Biology subjects

Sallet, J.

Publications and source records attributed to Sallet, J..

33 records · Page 2Linked to original sources

bioRxiv2020

Differential functional connectivity underlying asymmetric reward-related activity in human and non-human primates

The orbitofrontal cortex (OFC) is a key brain region involved in complex cognitive functions such as reward processing and decision-making. Neuroimaging studies have shown unilateral OFC response to reward-related variables, however, those studies rarely discussed the lateralization of this effect. Yet, some lesion studies suggest that the left and right OFC contribute differently to cognitive processes. We hypothesized that the OFC asymmetrical response to reward could reflect underlying hemispherical difference in OFC functional connectivity. Using restingstate and reward-related MRI data from humans and from rhesus macaques, we first identified a specific asymmetrical response of the lateral OFC to reward in both species. Crucially, the subregion showing the highest reward-related asymmetry (RRA) overlapped with the region showing the highest functional connectivity asymmetry (FCA). Furthermore, the two types of functional asymmetries were found to be significantly correlated across humans. Altogether, our results suggest a similar pattern of functional specialization between the left and right OFC is present in two primate species.

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bioRxiv2019

Primate homologs of mouse cortico-striatal circuits

With the increasing necessity of animal models in biomedical research, there is a vital need to harmonise findings across species by establishing similarities and differences in rodent and primate neuroanatomy. Using a connectivity fingerprint matching approach, we compared cortico-striatal circuits across humans, non-human primates, and mice using resting state fMRI data in all species. Our results suggest that the connectivity patterns for both the nucleus accumbens and cortico-striatal motor circuits (posterior/lateral putamen) were conserved across species, making them reliable targets for cross-species comparisons. However, a large number of human and macaque striatal voxels were not matched to any mouse cortico-striatal circuit (mouse->human: 85% unassigned; mouse->macaque 69% unassigned; macaque->human; 31% unassigned). These unassigned voxels were largely localised to the caudate nucleus and anterior putamen, overlapping with executive function and social/language regions of the striatum, and connected to prefrontal-projecting cerebellar lobules and anterior prefrontal cortex, forming circuits that seem to be unique for non-human primates and humans. Our results demonstrate the potential of connectivity fingerprint matching to bridge the gap between rodent and primate neuroanatomy.

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bioRxiv2019

XTRACT - Standardised protocols for automated tractography and connectivity blueprints in the human and macaque brain

We present a new software package with a library of standardised tractography protocols devised for the robust automated extraction of white matter tracts both in the human and the macaque brain. Using in vivo data from the Human Connectome Project (HCP) and the UK Biobank and ex vivo data for the macaque brain datasets, we obtain white matter atlases, as well as atlases for tract endpoints on the white-grey matter boundary, for both species. We illustrate that our protocols are robust against data quality, generalisable across two species and reflect the known anatomy. We further demonstrate that they capture inter-subject variability by preserving tract lateralisation in humans and tract similarities stemming from twinship in the HCP cohort. Our results demonstrate that the presented toolbox will be useful for generating imaging-derived features in large cohorts, and in facilitating comparative neuroanatomy studies. The software, tractography protocols, and atlases are publicly released through FSL, allowing users to define their own tractography protocols in a standardised manner, further contributing to open science.

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bioRxiv2019

Noradrenergic but not dopaminergic neurons signal task state changes and predict re-engagement after a failure

The two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behaviour. Both noradrenergic and dopaminergic neurons respond to salient cues predicting reward availability and to stimulus novelty, and shape action selection strategies. However, their roles in motivation have seldom been directly compared. We therefore examined the activity of noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with the likelihood of engaging with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) sensitive to the task state change, the discovery of the new task condition in unrepeated trials. This indicates that while dopamine is primarily important for the promotion of actions directed towards currently available rewards, noradrenergic neurons play a crucial complementary role in mobilizing resources to promote future engagement.

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bioRxiv2019

Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques

One of the most influential accounts of central orbitofrontal cortex- that it mediates behavioral flexibility - has been challenged by the finding that discrimination reversal in macaques -the classic test of behavioral flexibility -is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.

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bioRxiv2019

Two fiber pathways connecting amygdala and prefrontal cortex in humans and monkeys

The interactions between amygdala and prefrontal cortex are pivotal to many neural processes involved in learning, decision-making, emotion, and social regulation. The broad functional role of amygdala-prefrontal interplay may reflect the diversity of its anatomical connections. Little, however, is known of the structural wiring linking amygdala and prefrontal cortex in humans. Using diffusion imaging techniques, we reconstructed connections between amygdala, anterior temporal and prefrontal cortex in human and macaque brains. First, by studying macaques we were able to assess which aspects of connectivity known from tracer studies could be identified with diffusion imaging. Second, by comparing diffusion imaging results in humans and macaques we were able to estimate amygdala-prefrontal connection patterns in humans and compare them with those in the monkey. We observed a prominent and well-preserved bifurcation of connections between amygdala and frontal lobe into two fiber networks - an amygdalofugal path and an uncinate fascicle path - in both species.

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bioRxiv2019

Sulcal organization in the medial frontal cortex reveals insights into primate brain evolution

Although the relative expansion of the frontal cortex in primate evolution is generally accepted, the nature of the human uniqueness, if any, and between-species anatomo-functional comparisons of the frontal areas remain controversial. To provide a novel interpretation of the evolution of primate brains, sulcal morphological variability of the medial frontal cortex was assessed in old-world monkeys (macaque, baboon) and Hominoidea (chimpanzee, human). We discovered that both Hominoidea do possess a paracingulate sulcus, which was previously thought to be uniquely human and linked to higher cognitive functions like mentalizing. Also, we revealed systematic sulcal morphological organisations of the medial frontal cortex that can be traced from multiple old-world monkey to Hominoidea species, demonstrating an evolutionary conserved organizational principle. Our data provide a new framework to compare sulcal morphology, cytoarchitectonic areal distribution, connectivity, and function across the primate order, leading to clear predictions on how other primate brains might be anatomo-functionally organized.

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bioRxiv2018

Intact extrastriate visual network without primary visual cortex in a Rhesus macaque with naturally occurring Blindsight

Lesions of primate primary visual cortex (V1) lead to loss of conscious visual perception, and are often devastating to those affected. Understanding the neural consequences of such damage may aid the development of rehabilitation methods. In this rare case of a Rhesus macaque (monkey S), likely born without V1, we investigated the brain structures underlying residual visual abilities using multimodal magnetic resonance imaging. In-group behaviour was unremarkable. Compared to controls, visual structures outside of monkey Ss lesion appeared normal. Visual stimulation under anaesthesia with checkerboards activated lateral geniculate nucleus of monkey S, but not the pulvinar, while full-field moving dots activated the pulvinar. Functional connectivity analysis revealed a network of bilateral dorsal visual areas temporally correlated with V5/MT, consistent across lesion and control animals. Overall, we found an intact network of visual cortical areas even without V1, but little evidence for strengthened subcortical input to V5/MT supporting residual visual function.

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bioRxiv2018

The human ventromedial prefrontal cortex sulcal morphology and its influence on its functional organization.

The ventromedial prefrontal cortex (vmPFC), which comprises several distinct cytoarchitectonic areas, is a key brain region supporting decision-making processes and it has been shown to be one of the main hubs of the Default Mode Network, a network classically activated during resting state. We here examined the inter-individual variability in the vmPFC sulcal morphology in 57 humans (37 females) and demonstrated that the presence/absence of the inferior rostral sulcus and the subgenual intralimbic sulcus influences significantly the sulcal organization of this region. Furthermore, the sulcal organization influences the location of the vmPFC peak of the Default Mode Network, demonstrating that the location of functional activity can be affected by local sulcal patterns. These results are critical for the investigation of the function of the vmPFC and show that taking into account the sulcal variability might be essential to guide the interpretation of neuroimaging studies.\n\nSIGNIFICANCE STATEMENTThe ventromedial prefrontal cortex (vmPFC) is one of the main hubs of the Default Mode Network and plays a central role in value coding and decision-making. The present study provides a complete description of the inter-individual variability of anatomical morphology of this large portion of prefrontal cortex and its relation to functional organization. We have shown that two supplementary medial sulci predominantly determine the organization of the vmPFC, which in turn affect the location of the functional peak of activity in this region. Those results show that taking into account the variability in sulcal patterns might be essential to guide the interpretation of neuroimaging studies of the human brain and of the vmPFC in particular.

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bioRxiv2018

The macaque anterior cingulate cortex translates counterfactual choice value into actual behavioral change

The neural mechanisms mediating sensory-guided decision making have received considerable attention but animals often pursue behaviors for which there is currently no sensory evidence. Such behaviors are guided by internal representations of choice values that have to be maintained even when these choices are unavailable. We investigated how four macaque monkeys maintained representations of the value of counterfactual choices - choices that could not be taken at the current moment but which could be taken in the future. Using functional magnetic resonance imaging, we found two different patterns of activity co-varying with values of counterfactual choices in a circuit spanning hippocampus, anterior lateral prefrontal cortex, and anterior cingulate cortex (ACC). ACC activity also reflected whether the internal value representations would be translated into actual behavioral change. To establish the causal importance of ACC for this translation process, we used a novel technique, Transcranial Focused Ultrasound Stimulation, to reversibly disrupt ACC activity.

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bioRxiv2018

Manipulation of deep brain activity in primates using transcranial focused ultrasound stimulation

The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their focal application particularly in deep areas of the primate brain. Here we demonstrate a transcranial focused ultrasound stimulation (TUS) protocol that manipulates activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, anterior cingulate cortex (ACC, experiment 2), in macaques. TUS neuromodulatory effects were measured by examining relationships between activity in each area and the rest of the brain using functional magnetic resonance imaging (fMRI). In control conditions without sonication, activity in a given area is related to activity in interconnected regions but such relationships are reduced after sonication. Dissociable and focal effects on neural activity could not be explained by auditory artefacts.

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bioRxiv2018

Offline impact of transcranial focused ultrasound on cortical activation in primates

To understand brain circuits it is necessary both to record and manipulate their activity. Despite increased availability of techniques for manipulating neural activity in rodents, manipulating neural activity in primates remains difficult. Here we show that a minimally invasive technique, transcranial focused ultrasound stimulation (TUS), induced offline changes to activity of circumscribed brain regions in the macaque. Applying TUS to the supplementary motor area or frontal polar cortex resulted in spatially specific patterns of activity change measurable with functional magnetic resonance imaging. In each case changes reflected each areas known network of interactions with the rest of the brain. Independent of these specific neural effects, TUS over these regions also induced widespread signal changes that might have a non-neuronal origin possibly mediated by the cerebral spinal fluid compartment. Although sustained for more than one hour beyond the 40s stimulation period, TUS effects were reversible and not associated with histological changes.\n\nHighlights O_LIMany studies of ultrasound neuromodulation focus on online effects in rodents.\nC_LIO_LIWe use fMRI connectivity to investigate its offline impact in the primate brain.\nC_LIO_LI40 s of ultrasound leads to a sustained, specific, reversible neural modulation.\nC_LIO_LIUltrasound caused a sharpening of the stimulated regions connectivity profile.\nC_LI\n\nIn BriefA new application of focused ultrasound safely modulates brain activation in primates for up to 2 hours after 40 seconds of stimulation. Ultrasound caused the stimulated area to interact more selectively with the rest of the brain.

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bioRxiv2018

Whole brain comparative anatomy using connectivity blueprints

Comparing the brains of related species faces the challenges of establishing homologies whilst accommodating evolutionary specializations. Here we propose a general framework for understanding similarities and differences between the brains of primates. The approach uses white matter blueprints of the whole cortex based on a set of white matter tracts that can be anatomically matched across species. The blueprints provide a common reference space that allows us to navigate between brains of different species, identify homologue cortical areas, or to transform whole cortical maps from one species to the other. Specializations are cast within this framework as deviations between the species blueprints. We illustrate how this approach can be used to compare human and macaque brains.

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bioRxiv2017

An open resource for nonhuman primate imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience.\n\nUnfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMate Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 13 independent data collections aggregated across 11 sites (total = 98 macaque monkeys). We also outline the unique pitfalls and challenges that should be considered in the analysis of the non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

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bioRxiv2017

Independent contributions of noradrenaline to behavioural flexibility and motivation

Among neuromodulatory systems, the noradrenergic system remains one of the least understood. Several theories have pointed out its implication in behavioural flexibility and more recently in motivation, with a strong role in effort processing. Here, we designed a sequential cost/benefit decision task to test the causal role of noradrenaline in these two functions. We manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels. Clonidine had two distinct effects: it decreased choice volatility (without affecting the cost/benefit trade off) and reduced force production. Because the effects were independent, they cannot be accounted for by a non-specific effect on arousal. Altogether, these results support the global implication of noradrenaline in facing challenging situations in two complementary ways: by modulating behavioural volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges.

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