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 11 C-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, 11 C-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: DTIguided 11 C-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.

Rigidity or hypertonicity is a cardinal symptom of Parkinson's disease (PD). We hypothesized that hypertonicity of the body axis affects functional performance of tasks involving balance, walking and turning. The magnitude of axial postural tone in the neck, trunk and hip segments of 15 subjects with PD (both ON and OFF levodopa) and 15 control subjects was quantified during unsupported standing in an axial twisting device in our laboratory as resistance to torsional rotation. Subjects also performed six functional tests (walking in a figure of eight [Figure of Eight], Timed Up & Go, Berg Balance Scale, supine rolling task [rollover], Functional Reach, and standing 360-deg turn-in-place) in the ON and OFF state. Results showed that PD subjects had increased tone throughout the axis compared to control subjects (p=0.008) and that this increase was most prominent in the neck. In PD subjects, axial tone was related to functional performance, but most strongly for tone at the neck and accounted for an especially large portion of the variability in the performance of the Figure of Eight test (rOFF=0.68 and rON=0.74, p<0.05) and the Rollover test (rOFF=0.67and rON=0.55, p<0.05). Our results suggest that neck tone plays a significant role in functional mobility and that abnormally high postural tone may be an important contributor to balance and mobility disorders in individuals with PD.

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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 (DrCBF) 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, DrCBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in DrCBF 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 DrCBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS.