RESUMEN
Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.
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Evolución Biológica , Haplorrinos , Corteza Motora , Destreza Motora , Neuronas , Animales , Ratones , Haplorrinos/fisiología , Haplorrinos/psicología , Corteza Motora/citología , Corteza Motora/fisiología , Destreza Motora/fisiología , Movimiento/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Pensamiento/fisiologíaRESUMEN
The fluid movement of an arm requires multiple spatiotemporal parameters to be set independently. Recent studies have argued that arm movements are generated by the collective dynamics of neurons in motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independent components of the neural dynamics. Using a task where three male monkeys made a sequence of reaching movements to randomly placed targets, we show that the spatial and temporal parameters of arm movements are independently encoded in the low-dimensional trajectories of population activity in motor cortex: Each movement's direction corresponds to a fixed neural trajectory through neural state space and its speed to how quickly that trajectory is traversed. Recurrent neural network models show this coding allows independent control over the spatial and temporal parameters of movement by separate network parameters. Our results support a key prediction of the dynamical systems view of motor cortex, but also argue that not all parameters of movement are defined by different trajectories of population activitySignificance Statement From delicate strokes while drawing to ballistic swings while playing tennis, a skilled arm movement requires precise control of both its direction and speed. Motor cortex is thought to play a key role in controlling both, but it is unclear how they are jointly controlled. We show here that the population activity in motor cortex represents both the spatial and temporal properties of arm movements in the same low-dimensional signal. This representation was remarkably simple: the movement's direction is represented by the trajectory that signal takes; the movement's speed by how quickly the signal moves along its trajectory. Our network modelling shows this encoding allows an arm movement's direction and speed to be simultaneously and independently controlled.
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Prominent models of spike trains assume only one source of variability - stochastic (Poisson) spiking - when stimuli and behavior are fixed. However, spike trains may also reflect variability due to internal processes such as planning. For example, we can plan a movement at one point in time and execute it at some arbitrary later time. Neurons involved in planning may thus share an underlying time course that is not precisely locked to the actual movement. Here we combine the standard Linear-Nonlinear-Poisson (LNP) model with Dynamic Time Warping (DTW) to account for shared temporal variability. When applied to recordings from macaque premotor cortex, we find that time warping considerably improves predictions of neural activity. We suggest that such temporal variability is a widespread phenomenon in the brain which should be modeled.
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Potenciales de Acción/fisiología , Modelos Neurológicos , Neuronas/fisiología , Dinámicas no Lineales , Animales , Humanos , Distribución de Poisson , Factores de TiempoRESUMEN
Although primary motor cortex (M1) is intimately involved in the dynamics of limb movement, its inputs may be more closely related to higher-order aspects of movement and multi-modal sensory feedback. Motor learning is thought to result from the adaption of internal models that compute transformations between these representations. While the psychophysics of motor learning has been studied in many experiments, the particular role of M1 in the process remains the subject of debate. Studies of learning-related changes in the spatial tuning of M1 neurons have yielded conflicting results. To resolve the discrepancies, we recorded from M1 during curl field adaptation in a reaching task. Our results suggest that aside from the addition of the load itself, the relation of M1 to movement dynamics remains unchanged as monkeys adapt behaviorally. Accordingly, we implemented a musculoskeletal model to generate synthetic neural activity having a fixed dynamical relation to movement and showed that these simulated neurons reproduced the observed behavior of the recorded M1 neurons. The stable representation of movement dynamics in M1 suggests that behavioral changes are mediated through progressively altered recruitment of M1 neurons, while the output effect of those neurons remained largely unchanged.
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Adaptación Fisiológica/fisiología , Conducta Animal/fisiología , Actividad Motora/fisiología , Corteza Motora/fisiología , Neuronas/fisiología , Animales , Electroencefalografía , Macaca mulatta , Masculino , Corteza Motora/citologíaRESUMEN
Landmark universal function approximation results for neural networks with trained weights and biases provided impetus for the ubiquitous use of neural networks as learning models in Artificial Intelligence (AI) and neuroscience. Recent work has pushed the bounds of universal approximation by showing that arbitrary functions can similarly be learned by tuning smaller subsets of parameters, for example the output weights, within randomly initialized networks. Motivated by the fact that biases can be interpreted as biologically plausible mechanisms for adjusting unit outputs in neural networks, such as tonic inputs or activation thresholds, we investigate the expressivity of neural networks with random weights where only biases are optimized. We provide theoretical and numerical evidence demonstrating that feedforward neural networks with fixed random weights can be trained to perform multiple tasks by learning biases only. We further show that an equivalent result holds for recurrent neural networks predicting dynamical system trajectories. Our results are relevant to neuroscience, where they demonstrate the potential for behaviourally relevant changes in dynamics without modifying synaptic weights, as well as for AI, where they shed light on multi-task methods such as bias fine-tuning and unit masking.
