Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop.

BACKGROUND AND PURPOSE: In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks. We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation. METHODS: Patients were assigned to 10 sessions of real or sham 1-Hz stimulation over the right posterior superior temporal gyrus. Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by a speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at Weeks 6 and 10 after the baseline. RESULTS: Altogether, data from 33 patients were analyzed. A linear mixed model revealed significant time-by-group interaction (p = 0.006) for the relative changes of fractional anisotropy of the AAF; the value increases were associated with the temporal evolution of the Phonetics score (R = 0.367, p = 0.028) in the real stimulation group. CONCLUSIONS: Real rTMS treatment for HD in PD as compared to sham stimulation led to increases of white matter integrity of the auditory-motor loop during the 2-month follow-up period. The changes were related to motor speech improvements.

Diffusion kurtosis imaging detects the time-dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease.

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2 months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2 months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments.

Brain structure changes in nondemented seniors after six-month dance-exercise intervention.

OBJECTIVES: To evaluate effects of a six-month intensive dance-exercise intervention (DI) on cognition and brain structure in a mixed group of healthy seniors and people with mild cognitive impairment. METHODS: Subjects (aged Ëƒ 60 years with no dementia or depression) were randomly assigned to either a DI group or a life as usual (LAU) group. Detailed neuropsychological testing, measures of physical fitness and brain MRI encompassing T1 structural and diffusion tensor imaging (DTI) were performed at baseline and after 6 months. We assessed changes in cortical thickness and DTI parameters derived from tract-based spatial statistics. RESULTS: Altogether 62 individuals (n = 31 in the DI group) completed the protocol. The groups were matched for their demographic and clinical variables. After 6 months, we found significant cortical thickening in the right inferior temporal, fusiform and lateral occipital regions in the dancers compared to controls. Significant increases of radial and mean diffusivity were observed in various white matter tracts in the dancers; however, no differences were observed between the DI and LAU groups. The DI group as compared to the LAU group showed subtle improvements in executive functions. CONCLUSIONS: We observed DI-induced improvement in executive functions and increases of cortical thickness in the lateral occipitotemporal cortex which is engaged in action observation, visuomotor integration and action imitation, that is activities that are all important for motor learning and executing skilled movements.

Multishell Diffusion MRI Reflects Improved Physical Fitness Induced by Dance Intervention.

Using multishell diffusion MRI and both tract-based spatial statistics (TBSS) and probabilistic tracking of specific tracts of interest, we evaluated the neural underpinnings of the impact of a six-month dance intervention (DI) on physical fitness and cognitive outcomes in nondemented seniors. The final cohort had 76 nondemented seniors, randomized into DI and control (life as usual) groups. Significant effects were observed between the DI and control groups in physical fitness measures and in attention. We detected associations between improved physical fitness and changes in diffusion tensor imagining (DTI) measures in the whole white matter (WM) skeleton and in the corticospinal tract and the superior longitudinal fascicle despite the fact that no significant differences in changes to the WM microstructure were found between the two groups.

Impact of cognitive reserve on dance intervention-induced changes in brain plasticity.

Dance is a complex sensorimotor activity with positive effects on physical fitness, cognition, and brain plasticity in the aging population. We explored whether individual levels of cognitive reserve (CR) proxied by education moderate dance intervention (DI)-induced plasticity assessed by resting-state functional connectivity (rs-FC) changes of the sensorimotor network (SMN), and between the dorsal attention network (DAN) and anterior default mode network (aDMN). Our cohort consisted of 99 subjects, randomly assigned to either a DI group who underwent a 6-month intervention (n = 49, Mage = 69.02 ± 5.40) or a control group (n = 50, Mage = 69.37 ± 6.10). Moderation analyses revealed that CR moderated DI-induced increase of the SMN rs-FC with significant changes observed in participants with ≥ 15 years of education (b = 0.05, t(62) = 3.17, p = 0.002). Only DI alone was a significant predictor of the DAN-aDMN crosstalk change (b = 0.06, t(64) = 2.16, p = 0.035). The rs-FC increase in the SMN was correlated with an improved physical fitness measure, and changes in the DAN-aDMN connectivity were linked to better performance on figural fluency. Consistent with the passive CR hypothesis, we observed that CR correlated only with baseline behavioral scores, not their change.

Patterns of diffusion kurtosis changes in Parkinson's disease subtypes.

BACKGROUND: Diffusion kurtosis imaging has been applied to evaluate white matter and basal ganglia microstructure in mixed Parkinson's disease (PD) groups with inconclusive results. OBJECTIVES: To evaluate specific patterns of kurtosis changes in PD and to assess the utility of diffusion imaging in differentiating between healthy subjects and cognitively normal PD, and between PD with and without mild cognitive impairment. METHODS: Diffusion scans were obtained in 92 participants using 3T MRI. Differences in white matter were tested by tract-based spatial statistics. Gray matter was evaluated in basal ganglia, thalamus, hippocampus, and motor and premotor cortices. Brain atrophy was also assessed. Multivariate logistic regression was used to identify a combination of diffusion parameters with the highest discrimination power between groups. RESULTS: Diffusion kurtosis metrics showed a significant increase in substantia nigra (p = 0.037, Hedges' g = 0.89), premotor (p = 0.009, Hedges' g = 0.85) and motor (p = 0.033, Hedges' g = 0.87) cortices in PD with normal cognition compared to healthy participants. Combined diffusion markers in gray matter reached 81% accuracy in differentiating between both groups. Significant white matter microstructural changes, and kurtosis decreases in the cortex were present in cognitively impaired versus cognitively normal PD. Diffusion parameters from white and gray matter differentiated between both PD phenotypes with 78% accuracy. CONCLUSIONS: Increased kurtosis in gray matter structures in cognitively normal PD reflects increased hindrance to water diffusion caused probably by alpha-synuclein-related microstructural changes. In cognitively impaired PD, the changes are mostly driven by decreased white matter integrity. Our results support the utility of diffusion kurtosis imaging for PD diagnostics.