Biology subjects

Everling, S.

Publications and source records attributed to Everling, S..

At least 19 recordsLinked to original sources

bioRxiv2026

α-synuclein pathology drives multi-scale reorganization of fronto-limbic networks and cognitive flexibility in the common marmoset

Understanding how -synuclein misfolding and spreading affect brain systems is central to synucleinopathy research, yet evidence from primate models remains limited. Here, we combined histology, awake structural MRI, awake resting-state fMRI, regional homogeneity, actimetry and touchscreen behavioral testing to longitudinally track the consequences of striatal -synuclein seeding in the common marmoset. Phosphorylated -synuclein inclusions were detected from 2 months post-injection and spread progressively to distributed cortical and subcortical regions bilaterally, accompanied by regionally specific structural atrophy. Functional imaging revealed widespread disruption of large-scale networks, particularly within fronto-limbic circuits, alongside reductions in local functional coherence. Despite the absence of overt motor or sleep deficits, animals exhibited a selective impairment in cognitive flexibility, with preserved learning and task engagement. These findings indicate that striatal -synuclein seeding induces a multi-scale reorganization of brain networks preferentially affecting circuits supporting cognitive flexibility and limbic processing, establishing a primate platform for studying early stages of synucleinopathy.

animal behavior and cognition↗

bioRxiv2026

Influence of distractors on spatial working memory and neural activity in marmoset prefrontal cortex

The prefrontal cortex (PFC) plays a critical role in maintaining working memory (WM) representations while filtering irrelevant distractors. In macaques, PFC neurons exhibit persistent delay period activity that is robust to distractor interference. The common marmoset has emerged recently as a complementary primate model for investigating the neural basis of cognitive processes including WM, in part because the relatively lissencephalic cortex of this species enables laminar recordings which could provide substantial insight into the microcircuit basis of these functions. It remains unknown however, whether marmoset WM performance is robust to distractors presented during delay periods of WM tasks, and how such distractor filtering may be implemented in PFC circuits. Here, we addressed this gap by conducting wireless recordings of PFC in freely moving marmosets performing a touchscreen-based delayed-match-to-location (DML) task in which a salient visual distractor was presented during the delay period on a subset of trials. Marmosets maintained WM performance on distractor trials, showing a decrease in accuracy of only 5%. Consistent with prior observations in both the macaque and marmoset models, we found that many PFC neurons exhibited activity related to the stimulus sample, during the delay period, and around the time of the behavioural response. In a subset of neurons, we observed distractor-mediated modulations of persistent delay period activity which were associated with a greater incidence of performance errors on the DML task. These findings reveal that marmoset WM is robust to distractor interference, and that the PFC mechanisms instantiating WM and distractor filtering are conserved in this primate species. Taken together, they support the common marmoset as a complementary model for investigating the contribution of PFC circuits to mnemonic and attentional processes.

neuroscience↗

bioRxiv2025

A Context-Sensitive Neural Hierarchy for Evaluating Temporal Structure in Primate Vocalizations

Understanding how the brain encodes temporal order in communication is central to explaining how complex interactions are perceived as coherent events. In humans, disrupting the sequence of words or scenes abolishes characteristic activity in higher-order networks, but whether similar mechanisms exist in nonhuman primates remains unknown. Here we used ultra-high-field fMRI (9.4 T) in awake marmosets to test how the marmoset brain evaluates temporal structure in natural conspecific vocalizations. Animals heard vocal sequences from three social contexts (angry, conversational, food-related) presented in intact, reversed, or randomized order, with call identity held constant. Disrupting sequence order altered responses across a distributed cortical-subcortical network. Contrast to reversed order, intact sequences drove stronger activation in prefrontal, cingulate, parietal, and somatosensory regions, whereas randomization produced the most widespread disruptions, additionally recruiting motor, insular, hippocampal, and thalamic territories. Uni- and multivariate analyses revealed a core network--including prefrontal area 8, cingulate areas 24/32, somatosensory cortex, and parietal Tpt--consistently sensitive to temporal coherence, with broader recruitment under severe disruption. Network-level dynamics further varied by context: conversation elicited earlier sensitivity to sequence disruptions, angry peaked later, and food built more gradually. These findings provide the first whole-brain evidence that marmosets engage hierarchically organized, context-sensitive networks to evaluate multi-agent vocal sequence structure, establishing a cross-species bridge to human narrative processing.

neuroscience↗

bioRxiv2025

Modular dynamics of conscious and unconscious states in marmoset cortex

General anesthetics are routinely used to induce unconsciousness. While much is known about their effects on receptor function and the activity of individual neurons, much less is known about how these local effects are manifest at the level of largescale, distributed brain networks. Using functional magnetic resonance imaging (fMRI) with the common marmoset (Callithrix jacchus) we investigated the effects of the anaesthetic isoflurane on functional brain networks and their temporal dynamics, comparing network measures during wakeful rest and induced unconsciousness. The anaesthetic condition was characterised by weak functional networks that were more similar to anatomical structure and more fragmented than during wakeful rest. Conversely, the awake condition was characterised by coordinated network reconfiguration and more distinct subnetwork composition. Our findings are consistent with the view that consciousness is an emergent property of the dynamics of functional brain networks, and that anaesthetics impoverish these dynamics by reducing the efficacy of synaptic transmission.

neuroscience↗

bioRxiv2025

Mapping Functional Homologies Between Human and Marmoset Brain Networks Using Movie-Driven Ultra-High Field fMRI

Naturalistic stimuli, such as movies, offer a powerful tool for probing functional brain organization across species. Using movie-driven functional magnetic resonance imaging (md-fMRI), we recorded brain activity in humans and awake marmosets exposed to the same dynamic audiovisual stimulus. We applied tensor independent component analysis (tICA) to identify functional networks in each species, hierarchically clustered these components, and examined their within- and between-species temporal correlations to assess functional homologies. We found strong interspecies correspondence in core sensory networks, particularly those involved in visual and auditory processing, suggesting conserved mechanisms for sensory integration. In contrast, networks associated with higher-order cognition, including prefrontal and temporoparietal areas, were observed primarily in humans, highlighting species-specific specializations. These findings demonstrate the value of naturalistic paradigms and data-driven approaches in revealing both shared and divergent brain network architectures. By openly sharing our data and analysis pipelines, we aim to support future comparative studies and advance the marmoset as a model for investigating the evolutionary foundations of brain function.

neuroscience↗

bioRxiv2025

Resting State Functional Connectivity of the Marmoset Claustrum

The common marmoset (Callithrix jacchus) has been recently developed as a nonhuman primate model useful for studying behaviour, neurology, and higher-level cognitive processes considering their phylogenetic proximity to humans. Here, we investigated the resting state functional connectivity (RSFC) of the marmoset claustrum, a small, highly connected subcortical structure. Using an open resource of 234 functional MRI scans from awake marmosets, we found claustrum connectivity to the prefrontal cortex, posterior parietal cortex, temporal cortices, cingulate cortex, sensory cortices, limbic areas, basal ganglia, and cerebellum. We also found strong functional connectivity to regions and hubs involved in marmoset resting state networks. These findings demonstrate marmoset claustrum RSFC similar to previous human and rodent studies and validate the integration of marmosets into claustrum research.

neuroscience↗

bioRxiv2025

Marmoset Anterior Cingulate Area 32 Neurons Exhibit Responses to Presented and Produced Calls During Naturalistic Vocal Communication

Vocal communication is a complex social behavior that entails the integration of auditory perception and vocal production. Both anatomical and functional evidence have implicated the anterior cingulate cortex (ACC), including area 32, in these processes, but the dynamics of neural responses in area 32 during naturalistic vocal interactions remain poorly understood. Here, we addressed this by recording the activity of single area 32 neurons using chronically implanted ultra high density Neuropixels probes in freely moving common marmosets (Callithrix jacchus) engaged in an antiphonal calling paradigm in which they exchanged long-distance "phee" calls with a virtual conspecific. We found that many neurons exhibited complex modulations in discharge rates in response to presented calls, prior to and following self-generated calls, and during the interval between presented and produced vocalizations. These findings are consistent with the conceptualization of area 32 as an audiovocal interface integrating auditory information, cognitive processes, and motor outputs in the service of vocal communication. Significance StatementVocal communication is indispensable in the daily lives of social animals including primates. This sophisticated ability requires processing and production of vocalizations across fluid social contexts. Vocal behavior is controlled by a large network of brain areas. Area 32 within the anterior cingulate cortex may be a linchpin of this network, as it is interconnected with both auditory cortical areas and subcortical structures engaging vocal control. This position is ideal for integrating auditory, motor, and cognitive signals serving vocal behaviour. We show for the first time that neural correlates of these three signal types are present in area 32 neurons recorded in freely moving marmosets during naturalistic vocal exchanges. We conclude that area 32 exhibits the properties of an audiovocal interface.

neuroscience↗

bioRxiv2024

Single neuron diversity supports area functional specialization along the visual cortical pathways

Humans and other primates have specialized visual pathways composed of interconnected cortical areas. The input area V1 contains neurons that encode basic visual features, whereas downstream in the lateral prefrontal cortex (LPFC) neurons acquire tuning for novel complex feature associations. It has been assumed that each cortical area is composed of repeatable neuronal subtypes, and variations in synaptic strength and connectivity patterns underlie functional specialization. Here we test the hypothesis that diversity in the intrinsic make-up of single neurons contributes to area specialization along the visual pathways. We measured morphological and electrophysiological properties of single neurons in areas V1 and LPFC of marmosets. Excitatory neurons in LPFC were larger, less excitable, and fired broader spikes than V1 neurons. Some inhibitory fast spiking interneurons in the LPFC had longer axons and fired spikes with longer latencies and a more depolarized action potential trough than in V1. Intrinsic bursting was found in subpopulations of both excitatory and inhibitory LPFC but not V1 neurons. The latter may favour temporal summation of spikes and therefore enhanced synaptic plasticity in LPFC relative to V1. Our results show that specialization within the primate visual system permeates the most basic processing level, the single neuron.

neuroscience↗

bioRxiv2024

An Open Access Resource for Marmoset Neuroscientific Apparatus

The use of the common marmoset (Callithrix jacchus) for neuroscientific inquiry has grown precipitously over the past two decades. Despite windfalls of grant support from funding initiatives in North America, Europe, and Asia to model human brain diseases in the marmoset, marmoset- specific apparatus are of sparse availability from commercial vendors and thus are often developed and reside within individual laboratories. Through our collective research efforts, we have designed and vetted myriad designs for awake or anesthetized magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), as well as focused ultrasound (FUS), electrophysiology, optical imaging, surgery, and behavior in marmosets across the age- span. This resource makes these designs openly available, reducing the burden of de novo development across the marmoset field. The computer-aided-design (CAD) files are publicly available through the Marmoset Brain Connectome (MBC) resource (https://www.marmosetbrainconnectome.org/apparatus/) and include dozens of downloadable CAD assemblies, software and online calculators for marmoset neuroscience. In addition, we make available a variety of vetted touchscreen and task-based fMRI code and stimuli. Here, we highlight the online interface and the development and validation of a few yet unpublished resources: Software to automatically extract the head morphology of a marmoset from a CT and produce a 3D printable helmet for awake neuroimaging, and the design and validation of 8-channel and 14- channel receive arrays for imaging deep structures during anatomical and functional MRI.

bioengineering↗

bioRxiv2024

Anterior cingulate neurons display subregion-specific interaction with frontal eye fields as revealed by combined antidromic stimulation and resting state imaging

