Biology subjects

Hernandez-Castillo, C. R.

Publications and source records attributed to Hernandez-Castillo, C. R..

7 recordsLinked to original sources

bioRxiv2026

Longitudinal Reorganization of Cortical and Cerebellar Functional Networks in Spinocerebellar Ataxia Type 7

Spinocerebellar ataxia type 7 (SCA7) is a rare neurodegenerative disorder characterized by progressive cerebellar ataxia and visual impairment. We investigated longitudinal changes in resting-state functional connectivity and their clinical associations. Resting-state functional MRI was acquired from 16 individuals with SCA7 and 16 age- and sex-matched healthy controls across three visits over 24 months. Network-to-network functional connectivity was quantified, and machine-learning models were trained using functional connectivity features. SCA7 showed lower MoCA (p = 0.045) and MMSE (p = 0.025) scores and progressive worsening of ataxia (SARA, p < 0.001). Significant Group x Visit interactions were observed for Visual-Default Mode (p = 0.012) and Somatomotor-Cerebellar Dorsal Attention connectivity (p = 0.038). Functional connectivity abnormalities involved cortical, cortico-cerebellar, and cerebellar networks that became more widespread at the final follow-up assessment, with the visual network emerging as the most consistently affected system across analyses. Functional connectivity abnormalities were associated with cognitive performance (MMSE: r = -0.62, p = 0.01) and disease severity (SARA: r = 0.589, p = 0.016). Functional connectivity features accurately classified SCA7 and healthy controls (accuracy = 96.4%, F1 = 0.969). These findings support resting-state functional connectivity as a candidate biomarker warranting further validation in larger, independent cohorts.

neuroscience↗

bioRxiv2026

Dissecting heterogeneous brain development and aging using voxelwise normative models

Brain disorders are often characterized by biological heterogeneity that is poorly captured by group-average analyses. Normative modeling has emerged as a promising tool to parse out such heterogeneity, yet existing lifespan reference models rely on coarse parcellations, which may obscure individual variability. Using an aggregated reference sample (n=58,597 scans from n=51,107 participants), we provide openly available normative models of brain morphometry at the voxel level across the lifespan, and we illustrate their potential utility with two complementary applications. First, we investigated long-term brain development after preterm birth across two independent cohorts (n=284; n=304) and found individualized, replicable and persistent brain alterations. Second, we extracted high-resolution patient-level morphometric deviations in two samples with rare, genetic neurodegenerative disorders (spinocerebellar ataxia type 1 and 3; n=29, n=15), which showed marked heterogeneity. Together, our findings highlight that voxelwise normative modeling can detect clinically relevant, individualized deviations from a reference model with high spatial precision.

neuroscience↗

bioRxiv2025

Functional Connectivity Alterations in Spinocerebellar Ataxia Type 10: Insights from Gray Matter Atrophy

Spinocerebellar ataxia type 10 (SCA10) is a rare, inherited neurological disorder caused by an expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. It is characterized by cerebellar ataxia and epilepsy. Previous research has demonstrated extensive white and gray matter degeneration, particularly in the cerebellum. However, the impact of the SCA10 mutation on functional connectivity (FC) remains unexplored. This study aimed to characterize intrinsic FC changes in SCA10 patients and their relationship to clinical manifestations. Structural and resting-state MRIs were obtained from 26 SCA10 patients and 26 control subjects. Voxel-based morphometry (VBM) and seed-ROI and Independent Components Analysis (ICA) were performed to identify cerebral atrophy and FC changes respectively. Additionally, correlation analyses were conducted between FC changes and scores from the Scale for the Assessment and Rating of Ataxia (SARA) and the Montreal Cognitive Assessment (MoCA). In SCA10 patients, VBM analysis revealed extensive gray matter loss in motor cortices and the cerebellum. FC analysis identified significant FC changes originating from seed-ROIs in the right cerebellar VI and left precentral gyrus. Furthermore, group comparison using ICA components showed that SCA10 patients exhibited higher FC in the sensorimotor and cerebellar functional networks. Moreover, the average BOLD signal within the cerebellar network negatively correlated with MoCA scores. In summary, SCA10 patients exhibited enhanced FC in brain regions that displayed gray matter atrophy, underscoring the impact of SCA10 degeneration on resting state networks and induction of potential maladaptive FC compensatory mechanisms.

neuroscience↗

bioRxiv2024

The Pattern and Staging of Brain Atrophy in Spinocerebellar Ataxia Type 2 (SCA2): MRI Volumetrics from ENIGMA-Ataxia

ObjectiveSpinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterised by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2, however the evolution and pattern of whole-brain atrophy in SCA2 remain unclear. We undertook a multi-site, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2. MethodsVoxel-based morphometry analyses of 110 participants with SCA2 and 128 controls were undertaken to assess groupwise differences in whole-brain volume. Correlations with clinical severity and genotype, and cross-sectional profiling of atrophy patterns at different disease stages, were also performed. ResultsAtrophy in SCA2 relative to controls was greatest (Cohens d>2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects (d>1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In cerebellar grey matter (GM), large effects (d>0.8) mapped to areas related to both motor coordination and cognitive tasks. Strong correlations (|r|>0.4) between volume and disease severity largely mirrored these groupwise outcomes. Stratification by disease severity showed a degeneration pattern beginning in cerebellar and pontine WM in pre-clinical subjects; spreading to the cerebellar GM and cerebro-cerebellar/corticospinal WM tracts; then finally involving the thalamus, striatum, and cortex in severe stages. InterpretationThe magnitude and pattern of brain atrophy evolves over the course of SCA2, with widespread, non-uniform involvement across the brainstem, cerebellar tracts, and cerebellar cortex; and late involvement of the cerebral cortex and striatum.

neuroscience↗

bioRxiv2021

The role of feedback in the production of skilled finger sequences

Actions involving fine control of the hand, for example grasping an object, rely heavily on sensory information from the fingertips. While the integration of feedback during execution of individual movements is well understood, less is known about the use of sensory feedback in the control of skilled movement sequences. To address this gap, we trained participants to produce sequences of finger movements on a keyboard-like device over a four-day training period. Participants received haptic, visual, and auditory feedback indicating the occurrence of each finger press. We then either transiently delayed or advanced the feedback for a single press by a small amount of time (30 or 60 ms). We observed that participants rapidly adjusted their ongoing finger press by either accelerating or prolonging the ongoing press, in accordance with the direction of the perturbation. Furthermore, we could show that this rapid behavioural modulation was driven by haptic feedback. While these feedback-driven adjustments reduced in size with practice, they were still clearly present at the end of training. In contrast to the directionally-specific effect we observed on the perturbed press, a feedback perturbation resulted in a delayed onset of the subsequent presses irrespective of perturbation direction or feedback modality. This observation is consistent with a hierarchical organization of skilled movement sequences, with different levels reacting distinctly to sensory perturbations.

neuroscience↗

bioRxiv2019

Sensory information from a slipping object elicits a rapid and automatic shoulder response

Humans have the remarkable ability to hold, grasp, and manipulate objects. Previous work has reported rapid and coordinated reactions in hand and shoulder muscles in response to external perturbations to the arm during object manipulation; however, little is known about how somatosensory feedback of an object slipping in the hand influences responses of the arm. We built a hand-held device to stimulate the sensation of slipping at all five fingertips. The device was integrated into an exoskeleton robot that supported it against gravity. The setup allowed us to decouple somatosensory stimulation in the fingers from forces applied to the arm-- two variables that are highly interdependent in real-world scenarios. Fourteen participants performed three experiments in which we measured their arm feedback responses during slip stimulation. Slip stimulations were applied horizontally, in one of two directions, and participants were either instructed to follow the slip direction, or to move the arm in the opposite direction. Participants showed responses within [~]67 ms of slip onset when following the direction of slip, but significantly slower responses when instructed to move in the opposite direction. Arm responses were modulated by the speed but not the distance of the slip. Finally, when slip stimulation was combined with mechanical perturbations to the arm, we found that sensory information from the fingertips significantly modulated the shoulder feedback response. Overall, the results demonstrate the existence of a rapid feedback system that stabilizes hand-held objects.\n\nNEW & NOTHEWORTHYWe tested whether the sensation of an object slipping from the fingers modulates shoulder feedback responses. We found rapid shoulder feedback responses when participants were instructed to follow the slip direction with the arm. Shoulder responses following mechanical joint perturbations were also potentiated when combined with slipping. These results demonstrate the existence of fast and automatic feedback responses in the arm in reaction to sensory input to the fingertips that maintain grip on hand-held objects.

neuroscience↗

bioRxiv2018

A Multi-Domain Task Battery Reveals Functional Boundaries in the Human Cerebellum

There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional sub-regions. To address this question, we employed a rich task battery, designed to tap into a broad range of cognitive processes. During four functional magnetic resonance imaging (fMRI) sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex, and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional sub-regions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. This multi-domain task approach offers novel insights into the functional heterogeneity of the cerebellar cortex.

neuroscience↗