Striato-cortical functional connectivity changes in mild cognitive impairment with Lewy bodies.

BACKGROUND: Functional connectivity changes in clinically overt neurodegenerative diseases such as dementia with Lewy bodies have been described, but studies on connectivity changes in the pre-dementia phase are scarce. OBJECTIVES: We concentrated on evaluating striato-cortical functional connectivity differences between patients with Mild Cognitive Impairment with Lewy bodies and healthy controls and on assessing the relation to cognition. METHODS: Altogether, we enrolled 77 participants (47 patients, of which 35 met all the inclusion criteria for the final analysis, and 30 age- and gender-matched healthy controls, of which 28 met all the inclusion criteria for the final analysis) to study the seed-based connectivity of the dorsal, middle, and ventral striatum. We assessed correlations between functional connectivity in the regions of between-group differences and neuropsychological scores of interest (visuospatial and executive domains z-scores). RESULTS: Subjects with Mild Cognitive Impairment with Lewy Bodies, as compared to healthy controls, showed increased connectivity from the dorsal part of the striatum particularly to the bilateral anterior part of the temporal cortex with an association with executive functions. CONCLUSIONS: We were able to capture early abnormal connectivity within cholinergic and noradrenergic pathways that correlated with cognitive functions known to be linked to cholinergic/noradrenergic deficits. The knowledge of specific alterations may improve our understanding of early neural changes in pre-dementia stages and enhance research of disease modifying therapy.

Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension.

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

Is the vertex a good control stimulation site? Theta burst stimulation in healthy controls.

The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs. A three-dimensional finite-element model (FEM) was used to calculate the vertex TBS-induced electrical field (E-field) in the adjacent regions of interest (ROIs). Correlation analyses were performed between E-fields in the ROIs and cognitive outcomes. We found a significant effect only of the stimulation time factor (F (1,12) = 65.37, p < 0.001) on RT shortening, with no superiority of the active site stimulation compared to the vertex stimulation. In 73.5% of vertex TBS sessions, a significant E-field was induced in at least one ROI. We found a negative association between the magnitude of the iTBS-induced E-fields and RT changes (R = - 0.54, p = 0.04). TBS protocols may lead to changes in CP when applied over the craniometrically targeted vertex. We therefore suggest not using a conventional approach as a vertex targeting method.

Dance Intervention Impact on Brain Plasticity: A Randomized 6-Month fMRI Study in Non-expert Older Adults.

Background: Dance is a complex activity combining physical exercise with cognitive, social, and artistic stimulation. Objectives: We aimed to assess the effects of dance intervention (DI) on intra and inter-network resting-state functional connectivity (rs-FC) and its association to cognitive changes in a group of non-demented elderly participants. Methods: Participants were randomly assigned into two groups: DI and life as usual (LAU). Six-month-long DI consisted of supervised 60 min lessons three times per week. Resting-state fMRI data were processed using independent component analysis to evaluate the intra and inter-network connectivity of large-scale brain networks. Interaction between group (DI, LAU) and visit (baseline, follow-up) was assessed using ANOVA, and DI-induced changes in rs-FC were correlated with cognitive outcomes. Results: Data were analyzed in 68 participants (DI; n = 36 and LAU; n = 32). A significant behavioral effect was found in the attention domain, with Z scores increasing in the DI group and decreasing in the LAU group (p = 0.017). The DI as compared to LAU led to a significant rs-FC increase of the default mode network (DMN) and specific inter-network pairings, including insulo-opercular and right frontoparietal/frontoparietal control networks (p = 0.019 and p = 0.023), visual and language/DMN networks (p = 0.012 and p = 0.015), and cerebellar and visual/language networks (p = 0.015 and p = 0.003). The crosstalk of the insulo-opercular and right frontoparietal networks were associated with attention/executive domain Z-scores (R = 0.401, p = 0.015, and R = 0.412, p = 0.012). Conclusion: The DI led to intervention-specific complex brain plasticity changes that were of cognitive relevance.

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.

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.