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Structural Brain and Spinal Cord Signature of Spinocerebellar Ataxia 27B: A Multisite MRI-Based Study.
(Movement Disorders, 2026-09-28) Santos, Nadson Bruno Serra; Lobo, Camila Caroso; Rezende, Thiago Junqueira Ribeiro; Martinez, Alberto Rolim Muro; Corazza, Luiza A; Novis, Luiz Eduardo; Barsottini, Orlando Graziani Povoas; Pedroso, José Luiz; Tomaselli, Pedro José; Marques, Wilson; Dos Santos, Antônio Carlos; Pellerin, David; Brais, Bernard; Piana, Roberta La; Harding, Jemimah; Snell, Penny; Lockhart, Paul J; Szmulewicz, David; Harding, Ian H; França, Marcondes Cavalcante
BACKGROUND: SCA27B is a recently described ataxia, the precise anatomical basis of which remains unclear.
OBJECTIVE: The goal was to characterize the structural brain and spinal cord magnetic resonance imaging (MRI) signature of spinocerebellar ataxia 27B (SCA27B) using multimodal quantitative imaging.
METHODS: In this cross-sectional, multisite study, 28 genetically confirmed SCA27B patients underwent standardized 3 T brain and cervical spinal cord MRI. A group of age- and sex-matched healthy controls was recruited at participating centers using harmonized acquisition protocols. Cerebral and cerebellar volumetry were performed using FastSurfer and CerebNet, respectively. Diffusion tensor imaging was used to assess microstructural integrity in supratentorial white matter. Spinal cord gray and white matter areas were quantified at the cervical level using the SCT toolbox. Between-group comparisons were conducted using general linear models adjusted for age, sex, and site.
RESULTS: Mean age and Scale for the Assessment and Rating of Ataxia score of the SCA27B cohort were 68.7 ± 13.3 years and 10.5 ± 5.8 points. Compared with healthy controls, SCA27B patients exhibited significant volumetric reduction of the cerebellar vermis (lobules I to IV and vermis VIII). Diffusion analyses revealed widespread fractional anisotropy reduction in subcortical cerebral white matter, consistent with microstructural disruption. At the cervical spinal cord level, patients demonstrated significant gray matter area reduction, whereas white matter area was comparatively preserved. The combined pattern of vermian atrophy, supratentorial white matter diffusivity abnormalities, and spinal cord gray matter loss delineated a distinct structural signature of SCA27B.
CONCLUSION: SCA27B is associated with a structural phenotype extending beyond the cerebellum, involving subcortical white matter microstructure and spinal cord gray matter. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Multimodal Magnetic Resonance Imaging and Machine Learning Uncovers Distinct Progression Patterns in Friedreich Ataxia.
(Movement Disorders, 2026-09-27) Saha, Susmita; Georgiou-Karistianis, Nellie; Teo, Vivienne; Corben, Louise A; Szmulewicz, David J; Strike, Lachlan T; França, Marcondes C; Rezende, Thiago J R; Harding, Ian H
BACKGROUND: Friedreich ataxia (FRDA) is a rare neurodegenerative disorder with heterogenous clinical progression, complicating prognosis and trial design. Neuroimaging offers objective biomarkers of disease progression, yet variability in progression patterns remains poorly understood.
OBJECTIVE: The objective of this study is to identify distinct neurodegenerative progression patterns in FRDA using longitudinal multimodal magnetic resonance imaging (MRI) and to evaluate associations with clinical, demographic, and genetic factors.
METHODS: Longitudinal structural and diffusion MRI data from 54 patients with FRDA and 57 controls were analyzed. Annualized progression rates of macrostructural (volumetric) and microstructural (diffusion) features across cerebellum, brainstem, and spinal cord regions were clustered using Gaussian Mixture Models. Following model selection, clusters were evaluated for biological plausibility of longitudinal imaging trajectories, bootstrap and subsampling reproducibility, and consistency of case-control composition. Associations with demographic, genetic, and clinical variables were examined, and Random Forest modeling assessed predictors of cluster membership.
RESULTS: Four statistical clusters were identified, three of which represented robust, biologically interpretable progression patterns characterized by predominant microstructural degeneration, predominant macrostructural atrophy, and minimal measurable progression. The microstructure- and macrostructure-dominant patterns were enriched for FRDA participants, whereas the minimal-progression pattern contained more controls. GAA1 repeat length was the only variable consistently associated with cluster membership, with larger expansions observed in the microstructure-dominant pattern. Disease duration and clinical progression rates did not significantly differentiate progression patterns.
CONCLUSIONS: Longitudinal multimodal MRI shows distinct neurodegenerative progression patterns in FRDA that are not fully captured by conventional clinical measures. This data-driven framework provides a basis for investigating imaging-derived disease heterogeneity and its potential relevance to participant stratification in clinical trials. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Endovascular neuromodulation: feasibility of endovascular stimulation near the cerebellum.