The anterior cingulate cortex (ACC) is thought to exert cognitive control over saccade generation in the frontal eye fields (FEF), but the nature of this interaction remains unclear. Although prior imaging studies have suggested ACC interacts with FEF, few studies have confirmed this by electrophysiological recordings. This study aimed to characterize the functional connectivity between ACC and medial and lateral FEF during cognitive saccade tasks. We combined resting-state functional MRI (rs-fMRI) with single-unit electrophysiology in two macaque monkeys performing memory-guided saccade and pro-/anti-saccade tasks. Anti- and ortho-dromic stimulation was used to electrophysiologically identify ACC neurons mono- and polysynaptically connected to FEF. We analyzed ACC neuronal selectivity for different task aspects and correlated these properties with both positive and negative rs-fMRI functional connectivity between ACC and FEF subregions. Anti- and ortho-dromically identified ACC neurons were predominantly connected to medial FEF, which showed stronger positive functional connectivity with ACC compared to lateral FEF. Sites with higher proportions of task-selective neurons yielded stronger functional connectivity with FEF. This stronger functional connectivity was particularly related to the delay and saccadic periods of different cognitive saccade tasks. Using combined imaging and electrophysiology, our findings provide converging evidence for functional interactions between ACC and FEF, predominantly medial FEF regions which encode large amplitude saccades. The correlation between functional connectivity and task-related neuronal selectivity supports ACCs interaction with FEF in the modulation of saccade generation and cognitive control. Additionally, we report suggestive evidence that mono- and poly-synaptic connections may be related to positive functional connectivity, but we found no such relationship for negative functional connectivity (anticorrelations). These results advance our understanding of prefrontal cortical interactions in oculomotor control and the electrophysiological mechanisms of positive and negative resting-state functional connectivity.

neuroscience↗

bioRxiv2024

Stimulus-modulated approach to steady-state: A new paradigm for event-related fMRI.

Functional MRI (fMRI) studies discard the initial volumes acquired during the approach of the magnetization to its steady-state value. Here, we leverage the higher temporal signal-to-noise ratio (tSNR) of these initial volumes to increase the sensitivity of event-related fMRI experiments. To do this, we introduce Acquisition Free Periods (AFPs) that allow for the full recovery of the magnetization, followed by task or baseline acquisition blocks (AB) of fMRI volumes. An appropriately placed stimulus in the AFP produces a Blood Oxygenation-Level-Dependent (BOLD) response that peaks during the initial high tSNR phase of the AB, yielding up to a [~]50% reduction in the number of trials needed to achieve a given statistical threshold relative to conventional fMRI. The silent AFP can be exploited for the presentation of auditory stimuli or uncontaminated electrophysiological recording and its variable duration allows aperiodic stimulus or response-locked signal averaging as well as gating to physiology or motion.

physiology↗

bioRxiv2024

Vocal processing networks in the human and marmoset brain

Understanding the brain circuitry involved in vocal processing across species is crucial for unraveling the evolutionary roots of human communication. While previous research has pinpointed voice-sensitive regions in primates, direct cross-species comparisons using standardized protocols are limited. This study utilizes ultra-high field fMRI to explore vocal processing mechanisms in humans and marmosets. By employing voice-sensitive regions of interest (ROIs) identified via auditory localizers, we analyzed response time courses to species-specific vocalizations and non-vocal sounds using a dynamic auditory-stimulation paradigm. This approach gradually introduced sounds into white noise over 33 seconds. Results revealed that both species have responsive areas in the temporal, frontal, and cingulate cortices, with a distinct preference for vocalizations. Significant differences were found in the response time courses between vocal and non-vocal sounds, with humans displaying faster responses to vocalizations than marmosets. We also identified a shared antero-ventral auditory pathway in both species for vocal processing, originating from the superior temporal gyrus. Conversely, a posterior-dorsal pathway was more prominent in humans, whereas in marmosets, this pathway processed both sound types similarly. This comparative study sheds light on both conserved and divergent auditory pathways in primates, providing new insights into conspecific vocalization processing.

