Biology subjects

Sallet, J.

Publications and source records attributed to Sallet, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Quantitative evaluation of enrichment protocols on rhesus macaques welfare in laboratory environment.

Non-human primates are crucial animal models in biomedical research including neurosciences. Legal frameworks ensure that participation of monkeys in biomedical research follows an ethical assessment, driven by specific guidelines for ensuring animal well-being. Those guidelines promote continued refinement of practices to improve animal wellbeing, yet quantitative data to inform such refinements is limited. In this context, we investigated the impact of modifications to the housing that created either navigational complexity or visual access to neighbouring animals on the behaviour of rhesus macaques. Then we quantified the value of different enrichment programmes based on manipulable objects. We showed that making navigation within a modular housing more complex, or adding transparent separations between housing units is associated with significant reduction of severe aggression, stereotypical behaviours and a significant increase of appeasing behaviours. We also observed a positive effect of manipulable objects with an increase in the expression of appeasing behaviours and a decrease in abnormal or stereotypical behaviours. Finally, our study revealed significant inter-individual variability that was not explained by sex, age, social network size or social status. Overall, our results point to the importance and benefits of environmental changes and enrichment protocols, and of the critical need for personalised enrichment programmes.

animal behavior and cognition↗

bioRxiv2025

Transcranial ultrasound stimulation selectively enhances fronto-temporal context-guided memory

There is substantial scientific interest in advancing knowledge on the control mechanisms supporting adaptive memory and improving approaches that can enhance cognition through brain stimulation. We implemented a non-invasive focal Transcranial Ultrasound Stimulation (TUS) approach with known longer-lasting post-stimulation effects in two rhesus macaques performing a novel context-dependent memory-sequencing task implemented on multiple touchscreens within their home units. Consistently in both monkeys, TUS to the anterior, but not posterior, medial temporal lobe enhanced performance under stable memory-sequencing contexts. TUS to the medial prefrontal cortex, on the other hand, selectively improved performance when contexts were unstable and the monkey needed to adapt to both a change in context and temporal sequence. These findings provide positive causal evidence of a functional dissociation within fronto-temporal memory circuits and pave the way for advancing non-invasive approaches to improve cognitive function and the study of neural circuits under focal enhancement across species. IMPACT STATEMENTTranscranial ultrasound stimulation of the prefrontal-hippocampal network selectively enhances context-guided memory in macaques, demonstrating that non-invasive brain stimulation can causally improve, rather than only disrupt, memory circuits.

neuroscience↗

bioRxiv2025

Single-cell, multi-region profiling of the macaque brain across the lifespan

Brain aging is a complex process with profound health and societal consequences. However, the molecular and cellular pathways that govern its temporal progression-along with any cell type-, region-, and sex-specific heterogeneity in such progression-remain poorly defined. Here, we present a transcriptomic atlas of 5.3 million cells from 582 samples spanning 11 brain regions of 55 rhesus macaques (29 female, 26 male), aged 5 months (early life) to 21 years (late adulthood). We annotate 12 major cell classes and 225 subclusters, including region-specific subtypes of excitatory and inhibitory neurons, astrocytes, and ependymal cells. We identify a vulnerable excitatory neuron population in the superficial cortical lamina and a cortical interneuron population that are less abundant later in life, along with subtle, region-specific, age-associated compositional differences in subpopulations of microglia and oligodendrocytes, whose detection required single-cell resolution. Finally, we chart convergent and divergent age-associated molecular signatures across brain regions and cell classes-where some of these signatures are sex-specific and could underlie sex biases in neurological disorders. We find that age-associated transcriptional programs not only overlap substantially with those seen in Alzheimers disease (AD), but also unfold along distinct temporal trajectories across brain regions, suggesting that aging and AD may share molecular roots that emerge at different life stages and in region-specific, sex-specific windows of vulnerability. This work provides a temporal, regional, and sex-stratified atlas of the aging primate brain, offering insights into cell type-specific vulnerabilities and regional heterogeneity with translational human relevance.

