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Correlation of Electrical Impedance and Evoked Potentials With Properties of the Electrode Interface Using in Situ Block-Face Imaging of the Rat Pelvic Nerve.
(Neuromodulation: Technology at the Neural Interface, 2025-09-30) Payne, Sophie C; Bowman, Christopher; Keast, Janet R; Trang, Ella P; Osborne, Peregrine B; Fallon, James B
Electrical stimulation is an emerging therapy for urologic disorders. The interface between electrode and neural tissue is a critical region of interest given it affects thresholds of neural activation. Measures of electrode impedance are used clinically to estimate tissue fibrosis at the interface; however, the relationship between impedance and fibrosis is not well defined.
Selective Optogenetic Inhibition of Slow Conducting Fibers at the Level of the Sciatic Nerve Trunk in the Mouse.
(Neuromodulation: Technology at the Neural Interface, 2025-10-21) Ardren, Mary G; Matarazzo, Jerico V; Ajay, Elise A; Thompson, Alex C; Payne, Sophie C; Fallon, James B; Richardson, Rachael T
Peripheral nerve stimulation is a drug-free alternative for chronic pain management, suppressing nociception through gating mechanisms in the spine. However, excitation through electrical stimulation does not easily discriminate between sensory and motor fibers or their functional subtypes, and can cause off-target effects. Targeted optogenetic inhibition may be a more selective method to suppress nociceptive activity directly while leaving neighboring fibers unaffected.
Best Oculomotor Endpoints for Clinical Trials in Hereditary Ataxias: A Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital‑Motor Biomarkers
(Springer Science and Business Media LLC, 2025-08-13) Pretegiani, Elena; Garces, Pilar; Antoniades, Chrystalina A.; Sobanska, Anna; Kovacs, Norbert; Ying, Sarah H.; Gupta, Anoopum S.; Perlman, Susan; Szmulewicz, David J.; Pane, Chiara; Németh, Andrea H.; Jardim, Laura B.; Coarelli, Giulia; Kuzmiak, Michaela; Milovanovic, Andona; Traschütz, Andreas; Tarnutzer, Alexander A.
Oculomotor deficits are common in hereditary cerebellar ataxias (HCAs) and their quantitative assessment offers a sensitive and reliable manner to capture disease-severity and progression. As a group of experts of the Ataxia Global Initiative to support trial readiness, we previously established harmonized methodology for quantitative oculomotor assessments in HCAs. Here, we aimed to identify to most promising oculomotor/vestibular outcomes as endpoints for future trials. Through a systematic MEDLINE search we identified 130 articles reporting oculomotor/vestibular recordings in patients with HCAs. A total of 2,018 subjects were included: 1,776 with genetically-confirmed and 242 with clinically-defined HCAs. Studied diseases included spinocerebellar ataxias (SCA) 1/2/3/6/7/27B, episodic ataxia type 2, Friedreich ataxia, RFC1-related ataxia, fragile X-associated tremor/ataxia syndrome, cerebrotendinous xanthomatosis, ataxia-telangiectasia, ataxia with oculomotor apraxia types 1&2, and Niemann-Pick disease type C. We identified up to four oculomotor/vestibular outcomes per diagnostic entity, based on their ability to robustly discriminate patients from controls, correlate with disease-severity, detect longitudinal change, and represent different disease stages. For each parameter we provide recommendations for recordings. While the implementation of quantitative assessments into clinical trials offers a unique opportunity to track dysfunction of oculomotor/vestibular networks and to assess the impact of interventions, in some HCAs, endpoint qualification of available outcomes requires further validation to characterize their reliability, sensitivity to change, and minimally important change to patients. For all HCAs for which quantitative data are scarce or lacking, there is an urgent need for prospective studies covering a broader range of oculomotor/vestibular domains as approaching new treatments require harmonized and reliable endpoints.
Psychomotor and non-motor correlates of cognition in spinocerebellar ataxias Types 1, 2, 3, and 6.
(Brain Communications, 2025-10-28) Selvadurai, Louisa P; Gullia, Sheryl; Morgan, James; Wallis, Sarah; Kumar, Kishore R; Szmulewicz, David J; Harding, Ian H
There is growing evidence of cognitive deficits in spinocerebellar ataxias, with the Cerebellar Cognitive Affective Syndrome Scale (CCAS-S) an increasingly common measure of this dysfunction. There remain ongoing questions as to how Cerebellar Cognitive Affective Syndrome Scale performance relates to day-to-day cognitive function, non-motor and motor features of spinocerebellar ataxias and demographic factors. Via an online study, we evaluated Cerebellar Cognitive Affective Syndrome Scale performance amongst individuals with spinocerebellar ataxia Type 1 (n = 14), Type 2 (n = 16), Type 3 (n = 18), and Type 6 (n = 26) relative to demographically-matched control groups. Furthermore, amongst individuals with spinocerebellar ataxia, we examined associations between performance and (i) age and education, (ii) ataxia motor severity, (iii) psychomotor function measured by computerized finger tapping and reaction time tasks and (iv) self-rated cognition, depression, emotional regulation, psychosocial function and fatigue. Cerebellar Cognitive Affective Syndrome Scale performance was significantly reduced in spinocerebellar ataxia Types 2, 3, and 6 compared to controls, although substantial inter-individual variability in performance was observed in the spinocerebellar ataxia cohort (43.2%/24.3%/21.6%/10.8% met criteria for Definite, Probable, Possible, and No CCAS). Performance in individuals with spinocerebellar ataxias correlated significantly with self-reported ataxia motor severity, fine motor speed, psychomotor trial-by-trial variability, and one of two measures of day-to-day cognitive function. Significant correlations were not observed against age, education, age at disease onset, disease duration, psychomotor reaction time, depression, emotional regulation, psychosocial function, or fatigue. We present evidence that motor function and psychomotor variability are more important correlates of inter-individual variability in cognitive performance amongst people with spinocerebellar ataxia Types 1, 2, 3 and 6, compared to demographic factors, fatigue, or emotional function. Importantly, formalized cognitive testing using the Cerebellar Cognitive Affective Syndrome Scale correlates with self-reported cognitive functioning. This study highlights cognitive dysfunction as a functionally impactful feature of certain spinocerebellar ataxias, and motivates further investigation into the disease- and individual-specific profiles of cognitive impairment in this population.
Vestibular Evoked Myogenic Potentials (VEMPs) in Parkinson’s Disease Patients with Monopolar Deep Brain Stimulation
(MDPI AG, 2025-02-21) Hawkins, Kim E.; Holden, John; Chiarovano, Elodie; Lewis, Simon J. G.; Curthoys, Ian S.; MacDougall, Hamish G.