neuroscience↗

bioRxiv2024

Identifying Functional Homologues in Human and Marmoset Brain Networks via Movie-Driven Ultra-High Field fMRI

Numerous task-based functional magnetic resonance imaging (fMRI) studies have demonstrated that complex neural functions such as language processing, action observation, face recognition, and motor coordination are governed by widespread, intricate networks that span both cortical and subcortical areas. Nonhuman primate models are indispensable for advancing our understanding of the evolution of these networks and provide unique opportunities for experimental interventions that are not feasible in humans. In this study, we utilized movie-driven fMRI (md-fMRI) to investigate and delineate homologous functional networks in the common marmoset (Callithrix jacchus). Both marmosets and human subjects watched the same movie which incorporated a variety of visual and auditory stimuli. This method enabled the identification of potential homologues of large-scale functional networks involved in visual, auditory, cognitive, motor, and limbic functions in marmosets, offering new insights into the shared neurofunctional architecture across species.

neuroscience↗

bioRxiv2024

Spike frequency adaptation in primate lateral prefrontal cortex neurons results from interplay between intrinsic properties and circuit dynamics

Recordings of cortical neurons isolated from brain slices and dissociated from their networks, display intrinsic spike frequency adaptation (I-SFA) to a constant current input. Interestingly, extracellular recordings in behaving subjects also show extrinsic-SFA (E-SFA) in response to sustained visual stimulation. Because neurons are isolated from brain networks in slice recordings, it is challenging to infer how I-SFA contributes to E-SFA in interconnected brains during behavior. To investigate this, we recorded responses of macaque lateral prefrontal cortex neurons in vivo during a visually guided saccade task and in acute brain slices in vitro. Broad spiking (BS) putative pyramidal cells and narrow spiking (NS) putative inhibitory interneurons exhibited E-SFA in vivo. In acute brain slices, both cell types displayed I-SFA though their magnitudes differed. To investigate how in vitro I-SFA contributes to in vivo E-SFA, we developed a data-driven hybrid circuit model in which local NS neurons are driven by BS input. We observed that model NS cell responses show longer SFA than observed in vivo. Introducing inhibition of NS cells to the model circuit removed this discrepancy. Our results indicate that both I-SFA and inhibitory circuit dynamics contribute to E-SFA in LPFC neurons. They highlight the contribution of single neuron and network dependent computations to neural activity underlying behavior.

neuroscience↗

bioRxiv2024

Neural activity for complex sounds in the marmoset medial prefrontal cortex

Vocalizations play an important role in the daily life of nonhuman primates and are likely precursors of human language. Recent functional imaging studies in the highly vocal common marmoset (Callithrix jacchus) have suggested that medial prefrontal cortex area 32 may be a part of a vocalization-processing network but the response properties of area 32 neurons to auditory stimuli remain unknown. Here, we performed electrophysiological recordings in area 32 with high-density Neuropixels probes and characterized neuronal responses to a variety of sounds including conspecific vocalizations. More than half of the neurons in area 32 responded to conspecific vocalizations and other complex auditory stimuli. These responses exhibited dynamics consisting of an initially non-selective reduction in neural activity, followed by an increase in activity that immediately conveyed sound selectivity. Our findings demonstrate that primate mPFC area 32 plays a critical role in processing species-specific and biologically relevant sounds.

neuroscience↗

bioRxiv2024

Unique cortical and subcortical activation patterns for different conspecific calls in marmosets

