Biology subjects

Froudist-Walsh, S.

Publications and source records attributed to Froudist-Walsh, S..

At least 19 recordsLinked to original sources

bioRxiv2025

Spatial layout of visual specialization is shaped by competing default mode and sensory networks

Understanding how the brain encodes information started with a map but turned into a maze: paths multiplied; boundaries blurred. Neurons tuned to specific features are not confined to single regions, but distributed across the cortex. Retinotopy, once thought limited to early visual areas, now appears in over 20 cortical regions--from the tip of the occipital cortex to the shore of the lateral frontal cortex. To describe and understand these complex mosaics of functional specialization, we focus on the spatial influences that shape their emergence across the cortical sheet. To this end, we developed Spatial Component Decomposition (SCD), a sparse dictionary learning framework that locates sources of spatial influence without relying on prior assumptions from systems neuroscience. Applied to MRI data capturing retinotopic maps, SCD reveals a dominant linear gradient extending over 60 mm from V1 and covering all the known posterior visual areas. Yet, it also revealed systematic competition from other primary sensory areas and default mode transmodal hubs. These suppressive influences shape the cortical embedding of visual information, even during purely visual tasks. Our results suggest that functional specialization emerges from spatial competition between representational systems--not just from feedforward inputs.

neuroscience↗

bioRxiv2025

In vivo cartography of state-dependent signal flow hierarchy in the human cerebral cortex

Understanding the principle of information flow across distributed brain networks is of paramount importance in neuroscience. Here, we introduce a novel neuroimaging framework, leveraging integrated effective connectivity (iEC) and unconstrained signal flow mapping for data-driven discovery of the human cerebral functional hierarchy. Simulation and empirical validation demonstrated the high fidelity of iEC in recovering connectome directionality and its potential relationship with histologically defined feedforward and feedback pathways. Notably, the iEC-derived hierarchy revealed a monotonically increasing level along the axis where the sensorimotor, association, and paralimbic areas are sequentially ordered - a pattern supported by the Structural Model of laminar connectivity. This hierarchy was further demonstrated to flexibly reorganize across brain states: flattening during an externally oriented condition, evidenced by a reduced slope in the hierarchy, and steepening during an internally focused condition, reflecting heightened engagement of interoceptive regions. Our study highlights the unique role of macroscale directed functional connectivity in uncovering a biologically interpretable state-dependent signal flow hierarchy.

neuroscience↗

bioRxiv2025

Three cortical streams for somatosensory information processing

AbstractThe somatosensory cortex processes information hierarchically, transforming sensory input into appropriate responses. This hierarchy, in turn, provides a fundamental principle for the organization of anatomical and functional properties across the somatosensory cortex. While the local somatosensory hierarchy has been studied, a comprehensive model that fully illustrates somatosensory information transmission in fine detail remains lacking. In this study, we examine multimodal connectivity patterns of the entire macaque somatosensory cortex by integrating the information from receptor covariance (RC) and structural (SC) or functional connectivity (FC). Our findings not only reveal the hierarchical relationships but also propose a model of somatosensory processing streams. In this model, area 3bl serves as the initial cortical stage for somatosensory signals, projecting to areas 3al, 1, and 2. From there, somatosensory signals follow three major pathways: ventrally to the SII complex, medially to the medial SI and TSA, and posteriorly to somatosensory association areas in the parietal lobe. Further analysis shows that RC is not only closely linked to SC and FC but in addition displays unique characteristics that likely relate to the hierarchical processing across sensory modalities. This study deepens our understanding of brain connectivity patterns across different modalities and links the structural, chemoarchitectonic, and functional organization of the macaque somatosensory cortex.

neuroscience↗

bioRxiv2024

Short- and long-term reconfiguration of rat prefrontal cortical networks following single doses of psilocybin

We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3mg/kg or 1mg/kg i.p.) unmasked 100Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1h post-injection and were accompanied by decreased net pyramidal cell firing rates and reduced signal complexity. These acute effects were more prominent during resting behaviour than during a sustained attention task. LFP 1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20-60Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.

neuroscience↗

bioRxiv2024

Cognitive networks interactions through communication subspaces in large-scale models of the neocortex