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Animals can quickly adapt learned movements to external perturbations, and their existing motor repertoire likely influences their ease of adaptation. Long-term learning causes lasting changes in neural connectivity, which shapes the activity patterns that can be produced during adaptation. Here, we examined how a neural population's existing activity patterns, acquired through de novo learning, affect subsequent adaptation by modeling motor cortical neural population dynamics with recurrent neural networks. We trained networks on different motor repertoires comprising varying numbers of movements, which they acquired following various learning experiences. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural 'structure'-organization in the available population activity patterns. This structure facilitated adaptation, but only when the changes imposed by the perturbation were congruent with the organization of the inputs and the structure in neural activity acquired during de novo learning. These results highlight trade-offs in skill acquisition and demonstrate how different learning experiences can shape the geometrical properties of neural population activity and subsequent adaptation.
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Adaptación Fisiológica , Aprendizaje , Modelos Neurológicos , Corteza Motora , Aprendizaje/fisiología , Adaptación Fisiológica/fisiología , Corteza Motora/fisiología , Animales , Redes Neurales de la Computación , Neuronas/fisiología , Movimiento/fisiología , Red Nerviosa/fisiologíaRESUMEN
The fluid movement of an arm is controlled by multiple parameters that can be set independently. Recent studies argue that arm movements are generated by the collective dynamics of neurons in motor cortex. An untested prediction of this hypothesis is that independent parameters of movement must map to independently-specifiable dynamics. Using a task where monkeys made sequential, varied arm movements, we show that independent parameters of arm movements are independently encoded in the low-dimensional trajectories of population activity: each movement's direction by a fixed neural trajectory and its urgency by how quickly that trajectory was traversed. Network models show this latent coding allows the direction and urgency of arm movement to be independently controlled. Our results support a key prediction of the dynamical systems view of motor cortex, but also argue that not all parameters of movement are defined by the initial conditions of those dynamics.
RESUMEN
Animals can quickly adapt learned movements in response to external perturbations. Motor adaptation is likely influenced by an animal's existing movement repertoire, but the nature of this influence is unclear. Long-term learning causes lasting changes in neural connectivity which determine the activity patterns that can be produced. Here, we sought to understand how a neural population's activity repertoire, acquired through long-term learning, affects short-term adaptation by modeling motor cortical neural population dynamics during de novo learning and subsequent adaptation using recurrent neural networks. We trained these networks on different motor repertoires comprising varying numbers of movements. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural 'structure'-organization created by the neural population activity patterns corresponding to each movement. This structure facilitated adaptation, but only when small changes in motor output were required, and when the structure of the network inputs, the neural activity space, and the perturbation were congruent. These results highlight trade-offs in skill acquisition and demonstrate how prior experience and external cues during learning can shape the geometrical properties of neural population activity as well as subsequent adaptation.
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Our ability to use deep learning approaches to decipher neural activity would likely benefit from greater scale, in terms of both model size and datasets. However, the integration of many neural recordings into one unified model is challenging, as each recording contains the activity of different neurons from different individual animals. In this paper, we introduce a training framework and architecture designed to model the population dynamics of neural activity across diverse, large-scale neural recordings. Our method first tokenizes individual spikes within the dataset to build an efficient representation of neural events that captures the fine temporal structure of neural activity. We then employ cross-attention and a PerceiverIO backbone to further construct a latent tokenization of neural population activities. Utilizing this architecture and training framework, we construct a large-scale multi-session model trained on large datasets from seven nonhuman primates, spanning over 158 different sessions of recording from over 27,373 neural units and over 100 hours of recordings. In a number of different tasks, we demonstrate that our pretrained model can be rapidly adapted to new, unseen sessions with unspecified neuron correspondence, enabling few-shot performance with minimal labels. This work presents a powerful new approach for building deep learning tools to analyze neural data and stakes out a clear path to training at scale.
