Reorganization of effective connectivity in the motor system after stroke

Background:

Functional neuroimaging studies frequently demonstrated that stroke patients show bilateral activity in motor and premotor areas during movements of the paretic hand rather than the contralateral pattern seen in healthy subjects (1). A recent study applying effective connectivity analyses by dynamic causal modelling (DCM) to fMRI data of patients with chronic impairments found reduced connectivity within the ipsilesional motor network as well as a disturbed interhemispheric communication. Furthermore, there was an enhanced inhibition from contralesional to ipsilesional primary motor cortex (M1) (2). However, not much is known about the temporary evolution of intra- and interhemispheric (dys-) connectivity stroke. Therefore, our study aimed at identifying changes in effective connectivity between cortical motor areas and their correlation with clinical recovery from the first days after ischemia up to the 6 months post-stroke in first-ever stroke patients.

Methods:

We studied 12 patients with mild to severe hemiparesis after a first-ever ischemic middle cerebral artery stroke. Patients were scanned using fMRI while performing a visually cued rhythmic motor task with the left or right hand. The first fMRI session was performed within 1–3 days after the incident followed by a second assessment after 2 weeks. Nine patients participated at a third session after 4 to 6 months. At each session, clinical data such as NIH stroke scale, maximal grip force and action research arm test (ARAT) were assessed to monitor functional recovery. For control group comparisons, we also investigated 15 age-matched healthy control subjects. For fMRI data analysis, we applied DCM to model the causal interactions between cortical motor regions while patients moved their affected hand.

Results:

Within the ipsilesional hemisphere, the neural coupling from premotor areas towards ipsilesional M1 was significantly reduced compared to healthy subjects in the first 1–3 days post-stroke. At 2 weeks post-stroke, excitatory influences towards ipsilesional M1 (especially from SMA) recovered concomitant to clinical improvements. Changes in neural coupling within the contralesional hemisphere showed a different pattern: In the first days post stroke, inhibitory influences towards the contralesional M1 were significantly reduced, and persisted 2 weeks post stroke. The amount of disinhibition was correlated with poor motor performance of the affected hand. After 4–6 months, there was no statistically significant difference in neural coupling within and between both hemispheres compared to healthy subjects. Especially the restoration of inhibitory effects upon contralesional M1 within 4–6 months post-stroke was indicative for clinical improvement.

Conclusion:

Effective connectivity from bilateral premotor areas towards ipsilesional M1 was reduced early after stroke, and increased concomitant to clinical recovery. The positive relationship between transient disinhibition of contralesional M1 activity and clinical improvements 2 weeks post-stroke suggests rather a beneficial than detrimental role of contralesional M1 activity for cortical reorganization after stroke.

References: [1] Ward NS, Frackowiak RS (2006). J Physiol Paris 99:425–436. [2] Grefkes C, Nowak D, Eickhoff SB, et al. (2008). Ann Neurol 63:236–46.

Fig.1: Stroke patients, movements of the affected hand

Fig.2: Control subjects, movements of the right hand