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Modulation of brain functions in stroke patients: paradigms for pharmacological interventions

In recent years, several novel approaches have been suggested to support functional recovery from stroke.

At present, the promising approaches comprise pharmacological stimulation of specific neurotransmitter systems. Studies in both animals and humans suggested that stimulation of the adrenergic system may facilitate motor recovery, especially in combination with physical therapy.

Reboxetine: Potential for Neurorehabilitation

In one of our recent studies we demonstrated that a single dose of the selective noradrenaline reuptake inhibitor reboxetine can improve motor performance in healthy subjects in various visuomotor tasks when compared to placebo. The imaging data show that these behavioural improvements were associated with increased neural activity in right fronto-parietal circuits known to be involved in eye-hand coordination and visuomotor transformation. Thus, boosting of activity in these task-relevant areas may have improved the performance to guide the joystick cursor.

Figure:
(A) Subjects used a joystick to guide a cursor from the center to a peripheral circle while being scanned with fMRI. The behavioural data showed that movement times were significantly faster for RBX (8 mg) compared to placebo.
(B) Group fMRI analysis revealed increased neural activity in right parietofrontal areas when subjects were stimulated with RBX. Such areas are known to be involved in eye-hand coordination, visuomotor transformation and visuospatial attention (Grefkes and Fink, 2005), which all are important components of the joystick task tested in this study.

These results underpin the potential of RBX as a drug in neurorehabilitation. Neuroimaging studies have demonstrated that stroke patients often show increased activation in somatosensory, premotor, parietal and occipital visual areas when using the paretic hand (Grefkes et al., 2008). Thus, increasing visuomotor abilities by RBX might support such adaptive processes following stroke.

Furthermore, the mechanisms underlying recovery from stroke resemble those for learning new motor programs. We plan to investigate issues of safety and efficacy in terms of RBX in longitudinal study designs. Such designs will also consider the combination of a pharmacological stimulation with behavioral training (e.g., physical therapy) and other stimulation techniques such as repetitive TMS.

Research topics in detail:

Modulating neural functions in stroke patients using

pharmacological interventions
rTMS or tDCS

Acute stroke