Differential spatial distribution of white matter lesions in Parkinson's and Alzheimer's diseases and cognitive sequelae.

White Matter Lesions (WML) are a radiological finding common in aged subjects. We explored the impact of WML on underlying neurodegenerative processes. We focused on the impact of WML on two neurodegenerative diseases with different pathology. In this cross-sectional study of 137 subjects (78 female, 59 men, mean age 67.2; 43-87 years), we compared WML in healthy controls (HC; n = 55), patients with Alzheimer's disease and amnestic Mild Cognitive Impairment (aMCI), and Parkinson's disease patients with normal cognition and with MCI. Subjects with AD and aMCI were treated as one group (n = 40), subjects with PD and PDMCI were another group (n = 42). MRI T2_FLAIR sequences were analyzed. WML were divided into periventricular (pWML) or subcortical (sWML) depending on their distance from the ventricles. Subjects from the AD + aMCI group, had a significantly greater volume of WML than both HC and the PD + PDMCI group. The volume of WML was greater in the PD + PDMCI than in HC but the difference was not significant. In AD + aMCI subjects, sWML and not pWML were related to a decrease in global cognitive functioning despite greater volume of pWML. In PD + PDMCI, pWML correlate with decline in executive functions and working memory. In HC, pWML correlated with the multidomain decrease corresponding with the aging. This points to a difference between normal aging and pathological aging due to AD and PD brain pathology. The WML location together with underlying disease related neurodegeneration may play a role in determining the effect of WML on cognition. Our results suggest that the impact of WML is not uniform in all patients; rather, their volume, location and cognitive effect may be disease-specific.

Neuroplasticity in Motor Learning Under Variable and Constant Practice Conditions-Protocol of Randomized Controlled Trial.

Background: There is numerous literature on mechanisms underlying variability of practice advantages. Literature includes both behavioral and neuroimaging studies. Unfortunately, no studies are focusing on practice in constant conditions to the best of our knowledge. Hence it is essential to assess possible differences in mechanisms of neuroplasticity between constant vs. variable practice conditions. The primary objectives of the study described in this protocol will be: (1) to determine the brain's structural and functional changes following constant and variable practice conditions in motor learning (structural and functional magnetic resonance imaging, MRI); (2) to determine the EEG activation and connectivity between cognitive, sensory, and motor cerebral cortex areas (central, temporal, parietal, occipital) in constant and variable practice conditions and as a function of practice time. Methods: The study will follow the interventional (experimental) design with two arms (parallel groups). Fifty participants will be randomly assigned to two groups practicing in constant (CG) and variable conditions (VG). CG will be practicing only one pattern of step isometric contractions during unimanual index finger abduction, i.e., 90 trials in all training sessions, whereas VG will practice three different patterns. Each will be practiced 30 times per session in variable conditions. Resting-state fMRI, EEG (cortical networking), and motor task proficiency will be examined before (pre-) and after practice (post- and retentions tests). Discussion: Findings will enhance our understanding of structural and functional neural changes following practice in constant and variable conditions. Therefore, the study can be considered pure (basic) research (clinical research in healthy individuals). Clinical Trial Registration: Study registered at clinicaltrials.gov (ID# NCT04921072) on 9 June 2021. Last version update: 21 December 2021.The protocol has been prepared according to the complete SPIRIT checklist (http://www.spirit-statement.org/), although the item order has been modified in order to comply with the manuscript structure.

Shannon entropy: A novel parameter for quantifying pentagon copying performance in non-demented Parkinson's disease patients.

INTRODUCTION: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI). METHODS: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001. RESULTS: PD patients differed from HC in attention domain z-scores (p < 0.0001). In terms of tablet parameters, the groups differed in Shannon entropy (horizontal in-air, p = 0.003), which quantifies the movements between two strokes. In PD, a correlation was found between the median of Shannon entropy (horizontal in-air) and attention z-scores (R = -0.55, p = 0.006). The VBM revealed an association between our drawing parameter of interest and gray matter (GM) volume variability in the right superior parietal lobe (SPL). CONCLUSION: Using a digitizing tablet during the PCT, we identified a novel entropy-based parameter that differed between the nondemented PD and HC groups. This in-air parameter correlated with the level of attention and was linked to GM volume variability of the region engaged in spatial attention.

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.

Non-invasive brain stimulation for speech in Parkinson's disease: A randomized controlled trial.

BACKGROUND: Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson's disease (PD). OBJECTIVES: We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. METHODS: A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. RESULTS: Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. CONCLUSIONS: This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.

Articulatory network reorganization in Parkinson's disease as assessed by multimodal MRI and acoustic measures.

