The influence of Parkinson's disease on the functional connectivity of the motor loop of human basal ganglia

This study investigated the ability of individuals with Parkinson’s disease (PD) to synthesize temporal information across the senses, namely audition and vision. Auditory signals (A) are perceived as lasting longer than visual signals (V) when they are compared together, since attention is captured and sustained more easily than for visual information. We used the audiovisual illusion to probe for disturbances in brain networks that govern the resolution of time in two intersensory conditions that putatively differ in their attention demands. PD patients and controls judged the relative duration of successively presented pairs of unimodal (AA, VV) and crossmodal (VA, AV) signals whilst undergoing fMRI. There were four main findings. First, underestimation of time was exaggerated in PD when timing depended on controlled attention (AV), whereas subtle deficits were found when audition dominated and attention was more easily sustained (VA). Second, group differences in regional activation were observed only for the AV-unimodal comparison, where the PD group failed to modulate basal ganglia, anterior insula, and inferior cerebellum activity in accord with the timing condition. Third, the intersensory timing conditions were dissociated by patterns of abnormal functional connectivity. When intersensory timing emphasized controlled attention, patients showed weakened connectivity of the cortico-thalamus-basal ganglia (CTBG) circuit and the anterior insula with widespread cortical regions, yet enhanced cerebellar connectivity. When audition dominated intersensory timing, patients showed enhanced connectivity of CTBG elements, the anterior insula, and the cerebellum with the caudate tail and frontal cortex. Fourth, abnormal connectivity measures showed excellent sensitivity and specificity in accurately classifying subjects. The results demonstrate that intersensory timing deficits in PD were well characterized by context-dependent patterns of functional connectivity within a presumed core timing system (CTBG) and a ventral attention hub (anterior insula), and enhanced cerebellar connectivity irrespective of the hypothesized attention demands of timing.

Download Full-text

4302 Decreased structural basal ganglia motor loop connections in Vascular Parkinsonism compared to Parkinson’s disease and healthy aging

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.295 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 94-94

Author(s):

Christine Cooper ◽

Federico Rodriguez-Porcel ◽

Travis Turner ◽

Gonzalo Revuelta ◽

Jens Jensen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Healthy Aging ◽

Lower Body ◽

Vascular Parkinsonism ◽

Whole Brain ◽

Brain Connectome ◽

Clinical Scores ◽

Motor Loop

OBJECTIVES/GOALS: This study uses diffusion kurtosis imaging (DKI) to investigate the structural profiles of basal ganglia (BG) motor circuitry in Vascular Parkinsonism (VP), Parkinson’s disease (PD), and healthy aging controls (HC). VP is a clinical diagnosis of lower body predominant parkinsonism without significant benefit from levodopa. VP is distinct from PD, yet the concept of VP remains debated due to the inability of prior studies to identify specific causative changes. One reason for this may be limitations in measuring intricate BG connectivity in vivo. Given the predominant lower body parkinsonism symptoms in VP, we hypothesized that VP would be associated with decreased connectivity specifically within the BG motor loop. METHODS/STUDY POPULATION: We obtained DKI brain imaging in subjects with VP (N = 7), PD (N = 21), and HCs (N = 58), the latter of which had cardiovascular risk factors but no neurological symptoms. The VP and PD groups were evaluated by a parkinsonism-focused motor exam and brief cognitive testing. We compared BG motor loop connectivity between groups and investigated for correlation between connectivity and clinical scores. To account for differences in fiber counts due to the different imaging scanners and protocols between cohorts, we used a BG motor loop proportion, which was the ratio of the BG motor loop fiber count over a control loop, the visual processing pathway. We used Kruskal-Wallis rank sum test with post-hoc Dunn tests to assess imaging findings between subject groups, and Pearson’s correlation to look for correlation between clinical scores and fiber counts. RESULTS/ANTICIPATED RESULTS: The whole brain connectome showed the fewest number of fibers in VP, followed by PD, and then HC (p<0.0001). The BG motor loop proportion fiber count of the BG motor loop was lower in the VP group, compared to the PD and HC cohorts (p = 0.031). In the VP group, the whole brain connectome fiber count correlated with a gait and balance subscore of the Movement Disorders Society - Unified Parkinson Disease Rating Scale (R = −0.87, p = 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study indicates that VP is associated with decreased structural connectivity, with a disproportionate degree of loss in the BG motor circuitry. While the etiology for this susceptibility to injury and preferential damage to BG remains to be defined, these findings can provide an important starting point for a biological understanding of VP, and a potential future marker for diagnosis and tracking disease progression.

Download Full-text

Bilateral Functional Connectivity of the Basal Ganglia in Patients with Parkinson’s Disease and Its Modulation by Dopaminergic Treatment

PLoS ONE ◽

10.1371/journal.pone.0082762 ◽

2013 ◽

Vol 8 (12) ◽

pp. e82762 ◽

Cited By ~ 33

Author(s):

Simon Little ◽

Huiling Tan ◽

Anam Anzak ◽

Alek Pogosyan ◽

Andrea Kühn ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity

Download Full-text

Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease

NeuroImage Clinical ◽

10.1016/j.nicl.2015.04.003 ◽

2015 ◽

Vol 8 ◽

pp. 126-132 ◽

Cited By ~ 25

Author(s):

Michal Rolinski ◽

Ludovica Griffanti ◽

Konrad Szewczyk-Krolikowski ◽

Ricarda A.L. Menke ◽

Gordon K. Wilcock ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity

Download Full-text

Increased functional connectivity of thalamic subdivisions in patients with Parkinson’s disease

10.1101/19002139 ◽

2019 ◽

Author(s):

Conor Owens-Walton ◽

David Jakabek ◽

Brian D. Power ◽

Mark Walterfang ◽

Dennis Velakoulis ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity ◽

Dopaminergic Neurons ◽

Supplementary Motor Area ◽

Critical Role ◽

Dorsolateral Prefrontal ◽

Precise Role ◽

Prefrontal Cortices

AbstractParkinson’s disease (PD) affects 2-3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry.

