Biology subjects

Rossi-Pool, R.

Publications and source records attributed to Rossi-Pool, R..

12 recordsLinked to original sources

bioRxiv2025

Assessing the degree of cortical dislamination through electrical pattern analysis

Focal cortical dysplasia (FCD) is a leading cause of pharmacoresistant epilepsy in pediatric populations, although its contribution to epileptogenesis remains incompletely understood. Recent findings indicate that hyperexcitability might stem from peripheral areas that are not dysplastic, rather than from the malformation itself. However, consid-ering the significant variability associated with these malformations, it remains challenging to clarify whether this degree of disorganization contributes to changes in activity. In this study, we used the carmustine-induced animal model to investigate how varying degrees of cortical malformation influence neural dynamics. Local field potentials (LFP) were recorded using a multielectrode array (MEA) during both spontaneous activity and external perturbation. We developed a novel metric to quantify spatial heterogeneity in signal organization and evaluated its association with excitation-inhibition (E/I) balance. Our results reveal that alterations such as the aperiodic exponent value and the sparcity of clustering in signal classification are related to the extent and distribution of cortical abnormalities, underscoring the functional relevance of cytoarchitectural variability. This work advances the understanding of FCD-related network dysfunction and introduces analytical approaches with potential translational value for neuroscience research and pre-surgical evaluation.

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bioRxiv2025

Relevance of Nonlinear Dimensionality Reduction for Efficient and Robust Spike Sorting

Spike sorting is one of the cornerstones of extracellular electrophysiology. By leveraging advanced signal processing and data analysis techniques, spike sorting makes it possible to detect, isolate, and map single neuron spiking activity from both in vivo and in vitro extracellular electrophysiological recordings. A crucial step of any spike sorting pipeline is to reduce the dimensionality of the recorded spike waveform data. Reducing the dimensionality of the processed data is a near-universal practice, fundamentally motivated by the use of clustering algorithms responsible to detect, isolate, and sort the recorded putative neurons. In this paper we propose and illustrate on both synthetic and experimental data that employing the nonlinear dimensionality reduction technique Uniform Manifold Approximation and Projection (UMAP) can drastically improve the performance, efficiency, robustness, and scalability of spike sorting pipelines without increasing their computational cost. We show how replacing the linear or ad hoc, expert-defined, supervised nonlinear dimensionality reduction methods commonly used in spike sorting pipelines by the unsupervised, mathematically grounded, nonlinear dimensionality reduction method provided by UMAP drastically increases the number of correctly sorted neurons, makes the identification of quieter, seldom spiking neurons more reliable, enables deeper and more precise explorations and analysis of the neural code, and paves new ways toward more efficient and end-to-end automatable spike sorting pipelines of large-scale extracellular neural recording as those produced by high-density multielectrode arrays.

neuroscience↗

bioRxiv2024

Multi-Stable Bimodal Perceptual Coding within the Ventral Premotor Cortex

Neurons in the primate ventral premotor cortex (VPC) respond to both tactile and acoustic stimuli, yet how they integrate and process information from these sensory modalities remains unclear. To investigate this, we recorded VPC neuronal activity in two trained monkeys performing a bimodal detection task (BDT), in which they reported the presence or absence of either a tactile or an acoustic stimulus. Single-cell analyses revealed diverse response types, including purely tactile, purely acoustic, bimodal, and neurons with sustained activity during the decision maintenance delay--the period between stimulus offset and motor response. To further examine VPCs role in the BDT, we applied dimensionality reduction techniques to uncover low-dimensional latent dynamics in the neuronal population and conducted parallel analyses using a recurrent neural network (RNN) model trained on the same task. Neural trajectories for tactile and acoustic responses diverged sharply, whereas in stimulus-absent trials, the dynamics remained at rest. During the delay period, the trajectories exhibited a pronounced rotational dynamic, shifting toward a subspace orthogonal to the sensory response space, suggesting memory maintenance through stable equilibria. This indicates that network dynamics can sustain distinct stable states corresponding to the three potential task outcomes. Using low-dimensional modeling, we propose a universal dynamical mechanism that underlies the transition from sensory processing to memory retention, aligning with both experimental and computational findings. These results demonstrate that VPC neurons encode bimodal information, integrate competing sensory inputs, and maintain decisions across the delay period, regardless of sensory modality.