INTRODUCTION: Hypokinetic dysarthria (HD) is common in Parkinson's disease (PD). Our objective was to evaluate articulatory networks and their reorganization due to PD pathology in individuals without overt speech impairment using a multimodal MRI protocol and acoustic analysis of speech. METHODS: A total of 34 PD patients with no subjective HD complaints and 25 age-matched healthy controls (HC) underwent speech task recordings, structural MRI, and reading task-induced and resting-state fMRI. Grey matter probability maps, task-induced activations, and resting-state functional connectivity within the regions engaged in speech production (ROIs) were assessed and compared between groups. Correlation with acoustic parameters was also performed. RESULTS: PD patients as compared Tto HC displayed temporal decreases in speech loudness which were related to BOLD signal increases in the right-sided regions of the dorsal language pathway/articulatory network. Among those regions, activation of the right anterior cingulate was increased in PD as compared to HC. We also found bilateral posterior superior temporal gyrus (STG) GM loss in PD as compared to HC that was strongly associated with diadochokinetic (DDK) irregularity in the PD group. Task-induced activations of the left STG were increased in PD as compared to HC and were related to the DDK rate control. CONCLUSIONS: The results provide insight into the neural correlates of speech production control and distinct articulatory network reorganization in PD apparent already in patients without subjective speech impairment.

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.

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.

Gray Matter Changes in Parkinson's and Alzheimer's Disease and Relation to Cognition.

PURPOSE OF REVIEW: We summarize structural (s)MRI findings of gray matter (GM) atrophy related to cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD) in light of new analytical approaches and recent longitudinal studies results. RECENT FINDINGS: The hippocampus-to-cortex ratio seems to be the best sMRI biomarker to discriminate between various AD subtypes, following the spatial distribution of tau pathology, and predict rate of cognitive decline. PD is clinically far more variable than AD, with heterogeneous underlying brain pathology. Novel multivariate approaches have been used to describe patterns of early subcortical and cortical changes that relate to more malignant courses of PD. New emerging analytical approaches that combine structural MRI data with clinical and other biomarker outcomes hold promise for detecting specific GM changes in the early stages of PD and preclinical AD that may predict mild cognitive impairment and dementia conversion.

Cognitive effects of dance-movement intervention in a mixed group of seniors are not dependent on hippocampal atrophy.

Dance-movement intervention (DMI) offers multi-component stimulation of cognitive functions, and it may ameliorate cognitive deficits in the elderly. We investigated the effects of intensive DMI on the cognitive performances of healthy seniors (HS) and patients with mild cognitive impairment (MCI). In addition, we evaluated whether the baseline MRI hippocampus-to-cortex volume (HV:CTV) ratio (i.e., a marker of a typical AD-specific brain atrophy and of distribution of neurofibrillary tangles in the brain) has any impact on the DMI-induced cognitive changes. The research cohort consisted of 99 subjects who were randomly assigned (in a 1:1 ratio) to a DMI group or to a control (life-as-usual) group. The DMI group consisted of 49 subjects with an average age of 69.16 years (SD = 5.36), of which 34 were HS (69.4%) and 15 had MCI (30.6%). The control group consisted of 50 subjects aged 68.37 years (SD = 6.10), of which 31 were HC (62%) and 19 (38%) had MCI. The DMI group underwent a 6-month intervention, which consisted of 60 lessons supervised by a qualified instructor. Statistical analysis yielded a significant improvement of the figural fluency task as measured by the five-point test in the DMI group as compared to the control group [t (97) = 2.72; p = 0.008]. The baseline HV:CTV ratio was not associated with cognitive changes on that task or with changes in any cognitive domain's Z scores. We observed DMI-induced effect on the test evaluating executive functions across the spectrum of HS and MCI, which was not dependent on the magnitude of AD-related brain pathology.

Connectivity Between Brain Networks Dynamically Reflects Cognitive Status of Parkinson's Disease: A Longitudinal Study.

BACKGROUND: Cognitive impairment in Parkinson's disease (PD) is associated with altered connectivity of the resting state networks (RSNs). Longitudinal studies in well cognitively characterized PD subgroups are missing. OBJECTIVES: To assess changes of the whole-brain connectivity and between-network connectivity (BNC) of large-scale functional networks related to cognition in well characterized PD patients using a longitudinal study design and various analytical methods. METHODS: We explored the whole-brain connectivity and BNC of the frontoparietal control network (FPCN) and the default mode, dorsal attention, and visual networks in PD with normal cognition (PD-NC, n = 17) and mild cognitive impairment (PD-MCI, n = 22) as compared to 51 healthy controls (HC). We applied regions of interest-based, partial least squares, and graph theory based network analyses. The differences among groups were analyzed at baseline and at the one-year follow-up visit (37 HC, 23 PD all). RESULTS: The BNC of the FPCN and other RSNs was reduced, and the whole-brain analysis revealed increased characteristic path length and decreased average node strength, clustering coefficient, and global efficiency in PD-NC compared to HC. Values of all measures in PD-MCI were between that of HC and PD-NC. After one year, the BNC was further increased in the PD-all group; no changes were detected in HC. No cognitive domain z-scores deteriorated in either group. CONCLUSION: As compared to HC, PD-NC patients display a less efficient transfer of information globally and reduced BNC of the visual and frontoparietal control network. The BNC increases with time and MCI status, reflecting compensatory efforts.

