Biology subjects

Monaco, S.

Publications and source records attributed to Monaco, S..

12 recordsLinked to original sources

bioRxiv2026

Modular Integration of Auditory Instructions and Visual Cues into the Cortical Reach Network

Humans often need to integrate bottom-up stimulus attributes (e.g., object shape) with top-down instructions (e.g., how to pick it up) for adaptive behavior. To investigate how such cues are integrated into the cortical reach network, we employed an fMRI paradigm where participants viewed a cube to their left or right (visual cue) and were verbally instructed to use a horizontal or vertical grip (auditory cue), in varying order. Univariate voxel-wise and region-of-interest analysis confirmed the expected order-dependent activation of sensory regions, followed by robust parietofrontal activation. Graph-theory analysis revealed two significant subnetworks (modules): an Occipital-Parietal module (likely integrating the visual cue into the reach plan) and a Temporal-Frontal module (likely integrating the auditory cue into the grasp plan), both converging in somatomotor cortex. Cue-order influenced modularity, i.e., the module corresponding to the first cue tended to dominate contralateral motor cortex, and conversely a classification model decoded cue-order based on modularity. Local network hubs were order-independent and occupied traditional reach areas, whereas global (between module) hubs were order-dependent and more distributed. Overall, these results suggest that multisensory integration of top-down and bottom-up cues for action is a network phenomenon that relies on both lateral and serial communication between parallel sensorimotor modules.

neuroscience↗

bioRxiv2025

On-cell Saturation Transfer Difference (STD) NMR on ion channels: characterizing negative allosteric modulator binding interactions of P2X7.

P2X7 receptors are important drug targets involved in pathologies ranging from psychiatric disorders to cancer. Being membrane embedded receptors, they are challenging for structural characterisation and at present we only have a small number of X-ray and cryoEM structures for P2X7 bound to antagonists. We demonstrate that Saturation Transfer Difference (STD) NMR on live mammalian cells (on-cell STD NMR) overexpressing P2X7 receptors allows further structural insight on the complexes of P2X7 with two potent negative allosteric modulators, namely AZ10606120 and JNJ-47465567, via the determination of the binding epitope mapping of the interactions e.g. the main region of contact between the ligand and the binding pocket. This approach, reported for the first time on membrane-embedded ion channels, in combination with molecular docking, allows us to propose the first NMR-validated 3D molecular models for two antagonists as bound to human P2X7 receptors, and to correlate the structural knowledge acquired with the pharmacology data. We highlight the transformative potential of this application to aid drug design efforts in a less resource-demanding fashion than X-ray crystallography and cryo-EM and we envisage on-cell STD NMR to fast become an asset for structure-activity-relationship studies helping knowledge-based development of efficient drugs targeting P2X7 and other ion channels/membrane-embedded proteins.

pharmacology and toxicology↗

bioRxiv2023

Computational Scoring and Experimental Evaluation of Enzymes Generated by Neural Networks

In recent years, generative protein sequence models have been developed to sample novel sequences. However, predicting whether generated proteins will fold and function remains challenging. We evaluate computational metrics to assess the quality of enzyme sequences produced by three contrasting generative models: ancestral sequence reconstruction, a generative adversarial network, and a protein language model. Focusing on two enzyme families, we expressed and purified over 440 natural and generated sequences with 70-90% identity to the most similar natural sequences to benchmark computational metrics for predicting in vitro enzyme activity. Over three rounds of experiments, we developed a computational filter that improved experimental success rates by 44-100%. Surprisingly, neither sequence identity to natural sequences nor AlphaFold2 residue-confidence scores were predictive of enzyme activity. The proposed metrics and models will drive protein engineering research by serving as a benchmark for generative protein sequence models and helping to select active variants to test experimentally.

biochemistry↗

bioRxiv2022

Cortical areas involved in grasping and reaching actions with and without visual information: an ALE meta-analysis of neuroimaging studies