Neocortex-wide neural activity is organized into distinct networks of areas engaged in different cognitive processes. To elucidate the underlying mechanism of flexible network reconfiguration, we developed connectivity-constrained macaque and human whole-cortex models. In our model, within-area connectivity consists of a mixture of symmetric, asymmetric, and random motifs that give rise to stable (attractor) or transient (sequential) heterogeneous dynamics. Assuming sparse low-rank plus random inter-areal connectivity constrained by cognitive networks activation maps, we show that our model captures key aspects of the cognitive networks dynamics and interactions observed experimentally. In particular, the anti-correlation between the default mode network and the dorsal attention network. Communication between networks is shaped by the alignment of long-range communication subspaces with local connectivity motifs and is switchable in a bottom-up salience-dependent routing mechanism. Furthermore, the frontoparietal multiple-demand network displays a coexistence of stable and dynamic coding, suitable for top-down cognitive control. Our work provides a theoretical framework for understanding the dynamic routing in the cortical networks during cognition.

neuroscience↗

bioRxiv2024

Benchmarking macaque gene expression for horizontal and vertical translation

The spatial patterning of gene expression shapes cortical organization and emergent function. Advances in spatial transcriptomics make it possible to comprehensively map cortical gene expression in both humans and model organisms. The macaque is a particularly valuable model organism, due to its evolutionary similarity with the human. The translational potential of macaque gene expression rests on the assumption that it is a good proxy for spatial patterns of corresponding proteins (vertical translation) and for spatial patterns of ortholog human genes (horizontal translation). Here we systematically benchmark the spatial distribution of gene expression in the macaque cortex against (a) cortical receptor density in the macaque and (b) cortical gene expression in the human. We find that there is moderate cortex-wide correspondence between gene expression and protein density in the macaque, which is improved by considering layer-specific gene expression. We find greater correspondence between orthologous gene expression in the macaque and human. Inter-species correspondence of gene expression exhibits systematic regional heterogeneity, with greater correspondence in unimodal than transmodal cortex, mapping onto patterns of evolutionary cortical expansion. We extend these results to additional micro-architectural features using macaque immunohistochemistry and T1w:T2w ratio, and replicate them using macaque RNA-seq and human RNA-seq gene expression. Collectively, the present results showcase both the potential and limitations of macaque spatial transcriptomics as an engine of translational discovery within and across species.

neuroscience↗

bioRxiv2024

Dopamine D1 receptor expression in dlPFC inhibitory parvalbumin neurons may contribute to higher visuospatial distractibility in marmosets versus macaques

Marmosets and macaques are common non-human primate models of cognition, yet marmosets appear more distractible and perform worse in cognitive tasks. The dorsolateral prefrontal cortex (dlPFC) is pivotal for sustained attention, and prior macaque research suggests that dopaminergic modulation and inhibitory parvalbumin (PV) neurons could contribute to distractibility. Thus, we compared the two species using a visual fixation task with distractors, performed molecular and anatomical analyses in dlPFC, and linked functional microcircuitry with cognitive performance using computational modeling. We found that marmosets are more distractible than macaques, and that marmoset dlPFC PV neurons contain higher levels of dopamine-1 receptor (D1R) transcripts and protein, similar to their levels in mice. The modeling indicated that higher D1R expression in marmoset dlPFC PV neurons may increase distractibility by making dlPFC microcircuits more vulnerable to disruptions of their task-related persistent activity, especially when dopamine is released in dlPFC in response to unexpected salient stimuli. Declaration of InterestsThe authors have nothing to declare. Author ContributionsAFTA, MKPJ, TGI, and SFW designed the study; MKPJ collected and analyzed anatomical data; TGI designed the computational framework with guidance from RG and SFW; TGI performed the modeling simulations and data analysis; FM and SAM collected and analyzed transcriptomics data; GGB and DAL provided macaque brain tissue for transcriptomics performed by FM; SM and NS collected and analyzed phylogenetic transcriptomics dataset; JFM and ASN performed and analyzed the behavioral testing; IW and JMT provided the marmoset tissue for immunofluorescence; MKPJ, TGI, SFW, and AFTA wrote the first draft and all authors revised and edited subsequent drafts of the article.

neuroscience↗

bioRxiv2022

Predicting distributed working memory activity in a large-scale mouse brain: the importance of the cell type-specific connectome

Recent advances in connectome and neurophysiology make it possible to probe whole-brain mechanisms of cognition and behavior. We developed a large-scale model of the mouse multiregional brain for a cardinal cognitive function called working memory, the brains ability to internally hold and process information without sensory input. The model is built on mesoscopic connectome data for inter-areal cortical connections and endowed with a macroscopic gradient of measured parvalbumin-expressing interneuron density. We found that working memory coding is distributed yet exhibits modularity; the spatial pattern of mnemonic representation is determined by long-range cell type-specific targeting and density of cell classes. Cell type-specific graph measures predict the activity patterns and a core subnetwork for memory maintenance. The model shows numerous self-sustained internal states (each engaging a distinct subset of areas). This work provides a framework to interpret large-scale recordings of brain activity during cognition, while highlighting the need for cell type-specific connectomics.

