BackgroundVariation in physiological deficits underlying upper limb paresis after stroke could influence how people recover and to which physical therapy they best respond.ObjectivesTo determine whether functional strength training (FST) improves upper limb recovery more than movement performance therapy (MPT). To identify: (a) neural correlates of response and (b) whether pre-intervention neural characteristics predict response.DesignExplanatory investigations within a randomised, controlled, observer-blind, and multicentre trial. Randomisation was computer-generated and concealed by an independent facility until baseline measures were completed. Primary time point was outcome, after the 6-week intervention phase. Follow-up was at 6 months after stroke.ParticipantsWith some voluntary muscle contraction in the paretic upper limb, not full dexterity, when recruited up to 60 days after an anterior cerebral circulation territory stroke.InterventionsConventional physical therapy (CPT) plus either MPT or FST for up to 90 min-a-day, 5 days-a-week for 6 weeks. FST was “hands-off” progressive resistive exercise cemented into functional task training. MPT was “hands-on” sensory/facilitation techniques for smooth and accurate movement.OutcomesThe primary efficacy measure was the Action Research Arm Test (ARAT). Neural measures: fractional anisotropy (FA) corpus callosum midline; asymmetry of corticospinal tracts FA; and resting motor threshold (RMT) of motor-evoked potentials.AnalysisCovariance models tested ARAT change from baseline. At outcome: correlation coefficients assessed relationship between change in ARAT and neural measures; an interaction term assessed whether baseline neural characteristics predicted response.Results288 Participants had: mean age of 72.2 (SD 12.5) years and mean ARAT 25.5 (18.2). For 240 participants with ARAT at baseline and outcome the mean change was 9.70 (11.72) for FST + CPT and 7.90 (9.18) for MPT + CPT, which did not differ statistically (p = 0.298). Correlations between ARAT change scores and baseline neural values were between 0.199, p = 0.320 for MPT + CPT RMT (n = 27) and −0.147, p = 0.385 for asymmetry of corticospinal tracts FA (n = 37). Interaction effects between neural values and ARAT change between baseline and outcome were not statistically significant.ConclusionsThere was no significant difference in upper limb improvement between FST and MPT. Baseline neural measures did not correlate with upper limb recovery or predict therapy response.Trial registrationCurrent Controlled Trials: ISRCT 19090862,