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There is rich variety in the activity of single neurons recorded during behaviour. Yet, these diverse single neuron responses can be well described by relatively few patterns of neural co-modulation. The study of such low-dimensional structure of neural population activity has provided important insights into how the brain generates behaviour. Virtually all of these studies have used linear dimensionality reduction techniques to estimate these population-wide co-modulation patterns, constraining them to a flat "neural manifold". Here, we hypothesised that since neurons have nonlinear responses and make thousands of distributed and recurrent connections that likely amplify such nonlinearities, neural manifolds should be intrinsically nonlinear. Combining neural population recordings from monkey motor cortex, mouse motor cortex, mouse striatum, and human motor cortex, we show that: 1) neural manifolds are intrinsically nonlinear; 2) the degree of their nonlinearity varies across architecturally distinct brain regions; and 3) manifold nonlinearity becomes more evident during complex tasks that require more varied activity patterns. Simulations using recurrent neural network models confirmed the proposed relationship between circuit connectivity and manifold nonlinearity, including the differences across architecturally distinct regions. Thus, neural manifolds underlying the generation of behaviour are inherently nonlinear, and properly accounting for such nonlinearities will be critical as neuroscientists move towards studying numerous brain regions involved in increasingly complex and naturalistic behaviours.
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People with late-stage Parkinson's disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD.
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Estimulación Encefálica Profunda , Trastornos Neurológicos de la Marcha , Enfermedad de Parkinson , Masculino , Animales , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/terapia , Marcha/fisiología , Médula EspinalRESUMEN
The spiking activity of populations of cortical neurons is well described by the dynamics of a small number of population-wide covariance patterns, whose activation we refer to as 'latent dynamics'. These latent dynamics are largely driven by the same correlated synaptic currents across the circuit that determine the generation of local field potentials (LFPs). Yet, the relationship between latent dynamics and LFPs remains largely unexplored. Here, we characterised this relationship for three different regions of primate sensorimotor cortex during reaching. The correlation between latent dynamics and LFPs was frequency-dependent and varied across regions. However, for any given region, this relationship remained stable throughout the behaviour: in each of primary motor and premotor cortices, the LFP-latent dynamics correlation profile was remarkably similar between movement planning and execution. These robust associations between LFPs and neural population latent dynamics help bridge the wealth of studies reporting neural correlates of behaviour using either type of recordings.
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Corteza Motora , Potenciales de Acción/fisiología , Animales , Corteza Motora/fisiología , Movimiento/fisiología , Neuronas/fisiología , Dinámica PoblacionalRESUMEN
Animals rapidly adapt their movements to external perturbations, a process paralleled by changes in neural activity in the motor cortex. Experimental studies suggest that these changes originate from altered inputs (Hinput) rather than from changes in local connectivity (Hlocal), as neural covariance is largely preserved during adaptation. Since measuring synaptic changes in vivo remains very challenging, we used a modular recurrent neural network to qualitatively test this interpretation. As expected, Hinput resulted in small activity changes and largely preserved covariance. Surprisingly given the presumed dependence of stable covariance on preserved circuit connectivity, Hlocal led to only slightly larger changes in activity and covariance, still within the range of experimental recordings. This similarity is due to Hlocal only requiring small, correlated connectivity changes for successful adaptation. Simulations of tasks that impose increasingly larger behavioural changes revealed a growing difference between Hinput and Hlocal, which could be exploited when designing future experiments.
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Corteza Motora , Adaptación Fisiológica , Animales , MovimientoRESUMEN
Regaining arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control has limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury, using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts targeting specific spinal segments produced sustained arm movements, enabling monkeys with arm paralysis to perform an unconstrained reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that residual descending inputs were necessary to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.
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Traumatismos de la Médula Espinal , Extremidad Superior , Animales , Estimulación Eléctrica , Haplorrinos , Humanos , Movimiento/fisiología , Parálisis/terapia , Reproducibilidad de los Resultados , Médula Espinal , Traumatismos de la Médula Espinal/terapia , Raíces Nerviosas EspinalesRESUMEN
The neural control of behavior is distributed across many functionally and anatomically distinct brain regions even in small nervous systems. While classical neuroscience models treated these regions as a set of hierarchically isolated nodes, the brain comprises a recurrently interconnected network in which each region is intimately modulated by many others. Uncovering these interactions is now possible through experimental techniques that access large neural populations from many brain regions simultaneously. Harnessing these large-scale datasets, however, requires new theoretical approaches. Here, we review recent work to understand brain-wide interactions using multi-region 'network of networks' models and discuss how they can guide future experiments. We also emphasize the importance of multi-region recordings, and posit that studying individual components in isolation will be insufficient to understand the neural basis of behavior.
