Biology subjects

Menon, R. S.

Publications and source records attributed to Menon, R. S..

At least 19 recordsLinked to original sources

bioRxiv2026

Phosphorylated -Synuclein shapes changes in brain structure, task-related activity and functional connectivity in M83 mice

Phosphorylated -synuclein at S129 (pS129) is the predominant form of -synuclein in the aggregates known as Lewy bodies (LB) and Lewy neurites (LN), the pathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), collectively known as synucleinopathies. The toxic nature of these inclusions remains contentious. To improve our understanding of these aggregates and their role in the structural and functional changes observed in synucleinopathies, we combined non-invasive structural and functional MRI in awake head-fixed M83 mice with whole-brain light-sheet fluorescence microscopy (LSFM) in the same animals following a unilateral injection of either human preformed fibrils of -synuclein (PFF) or PBS into the dorsal striatum. We developed a multimodal framework integrating the non-invasive, mesoscopic nature of MRI with the cellular-level details of LSFM to further our understanding of the underlying pathology of synucleinopathies. Using this framework, we show that four months after injection, animals injected with PFFs showed ubiquitous spread of pS129 pathology throughout the whole brain and spinal cord consistent with anatomical connectivity from the seeding region, with some structures such as the midbrain more susceptible to pS129 accumulation. Compared to controls, PFF-injected animals showed widespread atrophy as well as a decrease in functional connectivity, while evoked activity in the somatosensory/somatomotor areas in response to spontaneous paw movements showed significant hypoactivation. These cellular, structural and functional changes were significantly associated with the proportion of pS129 accumulation determined in the same animals. Our results demonstrate the deleterious effects of pS129 accumulation and argue in favor of a toxic role played by these aggregates.

neuroscience↗

bioRxiv2026

Myelin maturation failure and oligodendrocyte precursor loss underlie default mode network disruption in a humanized APP knock-in model of Alzheimers disease

Alzheimers disease disrupts large-scale brain networks before cognitive symptoms emerge, yet the mechanisms underlying this progression remain unclear. In humans, default mode network (DMN) connectivity follows a biphasic trajectory, with a transition from hypersynchrony to hyposynchrony associated with increasing amyloid burden and cognitive decline. Using a mouse model of amyloidopathy that recapitulates this trajectory, we show that amyloid-{beta} accumulation arrests normal age-dependent myelin maturation, followed by progressive myelin loss and oligodendroglial dysfunction. In healthy animals, regional myelin coverage predicts DMN strength, revealing a coupling that is disrupted by amyloidopathy. Notably, DMN hypersynchrony emerges before substantial amyloid accumulation or overt myelin loss, whereas subsequent oligodendroglial dysfunction and myelin loss coincide with DMN disintegration and cognitive deficits. These findings identify disruption of myelin-network coupling as a potential mechanism underlying the biphasic evolution of network dysfunction in Alzheimers disease and suggest that restoring oligodendroglial function may provide cognitive benefits beyond those of amyloid-targeting strategies.

neuroscience↗

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↗

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

Multiplexed BOLD oscillations reveal the interplay of normalization and attention

Monkey electrophysiology has linked attention to divisive normalization, yet noninvasive evidence in humans remains limited. We use frequency-tagged fMRI to isolate visual cortical populations that simultaneously encode multiple competing inputs. We show that responses of these sites are suppressed during inattention and enhanced during attention - consistent with the normalization model, which predicts that attention selectively disinhibits competing inputs - offering a noninvasive translational bridge to study fine-grained computations underlying attentional selection.

neuroscience↗

bioRxiv2025

A non-invasive approach to awake mouse fMRI compatible with multi-modal techniques