neuroscience↗

bioRxiv2025

Neuroanatomical foundations of social tolerance across macaque species

The macaque genus includes 25 species with diverse social systems, ranging from low to high social tolerance grades. Such interspecific behavioral variability provides a unique model to tackle the evolutionary foundation of primate social brain. Yet, the neuroanatomical correlates of these social tolerance grades remain unknown. To address this question, we expressed social tolerance grades within a novel cognitive framework and analyzed post-mortem structural scans from 12 macaque species. Our results show that amygdala volume is a subcortical predictor of macaques social tolerance, with high tolerance species exhibiting larger amygdala than low tolerance ones. We further investigated the developmental trajectory of amygdala across social grades and found that intolerant species showed a gradual increase in relative amygdala volume across the lifespan. Unexpectedly, tolerant species exhibited a decrease in relative amygdala volume across the lifespan, contrasting with the age-related increase observed in intolerant species--a developmental pattern previously undescribed in primates. Taken together, these findings provide valuable insights into the cognitive, neuroanatomical and evolutionary basis of primates social behaviors.

neuroscience↗

bioRxiv2025

Motivational control is implemented by a cingulo-prefrontal pathway

The neuronal connections between the midcingulate cortex (MCC) and the dorsolateral prefrontal cortex (dlPFC) are associated with multiple cognitive functions, including rapid and long-term adaptive processes. Here we show that DREADD-mediated activation of MCC to dlPFC projection in macaques led to increased engagement in a foraging task, but did not alter their trial-to-trial adaptive strategy. We conclude that a critical role for MCC-dlPFC pathway is in the temporally extended control of behaviour rather than in rapid adaptation.

neuroscience↗

bioRxiv2024

Comparative neuroimaging of the carnivoran brain: Neocortical sulcal anatomy

Carnivorans are an important study object for comparative neuroscience, as they exhibit a wide range of behaviours, ecological adaptations, and social structures. Previous studies have mainly examined relative brain size, but a comprehensive understanding of brain diversity requires the investigation of other aspects of their neuroanatomy. Here, we obtained primarily post-mortem brain scans from twenty-six species of the order Carnivora, spanning across eight families with diverse representatives and including additional individuals for selected species, to create the largest Carnivoran brain collection to date. We then reconstructed their cortical surfaces, and examined neocortical sulcal anatomy to establish a framework for systematic inter-species comparisons. We observed distinct regional variations in sulcal anatomy, potentially related to the species behaviour and ecology. Arctoidea species with pronounced forepaw dexterity exhibited complex sulcal configurations in the presumed somatosensory cortex but low sulcal complexity in the presumed visual and auditory occipitotemporal cortex. Canidae had the largest number of unique major sulci with a unique sulcus in the occipital cortex and highly social canids featuring an additional frontal cortex sulcus. We also observed differentially complex occipito-temporal sulcal patterns in Felidae and Canidae, indicative of changes in auditory and visual areas that may be related to foraging strategies and social behaviour. In conclusion, this study presents an inventory of the sulcal anatomy of a number of rarely studied carnivoran brains including detailed digital atlases and establishes a framework and novel avenues for further investigations employing a variety of neuroimaging modalities to reveal more about carnivoran brain diversity.

neuroscience↗

bioRxiv2024

General mechanisms of task engagement in the primate frontal cortex

Staying engaged with a task is necessary to maintain goal-directed behaviors. Although engagement varies with the specific task at hand it also exhibits continuous, intrinsic fluctuations widely. This intrinsic component of engagement is difficult to isolate behaviorally or neurally in controlled experiments with humans. By contrast, animals spontaneously move between periods of complete task engagement and disengagement, even in experimental settings. We, therefore, looked at behavior in macaques in a series of four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement and to link it to neural activity. Across all tasks, we identified common patterns of neural activity linked to impending task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of task performance. Importantly, we were able to carefully control for task-specific factors such as the reward history, choice value, and other motivational effects, such as response vigor, as indexed by response time, when identifying neural activity associated with task engagement. Moreover, we showed pgACC activity had a causal link to task engagement; in one of our tasks, transcranial ultrasound stimulation of pgACC, but not of control regions, changed task engagement/disengagement patterns.

neuroscience↗

bioRxiv2024

Imaging the structural connectome with hybrid diffusion MRI-microscopy tractography

Neuroanatomical tract tracing methods are fundamental in providing "gold standard" estimates of brain connectivity. However, tracer methods cannot be performed in humans and even in animals, we can only study projections from typically one or two injection sites per animal sacrificed. Orientation-sensitive microscopy techniques such as PLI provide an alternative where they can visualise detailed fibre orientations at the micron-scale across the whole brain. However, these methods are often most informative on orientations within the 2D imaging plane, with less reliable or missing through-plane information, restricting 3D tract reconstruction. Conversely, dMRI can estimate fibre orientations in 3D but at low resolution, which leads to many false positive and negative estimates of fibre trajectories. To facilitate reconstruction of the microscopy-informed connectome, we develop a data-fusion method that complements 2D microscopy with through-plane information from diffusion MRI to construct 3D hybrid orientations that are both maximally informed by the high-resolution microscopy, have whole-brain coverage and can be input into existing tractography pipelines. Diffusion MRI can be readily acquired prior to microscopy meaning the same method is translatable across species, including in humans. Here we apply our method to an existing open-access macaque dataset and demonstrate (1) whole-brain microscopy-informed tractography (2) the advantages of hybrid tractography in two known tractography challenges, the gyral bias and bottleneck problem (3) how hybrid tractography appears to outperform diffusion-only tractography when compared to tracer data and (4) the generalisability of our hybrid method to different microscopy contrasts, facilitating wider translation.

bioengineering↗

bioRxiv2023

Transcranial ultrasound stimulation effect in the redundant and synergistic networks consistent across macaques

Low-intensity transcranial ultrasound stimulation (TUS) is a non-invasive technique that safely alters neural activity, reaching deep brain areas with good spatial accuracy. We investigated the effects of TUS at the level of macaque using a recent metric, the synergy minus redundancy rank gradient, that quantifies different kinds of causal neural information processing. We analyzed this high-order quantity on the fMRI data after TUS in two targets: the supplementary motor area (SMA-TUS) and the frontal polar cortex (FPC-TUS). The TUS produced specific changes at the limbic network at FPC-TUS and the motor network at SMA-TUS and altered, in both targets, the sensorimotor, temporal, and frontal networks, consistent across macaques. Moreover, there was a reduction in the structural and functional coupling after both stimulations. Finally, the TUS changed the intrinsic high-order network topology, decreasing the modular organization of the redundancy at SMA-TUS and increasing the synergistic integration at FPC-TUS.

neuroscience↗

bioRxiv2023

Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain

The hippocampus is involved in numerous cognitive functions, some of which have uniquely human aspects, such as autobiographical memory. Hippocampal anatomy, however, is typically considered conserved across primates and its evolutionary diversification is rarely studied. Comparing hippocampal structure and function is, therefore, critical for understanding human brain architecture. Here, we developed a novel comparative framework to study the hippocampus across species characterising its geometry, microstructure, and functional network embedding. In humans and macaques, we generated a new comparative space that represents the hippocampus as an unfolded surface, which respects its sheet-like anatomy. We mapped histological and MRI-derived markers of microstructure to the hippocampal surface and integrated it with low-dimensional embedding of resting-state MRI connectivity data. Our results demonstrate that the micro- and macro-structural organisation of the hippocampus are overall conserved in both species, showing consistent anterior-posterior and subfield-to-subfield differentiation. Furthermore, while hippocampal functional organisation also follows anterior-posterior trends in both species, hippocampal functional connectivity markedly reflected evolutionary reconfiguration of transmodal networks, in particular the default-mode network. Specifically, the inferior parietal lobe in the macaque mirrors an incomplete integration of the default mode network in non-human primates. By combining fine-grained anatomical investigation with large-scale functional imaging, we showed that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration, due to their embedding in higher-order association networks. SummaryWhile the hippocampus is key for uniquely human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro- and micro-structure, showing anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species also followed an anterior-posterior axis, the latter showed a marked evolutionary reconfiguration, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Our findings suggest that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding in heteromodal association networks.