The common marmoset (Callithrix jacchus) is known for its highly vocal nature, displaying a diverse range of different calls. Functional imaging in marmosets has shown that the processing of conspecific calls activates a brain network that includes fronto-temporal cortical and subcortical areas. It is currently unknown whether different call types activate the same or different networks. Here we show unique activation patterns for different calls. Nine adult marmosets were exposed to four common vocalizations (phee, chatter, trill, and twitter), and their brain responses were recorded using event-related fMRI at 9.4T. We found robust activations in the auditory cortices, encompassing core, belt, and parabelt regions, and in subcortical areas like the inferior colliculus, medial geniculate nucleus, and amygdala in response to these conspecific calls. Different neural activation patterns were observed among the vocalizations, suggesting vocalization-specific neural processing. Phee and twitter calls, often used over long distances, activated similar neural circuits, whereas trill and chatter, associated with closer social interactions, demonstrated a closer resemblance in their activation patterns. Our findings also indicate the involvement of the cerebellum and medial prefrontal cortex (mPFC) in distinguishing particular vocalizations from others. Significance StatementThis study investigates the neural processing of vocal communications in the common marmoset (Callithrix jacchus), a species with a diverse vocal repertoire. Utilizing event-related fMRI at 9.4T, we demonstrate that different marmoset calls (phee, chatter, trill, and twitter) elicit distinct activation patterns in the brain, challenging the notion of a uniform neural network for all vocalizations. Each call type distinctly engages various regions within the auditory cortices and subcortical areas, reflecting the complexity and context-specific nature of primate communication. These findings offer insights into the evolutionary mechanisms of primate vocal perception and provide a foundation for understanding the origins of human speech and language processing.

neuroscience↗

bioRxiv2024

Functional Specialization and Distributed Processing across Marmoset Lateral Prefrontal Subregions

A prominent aspect of the organization of primate lateral prefrontal cortex (lPFC) is its division into a number of cytoarchitecturally distinct subregions. Investigations in macaque lPFC using neurophysiological approaches have provided much insight into the functions associated with these subregions; however, our understanding is based largely on a patchwork of findings from many studies and across many animals, rarely covering the entire lPFC in individual subjects. Here, we leveraged the small size and lissencephalic cortex of the common marmoset (Callithrix jacchus) to characterize the responses of large numbers of single lPFC neurons to a diverse collection of test stimuli recorded across sets of lPFC subregions using high-density microelectrode arrays. Untethered extracellular electrophysiological recordings were obtained from two adult marmosets with 4 x 4 mm 96-channel Utah arrays implanted in lPFC, covering areas 8aD, 8aV, 9, 10, 46D, 46V and 47. We employed a test battery comprised of a variety of visual stimuli including faces and body parts, auditory stimuli including marmoset calls, and a spatial working memory task. Task-modulated units and units responsive to different stimulus modalities were distributed throughout the lPFC. Visual, auditory and call-selective units were distributed across all lPFC subregions. Neurons with contralateral visual receptive fields were found in 8aV and 8aD. Neurons responsive to faces and saccade-related units were found in 8aV, 8aD, 10, 46V and 47. These findings demonstrate that responses to some stimuli are relatively restricted within specific lPFC subregions, while others are more distributed throughout the marmoset lPFC.

neuroscience↗

bioRxiv2023

The marmoset default-mode network identified by deactivation in task-based fMRI studies

Understanding the default-mode network (DMN) in the common marmoset (Callithrix jacchus) has been challenging due to inconsistencies with human and marmoset DMNs. By analyzing task-negative activation in fMRI studies, we identified medial prefrontal cortical areas, rostral auditory areas, entorhinal cortex, posterior cingulate cortex area 31, hippocampus, hypothalamus, and basomedial amygdala as marmoset DMN components. Notable, medial and posterior parietal areas that were previously hypothesized to be part of the DMN were activated during visual task blocks. Seed analysis using resting-state fMRI showed strong connectivity between task-negative areas, and tracer data supported a structural network aligning with this functional DMN. These findings challenge previous definition of the marmoset DMN and reconcile many inconsistencies with the DMNs observed in humans, macaque monkeys, and even rodents. Overall, these results highlight the marmoset as a powerful model for DMN research, with potential implications for studying neuropsychiatric disorders where DMN activity and connectivity are altered.

animal behavior and cognition↗