Neuroimaging correlates of pathological changes in motor cortex electrophysiology: Convergence of fMRI and neuronavigated TMS in chronic stroke patients

Introduction:

Functional magnetic resonance imaging (fMRI) studies demonstrated that chronic stroke patients show bilateral enhancement of neural activity in motor areas during movements of the affected hand but not during movements of the unaffected hand (Grefkes et al. 2008). However, little is known on how contralesional BOLD (blood oxygenation level dependent) signal relates to motor performance of the paretic hand and to electrophysiological TMS parameters reflecting neural excitability (e.g., active motor threshold=aMT) or plasticity, such as intrahemispheric (e.g., short-interval cortical inhibition=SICI) and interhemispheric inhibition (=IHI).

Methods:

12 chronic stroke patients with persistent motor deficits following stroke in the middle cerebral artery territory were scanned with fMRI while performing visually-paced hand clenching alternating with both hands at a frequency individually adjusted to 30% of the maximal clenching frequency of the moving hand. Standard fMRI data analysis was performed using SPM8 (Grefkes et al. 2008). The following parameters were obtained at the motor hot spot of each hemisphere using a neuronavigated TMS device (Nexstim Ltd., Helsinki): (i) aMT, (ii) SICI (CS: 80% aMT; TS: 1mV; ISI=2ms), (iii) IHI (CS: 1mV; TS: 1mV; ISI=10ms).

Results:

The fMRI group analysis revealed that movements of the stroke-affected hand with 30% of the maximum clenching frequency showed stronger recruitment of contralesional motor areas than movements of the unaffected hand. Motor thresholds were increased in the lesioned hemisphere. Correlation analyses revealed that motor thresholds were associated with enhanced BOLD signal in ipsi- and contralesional M1. SICI was less pronounced in the affected hemisphere compared to the unaffected hemisphere. IHI targeting the affected hemisphere was less pronounced than IHI targeting the unaffected hemisphere. The correlation analyses showed that stronger SICI and IHI were associated with enhanced activity in contralesional SMA, while weaker SICI and IHI correlated with enhanced BOLD activity in ipsilesional M1, SMA, premotor cortex and SII.

Conclusion:

Our results suggest a tight relationship between pathological changes in motor cortex electrophysiology and BOLD activity in ipsilesional as well as contralesional motor areas. Such information increases our knowledge on the functional role of the contralesional hemisphere in order to develop therapeutic interventions based on individual parameters assessed with fMRI or TMS.

References: Grefkes C, Nowak DA, Eickhoff SB, Dafotakis M, Küst J, Karbe H, Fink GR. Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging. Ann Neurol. 2008 Feb;63(2):236–46.