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Zanini, A.

Publications and source records attributed to Zanini, A..

16 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Mapping of Facial and Vocal Processing in Common Marmosets with ultra-high field fMRI

Primate communication relies on multimodal cues, such as vision and audition, to facilitate the exchange of intentions, enable social interactions, avoid predators, and foster group cohesion during daily activities. Understanding the integration of facial and vocal signals is pivotal to comprehend social interaction. In this study, we acquired whole-brain ultra-high field (9.4T) fMRI data from awake marmosets (Callithrix jacchus) to explore brain responses to unimodal and combined facial and vocal stimuli. Our findings reveal that the multisensory condition not only intensified activations in the occipito-temporal face patches and auditory voice patches but also engaged a more extensive network that included additional parietal, prefrontal and cingulate areas, compared to the summed responses of the unimodal conditions. By uncovering the neural network underlying multisensory audiovisual integration in marmosets, this study highlights the efficiency and adaptability of the marmoset brain in processing facial and vocal social signals, providing significant insights into primate social communication.

neuroscience↗

A vocalization-processing network in marmosets

Vocalizations play an important role in the daily life of primates and likely form the basis of human language. Functional imaging studies have demonstrated that listening to language or reading activates a left-lateralized fronto-temporal language network in human participants. Here we acquired whole-brain ultrahigh field (9.4 Tesla) fMRI in awake marmosets (Callithrix jacchus) and demonstrate that these highly vocal small New World primates possess a similar fronto-temporal network, including subcortical regions, that is activated by the presentation of conspecific vocalizations. The findings suggest that the human language network has evolved from an ancestral vocalization network that predates the separation of New and Old World primates.

neuroscience↗

Gaze patterns and brain activations in humans and marmosets in the Frith-Happe; theory-of-mind animation task

Theory of Mind (ToM) refers to the ability to ascribe mental states to other individuals. This process is so strong that it extends even to the attribution of mental states to animations depicting interacting simple geometric shapes, such as in the Frith-Happe animations in which two triangles move either purposelessly (Random condition), or as if one triangle is reacting to the other triangles mental state (ToM condition). Currently, there is no evidence that nonhuman primates attribute mental states to moving abstract shapes. Here we investigated whether highly social marmosets (Callithrix jacchus) process ToM and Random Frith-Happe animations differently. Our results show that marmosets and humans (1) follow more closely one of the triangles during the observation of ToM compared to Random animations, and (2) activate large and comparable brain networks when viewing ToM compared to Random animations. These findings indicate that marmosets, like humans, process ToM animations differently from Random animations.

neuroscience↗

Perception of dynamic facial expressions activates a cortico-subcortico-cerebellar network in marmosets

The perception and identification of faces and facial emotional expressions are critical for social communication in the daily life of all primates. Here, we investigated the neural network activated by dynamic facial expressions in awake New World common marmosets with ultra-high field fMRI at 9.4T. Our results show that dynamic facial expressions activate several areas along the occipitotemporal axis (V2/V3, V4/TEO, FST, caudal TE, rostral TE, TPO), frontal cortex (areas 45/47, 13, 8a and orbital cortex), amygdala, motion-sensitive areas, premotor area, and in the posterior lobe of the cerebellum. Negative faces increased the monkeys respiration rates and elicited stronger responses along the occipitotemporal cortical axis, in the amygdala and in the hypothalamus. This cortico-subcortico-cerebellar network may play an important role in the perception of behaviorally relevant facial expressions that are vital for social communication in marmosets. Significance StatementRecent research has highlighted the importance of emotional content of faces in social communication in humans and non-human primates. The current study focuses on the neural responses to dynamic emotional facial expressions in the common marmoset (Callithrix jacchus), a New World primate species sharing several similarities of social behavior with humans. Using ultra-high-field fMRI, we show that negative facial expressions activate a cortico-subcortico-cerebellar network and, critically, negative faces increase the level of arousal of marmosets, possibly relayed through a modulation of the activity in the autonomic nervous system via stress-integrative brain centres in the hypothalamus. Our results reveal the existence of specific neural and physiological responses to negative emotional faces suggesting that behaviorally relevant facial expressions are vital for social communication in New World marmosets.

neuroscience↗

An action-observation network in the common marmoset identified by ultra-high field fMRI

The observation of others actions activates a network of temporal, parietal and premotor/prefrontal areas in macaque monkeys and humans. This action-observation network (AON) has been shown to play important roles in understanding the actions of others, learning by imitation, and social cognition in both species. It is unclear whether a similar network exists in New World primates, which separated from Old Word Primates [~] 35 million years ago. Here we used ultra-high field fMRI at 9.4T in awake common marmosets (Callithrix jacchus) while they watched videos depicting the upper-limb of conspecifics performing goal-directed (grasping food) or non-goal-directed actions. We found that the observation of goal-directed actions, compared to non-goal directed ones, activated a temporo-parieto-frontal network, including areas 6 and 45 in premotor and prefrontal cortices, areas PGa-IPa, FST and the TE complex in occipito-temporal region and areas V6A, MIP, LIP and PG in the occipito-parietal cortex. These results show remarkable overlap with the AON observed in humans and macaques. These results demonstrate the existence of an evolutionarily conserved AON that likely predates the separation of Old and New World primates.

neuroscience↗

Patterns of multisensory facilitation distinguish peripersonal from reaching space

Peripersonal space (PPS) is a multisensory representation of the space near body parts facilitating interactions with the close environment. Studies on non-human and human primates converge in showing that PPS is a body-part-centred representation that guides actions. Because of these characteristics, growing confusion conflates peripersonal and arm-reaching space (ARS), that is the space ones arm can reach. Despite neuroanatomical evidence favors their distinction, no study has contrasted directly their respective extent and behavioral features. Here, in five experiments (N=140) we found that PPS differs from ARS, as evidenced both by participants spatial and temporal performance and its modeling. We mapped PPS and ARS using both their respective gold standard tasks and a novel multisensory facilitation paradigm. Results show that 1) PPS is smaller than ARS; 2) multivariate analyses of spatial patterns of multisensory facilitation predict participants hand locations within ARS; 3) the multisensory facilitation map shifts isomorphically following hand positions, revealing hand-centred coding of PPS, therefore pointing to a functional similarity to the receptive fields of monkeys multisensory neurons. A control experiment further corroborated these results and additionally ruled out the orienting of attention as driving mechanism for the increased multisensory facilitation near the hand. In sharp contrast, ARS mapping results in a larger spatial extent, with undistinguishable patterns across hand positions, cross-validating the conclusion that PPS and ARS are distinct spatial representations. These findings urge for a refinement of theoretical models of PPS, which is relevant to constructs as diverse as self-representation, social interpersonal distance, and motor control.

neuroscience↗