Dataset Information

Compensatory dopaminergic-cholinergic interactions in conflict processing: Evidence from patients with Parkinson's disease.

ABSTRACT: Executive functions are complex both in the cognitive operations involved and in the neural structures and functions that support those operations. This complexity makes executive function highly vulnerable to the detrimental effects of aging, brain injury, and disease, but may also open paths to compensation. Neural compensation is often used to explain findings of additional or altered patterns of brain activations by older adults or patient populations compared to young adults or healthy controls, especially when associated with relatively preserved performance. Here we test the hypothesis of an alternative form of compensation, between different neuromodulator systems. 135 patients with Parkinson's Disease (PD) completed vesicular monoamine transporter type2 (VMAT2) and acetylcholinesterase PET scanning to assess the integrity of nigrostriatal dopaminergic, thalamic cholinergic, and cortical cholinergic pathways, and a behavioral test (Stroop + task-switching) that puts high demands on conflict processing, an important aspect of executive control. Supporting the compensatory hypothesis, regression models controlling for age and other covariates revealed an interaction between caudate dopamine and cortical cholinergic integrity: Cortical cholinergic integrity was a stronger predictor of conflict processing in patients with relatively low caudate dopaminergic function. These results suggest that although frontostriatal dopaminergic function plays a central role in executive control, cholinergic systems may also make an important contribution. The present results suggest potential pathways for remediation, and that the appropriate interventions for each patient may depend on their particular profile of decline. Furthermore, they help to elucidate the brain systems that underlie executive control, which may be important for understanding other disorders as well as executive function in healthy adults.

SUBMITTER: Kim K

PROVIDER: S-EPMC6041186 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Compensatory dopaminergic-cholinergic interactions in conflict processing: Evidence from patients with Parkinson's disease.

Kim Kamin K Bohnen Nicolaas I NI Müller Martijn L T M MLTM Lustig Cindy C

NeuroImage 20180111

Executive functions are complex both in the cognitive operations involved and in the neural structures and functions that support those operations. This complexity makes executive function highly vulnerable to the detrimental effects of aging, brain injury, and disease, but may also open paths to compensation. Neural compensation is often used to explain findings of additional or altered patterns of brain activations by older adults or patient populations compared to young adults or healthy cont ...[more]

PMID: 29337277

Similar Datasets

Project description:The most common genetic risk factors for Parkinson's disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with GBA1 mutations (GBA-PD) exhibit earlier age of onset and faster disease progression with more severe cognitive impairments, postural instability and gait problems. These GBA-PD features suggest more severe cholinergic system pathologies. PET imaging with the vesicular acetylcholine transporter ligand 18F-F-fluoroethoxybenzovesamicol (18F-FEOBV PET) provides the opportunity to investigate cholinergic changes and their relationship to clinical features in GBA-PD. The study investigated 123 newly diagnosed, treatment-naïve Parkinson's disease subjects-with confirmed presynaptic dopaminergic deficits on PET imaging. Whole-gene GBA1 sequencing of saliva samples was performed to evaluate GBA1 variants. Patients underwent extensive neuropsychological assessment of all cognitive domains, motor evaluation with the Unified Parkinson's Disease Rating Scale, brain MRI, dopaminergic PET to measure striatal-to-occipital ratios of the putamen and 18F-FEOBV PET. We investigated differences in regional cholinergic innervation between GBA-PD carriers and non-GBA1 mutation carriers (non-GBA-PD), using voxel-wise and volume of interest-based approaches. The degree of overlap between t-maps from two-sample t-test models was quantified using the Dice similarity coefficient. Seventeen (13.8%) subjects had a GBA1 mutation. No significant differences were found in clinical features and dopaminergic ratios between GBA-PD and non-GBA-PD at diagnosis. Lower 18F-FEOBV binding was found in both the GBA-PD and non-GBA-PD groups compared to controls. Dice (P < 0.05, cluster size 100) showed good overlap (0.7326) between the GBA-PD and non-GBA-PD maps. GBA-PD patients showed more widespread reduction in 18F-FEOBV binding than non-GBA-PD when compared to controls in occipital, parietal, temporal and frontal cortices (P < 0.05, FDR-corrected). In volume of interest analyses (Bonferroni corrected), the left parahippocampal gyrus was more affected in GBA-PD. De novo GBA-PD show a distinct topography of regional cholinergic terminal ligand binding. Although the Parkinson's disease groups were not distinguishable clinically, in comparison to healthy controls, GBA-PD showed more extensive cholinergic denervation compared to non-GBA-PD. A larger group is needed to validate these findings. Our results suggest that de novo GBA-PD and non-GBA-PD show differential patterns of cholinergic system changes before clinical phenotypic differences between carriers versus non-carrier groups are observable.

Project description:To examine regional cerebral vesicular acetylcholine transporter (VAChT) ligand [18F]fluoroethoxybenzovesamicol ([18F]-FEOBV) PET binding in Parkinson' disease (PD) patients with and without vestibular sensory conflict deficits (VSCD). To examine associations between VSCD-associated cholinergic brain deficits and postural instability and gait difficulties (PIGD). PD persons (M70/F22; mean age 67.6 ± 7.4 years) completed clinical assessments for imbalance, falls, freezing of gait (FoG), modified Romberg sensory conflict testing, and underwent VAChT PET. Volumes of interest (VOI)-based analyses included detailed thalamic and cerebellar parcellations. VSCD-associated VAChT VOI selection used stepwise logistic regression analysis. Vesicular monoamine transporter type 2 (VMAT2) [11C]dihydrotetrabenazine (DTBZ) PET imaging was available in 54 patients. Analyses of covariance were performed to compare VSCD-associated cholinergic deficits between patients with and without PIGD motor features while accounting for confounders. PET sampling passed acceptance criteria in 73 patients. This data-driven analysis identified cholinergic deficits in five brain VOIs associating with the presence of VSCD: medial geniculate nucleus (MGN) (P < 0.0001), para-hippocampal gyrus (P = 0.0043), inferior nucleus of the pulvinar (P = 0.047), fusiform gyrus (P = 0.035) and the amygdala (P = 0.019). Composite VSCD-associated [18F]FEOBV-binding deficits in these 5 regions were significantly lower in patients with imbalance (- 8.3%, F = 6.5, P = 0.015; total model: F = 5.1, P = 0.0008), falls (- 6.9%, F = 4.9, P = 0.03; total model F = 4.7, P = 0.0015), and FoG (- 14.2%, F = 9.0, P = 0.0043; total model F = 5.8, P = 0.0003), independent of age, duration of disease, gender and nigrostriatal dopaminergic losses. Post hoc analysis using MGN VAChT binding as the single cholinergic VOI demonstrated similar significant associations with imbalance, falls and FoG. VSCD-associated cholinergic network changes localize to distinct structures involved in multi-sensory, in particular vestibular, and multimodal cognitive and motor integration brain regions. Relative clinical effects of VSCD-associated cholinergic network deficits were largest for FoG followed by postural imbalance and falls. The MGN was the most significant region identified.

Dataset Information

Compensatory dopaminergic-cholinergic interactions in conflict processing: Evidence from patients with Parkinson's disease.

Publications

Compensatory dopaminergic-cholinergic interactions in conflict processing: Evidence from patients with Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets