Optimizing upper-extremity recovery post-stroke

Stroke, caused by occlusion of one or more of the cerebral blood vessels, is a leading cause of disability in the Western countries, with many patients displaying upper-extremity impairments that significantly impacts quality of life and activity of daily living. Current stroke rehabilitation guidelines recommend early initiated, goal-directed, task-specific, and repetitive to restore function. However, most patients do not regain their pre-stroke level of functioning. Furthermore, rehabilitation can be hindered by factors such as patient fatigue, severe symptoms, or limited clinical resources.
Non-invasive brain stimulation, such as transcranial direct current stimulation (TDCS), has gained interest as a potential method to enhance neuroplasticity and improve recovery post-stroke. TDCS delivers weak electrical direct current to the brain, thus modulating the neural activity to either increase (anodal TDCS) or decrease (cathodal) excitability in targeted regions. While previous stroke rehabilitation trials suggest TDCS may improve of upper-extremity function, many patients remain non-responders. It seems that a one-size-fits-all approach is not appropriate for TDCS application.
This PhD thesis explores three key aspects of post-stroke motor recovery:
I. The natural course of upper-extremity recovery with usual care
II. The neural mechanisms underlying motor network deficits
III. The potential of personalized TDCS to improve upper-extremity recovery.

In study I, we conducted a systematic review and meta-analysis to examine the upper-extremity recovery with usual care in the subacute phase post-stroke (within 12 weeks of index stroke). We analysed results from 54 included papers, both including observational cohort studies and usual care groups of randomized controlled trials. We concluded that most upper-extremity recovery occurs within the first 12 weeks and exceeds the clinically minimal important difference, which reinforces the importance of neurorehabilitation.
In study II, we investigated the neural mechanisms of upper-extremity motor impairment in subacute stroke patients compared to healthy aged controls. Using task-based functional MRI, we measured reaction time and inter-press-interval, i.e., time between second and first press, in milliseconds during a single-hand and bimanual sequential button press task. While there was no between-group difference in reaction time, stroke patients exhibited longer inter-press-intervals regardless of whether the affected or unaffected hand was measured. We also saw an increased bilateral brain activation upon bimanual button press. These findings suggest that motor deficits post-stroke is not merely due to muscle weakness but reflect disruptions in the motor network of both the affected an unaffected hemisphere.
In study III, we tested patient-tailored TDCS application during upper-extremity rehabilitation in a randomized, double-blinded feasibility- and pilot trial. A total of 24 subacute stroke patients were included and randomized to either TDCS or sham three times weekly for four weeks with assessments done at end-of-intervention and at 12 weeks follow-up. Using the field modelling tool, SimNIBS, anodal TDCS was targeted to the individual motor hand area in the affected hemisphere of each patient At end-of-intervention, the patients in the active TDCS showed significant improvement in the upper-extremity function (measured by Fugl-Meyer Assessment of upper-extremity) along with significantly improved level in activity of daily living, level of depression, and health related quality of life. However, recruitment was challenging with >1000 patients pre-screened, emphasizing the need for more clinically feasible protocols in future trials.

Together, these results show that while substantial upper-extremity recovery occurs within the first 12 weeks with usual care, many patients continue to experience motor deficits. These deficits arise from broader motor network disruptions in addition to muscle weakness. Patient-tailored TDCS combined with rehabilitation shows promising results in improving upper-extremity function in the short term. These findings highlight the potential of personalized neurostimulation as an add-on to conventional rehabilitation, which should be examined further in larger clinical trials to refine clinical applicability and optimize treatment protocols.