scholarly journals Dopamine Depletion Alters Macroscopic Network Dynamics in Parkinson’s Disease

2018 ◽  
Author(s):  
James M. Shine ◽  
Peter T. Bell ◽  
Elie Matar ◽  
Russell A. Poldrack ◽  
Simon J.G. Lewis ◽  
...  

AbstractParkinson’s disease is primarily characterised by diminished dopaminergic function, however the impact of these impairments on large-scale brain dynamics remains unclear. It has been difficult to disentangle the direct effects of Parkinson’s disease from compensatory changes that reconfigure the functional signature of the whole brain network. To examine the causal role of dopamine depletion in network-level topology, we investigated time-varying network structure in 37 individuals with idiopathic Parkinson’s disease, both ‘On’ and ‘Off’ dopamine replacement therapy, along with 50 age-matched, healthy control subjects using resting-state functional MRI. By tracking dynamic network-level topology, we found that the Parkinson’s disease ‘Off’ state was associated with greater network-level integration than in the ‘On’ state. The extent of integration in the ‘Off’ state inversely correlated with motor symptom severity, suggesting that a shift toward a more integrated network topology may be a compensatory mechanism associated with preserved motor function in the dopamine depleted ‘Off’ state. Furthermore, we were able to demonstrate that measures of both cognitive and brain reserve (i.e., premorbid intelligence and whole brain grey matter volume) had a positive relationship with the relative increase in network integration observed in the dopaminergic ‘Off’ state. This suggests that each of these factors plays an important role in promoting network integration in the dopaminergic ‘Off’ state. Our findings provide a mechanistic basis for understanding the PD ‘Off’ state and provide a further conceptual link with network-level reconfiguration. Together, our results highlight the mechanisms responsible for pathological and compensatory change in Parkinson’s disease.

2021 ◽  
Author(s):  
Julie Péron ◽  
Philippe Voruz ◽  
Jordan Pierce ◽  
Kévin Ahrweiller ◽  
Claire Haegelen ◽  
...  

Abstract Risk factors for long-term non-motor disorders and quality of life following subthalamic nucleus deep-brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson’s disease.Data were extracted for 52 patients with Parkinson’s disease (half with left-sided motor symptoms and half with right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests and neuropsychiatric and quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with left-sided motor symptoms. Performances of patients with right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients’ quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson’s disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.


2019 ◽  
Vol 34 (6) ◽  
pp. 969-969
Author(s):  
L Sabbah-Talasazan ◽  
J Miller ◽  
J Wertheimer

Abstract Objective Non-motor Symptoms (NMS) in Parkinson’s Disease (PD) are known to be diverse and may include cognitive, psychiatric and sleep disturbance, fatigue, and autonomic disorders (e.g., cardiovascular dysregulation, orthostatic hypotension, thermo-dysregulation, sexual dysfunction, urinary and bowel dyscontrol). The aim of this study was to define the NMS profile in a large sample of PD patients with and without Deep Brain Stimulation (DBS) and its impact on quality of life (QOL). Method Cross-sectional, survey-based research design was used. 1,164 individuals with PD participated in this survey: 275 participants who underwent DBS and 889 without DBS. Participants completed the Non-Motor Symptom Scale (NMSS) and answered questions assessing the impact of NMS on everyday life. Participants were divided into younger (ages 50-69) and older (ages 70+) age cohorts and disease duration cohorts with early stage ( < 6 years) and advanced stage (6-10 years; 11+ years) groups. Results 24 out of 31 NMS categories were experienced by more than 50% of the participants. Urination difficulty, fatigue, sleep, constipation, and cognitive difficulties were symptoms most frequently reported to adversely impact day-to-day living, and cognitive difficulties followed by sleep disturbance had the strongest impact to quality of life. Conclusions NMS burden drives quality of life for many individuals and has remained a relatively new frontier for exploration, at least in depth and scope as it relates to assessment and treatment of NMS. Management of NMS remains an unmet need for individuals with PD. Implications for neuropsychologists are discussed.


2011 ◽  
Vol 18 (1) ◽  
pp. 108-117 ◽  
Author(s):  
Karina Stavitsky ◽  
Sandy Neargarder ◽  
Yelena Bogdanova ◽  
Patrick McNamara ◽  
Alice Cronin-Golomb

AbstractIn healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention and executive function, memory and psychomotor function. In both groups, poor sleep was associated with worse performance on tests of attention/executive function but not memory or psychomotor function. In the PD group, attention/executive function was predicted by sleep efficiency, whereas memory and psychomotor function were not predicted by sleep quality. Psychomotor and memory function were predicted by motor symptom severity. This study is the first to demonstrate that sleep quality in PD is significantly correlated with cognition and that it differentially impacts attention and executive function, thereby furthering our understanding of the link between sleep and cognition. (JINS, 2012, 18, 108–117)


2021 ◽  
Vol 11 (9) ◽  
pp. 1224
Author(s):  
Kaoru Kinugawa ◽  
Tomoo Mano ◽  
Kazuma Sugie

Pain is an important non-motor symptom of Parkinson’s disease (PD). It negatively impacts the quality of life. However, the pathophysiological mechanisms underlying pain in PD remain to be elucidated. This study sought to use electroencephalographic (EEG) coherence analysis to compare neuronal synchronization in neuronal networks between patients with PD, with and without pain. Twenty-four patients with sporadic PD were evaluated for the presence of pain. Time-frequency and coherence analyses were performed on their EEG data. Whole-brain and regional coherence were calculated and compared between pain-positive and pain-negative patients. There was no significant difference in the whole-brain coherence between the pain-positive and pain-negative groups. However, temporal–temporal coherence differed significantly between the two groups (p = 0.031). Our findings indicate that aberrant synchronization of inter-temporal regions is involved in PD-related pain. This will further our understanding of the mechanisms underlying pain in PD.


2021 ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Joana B. Pereira

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by topological changes in large-scale functional brain networks. These networks are commonly analysed using undirected correlations between the activation signals of brain regions. However, this approach suffers from an important drawback: it assumes that brain regions get activated at the same time, despite previous evidence showing that brain activation features causality, with signals being typically generated in one region and then propagated to other ones. Thus, in order to address this limitation, in this study we developed a new method to assess whole-brain directed functional connectivity in patients with PD and healthy controls using anti-symmetric delayed correlations, which capture better this underlying causality. To test the potential of this new method, we compared it to standard connectivity analyses based on undirected correlations. Our results show that whole-brain directed connectivity identifies widespread changes in the functional networks of PD patients compared to controls, in contrast to undirected methods. These changes are characterized by increased global efficiency, clustering and transitivity as well as lower modularity. In addition, changes in the directed connectivity patterns in the precuneus, thalamus and superior frontal gyrus were associated with motor, executive and memory deficits in PD patients. Altogether, these findings suggest that directional brain connectivity is more sensitive to functional network changes occurring in PD compared to standard methods. This opens new opportunities for the analysis of brain connectivity and the development of new brain connectivity markers to track PD progression.


2021 ◽  
Author(s):  
Cécilia Tremblay ◽  
Johannes Frasnelli

Abstract Olfactory dysfunction (OD) is a highly frequent early non-motor symptom of Parkinson’s disease (PD). An important step to potentially use OD for the development of early diagnostic tools of PD is to differentiate PD-related OD from other forms of non-parkinsonian OD (NPOD: post-viral, sinunasal, post-traumatic and idiopathic OD). Measuring non-olfactory chemosensory modalities, especially the trigeminal system, may allow to characterize a PD-specific olfactory profile.We here review the literature on PD-specific chemosensory alteration patterns compared to NPOD. Specifically, we focused on the impact of PD on the trigeminal system and particularly on the interaction between olfactory and trigeminal systems. As this interaction is seemingly affected in a disease-specific manner, we propose a model of interaction between both chemosensory systems that is distinct for PD-related OD and NPOD. These patterns of chemosensory impairment still need to be confirmed in prodromal PD; nevertheless, appropriate chemosensory tests may eventually help to develop diagnostic tools to identify individuals at risks for PD.