neuroscience↗

bioRxiv2022

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome

Humans exhibit sex differences in the prevalence of many neurodevelopmental and neurodegenerative conditions. To better understand the translatability of a critical nonhuman primate model, the rhesus macaque, we generated one of the largest multibrain region bulk transcriptional datasets for this species and characterized sex-biased gene expression patterns. We demonstrate that these patterns are similar to those in humans and are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate the rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and validate the rhesus macaque model for the study of these conditions.

neuroscience↗

bioRxiv2022

The BigMac dataset: an open resource combining multi-contrast MRI and microscopy in the macaque brain

Understanding brain structure and function often requires combining data across different modalities and scales to link microscale cellular structures to macroscale features of whole brain organisation. Here we introduce the BigMac dataset, a resource combining in vivo MRI, extensive postmortem MRI and multi-contrast microscopy for multimodal characterisation of a single whole macaque brain. The data spans modalities (MRI and microscopy), tissue states (in vivo and postmortem), and four orders of spatial magnitude, from microscopy images with micrometre or sub-micrometre resolution, to MRI signals on the order of millimetres. Crucially, the MRI and microscopy images are carefully co-registered together to facilitate quantitative multimodal analyses. Here we detail the acquisition, curation, and first release of the data, that together make BigMac a unique, openly-disseminated resource available to researchers worldwide. Further, we demonstrate example analyses and opportunities afforded by the data, including improvement of connectivity estimates from ultra-high angular resolution diffusion MRI, neuroanatomical insight provided by polarised light imaging and myelin-stained histology, and the joint analysis of MRI and microscopy data for reconstruction of the microscopy-inspired connectome. All data and code are made openly available.

neuroscience↗

bioRxiv2022

Strategic exploration in the macaque prefrontal cortex

Humans have been shown to strategically explore. They can identify situations in which gathering information about distant and uncertain options is beneficial for the future. Because primates rely on scare resources when they forage, they are also thought to strategically explore, but whether they use the same strategies as humans and the neural bases of strategic exploration in monkeys are largely unknown. We designed a sequential choice task to investigate whether monkeys mobilize strategic exploration based on whether that information can improve subsequent choice, but also to ask the novel question about whether monkeys adjust their exploratory choices based on the contingency between choice and information, by sometimes providing the counterfactual feedback, about the option not chosen. We show that monkeys decreased their reliance on expected value when exploration could be beneficial, but this was not mediated by changes in the effect of uncertainty on choices. We found strategic exploratory signals in anterior and mid-cingulate cortex (ACC/MCC) and dorsolateral prefrontal cortex (dlPFC). This network was most active when a low value option was chosen which suggests a role in counteracting expected value signals, when exploration away from value should to be considered. Such strategic exploration was abolished when the counterfactual feedback was available. Learning from counterfactual outcome was associated with the recruitment of a different circuit centered on the medial orbitofrontal cortex (OFC), where we showed that monkeys represent chosen and unchosen reward prediction errors. Overall, our study shows how ACC/MCC-dlPFC and OFC circuits together could support exploitation of available information to the fullest and drive behavior towards finding more information through exploration when it is beneficial.

neuroscience↗

bioRxiv2021

The Forget-Me-Not dHCP study: 7 Tesla high resolution diffusion imaging in the unfixed post-mortem neonatal brain

Diffusion MRI of the neonatal brain allows investigation of the organisational structure of maturing fibres during brain development. Post-mortem imaging has the potential to achieve high resolution by using long scan times, enabling precise assessment of small structures. The Forget-Me-Not study, part of the Developing Human Connectome Project (dHCP), aims to acquire and publicly distribute high-resolution diffusion MRI data for unfixed post-mortem neonatal brain at 7T with a custom-built head coil. This paper describes how the study addressed logistical, technical and ethical challenges relating to recruitment pipeline, care pathway, tissue preservation, scan setup and protocol optimisation. Results from the first subject recruited to the study demonstrate high-quality diffusion MRI data. Preliminary voxel-wise and tractography-based analyses are presented for the cortical plate, subplate and white matter pathways, with comparison to age-matched in vivo dHCP data. These results demonstrate that high quality post-mortem data can be acquired and provide a sensitive means to explore the developing human brain, as well as altered diffusion properties consistent with post-mortem changes, at high resolution.