The functional specialization of the ventral stream in Perception and the dorsal stream in Action is the cornerstone of the leading model proposed by Goodale and Milner in 1982. This model is based on neuropsychological evidence and has been a matter of debate for almost three decades, during which the dual-visual stream hypothesis has received much attention, including support and criticisms. The advent of functional magnetic resonance imaging (fMRI) has allowed investigating the brain areas involved in Perception and Action and provided useful data on the functional specialization of the two streams. Research on this topic has been quite prolific, yet very little attempt has been made so far to identify consistent neuroimaging results across the available literature. In particular, no meta-analysis has explored the spatial convergence in the involvement of the two streams in Action. The present meta-analysis (N=53) was designed to reveal the specific neural activations associated with Action (i.e., grasping and reaching movements), and the extent to which visual information affects the involvement of the two streams during motor control. Our results provide a comprehensive view of the consistent and spatially convergent neural correlates of Action based on neuroimaging studies conducted over the past two decades. We discuss our results in light of the well-established dual-visual stream model and frame these findings in the context of recent discoveries obtained with advanced fMRI methods, such as multivoxel pattern analysis.

neuroscience↗

bioRxiv2021

Generating novel protein sequences using Gibbs sampling of masked language models

Recently developed language models (LMs) based on deep neural networks have demonstrated the ability to generate fluent natural language text. LMs pre-trained on protein sequences have shown state of the art performance on a variety of downstream tasks. Protein LMs have also been used to generate novel protein sequences. In the present work we use Gibbs sampling of BERT-style LMs, pre-trained on protein sequences using the masked language modeling task, to generate novel protein sequences. We evaluate the quality of the generated sequences by comparing them to natural sequences from the same family. In particular, we focus on proteins from the chorismate mutase type II family, which has been used in previous work as an example target for protein generative models. We find that the Gibbs sampling process on BERT-style models pretrained on millions to billions of protein sequences is able to generate novel sequences that retain key features of related natural sequences. Further, we find that smaller models fine-tuned or trained from scratch on family-specific data are able to equal or surpass the generation quality of large pre-trained models by some metrics. The ability to generate novel natural-like protein sequences could contribute to the development of improved protein therapeutics and protein-catalysts for industrial chemical production.

synthetic biology↗

bioRxiv2020

Isolation and characterization of Pseudomonas chlororaphis strain ST9 and its potential as a bioinoculant for agriculture

The development of biotechnologies based on beneficial microorganisms for improving soil fertility and crop yields could help addressing many current agriculture challenges, such as food security, climate change, pests control, soil depletion while decreasing the use of chemical fertilizers and pesticides. Plant Growth Promoting (PGP) microbes can be used as probiotics in order to increase plant tolerance/resistance to abiotic/biotic stresses and in this context strains belonging to the Pseudomonas chlororaphis group have shown to have potential as PGP candidates. In this work a new P. chlororaphis isolate is reported and tested for (i) in vitro PGP features, (ii) whole genome sequence analysis, and (iii) its effects on root microbiome, plant growth and on the expression of different plant genes in greenhouse experiments. The potential use of this P. chlororaphis strain as a plant probiotic is discussed.

microbiology↗

bioRxiv2019

Parietal Cortex Integrates Visual and Oculomotor Signals to Update Grasp Plans

Coordinated reach-to-grasp movements are often accompanied by rapid eye movements (saccades) that displace the desired object image relative to the retina. Parietal cortex compensates for this by updating reach goals relative to current gaze direction, but its role in the integration of oculomotor and visual orientation signals for updating grasp plans is unknown. Based on a recent perceptual experiment, we hypothesized that inferior parietal cortex (specifically supramarginal gyrus; SMG) integrates saccade and visual signals to update grasp plans in more superior parietal areas. To test this hypothesis, we employed a functional magnetic resonance adaptation paradigm, where saccades sometimes interrupted grasp preparation toward a briefly presented object that later reappeared (with the same/different orientation) just before movement. Right SMG and several parietal grasp areas, namely left anterior intraparietal sulcus (aIPS) and bilateral superior parietal lobe (SPL), met our criteria for transsaccadic orientation integration: during movement preparation, they showed task-dependent saccade modulations and, during grasp execution, they were specifically sensitive to changes in object orientation that followed saccades. Finally, SMG showed enhanced functional connectivity with both prefrontal saccade areas (consistent with oculomotor input) and aIPS / SPL (consistent with sensorimotor output). These results support the general role of parietal cortex for the integration of visuospatial perturbations, and provide specific cortical modules for the integration of oculomotor and visual signals for grasp updating. Significance StatementThe cortical mechanisms that update reach goals during eye movements are well documented, but it is not known how object features are linked to oculomotor signals when updating grasp plans. Here, we employed functional magnetic resonance imaging adaptation (fMRIa) and functional connectivity analysis to identify a cluster of inferior parietal (supramarginal gyrus) and superior parietal (intraparietal and superior parietal) regions that show functional connectivity with frontal cortex saccade centers, and also show saccade-specific modulations during unexpected changes in object / grasp orientation. This provides a network - complementary to the goal updater network - that integrates visuospatial updating into grasp plans, and may help explain some of the more complex symptoms associated with parietal damage such as constructional ataxia.

