Ravi S. Menon

Primate communication relies on the precise coordination of the orofacial complex. While New World monkeys are growing models for vocal communication research, the neural basis underlying their oromotor control remains underexplored. Here, we used ultra-high-field fMRI in awake common marmosets (Callithrix jacchus) to map the whole-brain neural networks engaged during spontaneous visible oromotor functions—including jaw and lip movements, tongue protrusion, swallowing, and vocalization—distinct from those recruited during the auditory processing of conspecific calls. The resulting oromotor maps reveal a widespread control substrate extending beyond primary sensorimotor cortices, encompassing dorsal prefrontal (areas 8aD, 8b), mid-cingulate, posterior parietal areas (PF, PFG, and PE), and auditory regions. The parietal engagement points to a role for sensorimotor integration in marmoset oromotor control. Subcortically, this network engages the thalamus, basal ganglia, and cerebellum, with additional activation in the medullary reticular formation and periaqueductal gray, brainstem regions implicated in rhythmic oromotor control. A predominantly dorsal pattern of activation, with limited ventral premotor engagement, defines this network and provides a foundational framework for future studies of vocal–motor control in this species and a comparative reference for the rhythmic oromotor substrates from which speech is hypothesized to have evolved.

Phosphorylated α-synuclein at S129 (pS129) is the predominant form of α-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 α-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.

Alzheimer's 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–β 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 Alzheimer's disease and suggest that restoring oligodendroglial function may provide cognitive benefits beyond those of amyloid-targeting strategies.

Understanding how α-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 α-synuclein seeding in the common marmoset. Phosphorylated α-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 α-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.

Purpose: In 3D SPACE and FLAIR sequences, designing single pTx RF pulse for excitation and refocusing pulses by scaling its amplitude can introduce artifacts. This study addresses this by designing multiple subject‐specific RF pulses online within clinically viable times, using subpopulation universal pulses (UPs) as initialization. Methods: Subpopulation UPs were calculated using and maps from 150 training subjects. During experiments, refocusing flip‐angles were grouped into five clusters. Starting from the subpopulation UP yielding the lowest error, a reference RF pulse was optimized for the cluster with mean flip‐angle closest to 90°. The remaining refocusing‐cluster and excitation RF pulses were optimized using the reference phase response, with refocusing RF pulses scaled to desired flip‐angles. Time‐symmetric RF and anti‐symmetric gradient waveforms were enforced as a constraint. For FLAIR, a new T2‐prepared inversion scheme was proposed, based on designing a symmetric 180° inversion pTx pulse and splitting it to obtain 90° pulses. Results: Compared to ‐shimming and single‐RF pulse optimization, the proposed method minimized artifacts resulting from RF pulse scaling, particularly in high regions. Online pulse calculations required ∼20 s and an additional ∼9 s for FLAIR. Across 120 test subjects, the multi‐RF approach demonstrated an 18% improvement in the simulated echo magnitude within high regions and 13% improvement within the brain. pTx inversion pulses achieved an 86% SAR reduction compared to adiabatic ones. Conclusion: The proposed method enables efficient subject‐specific RF pulse design for 3D SPACE and FLAIR.

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 cluster them, and examine 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 architectures. By openly sharing our data and pipelines, we aim to advance the marmoset as a model for investigating the evolutionary foundations of brain function.

Background: MS imaging studies have demonstrated an ependymal “surface-in” distribution of white matter damage. The origin of this effect and how it impacts myelinated axons in people with MS (PwMS) is poorly understood. Objectives: To investigate (1) whether there is clear evidence of tract-wise, periventricular damage, based on fractional anisotropy, mean diffusivity, axonal water fraction (AWF) and myelin volume fraction (MVF), in PwMS, (2) if such tissue damage is associated with T ₁ -“black-hole” (T ₁ -BH) and/or non-BH lesions, and (3) if periventricular quantitative MRI abnormalities are correlated with lateral ventricle (LV) and choroid plexus (CP) enlargement. Methods: We applied structural, MT-weighted, and multi-shell diffusion MRI in healthy controls and PwMS to quantify periventricular gradient damage to axons and myelin. We also evaluated the correlation between such gradient damage and both non-BH and T ₁ -BH lesion loads, and brain volume changes. Results: Clear periventricular gradients exist in both AWF and MVF measures in the Association and Projection Tracts. They are strongly correlated with T ₁ -BH lesion load, and with LV and CP enlargement in PwMS with EDSS > 2. Conclusions: Tract-specific, periventricular gradients in PwMS exist prominently in AWF and MVF, are strongly associated with T ₁ -BH lesion loads, and correlate with LV and CP enlargement.