2021 ◽  
Author(s):  
Haoting Wu ◽  
Cheng Zhou ◽  
Tao Guo ◽  
Jingjing Wu ◽  
Xueqin Bai ◽  
...  

Abstract Background The functional alternation of distinct brain networks contribute to motor impairment in Parkinson’s disease (PD) remains unclear. Identifying a whole-brain connectome-based predictive model (CPM) in drug-naïve patients and verifying its predictability among drug-managed patients would be helpful to detect generalizable brain-behavior association and reflect intrinsic functional underpinning of motor impairment. Methods Resting-state functional data of 47 drug-naïve patients were enrolled to construct a predictive model by using the CPM approach, which was subsequently validated in 115 drug-managed patients. The severity of motor impairment was assessed by calculating Unified Parkinson’s Disease Rating Scale part III (UPDRS III) scores. Predictive performance was evaluated with the correlation coefficient(rtrue) and the mean squared error (MSE) between observed and predicted scores. Results A CPM for predicting individual motor impairment in drug-naïve PD was identified with significant performance (rtrue=0.845, p < 0.001, MSE = 137.57). Two connection patterns were recognized according to the correlation coefficients between the connections’ strength and motor impairment severity. The negative motor-impairment-related network contained more within-network connections in the motor, visual-related, and default mode networks, while the positive motor-impairment-related network was constructed mostly with between-network connections coupled motor-visual, motor-limbic, and motor-basal ganglia networks. The predictability of constructed model was further confirmed in drug-managed patients (r = 0.209, p = 0.025, MSE = 182.96), suggesting generalizability in PD patients with lasting dopaminergic medication influence. Conclusions This study identified a whole-brain connectome-based model that could predict the severity of motor impairment for PD. The connection patterns generated from the model reflected that functional segregation of motor, visual-related, and default mode networks play an important role in PD motor impairment, and higher connections coupling motor and non-motor regions might demonstrate a compensatory mechanism to overcome motor impairment.


2018 ◽  
Vol 28 (8) ◽  
pp. 3296-3305 ◽  
Author(s):  
Pei-Lin Lee ◽  
Kun-Hsien Chou ◽  
Cheng-Hsien Lu ◽  
Hsiu-Ling Chen ◽  
Nai-Wen Tsai ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Wendy L. Arnott ◽  
David A. Copland ◽  
Helen J. Chenery ◽  
Bruce E. Murdoch ◽  
Peter A. Silburn ◽  
...  

Two semantic priming tasks, designed to isolate automatic and controlled semantic activation, were utilized to investigate the impact of dopamine depletion on semantic processing in Parkinson's disease (PD). Seven people with PD (tested whilst on and off levodopa medication) and seven healthy adults participated in the study. The healthy adult participants demonstrated intact automatic and controlled semantic activation. Aberrant controlled semantic activation was observed in the PD group on levodopa; however, automatic semantic activation was still evident. In contrast, automatic semantic activation was not evident in the PD group off levodopa. These results further clarify the impact of PD on semantic processing, demonstrating that dopamine depletion can cause disturbances in both automatic and controlled semantic activation.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Patrick McNamara ◽  
Karina Stavitsky ◽  
Raymon Durso ◽  
Erica Harris

Purpose. To assess the impact of clinical variables on social skills and behaviors in Parkinson's disease (PD) patients and patient versus examiner estimates of social functioning.Methods. Twenty-eight patients with PD and 32 controls with chronic disease were assessed with a battery of neuropsychologic, personality, mood, and social function tests.Results. Patients' estimates of their own social functioning were not significantly different from examiners' estimates. The impact of clinical variables on social functioning in PD revealed depression to be the strongest association of social functioning in PD on both the patient and the examiner version of the Social Adaptation Self-Evaluation Scale.Conclusions. PD patients appear to be well aware of their social strengths and weaknesses. Depression and motor symptom severity are significant predictors of both self- and examiner reported social functioning in patients with PD. Assessment and treatment of depression in patients with PD may improve social functioning and overall quality of life.


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