neuroscience↗

bioRxiv2022

Cytoarchitectonic, receptor distribution and functional connectivity analyses of the macaque frontal lobe

Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas and introduced a novel subdivision of Walkers areas 10, 9, 8B and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Since structural and functional organization of subdivisions encompassing areas 46 and 12 demonstrated significant differences in the interareal levels of 2 receptors. Furthermore, multivariate analysis included receptor fingerprints of previously identified 16 motor areas in the same macaque brains, and revealed five clusters encompassing frontal lobe areas. Based on the functional connectivity analysis, clustered areas showed similar connectivity distribution pattern. In particular, rostrally located areas (in clusters 1-2) were characterized by bigger fingerprints, i.e., higher receptor densities, and stronger regional interconnections. Whereas, more caudal areas (in clusters 3-5) had smaller fingerprints, but showed a widespread connectivity pattern with distant cortical regions. Taken together, present study provides a comprehensive insight into the molecular structure underlying the functional organization of the cortex and, thus, reconcile discrepancies between the structural and functional hierarchical organization of the primate frontal lobe. Finally, our data are publicly available via the EBRAINS and BALSA repositories for the entire scientific community.

neuroscience↗

bioRxiv2022

A connectome-based model of conscious access in monkey cortex

A growing body of evidence suggests that conscious perception of a sensory stimulus coincides with all-or-none activity across multiple cortical areas, a phenomenon called ignition. In contrast, the same stimulus, when undetected, induces only transient activity. In this work, we report a large-scale model of the macaque cortex based on recently quantified structural mesoscopic connectome data. We use this model to simulate a detection task, and demonstrate how a dynamical bifurcation mechanism produces ignition-like events in the model network. The model predicts that feedforward excitatory transmission is primarily mediated by the fast AMPA receptors to ensure rapid signal propagation from sensory to associative areas. In contrast, a greater proportion of the inter-areal feedback projections and local recurrent excitation depend on the slow NMDA receptors, to ensure ignition of distributed frontoparietal activity. Our model predicts, counterintuitively, that fast-responding sensory areas contain a higher ratio of NMDA to AMPA receptors compared to association cortical areas that show slow, sustained activity. We validate this prediction using cortex-wide in-vitro receptor autoradiography data. Finally, we show how this model can account for various behavioral and physiological effects linked to consciousness. Together, these findings clarify the neurophysiological mechanisms of conscious access in the primate cortex and support the concept that gradients of receptor densities along the cortical hierarchy contribute to distributed cognitive functions.

neuroscience↗

bioRxiv2021

Neural Basis of the Delayed Gratification

Balancing instant gratification versus delayed, but better gratification is important for optimizing survival and reproductive success. Although psychologists and neuroscientists have long attempted to study delayed gratification through human psychological and brain activity monitoring, and animal research, little is known about its neural basis. We successfully trained mice to perform a waiting-and-water-reward delayed gratification task and used these animals in physiological recording and optical manipulation of neuronal activity during the task to explore its neural basis. Our results showed that the activity of DA neurons in ventral tegmental area (VTA) increases steadily during the waiting period. Optical activation vs. silencing of these neurons, respectively, extends or reduces the duration of waiting. To interpret this data, we developed a reinforcement learning (RL) model that reproduces our experimental observations. In this model, steady increases in DAergic activity signal the value of waiting and support the hypothesis that delayed gratification involves real-time deliberation. TEASERSustained ramping dopaminergic activation helps individuals to resist impulsivity and wait for laerger but later return.

neuroscience↗

bioRxiv2021

Gradients of receptor expression in the macaque cortex

Dynamics and functions of neural circuits depend on synaptic interactions mediated by receptors. Therefore, a comprehensive map of receptor organization is needed to understand how different functions may emerge across distinct cortical regions. Here we use in-vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrate the receptor data with other anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of increasing receptor expression per neuron aligned with cortical hierarchy from early sensory cortex to higher cognitive areas. A second gradient, primarily driven by 5-HT1A receptors, peaks in the anterior and subcallosal cingulate, suggesting that the macaque may be a promising animal model for major depressive disorder. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration of information in higher cognitive areas.

neuroscience↗

bioRxiv2020

Multimodal 3D atlas of the macaque monkey motor and premotor cortex

In the present study we reevaluated the parcellation scheme of the macaque frontal agranular cortex by implementing quantitative cytoarchitectonic and multireceptor analyses, with the purpose to integrate and reconcile the discrepancies between previously published maps of this region. We applied an observer-independent and statistically testable approach to determine the position of cytoarchitectonic borders. Analysis of the regional and laminar distribution patterns of 13 different transmitter receptors confirmed the position of cytoarchitectonically identified borders. Receptor densities were extracted from each area and visualized as its "receptor fingerprint". Hierarchical and principal components analyses were conducted to detect clusters of areas according to the degree of (dis)similarity of their fingerprints. Finally, functional connectivity pattern of each identified area was analyzed with areas of prefrontal, cingulate, somatosensory and lateral parietal cortex and the results were depicted as "connectivity fingerprints" and seed-to-vertex connectivity maps. We identified 16 cyto- and receptor architectonically distinct areas, including novel subdivisions of the primary motor area 4 (i.e. 4a, 4p, 4m) and of premotor areas F4 (i.e. F4s, F4d, F4v), F5 (i.e. F5s, F5d, F5v) and F7 (i.e. F7d, F7i, F7s). Multivariate analyses of receptor fingerprints revealed three clusters, which first segregated the subdivisions of area 4 with F4d and F4s from the remaining premotor areas, then separated ventrolateral from dorsolateral and medial premotor areas. The functional connectivity analysis revealed that medial and dorsolateral premotor and motor areas show stronger functional connectivity with areas involved in visual processing, whereas 4p and ventrolateral premotor areas presented a stronger functional connectivity with areas involved in somatomotor responses. For the first time, we provide a 3D atlas integrating cyto- and multi-receptor architectonic features of the macaque motor and premotor cortex. This atlas constitutes a valuable resource for the analysis of functional experiments carried out with non-human primates, for modeling approaches with realistic synaptic dynamics, as well as to provide insights into how brain functions have developed by changes in the underlying microstructure and encoding strategies during evolution. HighlightsO_LIMultimodal analysis of macaque motor and premotor cortex reveals novel parcellation C_LIO_LI3D atlas with cyto- and multireceptor architectonic features of 16 (pre)motor areas C_LIO_LIPrimary motor area 4 is cyto- and receptor architectonically heterogeneous C_LIO_LI(Pre)motor areas differ in their functional connectivity fingerprints C_LI

neuroscience↗

bioRxiv2020

A dopamine gradient controls access to distributed working memory in monkey cortex

Dopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and biophysically-based model for distributed working memory that incorporates multiple neuron types and a dopamine gradient. The model captures an inverted U-shaped dependence of working memory on dopamine. The spatial distribution of mnemonic persistent activity matches that observed in over 90 experimental studies. We show that dopamine filters out irrelevant stimuli by enhancing inhibition of pyramidal cell dendrites. The level of cortical dopamine can also determine whether memory encoding is through persistent activity or an internal synaptic state. Taken together, our work represents a cross-level understanding that links molecules, cell types, recurrent circuit dynamics and a core cognitive function distributed across the cortex.

neuroscience↗

bioRxiv2019

Altered cortical gyrification in adults who were born very preterm and its associations with cognition and mental health

BackgroundThe last trimester of pregnancy is a critical period for the establishment of cortical gyrification and altered folding patterns have been reported following very preterm birth (< 33 weeks of gestation) in childhood and adolescence. However, research is scant on the persistence of such alterations in adulthood and their associations with cognitive and psychiatric outcomes. MethodsWe studied 79 very-preterm adults and 81 age-matched full-term controls. T1-weighted images were used to measure local gyrification index (LGI), indicating the degree of folding across multiple vertices of the reconstructed cortical surface. Group and group-sex LGI differences were assessed using per-vertex adjustment for cortical thickness and overall intracranial volume. Within-group correlations were also computed between LGI and functional outcomes, including general intelligence (IQ) and psychopathology. ResultsVery preterm adults had significantly reduced LGI in extensive cortical regions encompassing the frontal, anterior temporal and occipito-parietal lobes. Alterations in lateral fronto-temporal-parietal and medial occipito-parietal regions were present in both males and females, although males reported more extensive alterations. In both very preterm adults and controls, higher LGI was associated with higher IQ and lower psychopathology scores, with the spatial distribution of these associations substantially differing between the two groups. ConclusionsVery preterm adults brains are characterized by significant and widespread local hypogyria and these abnormalities might be implicated in cognitive and psychiatric outcomes. Gyrification reflects an early developmental process and provides a fingerprint for very preterm birth.

neuroscience↗

bioRxiv2019

Inter-individual Variability of Functional Connectivity in Awake and Anesthetized Rhesus Monkeys

