Cortico-basal white matter alterations occurring in Parkinson's disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Isaacs BR
PROVIDER: S-EPMC6699705 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Cortico-basal white matter alterations occurring in Parkinson's disease.
Isaacs Bethany R BR Trutti Anne C AC Pelzer Esther E Tittgemeyer Marc M Temel Yasin Y Forstmann Birte U BU Keuken Max C MC
PloS one 20190819 8
Magnetic resonance imaging studies typically use standard anatomical atlases for identification and analyses of (patho-)physiological effects on specific brain areas; these atlases often fail to incorporate neuroanatomical alterations that may occur with both age and disease. The present study utilizes Parkinson's disease and age-specific anatomical atlases of the subthalamic nucleus for diffusion tractography, assessing tracts that run between the subthalamic nucleus and a-priori defined cortic ...[more]
Similar Datasets
Project description:The ability to inhibit automatic versus voluntary saccade commands in demanding situations can be impaired in neurodegenerative diseases such as Huntington's disease (HD). These deficits could result from disruptions in the interaction between basal ganglia and the saccade control system. To investigate voluntary oculomotor control deficits related to the cortico-basal circuitry, we evaluated early HD patients using an interleaved pro- and anti-saccade task that requires flexible executive control to generate either an automatic response (look at a peripheral visual stimulus) or a voluntary response (look away from the stimulus in the opposite direction). The impairments of HD patients in this task are mainly attributed to degeneration in the striatal medium spiny neurons leading to an over-activation of the indirect-pathway thorough the basal ganglia. However, some studies have proposed that damage outside the indirect-pathway also contribute to executive and saccade deficits. We used the interleaved pro- and anti-saccade task to study voluntary saccade inhibition deficits, Voxel-based morphometry and Tract-based spatial statistic to map cortico-basal ganglia circuitry atrophy in HD. HD patients had voluntary saccade inhibition control deficits, including increased regular-latency anti-saccade errors and increased anticipatory saccades. These deficits correlated with white-matter atrophy in the inferior fronto-occipital fasciculus, anterior thalamic radiation, anterior corona radiata and superior longitudinal fasciculus. These findings suggest that cortico-basal ganglia white-matter atrophy in HD, disrupts the normal connectivity in a network controlling voluntary saccade inhibitory behavior beyond the indirect-pathway. This suggests that in vivo measures of white-matter atrophy can be a reliable marker of the progression of cognitive deficits in HD.
| S-EPMC5472191 | biostudies-literature
Project description:IntroductionWhile progressive MRI brain changes characterize advanced Parkinson's disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment.MethodsTwenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin.ResultsPD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p<0.02) and left (p<0.01) flipped data. The analysis of original, un-flipped data demonstrated elevated axial diffusivity (p<0.01) in the superior and anterior corona radiata, internal capsule, and external capsule in the left hemisphere of PD relative to HC, while higher mean and radial diffusivity were discovered in the right (p<0.02 and p<0.03, respectively) and left (p<0.02 and p<0.02, respectively) in the fronto-temporal WM utilizing flipped data.ConclusionsPD patients without cognitive impairment and GM atrophy demonstrated widespread alterations of WM microstructure. Thus, WM impairment in PD might be a sensitive sign preceding the neuronal loss in associated GM regions.
| S-EPMC5755732 | biostudies-literature
Project description:Parkinson's disease (PD) patients with postural instability and gait disorder phenotype (PIGD) are at high risk of cognitive deficits compared to those with tremor dominant phenotype (TD). Alterations of white matter (WM) integrity can occur in patients with normal cognitive functions (PD-N). However, the alterations of WM integrity related to cognitive functions in PD-N, especially in these two motor phenotypes, remain unclear. Diffusion tensor imaging (DTI) is a non-invasive neuroimaging method to evaluate WM properties and by applying DTI tractography, one can identify WM tracts connecting functional regions. Here, we 1) compared the executive function (EF) in PIGD phenotype with normal cognitive functions (PIGD-N) and TD phenotype with normal cognitive functions (TD-N) phenotypes; 2) used DTI tractography to evaluated differences in WM alterations between these two phenotypes within a task-based functional network; and 3) examined the WM integrity alterations related to EF in a whole brain network for PD-N patients regardless of phenotypes. Thirty-four idiopathic PD-N patients were classified into two groups based on phenotypes: TD-N and PIGD-N, using an algorithm based on UPDRS part III. Neuropsychological tests were used to evaluate patients' EF, including the Trail making test part A and B, the Stroop color naming, the Stroop word naming, the Stroop color-word interference task, as well as the FAS verbal fluency task and the animal category fluency tasks. DTI measures were calculated among WM regions associated with the verbal fluency network defined from previous task fMRI studies and compared between PIGD-N and TD-N groups. In addition, the relationship of DTI measures and verbal fluency scores were evaluated for our full cohort of PD-N patients within the whole brain network. These values were also correlated with the scores of the FAS verbal fluency task. Only the FAS verbal fluency test showed significant group differences, having lower scores in PIGD-N when compared to TD-N phenotype (p < 0.05). Compared to the TD-N, PIGD-N group exhibited significantly higher MD and RD in the tracts connecting the left superior temporal gyrus and left insula, and those connecting the right pars opercularis and right insula. Moreover, compared to TD-N, PIGD-N group had significantly higher RD in the tracts connecting right pars opercularis and right pars triangularis, and the tracts connecting right inferior temporal gyrus and right middle temporal gyrus. For the entire PD-N cohort, FAS verbal fluency scores positively correlated with MD in the superior longitudinal fasciculus (SLF). This study confirmed that PIGD-N phenotype has more deficits in verbal fluency task than TD-N phenotype. Additionally, our findings suggest: (1) PIGD-N shows more microstructural changes related to FAS verbal fluency task when compared to TD-N phenotype; (2) SLF plays an important role in FAS verbal fluency task in PD-N patients regardless of motor phenotypes.
| S-EPMC7750296 | biostudies-literature
Project description:Using a fixel-based analysis (FBA), we assessed the fiber-specific white matter (WM) alterations in nonmedicated patients with early-stage Parkinson's disease (PD) with tremor-dominant (TD; n = 53; mean age, 61.7 ± 8.7 years) and postural instability and gait disorder (PIGD; n = 27; mean age, 57.8 ± 8.1 years) motor subtypes and age- and sex-matched healthy controls (HC; n = 43; mean age, 61.6 ± 9.2 years) from Parkinson's Progression Markers Initiative dataset. FBA revealed significantly increased macrostructural fiber cross section and a combination of fiber density and cross section metrics within the corticospinal tract in patients with TD-PD compared with HC. Nonetheless, no significant changes in FBA-derived metrics were found in patients with PIGD-PD compared with HC or patients with TD-PD. Our results may provide evidence of WM neural compensation mechanisms in patients with TD-PD marked by increases in fiber bundle size and the ability to relay information between brain regions.
| S-EPMC8233424 | biostudies-literature
Project description:IntroductionDisruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease.MethodsFifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8 ± 6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24±2 months], and second follow-up [after a mean of 40 ± 3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3 ± 5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p < 0.05 was considered statistically significant.Results and discussionsEarly degeneration in the splenium of corpus callosum was identified as a typical alteration of Parkinson's disease over time. At follow-up, we observed significant FDC reductions compared with baseline in white matter, noticeably in corpus callosum; tapetum; cingulum, posterior thalamic radiation, corona radiata, and sagittal stratum. We also identified significant FC decreases that reflected damage to white matter structures involved in Parkinson's disease -related pathways. Fixel-based metrics were found to relate with a deterioration of 39-item Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale and activity of daily living. A Parkinson's disease -facilitated aging effect was observed in terms of white matter disruption.ConclusionThis study provides a thorough fixel-based profile of longitudinal white matter alterations occurring in patients with Parkinson's disease and new evidence of FC as an important role in white matter degeneration in this setting.
| S-EPMC6889638 | biostudies-literature
Project description:BackgroundApathy is the neuropsychiatric syndrome that correlates most highly with Huntington's disease progression, and, like early patterns of neurodegeneration, is associated with lesions to cortico-striatal connections. However, due to its multidimensional nature and elusive etiology, treatment options are limited.ObjectivesTo disentangle underlying white matter microstructural correlates across the apathy spectrum in Huntington's disease.MethodsForty-six Huntington's disease individuals (premanifest (N?=?22) and manifest (N?=?24)) and 35 healthy controls were scanned at 3-tesla and underwent apathy evaluation using the short-Problem Behavior Assessment and short-Lille Apathy Rating Scale, with the latter being characterized into three apathy domains, namely emotional, cognitive, and auto-activation deficit. Diffusion tensor imaging was used to study whether individual differences in specific cortico-striatal tracts predicted global apathy and its subdomains.ResultsWe elucidate that apathy profiles may develop along differential timelines, with the auto-activation deficit domain manifesting prior to motor onset. Furthermore, diffusion tensor imaging revealed that inter-individual variability in the disruption of discrete cortico-striatal tracts might explain the heterogeneous severity of apathy profiles. Specifically, higher levels of auto-activation deficit symptoms significantly correlated with increased mean diffusivity in the right uncinate fasciculus. Conversely, those with severe cognitive apathy demonstrated increased mean diffusivity in the right frontostriatal tract and left dorsolateral prefrontal cortex to caudate nucleus tract.ConclusionsThe current study provides evidence that white matter correlates associated with emotional, cognitive, and auto-activation subtypes may elucidate the heterogeneous nature of apathy in Huntington's disease, as such opening a door for individualized pharmacological management of apathy as a multidimensional syndrome in other neurodegenerative disorders.
| S-EPMC6700450 | biostudies-literature
Project description:In Parkinson's disease (PD), pathological microstructural changes occur and such changes might be detected using diffusion magnetic resonance imaging (dMRI). However, it is unclear whether dMRI improves PD diagnosis or helps differentiating between phenotypes, such as postural instability gait difficulty (PIGD) and tremor dominant (TD) PD. We included 105 patients with PD and 44 healthy controls (HC), all of whom underwent dMRI as part of the prospective Swedish BioFINDER study. Diffusion kurtosis imaging (DKI) and neurite density imaging (NDI) analyses were performed using regions of interest in the basal ganglia, the thalamus, the pons and the midbrain as well as tractography of selected white matter tracts. In the putamen, the PD group showed increased mean diffusivity (MD) (p = .003), decreased fractional anisotropy (FA) (p = .001) and decreased mean kurtosis (MK), compared to HC (p = .024). High MD and a low MK in the putamen were associated with more severe motor and cognitive symptomatology (p < .05). Also, patients with PIGD exhibited increased MD in the putamen compared to the TD patients (p = .009). In the thalamus, MD was increased (p = .001) and FA was decreased (p = .032) in PD compared to HC. Increased MD and decreased FA correlated negatively with motor speed and balance (p < .05). In the superior longitudinal fasciculus (SLF), MD (p = .019) and fiso were increased in PD compared to HC (p = .03). These changes correlated negatively with motor speed (p < .002) and balance (p < .037). However, most of the observed changes in PD were also present in cases with either multiple system atrophy (n = 11) or progressive supranuclear palsy (n = 10). In conclusion, PD patients exhibit microstructural changes in the putamen, the thalamus, and the SLF, which are associated with worse disease severity. However, the dMRI changes are not sufficiently specific to improve the diagnostic work-up of PD. Longitudinal studies should evaluate whether dMRI measures can be used to track disease progression.
| S-EPMC4928807 | biostudies-literature
Project description:Postmortem studies of Parkinson's disease (PD) suggest that Lewy body pathology accumulates in a predictable topographical sequence, beginning in the olfactory bulb, followed by caudal brainstem, substantia nigra, limbic cortex, and neocortex. Diffusion-weighted imaging (DWI) is sensitive, if not specific, to early disease-related white matter (WM) change in a variety of traumatic and degenerative brain diseases. Although numerous cross-sectional studies have reported DWI differences in cerebral WM in PD, only a few longitudinal studies have investigated whether DWI change exceeds that of normal aging or coincides with regional Lewy body accumulation. This study mapped regional differences in the rate of DWI-based microstructural change between 29 PD patients and 43 age-matched controls over 18 months. Iterative within- and between-subject tensor-based registration was completed on motion- and eddy current-corrected DWI images, then baseline versus follow-up difference maps of fractional anisotropy, mean, radial, and axial diffusivity were analyzed in the Biological Parametric Mapping toolbox for MATLAB. This analysis showed that PD patients had a greater decline in WM integrity in the rostral brainstem, caudal subcortical WM, and cerebellar peduncles, compared with controls. In addition, patients with unilateral clinical signs at baseline experienced a greater rate of WM change over the 18-month study than patients with bilateral signs. These findings suggest that rate of WM microstructural change in PD exceeds that of normal aging and is maximal during early stage disease. In addition, the neuroanatomic locations (rostral brainstem and subcortical WM) of accelerated WM change fit with current theories of topographic disease progression.
| S-EPMC6128734 | biostudies-literature
Project description:Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by dopamine deficiency. To elucidate network-level changes through the cortico-basal ganglia pathways in PD, we recorded neuronal activity in PD monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We applied electrical stimulation to the motor cortices and examined responses in the internal (GPi) and external (GPe) segments of the globus pallidus, the output and relay nuclei of the basal ganglia, respectively. In the normal state, cortical stimulation induced a triphasic response composed of early excitation, inhibition, and late excitation in the GPi and GPe. In the PD state, cortically evoked inhibition in the GPi mediated by the cortico-striato-GPi "direct" pathway was largely diminished, whereas late excitation in the GPe mediated by the cortico-striato-GPe-subthalamo (STN)-GPe pathway was elongated. l-DOPA treatment ameliorated PD signs, particularly akinesia/bradykinesia, and normalized cortically evoked responses in both the GPi and GPe. STN blockade by muscimol injection ameliorated the motor deficit and unmasked cortically evoked inhibition in the GPi. These results suggest that information flow through the direct pathway responsible for the initiation of movements is largely reduced in PD and fails to release movements, resulting in akinesia/bradykinesia. Restoration of the information flow through the direct pathway recovers execution of voluntary movements.
| S-EPMC8568006 | biostudies-literature
Project description:Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression.
| S-EPMC4827723 | biostudies-literature