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bioRxiv2024

Contextual Neural Dynamics During Time Perception in Primate Ventral Premotor Cortex

Understanding how time perception adapts to cognitive demands remains a significant challenge. In some contexts, the brain encodes time categorically (as "long" or "short"), while in others, it encodes precise time intervals on a continuous scale. Although the ventral premotor cortex (VPC) is known for its role in complex temporal processes, such as speech, its specific involvement in time estimation remains underexplored. In this study, we investigated how the VPC processes temporal information during a time interval comparison task (TICT) and a time interval categorization task (TCT) in primates. We found a notable heterogeneity in neuronal responses associated with time perception across both tasks. While most neurons responded during time interval presentation, a smaller subset retained this information during the working memory periods. Population-level analysis revealed distinct dynamics between tasks: in TICT, population activity exhibited a linear and parametric relationship with interval duration, whereas in TCT, neuronal activity diverged into two distinct dynamics corresponding to the interval categories. During delay periods, these categorical or parametric representations remained consistent within each task context. This contextual shift underscores the VPCs adaptive role in interval estimation and highlights how temporal representations are modulated by cognitive demands. Significance StatementThe neural representation of time has long intrigued neuroscientists, particularly how it adapts to cognitive demands. Depending on the task, the brain encodes time either categorically ("long" or "short") or as precise intervals. While the ventral premotor cortex (VPC) is known for its role in temporal processes, its role in time estimation remains underexplored. Here, we examined how the VPC processes temporal information in primates during a time interval comparison task (TICT) and a categorization task (TCT). The VPC exhibited heterogeneous neuronal responses with distinct dynamics: a linear, parametric relationship in TICT and bifurcated dynamics in TCT. These representations remained consistent during delay periods, underscoring the VPCs adaptive role in time interval estimation.

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bioRxiv2024

Basal ganglia output - entopeduncular nucleus - coding of contextual kinematics and reward in the freely moving mouse

The entopeduncular nucleus (EPN) is often termed as one of the output nuclei of the basal ganglia owing to their highly convergent anatomy. The rodent EPN has been implicated in reward and value coding whereas the primate analogue internal Globus Pallidus has been found to be modulated by some movements and in some circumstances. In this study we sought to understand how the rodent EPN might be coding kinematic, reward, and difficulty parameters, particularly during locomotion. Furthermore, we aimed to understand the level of movement representation: whole-body or specific body parts. To this end, mice were trained in a freely moving two-alternative forced choice task with two periods of displacement (return and go trajectories) and performed electrophysiological recordings together with video-based tracking. We found 1) robust reward coding but not difficulty. 2) Spatio-temporal variables better explain EPN activity during movement compared to kinematic variables, while both types of variables were more robustly represented in reward-related movement. 3) Reward sensitive units encode kinematics similarly to reward insensitive ones. 4) Population dynamics that best account for differences between these two periods of movement can be explained by allocentric references like distance to reward port. 5) The representation of paw and licks is not mutually exclusive, discarding a somatotopic muscle-level representation of movement in the EPN. Our data suggest that EPN activity represents movements and reward in a complex way: highly multiplexed, influenced by the objective of the displacement, where trajectories that lead to reward better represent spatial and kinematic variables. Interestingly, there are intertwining representations of whole-body movement kinematics with single paw and licking variables. Further, reward sensitive units encode kinematics similarly to reward insensitive ones, challenging the notion of distinct pathways for reward and movement processing. Significance StatementThe entopeduncular nucleus is one of the main outputs of the basal ganglia whose activity has been hypothesized to be inversely correlated with movement. This study examines motor and reward coding simultaneously, finding that besides the great level of multiplexing of these variables, spatio-temporal coding is better represented than kinematic coding. The level of movement representation seems to be greatly influenced by the goal of a movement, with spatially biased variables influencing the population dynamics of this nucleus. Further, we uncover the coexistence of EPN modulation by movement at different timescales and body parts. The simple overall activity of this output nucleus cannot explain kinematic coding, challenging leading theories of basal ganglia function.