bioengineering↗

bioRxiv2021

The Digital Brain Bank: an open access platform for post-mortem datasets

Post-mortem MRI provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy, and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes - Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank release includes twenty one distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen non-human primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our labs investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides crossscale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies.

neuroscience↗

bioRxiv2021

Frontal cortical functional connectivity is impacted by anaesthesia in macaques

AO_SCPLOWBSTRACTC_SCPLOWA critical aspect of neuroscience is to establish whether and how brain networks evolved across primates. To date, most comparative studies have used resting-state functional Magnetic Resonance Imaging (rs-fMRI) in anaesthetized non-human primates and in awake humans. However, anaesthesia strongly affects rs-fMRI signals. The present study investigated the impact of the awareness state (anaesthesia vs. awake) within the same group of macaque monkeys on the rs-fMRI functional connectivity (FC) organization of a well characterized network in the human brain, the cingulo-frontal lateral network. Results in awake macaques revealed a similar FC pattern to that previously uncovered in the human brain. Rostral seeds in the cingulate sulcus exhibited stronger correlation strength with rostral compared to caudal lateral frontal cortical areas while caudal seeds in the cingulate sulcus displayed stronger correlation strength with caudal compared to anterior lateral frontal cortical areas. Critically, this inverse rostro-caudal functional gradient was abolished under anaesthesia. This study demonstrates that the FC pattern of cingulo-frontal cortical networks is preserved from macaque to human but some of its properties can only be observed in the awake state, warranting significant caution when comparing FC patterns across species under different states.

neuroscience↗

bioRxiv2021

Social prediction modulates activity of macaque superior temporal cortex

The ability to attribute thoughts to others, also called theory of mind (TOM), has been extensively studied. Computationally, the basis of TOM in humans has been interpreted within the predictive coding framework and associated with activity in the temporo-parietal junction (TPJ). However, the evolutionary origins of these human mindreading abilities have been challenged since the concept was coined. Here we identify a brain region in the Rhesus macaque that shares computational properties with the human TPJ. We revealed, using a non-linguistic task and functional magnetic resonance imaging, that activity in a region of the macaque middle superior temporal cortex was specifically modulated by the predictability of social interactions. As in human TPJ, this region could be distinguished from other temporal regions involved in face processing. Our result suggests the existence of a precursor for the theory of mind ability in the last common ancestor of human and old-world monkeys.

neuroscience↗

bioRxiv2020

Perceived ambiguity of social interactions increases coupling between frontal and temporal nodes of the social brain

Social behaviour is coordinated by a network of brain regions, including those involved in the perception of social stimuli and those involved in complex functions like inferring perceptual and mental states and controlling social interactions. The properties and function of many of these regions in isolation is relatively well understood but little is known about how these regions interact whilst processing dynamic social interactions. To investigate whether social network connectivity is modulated by social context we collected fMRI data from monkeys viewing "affiliative", "aggressive", or "ambiguous" social interactions. We show activation relating to the perception of social interactions along both banks of the superior temporal sulcus, parietal, medial and lateral PFC and caudate nucleus. Within this network we demonstrate that fronto-temporal connectivity are significantly modulated by social context. Crucially, we link the observation of specific behaviours to changes in connectivity within our network. Viewing aggressive or affiliative behaviour was associated with a limited increase in temporo-temporal and premotor-temporal connectivity respectively. By contrast, viewing ambiguous interactions was associated with a pronounced increase in cingulate-cingulate, temporo-temporal, and cingulate-temporal connectivity. We hypothesise that this widespread network synchronisation occurs when cingulate and temporal areas coordinate their activity when more difficult social inferences are made.

neuroscience↗