Patterns of Grey Matter Atrophy at Different Stages of Parkinson's and Alzheimer's Diseases and Relation to Cognition.

Using MRI, a characteristic pattern of grey matter (GM) atrophy has been described in the early stages of Alzheimer's disease (AD); GM patterns at different stages of Parkinson's disease (PD) have been inconclusive. Few studies have directly compared structural changes in groups with mild cognitive impairment (MCI) caused by different pathologies (AD, PD). We used several analytical methods to determine GM changes at different stages of both PD and AD. We also evaluated associations between GM changes and cognitive measurements. Altogether 144 subjects were evaluated: PD with normal cognition (PD-NC; n = 23), PD with MCI (PD-MCI; n = 24), amnestic MCI (aMCI; n = 27), AD (n = 12), and age-matched healthy controls (HC; n = 58). All subjects underwent structural MRI and cognitive examination. GM volumes were analysed using two different techniques: voxel-based morphometry (VBM) and source-based morphometry (SBM), which is a multivariate method. In addition, cortical thickness (CT) was evaluated to assess between-group differences in GM. The cognitive domain z-scores were correlated with GM changes in individual patient groups. GM atrophy in the anterior and posterior cingulate, as measured by VBM, in the temporo-fronto-parietal component, as measured by SBM, and in the posterior cortical regions as well as in the anterior cingulate and frontal region, as measured by CT, differentiated aMCI from HC. Major hippocampal and temporal lobe atrophy (VBM, SBM) and to some extent occipital atrophy (SBM) differentiated AD from aMCI and from HC. Correlations with cognitive deficits were present only in the AD group. PD-MCI showed greater GM atrophy than PD-NC in the orbitofrontal regions (VBM), which was related to memory z-scores, and in the left superior parietal lobule (CT); more widespread limbic and fronto-parieto-occipital neocortical atrophy (all methods) differentiated this group from HC. Only CT revealed subtle GM atrophy in the anterior cingulate, precuneus, and temporal neocortex in PD-NC as compared to HC. None of the methods differentiated PD-MCI from aMCI. Both MCI groups showed distinct limbic and fronto-temporo-parietal neocortical atrophy compared to HC with no specific between-group differences. AD subjects displayed a typical pattern of major temporal lobe atrophy which was associated with deficits in all cognitive domains. VBM and CT were more sensitive than SBM in identifying frontal and posterior cortical atrophy in PD-MCI as compared to PD-NC. Our data support the notion that the results of studies using different analytical methods cannot be compared directly. Only CT measures revealed some subtle differences between HC and PD-NC.

Non-invasive stimulation of the auditory feedback area for improved articulation in Parkinson's disease.

INTRODUCTION: Hypokinetic dysarthria (HD) is a common symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated acute effects of repetitive transcranial magnetic stimulation (rTMS) of the motor and auditory feedback area on HD in PD using acoustic analysis of speech. METHODS: We used 10 Hz and 1 Hz stimulation protocols and applied rTMS over the left orofacial primary motor area, the right superior temporal gyrus (STG), and over the vertex (a control stimulation site) in 16 PD patients with HD. A cross-over design was used. Stimulation sites and protocols were randomised across subjects and sessions. Acoustic analysis of a sentence reading task performed inside the MR scanner was used to evaluate rTMS-induced effects on motor speech. Acute fMRI changes due to rTMS were also analysed. RESULTS: The 1 Hz STG stimulation produced significant increases of the relative standard deviation of the 2nd formant (p = 0.019), i.e. an acoustic parameter describing the tongue and jaw movements. The effects were superior to the control site stimulation and were accompanied by increased resting state functional connectivity between the stimulated region and the right parahippocampal gyrus. The rTMS-induced acoustic changes were correlated with the reading task-related BOLD signal increases of the stimulated area (R = 0.654, p = 0.029). CONCLUSION: Our results demonstrate for the first time that low-frequency stimulation of the temporal auditory feedback area may improve articulation in PD and enhance functional connectivity between the STG and the cortical region involved in an overt speech control.

Theta Burst Stimulation Enhances Connectivity of the Dorsal Attention Network in Young Healthy Subjects: An Exploratory Study.

We examined effects of theta burst stimulation (TBS) applied over two distinct cortical areas (the right inferior frontal gyrus and the left superior parietal lobule) on the Stroop task performance in 20 young healthy subjects. Neural underpinnings of the behavioral effect were tested using fMRI. A single session of intermittent TBS of the left superior parietal lobule induced certain cognitive speed enhancement and significantly increased resting-state connectivity of the dorsal attention network. This is an exploratory study that prompts further research with multiple-session TBS in subjects with cognitive impairment.