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bioRxiv2023

Orthogonality of sensory and contextual categorical dynamics embedded in a continuum of responses from the second somatosensory cortex

How does the brain simultaneously process signals that bring complementary information, like raw sensory signals and their transformed counterparts, without any disruptive interference? Contemporary research underscores the brain ss adeptness in using decorrelated responses to reduce such interference. Both neurophysiological findings and artificial neural networks (ANNs) support the notion of orthogonal representation for signal differentiation and parallel processing. Yet, where, and how raw sensory signals are transformed into more abstract representations remains unclear. Using a temporal pattern discrimination task (TPDT) in trained monkeys, we revealed that the second somatosensory cortex (S2) efficiently segregates faithful and transformed neural responses into orthogonal subspaces. Importantly, S2 population encoding for transformed signals, but not for faithful ones, disappeared during a non-demanding version of the task, which suggests that signal transformation and their decoding from downstream areas are only active on-demand. A mechanistic computation model points to gain modulation as a possible biological mechanism for the observed context-dependent computation. Furthermore, individual neural activities that underlie the orthogonal population representations exhibited a continuum of responses, with no well-determined clusters. These findings advocate that the brain, while employing a continuum of heterogeneous neural responses, splits population signals into orthogonal subspaces in a context-dependent fashion to enhance robustness, performance, and improve coding efficiency. SIGNIFICANCE STATEMENTAn important function of the brain is turning sensation into perception. Yet, how this function is implemented remains unknown. Current research, insights from artificial neural networks, highlights using of orthogonal representations as an effective means to transform sensory signals into perceptual signals while separating and simultaneously processing the two information streams. Neuronal recordings in S2 while trained monkeys performed the TPDT, revealed that this function is implemented at the population level. While S2 encodes sensory information independently of context, the encoding of categorical information, like task parameters, is only performed when the task demands it. Such distinct and flexible organization, enriched by a spectrum of neural activities, reflects the brains efficiency, resilience, and overall purpose for solving cognitive tasks.

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bioRxiv2022

An abstract categorical decision code in dorsal premotor cortex

The dorsal premotor cortex (DPC) has classically been associated with a role in preparing and executing the physical motor variables during cognitive tasks. While recent work has provided nuanced insights into this role, here we propose that DPC also participates more actively in decision-making. We recorded neuronal activity in DPC while two trained monkeys performed a vibrotactile categorization task, utilizing two distinct ranges of stimuli values that varied on two physical attributes: vibrotactile frequency and amplitude. We observed a broad heterogeneity across DPC neurons, the majority of which maintained the same response patterns across attributes and ranges, coding in the same periods, mixing temporal and categorical dynamics. The predominant categorical signal was maintained throughout the delay, movement periods and notably during the inter-trial period. Putting the entire populations data through two dimensionality reduction techniques, we found that imposing the sensory structure yielded pure categorical and temporal representations. Furthermore, projecting the activity of one population over the population axes of the other yielded identical categorical and temporal responses. Finally, we sought to identify functional subpopulations based on the combined activity of all stimuli, neurons, and time points, however we found a continuum of single-unit responses mixing temporal and categorical dynamics. All this points to DPC playing a more decision-related role than previously anticipated. SIGNIFICANCE STATEMENTThe DPCs role in the somatosensory processing network has been generally limited to movement, but our current results suggest a more abstract function. We recorded DPCs activity in two monkeys trained in a vibrotactile categorization task of two distinct physical attributes, and found a strong decision signal throughout the population, underpinned by purely temporal signals. Importantly, this abstract decision signal remains during the inter-trial period suggesting a consolidation role. Neurons maintained consistent and significant responses for both attributes, and the entire population activity converged to identical categorical representations, even when cross-projected between two contexts. These results suggest that DPC plays a larger role during decision-making and consolidation, regardless of the stimulus attributes that triggered the decision report.

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bioRxiv2022

Hierarchical unimodal processing within the primary somatosensory cortex during a bimodal detection task

