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Perich, M. G.

Publications and source records attributed to Perich, M. G..

At least 19 recordsLinked to original sources

Evolutionarily conserved neural dynamics across mice, monkeys, and humans

On evolutionary timescales, brain circuits adapt to support survival in each species ecological niche. While some anatomical aspects of neural circuitry are conserved across species with distant evolutionary origins, each species also exhibits specific circuit adaptations that enable its behavioral repertoire. It remains unclear whether homologous brain regions leverage analogous neural computations as different species perform common behaviors such as reaching and manipulating objects. Here, we directly assessed conservation of neural computations using intracortical recordings from mouse, monkey, and human motor cortex--a homologous region across many mammals--during motor behaviors crucial for survival. We hypothesized that, despite their phylogenetic distance, rodents and primates produce movements through conserved neural computations implemented by motor cortical population dynamics. Remarkably, we found that movement-related neural dynamics were highly conserved across species, while variations in behavioral output were uniquely captured in neural trajectory geometries. Strikingly, neural dynamics during movement across species were more conserved than those across brain regions in the same human and between motor preparation and execution in the same monkeys. Lastly, through manipulation of neural network models trained to perform reaching movements, we reinforce that conservation of neural dynamics across species likely stems from shared circuit constraints. We thus assert that evolution maintains neural computations across phylogeny even as behavioral repertoires expand.

neuroscience↗

BAND: Behavior-Aligned Neural Dynamics is all you need to capture motor corrections

Movement is the result of complex, dynamic interaction between cortical and subcortical circuits. These dynamic interactions implement both feedforward motor control, arising from preparatory states, and feedback control, triggered by unexpected sensory events during movement. We show that the neural responses for feedback-driven control can be transient and small in variance, posing difficulties for unsupervised inference methods. We thus propose the Behavior-Aligned Neural Dynamics (BAND) model, which exploits semi-supervised learning to extract latent dynamics that predict both feedforward planned movement and unplanned feedback corrections. Our analysis suggests that motor corrections during movement 1) are encoded on the population level in small neural variability in primary motor (M1), but not dorsal premotor (PMd) cortex; 2) are transient; and 3) are driven by sensory feedback. Our work highlights the importance of targeted closed-loop aware methods to extract and study neural dynamics underlying complex behavioral phenomena.

neuroscience↗

Brain-like neural dynamics for behavioral control develop through reinforcement learning

During development, neural circuits are shaped continuously as we learn to control our bodies. The ultimate goal of this process is to produce neural dynamics that enable the rich repertoire of behaviors we perform. What begins as a series of "babbles" coalesces into skilled motor output as the brain rapidly learns to control the body. However, the nature of the teaching signal underlying this normative learning process remains elusive. Here, we test two well-established and biologically plausible theories--supervised learning (SL) and reinforcement learning (RL)--that could explain how neural circuits develop the capacity for skilled movements. We trained recurrent neural networks to control a biomechanical model of a primate arm using either SL or RL and compared the resulting neural dynamics to populations of neurons recorded from the motor cortex of monkeys performing the same movements. Intriguingly, only RL-trained networks produced neural activity that matched their biological counterparts in terms of both the geometry and dynamics of population activity. We show that this similarity with biological brains depends critically on matching biomechanical properties of the limb. Dynamical analysis on network activity revealed that our RL-trained networks operate at the "edge of chaos", a dynamical regime known for its computational richness, greater memory capacity, and robust plasticity properties. We then demonstrated that monkeys and RL-trained networks, but not SL-trained networks, show a strikingly similar capacity for robust short-term behavioral adaptation to a movement perturbation, indicating a fundamental and general commonality in the neural control policy. Together, our results support the hypothesis that neural dynamics for behavioral control emerge through a process akin to reinforcement learning. The resulting neural circuits offer numerous advantages for adaptable behavioral control over simpler and more efficient learning rules and expand our understanding of how developmental processes shape neural dynamics.

neuroscience↗

Nonlinear manifolds underlie neural population activity during behaviour

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, mouse, and human motor cortex, and mouse striatum, we show that: 1) neural manifolds are intrinsically nonlinear; 2) their nonlinearity becomes more evident during complex tasks that require more varied activity patterns; and 3) manifold nonlinearity varies across architecturally distinct brain regions. 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.

neuroscience↗

Motor cortex latent dynamics encode arm movement direction and urgency independently

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 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 movements direction corre-sponds 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 activity. Significance StatementFrom 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 movements direction is represented by the trajectory that signal takes; the movements speed by how quickly the signal moves along its trajectory. Our network modelling shows this encoding allows an arm movements direction and speed to be simultaneously and independently controlled.

neuroscience↗

De novo motor learning creates structure in neural activity space that shapes adaptation

Animals can quickly adapt learned movements in response to external perturbations. Motor adaptation is likely influenced by an animals 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 populations 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.

neuroscience↗

Feedback-based motor control can guide plasticity and drive rapid learning

Animals use afferent feedback to rapidly correct ongoing movements in the presence of a perturbation. Repeated exposure to a predictable perturbation leads to behavioural adaptation that counteracts its effects. Primary motor cortex (M1) is intimately involved in both processes, integrating inputs from various sensorimotor brain regions to update the motor output. Here, we investigate whether feedback-based motor control and motor adaptation may share a common implementation in M1 circuits. We trained a recurrent neural network to control its own output through an error feedback signal, which allowed it to recover rapidly from external perturbations. Implementing a biologically plausible plasticity rule based on this same feedback signal also enabled the network to learn to counteract persistent perturbations through a trial-by-trial process, in a manner that reproduced several key aspects of human adaptation. Moreover, the resultant network activity changes were also present in neural population recordings from monkey M1. Online movement correction and longer-term motor adaptation may thus share a common implementation in neural circuits.

neuroscience↗

Preserved neural population dynamics across animals performing similar behaviour

Animals of the same species often exhibit similar behaviours that are advantageously adapted to their body and their environment. These behaviours are shaped by selection pressures over evolutionary timescales at the species level, yet each individual produces these behaviours using a different, uniquely constructed brain. It remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of a given individual. Here, we hypothesised that the adaptive behaviour of a species requires specific neural population latent dynamics. These latent dynamics should thus be preserved and identifiable across individuals within a species, regardless of the idiosyncratic aspects of each individuals brain. Using recordings of neural populations from monkey and mouse motor cortex, we show that individuals from the same species share surprisingly similar neural dynamics when they perform the same behaviour. The similarity in neural population dynamics extends beyond cortical regions to the dorsal striatum, an evolutionarily older structure, and also holds when animals con-sciously plan future movements without overt behaviour. These preserved dynamics are behaviourally-relevant, allowing decoding of intended and ongoing movements across individuals. We posit that these emergent neural population dynamics result from evolutionarily-imposed constraints on brain development, and reflect a fundamental property of the neural basis of behaviour.

neuroscience↗

Interpreting dynamics of neural activity after dimensionality reduction

Dimensionality reduction methods are frequently used to analyze high-dimensional activity of cortical neuron populations during behavior. The resulting oscillatory trajectories that consistently emerge from this analysis have been interpreted as a signature of latent dynamical systems. Here, we show that these oscillatory trajectories necessarily result from applying dimensionality reduction methods on recordings that approximately exhibit continuous variation in time, regardless of whether or not the recorded system incorporates latent dynamics.

neuroscience↗

Small, correlated changes in synaptic connectivity may facilitate rapid motor learning

Animals can rapidly adapt their movements to external perturbations. This adaptation is paralleled by changes in single neuron activity in the motor cortices. Behavioural and neural recording studies suggest that when animals learn to counteract a visuomotor perturbation, these changes originate from altered inputs to the motor cortices rather than from changes in local connectivity, as neural covariance is largely preserved during adaptation. Since measuring synaptic changes in vivo remains very challenging, we used a modular recurrent network model to compare the expected neural activity changes following learning through altered inputs (Hinput) and learning through local connectivity changes (Hlocal). Learning under Hinput produced small changes in neural activity and largely preserved the neural covariance, in good agreement with neural recordings in monkeys. Surprisingly given the presumed dependence of stable neural covariance on preserved circuit connectivity, Hlocal led to only slightly larger changes in neural activity and covariance compared to Hinput. This similarity is due to Hlocal only requiring small, correlated connectivity changes to counteract the perturbation, which provided the network with significant robustness against simulated synaptic noise. 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.

neuroscience↗

Local field potentials reflect cortical population dynamics in a region-specific and frequency-dependent manner

The spiking activity of populations of cortical neurons is well described by a small number of population-wide covariance patterns, the "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 (LFP). 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 across 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.

neuroscience↗

Inferring brain-wide interactions using data-constrained recurrent neural network models