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Encéfalo , Modelos Neurológicos , Mapeo EncefálicoRESUMEN
Animals readily execute learned behaviors in a consistent manner over long periods of time, and yet no equally stable neural correlate has been demonstrated. How does the cortex achieve this stable control? Using the sensorimotor system as a model of cortical processing, we investigated the hypothesis that the dynamics of neural latent activity, which captures the dominant co-variation patterns within the neural population, must be preserved across time. We recorded from populations of neurons in premotor, primary motor and somatosensory cortices as monkeys performed a reaching task, for up to 2 years. Intriguingly, despite a steady turnover in the recorded neurons, the low-dimensional latent dynamics remained stable. The stability allowed reliable decoding of behavioral features for the entire timespan, while fixed decoders based directly on the recorded neural activity degraded substantially. We posit that stable latent cortical dynamics within the manifold are the fundamental building blocks underlying consistent behavioral execution.
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Conducta Animal/fisiología , Corteza Cerebral/fisiología , Neuronas/fisiología , Animales , HaplorrinosRESUMEN
Despite rapid advances in machine learning tools, the majority of neural decoding approaches still use traditional methods. Modern machine learning tools, which are versatile and easy to use, have the potential to significantly improve decoding performance. This tutorial describes how to effectively apply these algorithms for typical decoding problems. We provide descriptions, best practices, and code for applying common machine learning methods, including neural networks and gradient boosting. We also provide detailed comparisons of the performance of various methods at the task of decoding spiking activity in motor cortex, somatosensory cortex, and hippocampus. Modern methods, particularly neural networks and ensembles, significantly outperform traditional approaches, such as Wiener and Kalman filters. Improving the performance of neural decoding algorithms allows neuroscientists to better understand the information contained in a neural population and can help to advance engineering applications such as brain-machine interfaces. Our code package is available at github.com/kordinglab/neural_decoding.
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Interfaces Cerebro-Computador , Corteza Motora , Algoritmos , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
Long-term learning of language, mathematics, and motor skills likely requires cortical plasticity, but behavior often requires much faster changes, sometimes even after single errors. Here, we propose one neural mechanism to rapidly develop new motor output without altering the functional connectivity within or between cortical areas. We tested cortico-cortical models relating the activity of hundreds of neurons in the premotor (PMd) and primary motor (M1) cortices throughout adaptation to reaching movement perturbations. We found a signature of learning in the "output-null" subspace of PMd with respect to M1 reflecting the ability of premotor cortex to alter preparatory activity without directly influencing M1. The output-null subspace planning activity evolved with adaptation, yet the "output-potent" mapping that captures information sent to M1 was preserved. Our results illustrate a population-level cortical mechanism to progressively adjust the output from one brain area to its downstream structures that could be exploited for rapid behavioral adaptation.
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Adaptación Fisiológica/fisiología , Aprendizaje/fisiología , Corteza Motora/fisiología , Neuronas/fisiología , Estimulación Luminosa/métodos , Desempeño Psicomotor/fisiología , Animales , Macaca mulatta , Masculino , Factores de TiempoRESUMEN
Populations of cortical neurons flexibly perform different functions; for the primary motor cortex (M1) this means a rich repertoire of motor behaviors. We investigate the flexibility of M1 movement control by analyzing neural population activity during a variety of skilled wrist and reach-to-grasp tasks. We compare across tasks the neural modes that capture dominant neural covariance patterns during each task. While each task requires different patterns of muscle and single unit activity, we find unexpected similarities at the neural population level: the structure and activity of the neural modes is largely preserved across tasks. Furthermore, we find two sets of neural modes with task-independent activity that capture, respectively, generic temporal features of the set of tasks and a task-independent mapping onto muscle activity. This system of flexibly combined, well-preserved neural modes may underlie the ability of M1 to learn and generate a wide-ranging behavioral repertoire.
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Macaca mulatta/fisiología , Corteza Motora/fisiología , Neuronas/fisiología , Animales , Fuerza de la Mano/fisiología , Masculino , Desempeño Psicomotor/fisiología , Muñeca/fisiologíaRESUMEN
Our bodies and the environment constrain our movements. For example, when our arm is fully outstretched, we cannot extend it further. More generally, the distribution of possible movements is conditioned on the state of our bodies in the environment, which is constantly changing. However, little is known about how the brain represents such distributions, and uses them in movement planning. Here, we record from dorsal premotor cortex (PMd) and primary motor cortex (M1) while monkeys reach to randomly placed targets. The hand's position within the workspace creates probability distributions of possible upcoming targets, which affect movement trajectories and latencies. PMd, but not M1, neurons have increased activity when the monkey's hand position makes it likely the upcoming movement will be in the neurons' preferred directions. Across the population, PMd activity represents probability distributions of individual upcoming reaches, which depend on rapidly changing information about the body's state in the environment.