Where and how in the brain do neurons process more than one sensory modality? To answer these questions, scientists have generated a wide variety of studies at distinct space-time scales in different animal models, and often shown contradictory conclusions. Some conclude that this process occurs in early sensory cortices, but others that this occurs in areas central to sensory cortices. Here, we sought to determine whether sensory neurons process and encode physical stimulus properties of different modalities (tactile and acoustic). For this, we designed a bimodal detection task where the senses of touch and hearing compete from trial to trial. Two Rhesus monkeys performed this novel task, while neural activity was recorded in areas 3b and 1 of the primary somatosensory cortex (S1). We analyzed neurons coding properties and variability, organizing them by their receptive fields position relative to the stimulation zone. Our results indicate that neurons of areas 3b and 1 are unimodal, encoding only the tactile modality, both in the firing rate and variability, but not to the acoustic one. Moreover, we found that neurons of both subareas encode the tactile information differently, revealing a hidden processingbased hierarchy. Finally, using a powerful non-linear dimensionality reduction algorithm, we show that the activity from areas 3b and 1 can be separated, establishing a clear division in the functionality of these two subareas of S1. SIGNIFICANCE STATEMENTOur brain integrates information from all our senses to perceive the external world. But where and how in the brain this integration occurs? Here we ask if the primary somatosensory cortex (S1) encodes information from more than one sensory modality. We recorded the activity of single neurons from areas 3b and S1, while trained monkeys performed a bimodal detection task, where tactile and acoustic stimuli compete. The analysis showed that neurons from areas 3b and 1 responded only to the tactile modality both in their rate and variability. However, our results support that these two areas are different enough as to be considered functionally distinct entities.

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bioRxiv2020

Midbrain dopamine firing activity codes reward expectation and motivation in a parametric working memory task

Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected subjective stimulus perception. Contrastingly, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both WM activity and phasic responses before the second stimulus negatively correlated with reaction times of the animal after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation reduced noise in perception and, by decreasing the effect of the bias, improved performance, especially in difficult trials. Overall, our results show that DA activity was simultaneously involved in reward prediction, motivation and WM. Also, the ramping activity during the WM period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.

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bioRxiv2020

From an invariant sensory code to a perceptual categorical code in second somatosensory cortex

A crucial role of cortical networks is the conversion of sensory inputs into perception. In the cortical somatosensory network, neurons of the primary somatosensory cortex (S1) show invariant sensory responses, while frontal lobe neuron responses correlate with the animals perceptual behavior. But, where in the cortical somatosensory network are the sensory inputs transformed into perceptual behavior? Here, we report that in the secondary somatosensory cortex (S2), neurons with invariant sensory responses coexist with neurons whose responses correlate with the animals perceptual behavior. These distinct neural responses exhibit analogous timescales of intrinsic fluctuations, suggesting that they belong to the same hierarchical processing stage. Furthermore, during a non-demanding control task, the sensory responses remained unaltered while perceptual responses vanished. Conclusively, the S2 population responses exhibit intermediate dynamics between S1 and frontal lobe neurons. These results suggest that the conversion of touch into perception crucially depends on S2.

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bioRxiv2018

Internal bias controls dopamine perceptual decision-related responses

Dopamine neurons produce reward-related signals that regulate learning and guide behavior. Prior expectations about forthcoming stimuli and internal biases can alter perception and choices and thus could influence dopamine signaling. We tested this hypothesis studying dopamine neurons recorded in monkeys trained to discriminate between two tactile frequencies separated by a delay period, a task affected by the contraction bias. The bias greatly controlled the animals choices and confidence on their decisions. During decision formation the phasic activity reflected bias-induced modulations and simultaneously coded reward prediction errors. In contrast, the activity during the delay period was not affected by the bias, was not tuned to the value of the stimuli but was temporally modulated, pointing to a role different from that of the phasic activity.

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bioRxiv2018

Single-neuron interactions between the somatosensory thalamo-cortical circuits during perception

Sensory thalamo-cortical interactions are key components of the neuronal chains associated with stimulus perception, but surprisingly, they are poorly understood. We addressed this problem by evaluating a directional measure between simultaneously recorded neurons from somatosensory thalamus (VPL) and somatosensory cortex (S1) sharing the same cutaneous receptive field, while monkeys judged the presence or absence of a tactile stimulus. During the stimulus-presence, feedforward (VPL[->]S1) interactions increased, while pure feedback (S1[->]VPL) interactions were unaffected. Remarkably, bidirectional interactions (VPL{leftrightarrow}S1) emerged with high stimulus amplitude, establishing a functional thalamo-cortical loop. Furthermore, feedforward interactions were modulated by task context and error trials. Additionally, significant stimulus modulations were found on intra-cortical (S1[->]S1) interactions, but not on intra-thalamic (VPL[->]VPL) interactions. Thus, these results show the directionality of the information flow between the thalamo-cortical circuits during tactile perception. We suggest that these interactions may contribute to stimulus perception during the detection task used here.

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