Behavior arises from the coordinated activity of numerous anatomically and functionally distinct brain regions. Modern experimental tools allow unprecedented access to large neural populations spanning many interacting regions brain-wide. Yet, understanding such large-scale datasets necessitates both scalable computational models to extract meaningful features of inter-region communication and principled theories to interpret those features. Here, we introduce Current-Based Decomposition (CURBD), an approach for inferring brain-wide interactions using data-constrained recurrent neural network models that directly reproduce experimentally-obtained neural data. CURBD leverages the functional interactions inferred by such models to reveal directional currents between multiple brain regions. We first show that CURBD accurately isolates inter-region currents in simulated networks with known dynamics. We then apply CURBD to multi-region neural recordings obtained from mice during running, macaques during Pavlovian conditioning, and humans during memory retrieval to demonstrate the widespread applicability of CURBD to untangle brain-wide interactions underlying behavior from a variety of neural datasets.

neuroscience↗

Electrical Stimulation Of The Cervical Dorsal Roots Enables Functional Arm And Hand Movements In Monkeys With Cervical Spinal Cord Injury

Recovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically 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.

bioengineering↗

Motor cortical dynamics are shaped by multiple distinct subspaces during naturalistic behavior

Behavior relies on continuous influx of sensory information about the body. In primates, motor cortex must integrate somatic feedback to accurately reach and manipulate objects. Yet, prior work demonstrates that motor cortex is well-described with deterministic, rather than input-driven, dynamics. Deterministic dynamics facilitate robust movement generation, but flexible motor output requires rapid responses to unexpected inputs. Here, we resolved this paradox by simultaneously recording neural population activity in motor and somatosensory cortex from four monkeys performing a naturalistic object interaction behavior resulting in occasional errors. Motor cortex was strikingly input-driven surrounding behavioral error correction. Intriguingly, input-driven dynamics were isolated to a subspace of the population activity that putatively captured somatosensory feedback. Using electrical stimulation of ascending somatosensory tracts, we causally verified that this feedback subspace captured peripheral inputs to cortex. Our results demonstrate that cortical activity is compartmentalized within distinct subspaces, enabling flexible integration of salient inputs for robust behavior.

neuroscience↗

A VERSATILE ROBOTIC PLATFORM FOR THE DESIGN OF NATURAL, THREE-DIMENSIONAL REACHING AND GRASPING TASKS IN MONKEYS

Translational studies on motor control and neurological disorders require detailed monitoring of sensorimotor components of natural limb movements in relevant animal models. However, available experimental tools do not provide a sufficiently rich repertoire of behavioral signals. Here, we developed a robotic platform that enables the monitoring of kinematics, interaction forces, and neurophysiological signals during user-definable upper limb tasks for monkeys. We configured the platform to position instrumented objects in a three-dimensional workspace and provide an interactive dynamic force-field. We show the relevance of our platform for fundamental and translational studies with three example applications. First, we study the kinematics of natural grasp in response to variable interaction forces. We then show simultaneous and independent encoding of kinematic and forces in single unit intra-cortical recordings from sensorimotor cortical areas. Lastly, we demonstrate the relevance of our platform to develop clinically relevant brain computer interfaces in a kinematically unconstrained motor task

neuroscience↗

A stable, long-term cortical signature underlying consistent behavior

Animals readily execute learned motor behaviors in a consistent manner over long periods of time, yet similarly stable neural correlates remained elusive up to now. 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 capture the dominant co-variation patterns within the neural population, are preserved across time. We recorded from populations of neurons in premotor, primary motor, and somatosensory cortices for up to two years as monkeys performed a reaching task. Intriguingly, despite steady turnover in the recorded neurons, the low-dimensional latent dynamics remained stable. Such stability allowed reliable decoding of behavioral features for the entire timespan, while fixed decoders based on the recorded neural activity degraded substantially. We posit that latent cortical dynamics within the manifold are the fundamental and stable building blocks underlying consistent behavioral execution.

neuroscience↗

Linear-Nonlinear-Time-Warp-Poisson models of neural activity

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.

neuroscience↗

Multiple tasks viewed from the neural manifold: Stable control of varied behavior

How do populations of cortical neurons have the flexibility to perform different functions? We investigated this question in primary motor cortex (M1), where populations of neurons are able to generate a rich repertoire of motor behaviors. We recorded neural activity while monkeys performed a variety of wrist and reach-to-grasp motor tasks, each requiring a different pattern of neural activity. We characterized the flexibility of M1 movement control by comparing the \"neural modes\" that capture covariation across neurons, believed to arise from network connectivity. We found large similarities in the structure of the neural modes across tasks, as well as striking similarities in their temporal activation dynamics. These similarities were only apparent at the population level. Moreover, a subset of these well-preserved modes captured a task-independent mapping onto muscle commands. We hypothesize that this system of flexibly combined, stable neural modes gives M1 the flexibility to generate our wide-ranging behavioral repertoire.

neuroscience↗