaces

Brain-machine interfaces (BMIs) can restore motor function to people with paralysis but are currently limited by the accuracy of real-time decoding algorithms. Recurrent neural networks (RNNs) using modern training techniques have shown promise in accurately predicting movements from neural signals but have yet to be rigorously evaluated against other decoding algorithms in a closed-loop setting. Here we compared RNNs to other neural network architectures in real-time, continuous decoding of finger movements using intracortical signals from nonhuman primates. Across one and two finger online tasks, LSTMs (a type of RNN) outperformed convolutional and transformer-based neural networks, averaging 18% higher throughput than the convolution network. On simplified tasks with a reduced movement set, RNN decoders were allowed to memorize movement patterns and matched able-bodied control. Performance gradually dropped as the number of distinct movements increased but did not go below fully continuous decoder performance. Finally, in a two-finger task where one degree-of-freedom had poor input signals, we recovered functional control using RNNs trained to act both like a movement classifier and continuous decoder. Our results suggest that RNNs can enable functional real-time BMI control by learning and generating accurate movement patterns.

bioengineering↗

bioRxiv2022

Utah Array Characterization and Histological Analysis of a Multi-Year Implant in Non-Human Primate Motor and Sensory Cortices

The Utah array is widely used in both clinical studies and neuroscience. It has a strong track record of safety. However, it is also known that implanted electrodes promote the formation of scar tissue in the immediate vicinity of the electrodes, which negatively impacts the ability to record neural waveforms. This scarring response has been primarily studied in rats and mice, which may have a very different response than primate brain. Here, we present a rare nonhuman primate histological dataset (n=1 rhesus macaque) obtained 848 and 590 days after implantation in two brain hemispheres. For 2 of 4 arrays that remained within the cortex, NeuN was used to stain for neuron somata at 3 different electrode depths. Images were filtered and denoised, with neurons then counted in the vicinity of the arrays as well as a nearby section of control tissue. Additionally, 3 of 4 arrays were imaged with a scanning electrode microscope (SEM) to evaluate any materials damage that might be present. Overall, we found a 63% percent reduction in the number of neurons surrounding the electrode compared to control areas. In terms of materials, the arrays remained largely intact with metal and Parylene C present, though tip breakage and cracks were observed on many electrodes. Overall, these results suggest that the tissue response in the nonhuman primate brain shows similar neuron loss to previous studies using rodents. Electrode improvements, for example using smaller or softer probes, may therefore substantially increase the neuronal recording yield in primate cortex.

bioengineering↗

bioRxiv2022

The Impact of Task Context on Predicting Finger Movements in a Brain-Machine Interface

A key factor in the clinical translation of brain-machine interfaces (BMIs) for restoring hand motor function will be their robustness to changes in a task. With functional electrical stimulation (FES) for example, the patients own hand will be used to produce a wide range of forces in otherwise similar movements. To investigate the impact of task changes on BMI performance, we trained two rhesus macaques to control a virtual hand with their physical hand while we added springs to each finger group (index or middle-ring-small) or altered their wrist posture. Using simultaneously recorded intracortical neural activity, finger positions, and electromyography, we found that predicting finger kinematics and finger-related muscle activations across contexts led to significant increases in prediction error, especially for muscle activations. However, with respect to online BMI control of the virtual hand, changing either training task context or the hands physical context during online control had little effect on online performance. We explain this dichotomy by showing that the structure of neural population activity remained similar in new contexts, which could allow for fast adjustment online. Additionally, we found that neural activity shifted trajectories proportional to the required muscle activation in new contexts, possibly explaining biased kinematic predictions and suggesting a feature that could help predict different magnitude muscle activations while producing similar kinematics.

neuroscience↗

bioRxiv2022

Brain-Controlled Electrical Stimulation Restores Continuous Finger Function

Brain-machine interfaces have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a users own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand. In a one-dimensional, continuous, finger-related target acquisition task, the monkey improved his success rate to 83% (1.5s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5s median acquisition, equivalent to chance) when attempting to use his temporarily paralyzed hand. With two monkeys under general anesthesia, we found FES alone could control the monkeys fingers to rapidly reach targets in a median 1.1s but caused oscillation about the target. Finally, when attempting to perform a virtual two-finger continuous target acquisition task in brain-control mode following temporary hand paralysis, we found performance could be completely recovered by executing recalibrated feedback-intention training one time following temporary paralysis. These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting performance factor in a BCFES neuroprosthesis.

neuroscience↗

bioRxiv2022

A low-power communication scheme for wireless, 1000 channel brain-machine interfaces

ObjectiveBrain-machine interfaces (BMIs) have the potential to restore motor function but are currently limited by electrode count and long-term recording stability. These challenges may be solved through the use of free-floating "motes" which wirelessly transmit recorded neural signals, if power consumption can be kept within safe levels when scaling to thousands of motes. Here, we evaluated a pulse-interval modulation (PIM) communication scheme for infrared (IR)-based motes that aims to reduce the wireless data rate and system power consumption. ApproachTo test PIMs ability to efficiently communicate neural information, we simulated the communication scheme in a real-time closed-loop BMI with non-human primates. Additionally, we performed circuit simulations of an IR-based 1000-mote system to calculate communication accuracy and total power consumption. Main ResultsWe found that PIM at 1kb/s per channel maintained strong correlations with true firing rate and matched online BMI performance of a traditional wired system. Closed-loop BMI tests suggest that lags as small as 30 ms can have significant performance effects. Finally, unlike other IR communication schemes, PIM is feasible in terms of power, and neural data can accurately be recovered on a receiver using 3mW for 1000 channels. SignificanceThese results suggest that PIM-based communication could significantly reduce power usage of wireless motes to enable higher channel-counts for high-performance BMIs.

