Biology subjects

Chapman, C.

Publications and source records attributed to Chapman, C..

5 recordsLinked to original sources

bioRxiv2025

Neuromodulation of a peripheral nerve using fully polymeric cuff electrodes: Understanding predictability of selective stimulation

Peripheral nerve stimulation (PNS) offers therapeutic benefits across numerous clinical applications but suffers from limitations in high resolution spatial selectivity, especially in mixed nerves. This study presents a fully polymeric, transverse, multipolar nerve cuff made from a conductive elastomer (CE), designed for selective activation of individual fascicles. Fabricated with laser-based manufacturing techniques, the CE nerve cuff offers mechanical conformity and high charge injection capacity. Ex vivo experiments on the rat sciatic nerve demonstrate reliable compound action potential recordings and fascicular selectivity (SI > 0.65). The non-metal electrodes enable microCT-aided 3D reconstruction of nerve-electrode geometries without imaging artefacts, informing anatomically accurate simulations via the ASCENT pipeline. While in silico simulations predict some selective fascicular activation, discrepancies were observed between predicted and experimental selectivity magnitudes and electrode positions, particularly for the sural and tibial fascicles. The model was more sensitive to neuroanatomical variation than the experimental data, indicating limitations in current perineurium and CE electrode modelling assumptions. This work validates CE-based cuffs as viable alternatives to metallic devices for selective fascicular peripheral nerve activation and highlights the potential of imaging-informed simulations to optimize nerve interface design. Future improvements in electrode and nerve tissue modelling are needed to enhance in silico prediction accuracy and further advance spatially selective PNS technologies.

bioengineering↗

bioRxiv2025

Anxiety-associated behaviors following ablation of Miro1 from cortical excitatory neurons

Autism spectrum disorder, schizophrenia, and bipolar disorder are neuropsychiatric disorders that manifest early in life with a wide range of phenotypes, including repetitive behavior, agitation, and anxiety (American Psychological Association, 2013). While the etiology of these disorders is not completely understood, recent data implicate a role for mitochondrial dysfunction. To function optimally mitochondria must translocate to metabolically active intracellular compartments to support energetics and free-radical buffering; failure to achieve this localization results in cellular dysfunction (Picard et al., 2016). Mitochondrial Rho-GTPase 1 (Miro1) resides on the outer mitochondrial membrane and participates in neuronal microtubule-mediated mitochondrial motility and homeostasis (Fransson et al., 2003). Previous research implicates the loss of MIRO1 as a contributor to the onset/progression of neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimers disease, and Parkinsons disease (Kay et al., 2018). We have hypothesized that MIRO1 also has a role in nervous system development and function (Lin-Hendel et al., 2016). To test this, we ablated Miro1 from cortical excitatory progenitors by crossing floxed Miro1 mice with Emx1-cre mice. We found that mitochondrial mis-localization in migrating excitatory neurons was associated with reduced brain weight, decreased cortical volume, and subtle disruptions in cortical organization. Adult Miro1 conditional mutants exhibit agitative-like behaviors, including decreased nesting behavior and abnormal home cage activity. Open field testing revealed anxiety-like behavior and elevated plus maze and wide/narrow box testing found the mice avoided confined spaces. Our data link MIRO1 function with mitochondrial dynamics in the pathogenesis of several neuropsychiatric disorders and implicate mitochondrial localization in anxiety-like behaviors. SignificanceNeuropsychological disorders such as autism spectrum disorder, schizophrenia, and bipolar disorder have overlapping symptoms and behaviors. While the mechanisms underlying these disorders are not completely understood, recent evidence suggests mitochondrial dysfunction and mis-localization within a cell could play a role. Mitochondria are organelles that provide energy and other self-regulating processes to the cell. Previous research from our lab has shown distinct dynamic localization patterns within migrating excitatory and inhibitory neurons may be important during development. To further examine the importance of mitochondrial localization, we ablated MIRO1, a protein important for coupling mitochondria to motor proteins, in excitatory neurons. Mitochondria mis-localize in migrating excitatory neurons, and this is associated with a loss of motor skills and anxiety-like behavior in post-natal mice.

neuroscience↗

bioRxiv2021

Network diffusion model predicts neurodegeneration in limb-onset amyotrophic lateral sclerosis

The trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS. We measured degeneration in limb-onset ALS patients (n=14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n=12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. The cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Our findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.

neuroscience↗

bioRxiv2019

Serial assessment of iron in the motor cortex in limb-onset Amyotrophic Lateral Sclerosis using Quantitative Susceptibility Mapping

ObjectiveDysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with Amyotrophic Lateral Sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based Quantitative Susceptibility Mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a six-month period. MethodsIron concentration was investigated using magnetic resonance based -QSM in the primary motor cortex and the pre-motor area in thirteen limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and eleven age and sex-matched healthy controls. Nine ALS patients underwent follow-up scans at six months. ResultsSignificantly increased QSM was observed in the left posterior primary motor area (p = 0.02, Cohens d = 0.9) and right anterior primary motor area (p = 0.02, Cohens d = 0.92) in all individuals with limb-onset ALS compared to healthy controls. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to healthy controls. No significant change in QSM was observed at the six-month follow-up scans in the ALS patients. ConclusionsThe findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a radiological indicator in disease diagnosis, and in clinical trials in limb-onset ALS and its subtypes. HighlightsO_LISerial measurement of QSM in the motor cortex in limb-onset ALS was performed C_LIO_LIQSM changes in the motor cortex in ALS sub-groups were investigated C_LIO_LIHigher QSM was observed in the motor cortex in Lumbar ALS relative to controls C_LIO_LIQSM is sensitive to iron dysregulation in the motor cortex in limb-onset ALS C_LI

neuroscience↗

bioRxiv2018

Out with the old and in with the new: The role of intolerance of uncertainty in reversal of threat and safety

The ability to learn and reverse threat associations is crucial for survival. The extent to which old threat associations are inhibited and new threat associations are formed may depend on sensitivity to future threat uncertainty. To assess the extent to which Intolerance of Uncertainty (IU) predicts threat learning and reversal, we recorded expectancy ratings and skin conductance in 44 healthy participants during an associative learning paradigm, where threat and safety contingencies were reversed. During acquisition and reversal, we observed larger SCR magnitude and expectancy ratings for threat vs. safety cues. However, during reversal higher IU was associated with larger SCR magnitude to new threat vs. new safety cues, compared to lower IU. These results were specific to IU-related variance, over shared variance with trait anxiety (STAIX-2). Overall, these findings suggest that individuals high in IU are able to reverse threat and safety associations in the presence of direct threat. Such findings help us understand the recently revealed link between IU and threat extinction, where direct threat is absent. Moreover, these findings highlight the potential relevance of IU in clinical intervention and treatment for anxiety disorders.

neuroscience↗