Mouse functional magnetic resonance imaging (fMRI) studies contribute significantly to basic fundamental and translational neuroscience research. Performing fMRI in awake mice could facilitate complex tasks in the magnet and improve translational validity by avoiding anesthesia-related neural and neurovascular changes. Existing surgical approaches provide excellent motion control but are not desirable for all experiments aiming to scan awake mice. These include studies with transgenic mouse lines that are vulnerable to anesthesia or mice in longitudinal studies involving cognition. To address these needs, we propose a non-invasive restraint to scan mice in the awake state. The restraint was designed to be compatible with brain stimulation and recording approaches often combined with fMRI. It was evaluated on the basis of motion, fMRI data quality, and animal stress levels, and compared to a conventional headpost restraint. We found the proposed approach was effective at restraining mice across a broad range of weights without the need for any anesthesia for setup. The non-invasive restraint led to higher data attrition after censoring high motion volumes, but by acquiring roughly 25% more data we could obtain comparable network spatial specificity to the headpost approach. Our results demonstrate a simple open-source head restraint that can be used for awake mouse fMRI for certain cohorts, and we establish suitable acclimation and scanning protocols for use with this restraint.

neuroscience↗

bioRxiv2025

Attentional enhancement and suppression of stimulus-synchronized BOLD oscillations

Visual cortical neurons synchronize their firing rates to periodic visual stimuli. EEG is commonly used to study directed attention by frequency-tagging brain responses to multiple stimuli oscillating at different frequencies, but is limited by its coarse spatial resolution. Here we leverage frequency-tagging fMRI (ft-fMRI) to study the influence of directed attention on the fine-grained spatiotemporal dynamics of competing stimulus-driven visual cortical oscillations. Our analysis reveals that distinct populations of visual cortical neurons exhibit in-phase (enhancing) or anti-phase (suppressive) synchronization with the oscillating stimuli. Directed attention homogeneously increases the amplitude of anti-phase BOLD oscillations across the visual hierarchy, consistent with a distributed suppressive field. In contrast, attentional modulation of in-phase BOLD oscillations increases hierarchically from V1 to hV4. The strength of anti-phase, but not in-phase, modulation predicted psychophysical correlates of attentional performance. Our results strongly corroborate the biased competition model of attention and unveil a novel BOLD correlate of attentional suppression.

neuroscience↗

bioRxiv2024

Frequency-tagged fMRI: A platform for fine-grained spatiotemporal analysis of cortical function

Frequency tagging with functional MRI (ft-fMRI) enables precise mapping of neural dynamics by synchronizing oscillatory stimuli to stimulus-driven blood-oxygen-level-dependent (BOLD) responses. We developed and validated a dual-frequency tagging protocol to dissociate fundamental, multiplexed, and nonlinear intermodulation frequency responses across the human visual cortex at high spatial resolution. Using 3T and 7T fMRI, we reliably detected frequency-tagged BOLD responses at the level of individual vertices, revealing fine-grained cortical topographies and robust temporal synchronization to driving frequencies. Multiplexed responses, encoding multiple frequencies simultaneously, and nonlinear intermodulation components, were spatially dissociable and exhibited reproducible dynamics within and across experimental sessions. These findings establish ft-fMRI as a powerful tool for investigating fine-grained cortical computations, previously inaccessible to traditional fMRI. By bridging the spatiotemporal resolution gap between electrophysiology and fMRI, ft-fMRI provides a versatile platform for studying perception, attention, and multisensory integration in health and disease.

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

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

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↗

bioRxiv2023

No Replication of Direct Neuronal Activity-related (DIANA) fMRI in Anesthetized Mice

Direct imaging of neuronal activity (DIANA) by fMRI could be a revolutionary approach for advancing systems neuroscience research. To independently replicate this observation, we performed fMRI experiments in anesthetized mice. The BOLD response to whisker stimulation was reliably detected in the primary barrel cortex before and after DIANA experiments; however, no direct neuronal activity-like fMRI peak was observed in data of individual animals with the 50-300 trials. Extensively averaged data involving 1,050 trials in 6 mice showed a flat baseline and no detectable neuronal activity-like fMRI peak. However, spurious, non-replicable peaks were found when using a small number of trials, and artifactual peaks were detected when some outlier-like trials were excluded. Further, no detectable DIANA peak was observed in the BOLD-responding thalamus from the selected trials with the neuronal activity-like reference function in the barrel cortex. Thus, we were unable to replicate the previously reported results without data pre-selection.

