No abstract

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning.We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation.These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

ObjectivesTo numerically and experimentally investigate the robustness of intravoxel incoherent motion (IVIM) magnetic resonance imaging in measuring perfusion indexes in the human brain.MethodsEighteen healthy volunteers were imaged on a 3 T clinical system. Data of IVIM imaging (12 b-values ranging from 0 to 1000 s/mm2, 12 repetitions) were fitted with a bi-exponential model to extract blood volume fraction (f) and pseudo-diffusion coefficient (D*). The robustness of measurement was assessed by bootstrapping. Dynamic susceptibility contrast (DSC) imaging and arterial spin-labelling (ASL) imaging were performed for cross-modal comparison. Numerical simulations were performed to assess the accuracy and precision of f and D* estimates at varied signal-to-noise ratio (SNRb1000).ResultsBased on our experimental setting (SNRb1000 ~ 30), the average error/variability is ~5 %/25 % for f and ~100 %/30 % for D* in gray matter, and ~10 %/50 % for f and ~300 %/60 % for D* in white matter. Correlation was found between f and DSC-derived cerebral blood volume in gray matter (r = 0.29 – 0.48 across subjects, p < 10-5), but not in white matter. No correlation was found between f-D* product and ASL-derived cerebral blood flow.Conclusionsf may provide noninvasive measurement of cerebral blood volume, particularly in gray matter. D* has limited robustness and should be interpreted with caution.Key Points• A minimum SNRb1000of 30 is recommended for reliable IVIM imaging.• f may provide noninvasive measurement of cerebral blood volume.• f correlates with CBVDSCin gray matter.• There is no correlation between fD* and CBFASL.• D* has limited robustness and should be interpreted with caution.

We studied 6 advanced-stage Parkinson's disease patients with [18F] fluorodeoxyglucose/positron emission tomography before and 3 months after unilateral ablation of the subthalamic nucleus performed with microelectrode mapping. Operative changes in glucose metabolism were assessed by comparing baseline and postoperative scans. We also quantified operative changes in the activity of an abnormal Parkinson's disease-related metabolic network that we had identified in previous [18F] fluorodeoxyglucose/positron emission tomography studies. Following unilateral subthalamic nucleus ablation, a highly significant reduction in glucose utilization was present in the midbrain ipsilateral to the lesion site, most pronounced in the vicinity of the substantia nigra pars reticularis. Significant metabolic reductions were also present in the ipsilateral internal globus pallidus, ventral thalamus, and pons. Operative changes in Parkinson's disease network activity differed significantly for the lesioned and unlesioned hemispheres. In the lesioned hemisphere, network activity declined significantly following surgery, but was unaltered in the contralateral, unlesioned hemisphere. These results suggest that subthalamotomy reduces basal ganglia output through internal globus pallidus/substantia nigra pars reticularis and also influences downstream neural activity in the pons and ventral thalamus. This procedure also reduces the activity of abnormal Parkinson's disease-related metabolic brain networks, suggesting a widespread modulation of motor circuitry.

These findings indicate that subthalamotomy may have differential effects on each of the functional pathways that mediate parkinsonian symptomatology. Sustained relief of akinesia and rigidity is associated with suppression of a pathological network involving the GPi and its output. In contrast, the recurrence of tremor may relate to changes in the function of an STN-GPe oscillatory network.