Download Full-text

Function of the ‘direct’ and ‘indirect’ pathways of the basal ganglia motor loop: evidence from reciprocal aiming movements in Parkinson’s disease

Cognitive Brain Research ◽

10.1016/s0926-6410(00)00046-x ◽

2001 ◽

Vol 10 (3) ◽

pp. 329-332 ◽

Cited By ~ 10

Author(s):

Somporn Onla-or ◽

Carolee J. Winstein

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Aiming Movements ◽

Motor Loop

Download Full-text

Disrupted Functional Connectivity of Basal Ganglia across Tremor-Dominant and Akinetic/Rigid-Dominant Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2017.00360 ◽

2017 ◽

Vol 9 ◽

Cited By ~ 14

Author(s):

Xiaojun Guan ◽

Qiaoling Zeng ◽

Tao Guo ◽

Jiaqiu Wang ◽

Min Xuan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity

Download Full-text

Distinct large-scale networks are associated with motor and nonmotor symptoms in Parkinson’s disease

10.1101/2020.05.13.093724 ◽

2020 ◽

Author(s):

Sule Tinaz ◽

Serageldin Kamel ◽

Sai S. Aravala ◽

Mine Sezgin ◽

Mohamed Elfil ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity ◽

Large Scale ◽

Emotional Dysregulation ◽

Disease Stage ◽

Nonmotor Symptoms ◽

Large Scale Networks ◽

Brain Data

ABSTRACTParkinson’s disease (PD) is characterized clinically by various motor and nonmotor symptoms. The underlying neuroanatomical correlates of nonmotor symptoms in PD remain poorly understood. We investigated the differences and commonalities in the neuroanatomical correlates 1) between highly prevalent nonmotor features including fatigue, anxiety, depression, and apathy, and 2) between these nonmotor features and motor severity in nondemented subjects with mild PD (Hoehn & Yahr disease stage 2) using structural and functional magnetic resonance imaging. Compared to matched controls, the PD group showed atrophy in the basal ganglia and superior frontal cortex. Motor severity correlated with cortical thinning in frontotemporal regions, as well as with reduced functional connectivity between the frontostriatal and cerebellar networks. The composite nonmotor symptom severity did not show any correlation with the structural brain data, but correlated with reduced functional connectivity in a large-scale network consisting of frontostriatal, parietotemporal, and cerebellar nodes. The individual components of the nonmotor symptoms also mapped onto specific neural networks. Our study shows that motor and nonmotor features in PD are associated with distinct large-scale networks. The basal ganglia and cerebellum are core regions in all of these networks. The abnormal functional connectivity in the nonmotor network seems to be related to cognitive and emotional dysregulation and may have implications for future cognitive decline in PD.

Download Full-text

Functional connectivity in Parkinson’s disease candidates for deep brain stimulation

npj Parkinson s Disease ◽

10.1038/s41531-021-00268-6 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Luigi Albano ◽

Federica Agosta ◽

Silvia Basaia ◽

Camilla Cividini ◽

Tanja Stojkovic ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Basal Ganglia ◽

Functional Connectivity ◽

Brain Stimulation ◽

Regional Analysis ◽

Clustering Coefficient ◽

Clinical Indication ◽

Deep Brain

AbstractThis study aimed to identify functional neuroimaging patterns anticipating the clinical indication for deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). A cohort of prospectively recruited patients with PD underwent neurological evaluations and resting-state functional MRI (RS-fMRI) at baseline and annually for 4 years. Patients were divided into two groups: 19 patients eligible for DBS over the follow-up and 41 patients who did not meet the criteria to undergo DBS. Patients selected as candidates for DBS did not undergo surgery at this stage. Sixty age- and sex-matched healthy controls performed baseline evaluations. Graph analysis and connectomics assessed global and local topological network properties and regional functional connectivity at baseline and at each time point. At baseline, network analysis showed a higher mean nodal strength, local efficiency, and clustering coefficient of the occipital areas in candidates for DBS over time relative to controls and patients not eligible for DBS. The occipital hyperconnectivity pattern was confirmed by regional analysis. At baseline, a decreased functional connectivity between basal ganglia and sensorimotor/frontal networks was found in candidates for DBS compared to patients not eligible for surgery. In the longitudinal analysis, patient candidate for DBS showed a progressively decreased topological brain organization and functional connectivity, mainly in the posterior brain networks, and a progressively increased connectivity of basal ganglia network compared to non-candidates for DBS. RS-fMRI may support the clinical indication to DBS and could be useful in predicting which patients would be eligible for DBS in the earlier stages of PD.

Download Full-text