neuroscience↗

bioRxiv2023

Layer Dependence of Monocular and Binocular Responses in Human Ocular Dominance Columns at 7T using VASO and BOLD

The neurons located in the striate cortex (V1) preferentially respond to the input from one eye or another, forming a fingerprint-like pattern of ocular dominance columns (ODCs). At this mesoscopic scale, accessible by ultra-high field fMRI, V1 is supplied/drained by a network of surface (pial) vessels that connect to descending/ascending tangential vessels that penetrate the cortex and supply/drain a capillary bed whose density is also layer dependent. In this study, we measured the layer dependence of monocular and binocular responses of ocular dominance columns in V1 at 7T using Blood Oxygenation Level Dependent (BOLD) and VAscular Space Occupancy (VASO) contrasts. Our results indicate that the microvascular blood volume changes that give rise to VASO are well confined to the site of neural activity across the layers of the cortex and between the columns. Pial veins dominate the BOLD response and mix the signal between columns. When the GRE BOLD response was examined in only the VASO specific voxels (thus eliminating the pial vein signal), the laminar profile was very similar to VASO, however, the columnar response was still blurred. Caution needs to be exercised in the interpretation of signal changes in BOLD at the mesoscale both in terms of feedforward/feedback effects and inhibitory and excitatory effects. Highlights- VASO produced laminar profiles that were consistent with the known layer-dependent neuronal response to monocular and binocular stimulations. - VASO better differentiated the response between columns belonging to the left and right eyes. - GRE BOLD signal spatial specificity was poor in both laminar and columnar directions, however, when the pial veins were suppressed, the laminar BOLD signal was very similar to the VASO signal. - Caution needs to be exercised when interpreting cognitive neuroscience BOLD studies at the mesoscale level due to the confounding effects of pial and sub-pial veins and venules.

neuroscience↗

bioRxiv2023

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↗

bioRxiv2023

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↗

bioRxiv2021

Integration of a radiofrequency coil and commercial field camera for ultra-high-field MRI

PurposeTo develop an RF coil with an integrated commercial field camera for ultra-high field (7 T) neuroimaging. The RF coil will operate within a head-only gradient coil and be subject to the corresponding design constraints. The RF coil can thereafter be used for subject-specific correction of k-space trajectories--notably in gradient-sensitive sequences such as single-shot spiral imaging. MethodsThe transmit and receive performance was evaluated before and after the integration of field probes, while field probes were evaluated when in an optimal configuration external to the coil and after their integration. Diffusion-weighted EPI and single-shot spiral acquisitions were employed to evaluate the efficacy of correcting higher order field perturbations and the consequent effect on image quality. ResultsField probes had a negligible effect on RF-coil performance, including the transmit efficiency, transmit uniformity, and mean SNR over the brain. Modest reductions in field-probe signal lifetimes were observed, caused primarily by non-idealities in the gradient and shim fields of the head-only gradient coil at the probe positions. The field monitoring system could correct up to second-order field perturbations in single-shot spiral imaging. ConclusionThe integrated RF coil and field camera was capable of concurrent field monitoring within a 7T head-only scanner and facilitated the subsequent correction of k-space trajectories during spiral imaging.

biophysics↗

bioRxiv2021

Functional organization of frontoparietal cortex in the marmoset investigated with awake resting-state fMRI

Frontoparietal networks contribute to complex cognitive functions in humans and macaques such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, little is known about the organization of frontoparietal networks in the New World common marmoset monkey (Callithrix jacchus) which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal BOLD signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas while more anterior frontal regions (frontal eye field (FEF)) were connected to more posterior parietal areas (the area around lateral intraparietal area (LIP)). These overarching patterns of inter-areal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional homologies of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque. Significant StatementFrontoparietal networks contribute to many cognitive functions in humans and macaques, but little is known about the organization of frontoparietal networks in the New World common marmoset monkey. Here, we investigated the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. These frontoparietal connection showed overarching pattern of interareal organization consistent with Old world monkeys. These findings demonstrate parallel frontoparietal processing streams in marmosets.

neuroscience↗