Approximately two thirds of stroke patients have reduced motor function which have a large impact on both activities of daily living and quality of life. Only 12-34% achieve full motor recovery.~There is a growing interest in using non-invasive brain stimulation (NIBS) techniques to supplement neurorehabilitation. NIBS can modulate cortical excitability and is a powerful tool for motor rehabilitation post-stroke. Application Transcranial Direct Current Stimulation (TDCS) is currently emerging as a tool used in neurorehabilitaiton. Prior studies have shown that TDCS-stimulation prior to physical training may significantly improve of motor function post-stroke. However, up to 50% of the participants recieving active TDCS show no response to stimulation.~A one-size-fits-all approach to TDCS in stroke rehabilitation may not be optimal and a more precise and individualized targeting is warranted to stimulate functionally relevant areas.~In this study TDCS will be personalized for stroke patients with upper-extremity paresis using individual functional and structural Magnetic Resonance Imaging (MRI) and an electric field modelling pipeline developed at Danish Research Centre for Magnetic Resonance (DRMCR). Based on these measures the electric current induced by TDCS will individually target the area with residual neural activity during movement. The effect of personalized TDCS will be assessed by clinical measures of motor improvement. Sub-studies furthermore assess if the functional reorganization of motor networks is affected by personalized TDCS by application of functional magnetic resonance (fMRI) and.~The study will have 3 phases:~Personalization: The stimulation profile of each patient will be individualized using structural MRI a pipeline for simulation based on MRI (SimNIBS) to make individual anatomical head models in order to estimate the best montage and current dosage. Further, task-based fMRI will be used to estimate residual motor activity location. The target current is set in the area displaying the highest residual motor activity in sensorimotor areas.~Intervention: Four weeks upper extremity training program of specialized supervised physiotherapeutic training 3 times per week. Each training session consists of 2x 20 minutes of training with concurrent personalized TDCS stimulation or montage of equipment but no stimulation (sham). Each bloc of 20 minutes training is separated by a small break of 5-10 minutes. Both patient, therapist and investigator will be blinded to the stimulation mode (activ TDCS or sham)~Follow-up: Immediately after the 4 weeks of intervention and 12 weeks after intervention has ended, follow-up with clinical examination and brain MRI will be done.~Ad baseline Transcranial Magnetic Stimulation (TMS) will be done as well to assess corticospinal integrity as well as estimation of intracortical inhibition.~Hypothesis:~The main hypothesis is that personalized ipsi-lesional anodal TDCS during specialized individualized arm-training will lead to significantly greater improvements in upper-extremity motor function compared to sham.~Substudy with healthy controls:~A cohort of 20 healthy age- and sex matched controls will be recruited for one session of MRI and TMS identical to the procedure of the patients at baseline as well as the same questionnaires (Protocol amendment approved by the local Ethics Committee the 10th October 2022).~These data will be analyzed in a substudy for normative comparison between the stroke patients and healthy age- and sex-matched controls.~Hypothesis - Healthy Controls:~Stroke patients will exhibit a higher laterality index measured by fMRI and a stronger degree of interhemispheric inhibition at baseline compared to healthy controls measued by task-related fMRI and by TMS iSP and SICI.~The degree of interhemispheric inhibition in stroke patients will normalize during recovery and be similar to normal controls at the last follow-up after 12 weeks.~Further, the degree of normalization of the interhemispheric inhibition in stroke patients will be proportional to degree of improvement of the upper-extremity measured by UE-FMA.
In a double-blinded sham-controlled study the effect of patient-tailored transcranial direct current stimulation during rehabilitation training will be examined.