Imaging techniques document enhanced activity in multiple motor areas of the damaged and contralesional (intact) hemisphere (CON-H) after stroke. In the subacute stage, increased activity within motor areas in the CON-H during simple movements of the affected hand has been shown to correlate with poorer motor outcome. For those patients in the chronic stage who recovered well, the functional relevance of an increased activation within the CON-H is unclear. Using trains of repetitive transcranial magnetic stimulation (TMS) during performance of complex finger movements, we tested the behavioral relevance of regional functional magnetic resonance imaging (fMRI) activation within the CON-H for sequential finger movement performance of the recovered hand in seven patients who had experienced a subcortical stroke. TMS was navigated over fMRI activation maxima within anatomically preselected regions of the CON-H, and effects were compared with those of healthy controls. Stimulation over the dorsal premotor cortex (dPMC), the primary motor cortex (M1), and the superior parietal lobe (SPL) resulted in significant interference with recovered performance in patients. Interference with the dPMC and M1 induced timing errors only, SPL stimulation caused both timing and accuracy deficits. The present results argue for a persistent beneficial role of the dPMC, M1, and SPL of the CON-H on some aspects of effectively recovered complex motor behavior after subcortical stroke.

The functional neuroanatomy of executive function critically involves the dorsolateral prefrontal cortex. Transcranial direct current stimulation (tDCS) has been established as a noninvasive tool for transient modulation of cortical function. Here, we examined the effects of tDCS of the left dorsolateral prefrontal cortex on planning function by using the Tower of London task to evaluate performance during and after anodal, cathodal (1 mA, 15 min), and sham tDCS in 24 healthy volunteers. The key finding was a double dissociation of polarity and training phase: improved performance was found with cathodal tDCS applied during acquisition and early consolidation, when preceding anodal tDCS, but not in the later training session. In contrast, anodal tDCS enhanced performance when applied in the later sessions following cathodal tDCS. Our results indicate that both anodal and cathodal tDCS can improve planning performance as quantified by the Tower of London test. Most importantly, these data demonstrate training-phase-specific effects of tDCS. We propose that excitability decreasing cathodal tDCS mediates its early beneficial effect through noise reduction of neuronal activity, whereas a further adaptive configuration of specific neuronal connections is supported by excitability enhancing anodal tDCS in the later training phase by enhanced efficacy of active connections. This gain of function was sustained in a follow-up 6 and 12 months after training. In conclusion, the specific coupling of stimulation and training phase interventions may support the treatment of cognitive disorders involving frontal lobe functions.

Gait and balance disturbances typically emerge in advanced Parkinson’s disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson’s Disease Rating Scale score (Scale II items 13–15, Scale III items 27–31) at ‘3-week follow-up’. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the ‘3-week follow-up’. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no ‘global’ effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.