neuroscience↗

bioRxiv2018

Action intention modulates the representation of object features in early visual cortex

The role of the visual cortex has been extensively studied to determine its role in object recognition but to a lesser degree to determine how action planning influences the representation of objects features. We used functional MRI and pattern classification methods to determine if during action planning, object features (orientation and location) could be decoded in an action-dependent way. Sixteen human participants used their right dominant hand to perform movements (Align or Open reach) towards one of two 3D-real oriented objects that were simultaneously presented and placed on either side of a fixation cross. While both movements required aiming toward target location, Align but not Open reach movements required participants to precisely adjust hand orientation. Therefore, we hypothesized that if the representation of object features is modulated by the upcoming action, pre-movement activity pattern would allow more accurate dissociation between object features in Align than Open reach tasks. We found such dissociation in the anterior and posterior parietal cortex, as well as in the dorsal premotor cortex, suggesting that visuomotor processing is modulated by the upcoming task. The early visual cortex showed significant decoding accuracy for the dissociation between object features in the Align but not Open reach task. However, there was no significant difference between the decoding accuracy in the two tasks. These results demonstrate that movement-specific preparatory signals modulate object representation in the frontal and parietal cortex, and to a lesser extent in the early visual cortex, likely through feedback functional connections.

neuroscience↗

bioRxiv2018

Predictive coding of action intentions in dorsal and ventral visual stream is based on visual anticipations, memory-based information and motor preparation

Predictions of upcoming movements are based on several types of neural signals that span the visual, somatosensory, motor and cognitive system. Thus far, pre-movement signals have been investigated while participants viewed the object to be acted upon. Here, we studied the contribution of information other than vision to the classification of preparatory signals for action, even in absence of online visual information. We used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA) to test whether the neural signals evoked by visual, memory-based and somato-motor information can be reliably used to predict upcoming actions in areas of the dorsal and ventral visual stream during the preparatory phase preceding the action, while participants were lying still. Nineteen human participants (nine women) performed one of two actions towards an object with their eyes open or closed. Despite the well-known role of ventral stream areas in visual recognition tasks and the specialization of dorsal stream areas in somato-motor processes, we decoded action intention in areas of both streams based on visual, memory-based and somato-motor signals. Interestingly, we could reliably decode action intention in absence of visual information based on neural activity evoked when visual information was available, and vice-versa. Our results show a similar visual, memory and somato-motor representation of action planning in dorsal and ventral visual stream areas that allows predicting action intention across domains, regardless of the availability of visual information.

neuroscience↗

bioRxiv2018

Action-specific feature processing in the human visual cortex

Sensorimotor integration involves feedforward and reentrant processing of sensory input. Grasp-related motor activity precedes and is thought to influence visual object processing. Yet, while the importance of reentrant feedback is well established in perception, the top-down modulations for action and the neural circuits involved in this process have received less attention. Do action-specific intentions influence the processing of visual information in the human cortex? Using a cue-separation fMRI paradigm, we found that action-specific instruction (manual alignment vs. grasp) influences the cortical processing of object orientation several seconds after the object had been viewed. This influence occurred as early as in the primary visual cortex and extended to ventral and dorsal visual stream areas. Importantly, this modulation was unrelated to non-specific action planning. Further, the primary visual cortex showed stronger functional connectivity with frontal-parietal areas and the inferior temporal cortex during the delay following orientation processing for align than grasping movements, strengthening the idea of reentrant feedback from dorsal visual stream areas involved in action. To our knowledge, this is the first demonstration that intended manual actions have such an early, pervasive, and differential influence on the cortical processing of vision.

neuroscience↗

bioRxiv2018

Cortical Mechanisms for Reaches Versus Saccades: Progression of Effector-Specificity Through Target Memory to Movement Planning and Execution

Effector-specific cortical mechanisms can be difficult to establish using fMRI, in part because low time resolution might temporally conflate different signals related to target representation, motor planning, and motor execution. Here, we used an event-related fMRI protocol and a cue-separation paradigm to temporally separate these three major sensorimotor stages for saccades vs. reaches. In each trial, subjects (N=12) 1) briefly viewed a target 4-7{degrees} left or right of midline fixation on a touchscreen, followed by an 8 second delay (effector-independent target memory phase), 2) were instructed by an auditory cue to perform a reach or a saccade, followed by a second delay of 8 seconds (effector-specific planning phase), and finally 3) were prompted to move by reaching-to-touch or performing a saccade towards the remembered target (effector-specific execution phase). Our analysis of saccade and reach activation (vs. a non-spatial control task) revealed modest effector-agnostic target memory activity (left AG, bilateral mIPS) followed by independent effector parietofrontal sites and time courses during the motor components of the task, specifically: more medial (pIPS, mIPS, M1, and PMd) activity during both reach planning and execution, and more lateral (mIPS, AG, and FEF) activity only during saccade execution. These motor activations were bilateral, with a left (contralateral) preference for reach. A conjunction analysis revealed that left mIPS and right AG, PCu, SPOC, FEF/PMv and LOTC showed activation for both saccades and reaches. Overall, effector-preference contrasts (reach vs. saccade) revealed significantly more parietofrontal activation for reaches than saccades during both planning and execution, with the exception of FEF. Cross-correlation of reach, saccade, and reach-saccade activation through time revealed correlated activation both within and across effectors in each hemisphere, but with a tendency toward higher correlations in the right hemisphere, especially between the eye and hand. These results demonstrate substantially independent but temporally correlated cortical networks for human eye, hand, and eye-hand control, that follow explicit spatiotemporal rules for effector-specific timing, medial-lateral distribution, and hemispheric lateralization.

neuroscience↗

bioRxiv2018

Transsaccadic feature interactions in multiple reference frames: an fMRIa study

Transsaccadic integration of visual features can operate in various frames of reference, but the corresponding neural mechanisms have not been differentiated. A recent fMRIa (adaptation) study identified two cortical regions in supramarginal gyrus (SMG) and extrastriate cortex that were sensitive to transsaccadic changes in stimulus orientation (Dunkley et al., 2016). Here, we modified this paradigm to identify the neural correlates for transsaccadic comparison of object orientations in: 1) Spatially Congruent (SC), 2) Retinally Congruent (RC) or 3) Spatially Incongruent (SI)) coordinates. Functional data were recorded from 12 human participants while they observed a grating (oriented 45{degrees} or 135{degrees}) before a saccade, and then judged whether a post-saccadic grating (in SC, RC, or SI configuration) had the same or different orientation. Our analysis focused on areas that showed a significant repetition suppression (Different > Same) or repetition enhancement (Same > Different) BOLD responses. Several cortical areas were significantly modulated in all three conditions: premotor/motor cortex (likely related to the manual response), and posterior-middle intraparietal sulcus. In the SC condition, uniquely activated areas included left SMG and left lateral occipitotemporal gyrus (LOtG). In the RC condition, unique areas included inferior frontal gyrus and the left lateral BA 7. In the SI condition, uniquely activated areas included the frontal eye field, medial BA 7, and right LOtG. Overall, the SC results were significantly different from both RC and SI. These data suggest that different cortical networks are used to compare pre- and post-saccadic orientation information, depending on the spatial nature of the task.\n\nSignificance StatementEvery time one makes a saccade, the brain must compare and integrate stored visual information with new information. It has recently been shown that transsaccadic integration of visual object orientation involves specific areas within parietal and occipital cortex (Dunkley et al., 2016). Here, we show that this pattern of cortical activation also depends on the spatial nature of the task: when the visual object is fixed relative to space, the eye, or relative to neither space nor the eye, different frontal, parietal, and occipital regions are engaged. More generally, these findings suggest that different aspects of trans-saccadic integration flexibly employ different cortical networks.

neuroscience↗