Animal experiments suggest that 2 different types of activated microglia (AMG) cells occur in the brain after a stroke: local AMG in the area of the infarct and remote AMG, which occurs along affected fiber tracts. We used ¹¹C-PK11195 PET to image AMG in vivo after stroke in humans in a prospective longitudinal study to investigate the temporal dynamics of AMG and relate local and remote AMG activity to pyramidal tract (PT) damage using diffusion tensor imaging (DTI). Methods: Eighteen patients underwent DTI–MRI, ¹¹C-PK11195 PET, and behavioral testing within 2 wk and 6 mo of acute subcortical stroke. In 12 patients, the PT was affected by the stroke (PT group), and in 6 patients it was not (non-PT group). Standardized volumes of interest (VOIs) were placed along the PT at the level of the brain stem, semioval center, and infarct. Tracer uptake ratios (ipsilateral to contralateral) were calculated for each VOI and related to tract damage (measured as fractional anisotropy ratio) and clinical outcome. Six controls underwent the same protocol but only once. Results: In both patient groups, local AMG activity in the infarct was increased initially and significantly decreased over the follow-up period. In contrast, remote AMG was detected only in the PT group in the brain stem along the affected tract and persisted during follow-up. No AMG was observed retrograde to the lesion at any time. Remote AMG activity along the affected PT in the brain stem correlated with initial PT damage as measured by DTI in the same tract portion. Local AMG activity in the infarct correlated with anterograde PT damage only at follow-up. After controlling for PT damage, initial AMG activity in the brain stem showed a positive correlation with clinical outcome, whereas persisting AMG activity in the infarct tended to be negatively correlated. Conclusion: DTI-guided ¹¹C-PK11195 PET in acute subcortical stroke demonstrates differential temporal dynamics of local and remote AMG. Activity of both types related to anterograde PT damage as measured by DTI and might contribute differently to clinical outcome.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (⊿rBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with ¹⁵ O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ⊿rBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ⊿rBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ⊿rBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS.

Neuroimaging-derived markers are used to model post-stroke impairment. Among these, lesion size, corticospinal-tract lesion-load (CST-LL) and resting-state functional-connectivity (rs-FC) have been correlated with impairment. It has been shown that the sensory cortex (S1) is associated with motor learning and is essential for post-stroke recovery; yet stroke-induced changes in S1 connectivity alone are yet to be investigated. We aim to determine whether interhemispheric rs-FC could be used to refine imaging models of stroke-related impairment. Subjects’ post-stroke and age-matched controls underwent rs-fMRI. Stroke-related disability was correlated with lesion size, CST-LL and interhemispheric S1 and M1 rs-FC as independent seeds. Regression analyses were performed to assess the contribution of these markers in stroke-related deficits. Post-stroke subjects showed an asymmetrical pattern of rs-FC in which affected hemisphere S1 and M1 were mostly connected with ipsi-lesional regions. Correlations between rs-FC and stroke-severity were found. Adding rs-FC of S1 to the regression model of impairment decreased the variance 31% compared to lesion size only. After a stroke, S1 interhemispheric connectivity is decreased, with S1 only connected with ipsi-lesional regions. This asymmetry correlates with neurological and motor impairment. Furthermore, when combined with lesion anatomical measures, S1 connectivity might be an important marker in explaining stroke outcome.