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Hybrid optogenetic and electrical stimulation of retinal ganglion cells for artificial vision.
(Brain Stimulation, 2025-12-23) Kwan, William C; Brunton, Emma K; Goris, Toon; Begeng, James M; Kameneva, Tatiana; Stoddart, Paul R; Ibbotson, Michael R; Richardson, Rachael T; Tong, Wei
Millions of adults worldwide experience severe visual impairment due to photoreceptor loss from retinal diseases such as retinitis pigmentosa and macular degeneration. Retinal prostheses that provide artificial vision by stimulating the surviving retinal ganglion cells (RGCs) have emerged as a promising therapy. However, all clinically approved retinal prostheses that use electrical stimulation face the issue of electrical spread. As such, the quality of restored vision provided by existing devices has been limited. Optogenetic approaches provide greater spatial precision, however, they have poor temporal properties compared to electrical stimulation.
Two-year decline in performance on the Cerebellar Cognitive Affective Syndrome Scale in spinocerebellar ataxias.
(Journal of Neurology, 2025-12-11) Selvadurai, Louisa P; Lo Giudice, Chiara; Wallis, Sarah; Morgan, James; Kumar, Kishore R; Szmulewicz, David J; Harding, Ian H
Cognitive deficits are observed in a subset of individuals with spinocerebellar ataxias (SCAs); however, there is limited research on the longitudinal trajectory of such deficits. We investigated longitudinal cognitive performance amongst individuals with SCAs relative to controls, and the relationship of change in cognitive performance with change in self-reported function.
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.