BackgroundNonhuman primate models (NHP) are commonly used to advance our understanding of brain function and organization. However, to date, they have offered few insights into individual differences among NHPs. In large part, this is due to the logistical challenges of NHP research, which limit most studies to five subjects or fewer. MethodsWe leveraged the availability of a large-scale open NHP imaging resource to provide an initial examination of individual differences in the functional organization of the nonhuman primate brain. Specifically, we selected one awake fMRI dataset (Newcastle: n = 10) and two anesthetized fMRI data sets (Oxford: n = 19; UC-Davis: n = 19) to examine individual differences in functional connectivity characteristics across the cortex, as well as potential state dependencies. ResultsWe noted significant individual variations of functional connectivity across the macaque cortex. Similar to the findings in human, during the awake state, the primary sensory and motor cortices showed lower variability than the high-order association regions. This variability pattern was significantly correlated with T1w/T2w map, the degree of long-distance connectivity, but not short-distance connectivity. However, the inter-individual variability under anesthesia exhibited a very distinct pattern, with lower variability in medial frontal cortex, precuneus and somatomotor regions and higher variability in the lateral ventral frontal and insular cortices. ConclusionsThis work has implications for our understanding of the evolutionary origins of individual variation in the human brain, as well as methodological implications that must be considered in any pursuit to study individual variation in NHP models.

neuroscience↗

bioRxiv2017

A Dimensional Approach To Assessing Psychiatric Risk In Adults Born Very Preterm

BackgroundIndividuals who were born very preterm have higher rates of psychiatric diagnoses compared to term-born controls; however, it remains unclear whether they also display increased sub-clinical psychiatric symptomatology. Hence our objective is to utilise a dimensional approach to assess psychiatric symptomatology in adults who were born very preterm.\n\nMethods152 adults who were born very preterm (before 33 weeks gestation; gestational range 24-32 weeks) and 96 term-born controls. We examined participants clinical profile using the Comprehensive Assessment of At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that yields seven subscales including general psychopathology, positive, negative, cognitive, behavioural, motor and emotional symptoms, in addition to a total psychopathology score. Intellectual abilities were examined using the Wechsler Abbreviated Scale of Intelligence.\n\nResultsBetween-group differences on the CAARMS showed elevated symptomatology in very preterm participants compared to controls in positive, negative, cognitive and behavioural symptoms. Total psychopathology scores were significantly correlated with IQ in the very preterm group only. In order to examine the characteristics of participants clinical profile a principal component analysis was conducted. This revealed two components, one reflecting a non-specific psychopathology dimension, and the other indicating a variance in symptomatology along a positive-to-negative symptom axis. K-means (k=4) were used to further separate the study sample into clusters. Very preterm adults were more likely to belong to the high non-specific psychopathology cluster compared to controls.\n\nConclusion and RelevanceVery preterm individuals demonstrated elevated psychopathology compared to full-term controls. Psychiatric risk was characterised by a non-specific clinical profile and was associated with lower IQ.

developmental biology↗

bioRxiv2017

The Effect Of Perinatal Brain Injury On Dopaminergic Function And Hippocampal Volume In Adult Life

BackgroundVery preterm birth (<32 weeks of gestation) is associated with long-lasting brain alterations and an increased risk of psychiatric disorders associated with dopaminergic abnormalities. Preclinical studies have shown perinatal brain injuries, including hippocampal lesions, cause lasting changes in dopamine function, but it is not known if this occurs in humans. The purpose of this study was to determine whether very preterm birth and perinatal brain injury were associated with altered dopamine synthesis and reduced hippocampal volume in humans in adulthood.\n\nMethodsWe compared adults who were born very preterm with associated perinatal brain injury to adults born very preterm without perinatal brain injury, and age-matched controls born at full term using [18F]-DOPA PET and structural MRI imaging.\n\nResultsDopamine synthesis capacity was significantly reduced in the perinatal brain injury group relative to both the group born very preterm without brain injury (Cohens d=1.36, p=0.02) and the control group (Cohens d=1.07, p=0.01). Hippocampal volume was reduced in the perinatal brain injury group relative to controls (Cohens d = 1.17, p = 0.01). There was a significant correlation between hippocampal volume and striatal dopamine synthesis capacity (r = 0.344, p= 0.03).\n\nConclusionsPerinatal brain injury, but not very preterm birth without macroscopic brain injury, is associated with persistent alterations in dopaminergic function and reductions in hippocampal volume. This is the first evidence in humans linking neonatal hippocampal injury to adult dopamine dysfunction, and has implications for understanding the mechanism underlying cognitive impairments and neuropsychiatric disorders following very preterm birth.

neuroscience↗