Multifeature quantitative motor assessment of upper limb ataxia including drawing and reaching.

OBJECTIVE: Voluntary upper limb movements are an ecologically important yet insufficiently explored digital-motor outcome domain for trials in degenerative ataxia. We extended and validated the trial-ready quantitative motor assessment battery "Q-Motor" for upper limb movements with clinician-reported, patient-focused, and performance outcomes of ataxia. METHODS: Exploratory single-center cross-sectional assessment in 94 subjects (46 cross-genotype ataxia patients; 48 matched controls), comprising five tasks measured by force transducer and/or position field: Finger Tapping, diadochokinesia, grip-lift, and-as novel implementations-Spiral Drawing, and Target Reaching. Digital-motor measures were selected if they discriminated from controls (AUC >0.7) and correlated-with at least one strong correlation (rho ≥0.6)-to the Scale for the Assessment and Rating of Ataxia (SARA), activities of daily living (FARS-ADL), and the Nine-Hole Peg Test (9HPT). RESULTS: Six movement features with 69 measures met selection criteria, including speed and variability in all tasks, stability in grip-lift, and efficiency in Target Reaching. The novel drawing/reaching tasks best captured impairment in dexterity (|rho9HPT| ≤0.81) and FARS-ADL upper limb items (|rhoADLul| ≤0.64), particularly by kinematic analysis of smoothness (SPARC). Target hit rate, a composite of speed and endpoint precision, almost perfectly discriminated ataxia and controls (AUC: 0.97). Selected measures in all tasks discriminated between mild, moderate, and severe impairment (SARA upper limb composite: 0-2/>2-4/>4-6) and correlated with severity in the trial-relevant mild ataxia stage (SARA ≤10, n = 20). INTERPRETATION: Q-Motor assessment captures multiple features of impaired upper limb movements in degenerative ataxia. Validation with key clinical outcome domains provides the basis for evaluation in longitudinal studies and clinical trial settings.

No robust online effects of transcranial direct current stimulation on corticospinal excitability.

Transcranial direct current stimulation (tDCS) has been used for over twenty years to modulate cortical (particularly motor corticospinal) excitability both during (online) and outlasting (offline) the stimulation, with the former effects associated to the latter. However, tDCS effects are highly variable, partially because stimulation intensity is commonly not adjusted individually (in contrast to transcranial magnetic stimulation, TMS). In Experiment 1, we therefore explored an empirical approach of personalizing tDCS intensity for the primary motor cortex (M1) based on dose-response curves (DRCs), individually relating tDCS Intensity (in steps from 0.3 to 2.0 mA) and Polarity (anodal, cathodal) to the online modulation of concurrent TMS motor evoked potentials (MEP), assessing DRC reliability across two separate days. No robust DRCs could be observed, neither at the individual nor at the group level, with the only robust effect being a (paradoxical) MEP facilitation during cathodal tDCS at 2.0 mA, but no modulation at traditional intensities of or near 1 mA. In Experiment 2, we therefore attempted to replicate the classical bidirectional online MEP modulation during 1 mA tDCS that had been reported by several of the early seminal tDCS papers. We either closely recreated stimulation parameters and temporal protocol of these original studies (Experiment 2A) or slightly modernized them according to current standards (Experiment 2B). In neither experiment did we observed any significant online MEP modulation. We conclude that an empirical titration of individually effective tDCS intensities may not be feasible as online tDCS effects do not appear to be sufficiently robust.