(Journal of Neural Engineering, 2026-08-26) Qi, Weijie; Villalobos, Joel; Liu, Jingyang; Xin, Huakun; Spencer, Martin J; Kazemi, Sepehr; Ho, Stella; West, Joseph; Grayden, David B; John, Sam E
Electrical stimulation and neural recording underpin neural prostheses for restoring function and treating neurological disorders, but clinical adoption is limited by the invasiveness of implantation. The Endovascular Neural Interface offers an alternative by accessing intracranial targets through the cerebral vasculature. This work presents the first strength-duration characterization of cortical evoked potentials, elicited by endovascular stimulation, adjacent to the cerebellum.A polymer-based stent-electrode array was deployed into the left transverse sinus of an ovine model. Biphasic current pulses targeting the cerebellum were delivered via the stent electrodes. Cortical responses were recorded using a subdural electrocorticography grid.Endovascular stimulation consistently evoked time-locked cortical potentials with early and late components at approximately 40 ms and 100 ms post-stimulation. Electrode functionality and stability were confirmed through impedance monitoring throughout the experiments. Strength-duration analysis revealed rheobase and chronaxie values, providing a quantitative basis for parameter selection and comparison with established intracranial stimulation modalities.These results demonstrate that endovascular electrodes may access non-superficial brain structures and evoke reproducible cortical responses without open neurosurgery. This work helps establish a foundational framework for endovascular neuromodulation and supports further investigation of its potential for future closed-loop and network-level neuromodulation research.
Recommendations on post-trial responsibility in implantable neural device research: a multidisciplinary consensus study.
(BMC Medical Ethics, 2026-05-12) Higgins, Nathan; Blakely, Brette; Everingham, Roland; Gilbert, Frederic; Griffin, Sarah; Harris, Alexander R; Herring, Sally; Ho, Calvin Wai Loon; Hoy, Kate; Kiel-Chisholm, Scott; Koplin, Julian; Lawn, Sharon; McCay, Allan; Phillipson, Nitya; Richards, Bernadette; Rosenfeld, Jeffrey V; Shamsi Gooshki, Ehsan; Viana, John Noel; Gardner, John; Carter, Adrian
The clinical development of implantable neural devices raises complex ethical questions about post-trial responsibilities to participants. Continued support for participants who continue to use investigational implantable neural devices requires ongoing specialist care, technical expertise, access to tertiary clinical infrastructure, and substantial financial resources to pay for the device and related procedures. However, continued access may not be possible if the trial shows no benefit, if financial barriers limit commercial viability, or if safety concerns lead to suspension or early termination. Specific ethical guidance on post-trial responsibility is urgently needed. To address this challenge within the Australian innovation context, we conducted a modified Delphi study with a multidisciplinary panel of 24 experts, including representatives from industry, bioethics, law, neurosurgery, clinical psychology/neuropsychology, clinical research, neural engineering, regulation and governance, and lived experience advocacy. The process involved two workshops and a survey, guided by established RAND/UCLA methods with context-specific modifications. Drawing on prior empirical research and regulatory review, the panel developed 11 consensus recommendations for responsible post-trial practices. All recommendations achieved high levels of agreement and were rated as highly important for addressing ethical risks in the Australian environment. These are the first jurisdiction-specific recommendations of their kind, and we anticipate they will substantially enhance ethical and practical standards for post-trial responsibility in implantable neural device research in Australia and internationally.
Clinical utility and prospective of TMS-EEG: Updated review from an international expert group.
(Clinical Neurophysiology, 2026-01-09) Ziemann U; Bai Y; Baumer FM; Beck MM; Belardinelli P; Belvisi D; Bender S; Bergmann TO; Bortoletto M; Casarotto S; Casula E; Chaves AR; de Andrade DC; Conte A; Daskalakis ZJ; Farzan F; Ferrarelli F; Fitzgerald PB; Gordon PC; Grefkes C; Harquel S; Hernandez-Pavon JC; Hill AT; Hoy KE; Hummel FC; Julkunen P; Kallioniemi E; Keller CJ; Kimiskidis VK; Kirkovski M; Koch G; Leodori G; Lioumis P; Määttä S; Maidan I; Massimini M; Mengel A; Metsomaa J; Miniussi C; Mutanen TP; Noda Y; Ozdemir RA; Raffin E; Rocchi L; Rogasch NC; Rosanova M; Santarnecchi E; Sarasso S; Schabrun SM; Shafi MM; Siebner HR; Tolner EA; Tomasevic L; Tremblay S; Tscherpel C; Veniero D; Versace V; Voineskos D; Vucic S; Zangen A; Zrenner C; Ilmoniemi RJ
Transcranial magnetic stimulation (TMS) is a non-invasive technique to stimulate the brain, while electroencephalography (EEG) is a non-invasive technique to record its electrical activity. Their combined use (TMS-EEG) has been established only relatively recently, after successful development of TMS-compatible EEG amplifiers. TMS-EEG offers the unparalleled opportunity to directly perturb the brain with TMS and simultaneously record its response with EEG. This allows inferences on causal input-output relationships, therefore going critically beyond purely observational techniques, such as resting-state EEG or functional MRI, in the study of brain dynamics. This consensus review updates the work of Tremblay and coworkers [Clin Neurophysiol 2019; 130: 802-844]. Since then, substantial advances have been made in understanding contamination of TMS-EEG signals by physiological and non-physiological artifacts, as well as in developing strategies to avoid or control them. In parallel, new insights have emerged regarding the physiological mechanisms underlying TMS-EEG responses and their diagnostic and prognostic utility in a broad range of psychiatric and neurological disorders. As such, TMS-EEG is rapidly shaping a dynamic new field in clinical neurophysiology and neuroscience. This review provides a critical and comprehensive synthesis of current knowledge, including practical guidance for implementing TMS-EEG in the clinical setting.