bioengineering↗

bioRxiv2021

Real-Time Brain-Machine Interface Achieves High-Velocity Prosthetic Finger Movements using a Biologically-Inspired Neural Network Decoder

Despite the rapid progress and interest in brain-machine interfaces that restore motor function, the performance of prosthetic fingers and limbs has yet to mimic native function. The algorithm that converts brain signals to a control signal for the prosthetic device is one of the limitations in achieving rapid and realistic finger movements. To achieve more realistic finger movements, we developed a shallow feed-forward neural network, loosely inspired by the biological neural pathway, to decode real-time two-degree-of-freedom finger movements. Using a two-step training method, a recalibrated feedback intention-trained (ReFIT) neural network achieved a higher throughput with higher finger velocities and more natural appearing finger movements than the ReFIT Kalman filter, which represents the current standard. The neural network decoders introduced herein are the first to demonstrate real-time decoding of continuous movements at a level superior to the current state-of-the-art and could provide a starting point to using neural networks for the development of more naturalistic brain-controlled prostheses.

neuroscience↗

bioRxiv2020

Real-Time Linear Prediction of Simultaneous and Independent Movements of Two Finger Groups Using an Intracortical Brain-Machine Interface

Modern brain-machine interfaces can return function to people with paralysis, but current hand neural prostheses are unable to reproduce control of individuated finger movements. Here, for the first time, we present a real-time, high-speed, linear brain-machine interface in nonhuman primates that utilizes intracortical neural signals to bridge this gap. We created a novel task that systematically individuates two finger groups, the index finger and the middle-ring-small fingers combined, presenting separate targets for each group. During online brain control, the ReFIT Kalman filter demonstrated the capability of individuating movements of each finger group with high performance, enabling a nonhuman primate to acquire two targets simultaneously at 1.95 targets per second, resulting in an average information throughput of 2.1 bits per second. To understand this result, we performed single unit tuning analyses. Cortical neurons were active for movements of an individual finger group, combined movements of both finger groups, or both. Linear combinations of neural activity representing individual finger group movements predicted the neural activity during combined finger group movements with high accuracy, and vice versa. Hence, a linear model was able to explain how cortical neurons encode information about multiple dimensions of movement simultaneously. Additionally, training ridge regressing decoders with independent component movements was sufficient to predict untrained higher-complexity movements. Our results suggest that linear decoders for brain-machine interfaces may be sufficient to execute high-dimensional tasks with the performance levels required for naturalistic neural prostheses.

bioengineering↗

bioRxiv2020

Stimulation of zona incerta selectively modulates pain in humans

Stimulation of zona incerta in rodent models has been shown to modulate behavioral reactions to noxious stimuli. Sensory changes observed in Parkinsonian patients with subthalamic deep brain stimulation suggest that this effect is translatable to humans. Here, we utilized the serendipitous placement of subthalamic deep brain stimulation leads to directly investigate the effects of zona incerta stimulation on human pain perception. We found that stimulation at 20 Hz, the physiological firing frequency of zona incerta, reduces experimental heat pain by a modest but significant amount, achieving a 30% reduction in one fifth of implants. Stimulation at higher frequencies did not modulate heat pain. Modulation was selective for heat pain and was not observed for warmth perception or pressure pain. These findings provide a mechanistic explanation of sensory changes seen in subthalamic deep brain stimulation patients and identify zona incerta as a potential target for neuromodulation of pain.

neuroscience↗

bioRxiv2020

G-CSF SECRETED BY EPIGENETICALLY REPROGRAMMED MUTANT IDH1 GLIOMA STEM CELLS REVERSES THE MYELOID CELLS'-MEDIATED IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT

Mutation in isocitrate dehydrogenase (mIDH) is a gain of function mutation resulting in the production of the oncometabolite, R-2-hydroxyglutarate, that inhibits DNA and histone demethylases. The resultant hypermethylation phenotype reprograms the glioma cells transcriptome and elicits profound effects on glioma immunity. We report that in mouse models and human gliomas, mIDH1 in the context of ATRX and TP53 inactivation results in global expansion of the granulocytic myeloid cells compartment. Single-cell RNA-sequencing coupled with mass cytometry analysis revealed that these granulocytes are mainly non-immunosuppressive neutrophils and pre-neutrophils; with a small fraction of polymorphonuclear myeloid-derived suppressor cells. The mechanism of mIDH1 mediated pre-neutrophils expansion involves epigenetic reprogramming which leads to enhanced expression of the granulocyte colony-stimulating factor (G-CSF). Blocking G-CSF restored the inhibitory potential of PMN-MDSCs and enhanced tumor progression. Thus, G-CSF induces remodeling of the inhibitory PMN-MDSCs in mIDH1 glioma rendering them non-immunosuppressive; and having significant therapeutic implications. SIGNIFICANCEmIDH1 is the most common mutation in gliomas associated with improved prognosis. Gliomas harboring mIDH1, together with ATRX and TP53 inactivation, exhibit higher circulating levels of G-CSF, ensuing the recruitment and expansion of non-suppressive neutrophils, pre-neutrophils and small fraction of PMN-MDSCs to the TME leading to an immune permissive phenotype.

cancer biology↗