Stroke-induced excitability changes in human motor cortex

Despite advances in acute treatment of stroke, over third of the patients suffer from a disability, most often upper-limb paresis, still five years after stroke. To improve rehabil- itation, further understanding of stroke-induced plasticity is required. During the plastic period, cortical excitability increases, likely promoting cortical reorganization. Afferent input modulates the rolandic 20-Hz rhythm. The modulation, reflecting motor- cortex excitability, is observable as the activation-associated suppression and inhibition- associated rebound of the 20-Hz rhythm. In this Thesis, motor-cortex excitability was monitored by applying two different afferent inputs while recording the 20-Hz rhythm with magnetoencephalography (MEG), first in healthy controls and then in stroke patients in a one-year longitudinal study. Study I, comprising 22 healthy controls, focused on the modulation of the 20-Hz rhythm to tactile stimulation and passive movement as proprioceptive stimulation. The suppres- sion of the rhythm was similar to both stimuli whereas the rebound was stronger to pas- sive movement. Thus, passive movement could better serve in studying motor-cortex excitability changes. In Studies II and III, modulation of the 20-Hz rhythm to afferent input was measured in 23 patients having their first-ever stroke in the territory of the middle cerebral artery and related upper-limb paresis. Passive movement of the index finger (Study II) and tactile stimulation (Study III) were applied during MEG recordings in the acute (T 0 ; 1–7 days), subacute (T 1 ; one month) and chronic (T 2 ; 12 months) phases after stroke onset in conjunction with clinical testing of hand motor performance. The results showed that in the acute phase, the rebound was strongly diminished to both stimuli compared to the controls and increased significantly during the first month. During the follow-up period, the rebound strengths to both stimuli correlated with motor performance of the impaired hand. The bilateral weakness of the rebounds in the acute phase indicate hyperexcitability of both hemispheres after stroke. The subsequent increase in the rebound strength during the first month, reflecting an increase in motor-cortex inhibition, is in line with earlier studies in animals and humans suggesting a sensitive and motor-recovery-related plastic period immediately after stroke. The rebound strength to impaired-hand stimulation correlatedwith hand motor performance across the follow-up indicating that adequate integration of afferent input with motor functions is important for motor recovery. During the follow- up, the 20-Hz rebound to both tactile and passive-movement stimuli increased similarly. However, the rebounds to tactile stimuli recovered to the level of the controls whereas those to proprioceptive stimuli did not. This might indicate that proprioception did not recover fully in our patients. It would be most important to be able to predict and evaluate the progress of an individual patient during recovery from stroke to intensify and tailor rehabilitation for individual needs. Though, the efficacy of rehabilitation may be evaluated with different neuroimag- ing methods and clinical tests in a group level, so far there are no objective biomarkers to evaluate rehabilitation in an individual level. The results of this Thesis indicate that the 20-Hz rebound magnitude strongly reflects motor-cortex excitability and thus could serve as a robust noninvasive marker of stroke-induced neurophysiological processes that are relevant for motor recovery. Such a biomarker may enable to assess the efficacy of new therapeutical methods in stroke rehabilitation in both group and individual levels.