scholarly journals Bilateral but not unilateral subthalamic stimulation promotes apathy: a translational study in rodents and Parkinson’s disease patients

2020 ◽  
Author(s):  
Yvan Vachez ◽  
Marie Bahout ◽  
Robin Magnard ◽  
Pierre-Maxime David ◽  
Carole Carcenac ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Acute Effect ◽  
Recent Experimental Data ◽  
Translational Study ◽  
Clinical Center ◽  
Subthalamic Stimulation ◽  
Operative Assessment ◽  
Stn Dbs

ABSTRACTApathy is frequently reported in Parkinson’s disease (PD) patients under subthalamic nucleus deep brain stimulation (STN-DBS). The prevailing clinical view for apathy following STN-DBS is the reduction of dopaminergic medication. However, few clinical reports and recent experimental data suggested the pathogenicity of bilateral STN-DBS on motivation, challenging the leading opinion. Here, we investigate whether bilateralism of STN-DBS influences apathy outcome after STN-DBS, combining pre-clinical and clinical approaches. We assess the motivational effects of chronic unilateral STN-DBS in rats in the exact same conditions having highlighted a loss of motivation under bilateral STN-DBS. Clinical data are obtained by the follow-up of a cohort of parkinsonian patients undergoing unilateral STN-DBS and coming from the clinical center that described apathy related to bilateral STN-DBS itself. Despite an acute effect, which fades rapidly, unilateral STN-DBS did not induce a loss of motivation reminiscent to apathy in rats. In patients, apathy did not increase between the preoperative and the post-operative assessment. Together, those data demonstrate that bilateral but not unilateral STN-DBS can induce a loss of motivation in both rats and patients. This constitutes another evidence of the role of STN-DBS itself for apathy in PD.

scholarly journals The Role of the Subthalamic Nucleus in Inhibitory Control of Oculomotor Behavior in Parkinson’s Disease

2019 ◽  
Author(s):  
Shahab Bakhtiari ◽  
Ayca Altinkaya ◽  
Christopher C. Pack ◽  
Abbas F. Sadikot
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Replacement Therapy ◽  
Subthalamic Nucleus ◽  
Error Rate ◽  
Oculomotor Behavior ◽  
Dopamine Replacement Therapy ◽  
Anti Saccades ◽  
Stn Dbs

AbstractThe ability to inhibit an inappropriate action in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple experimental task within the oculomotor repertoire that can be used to test this ability. The task involves an inhibition of a saccade to the peripheral target (pro-saccade) and generation of a voluntary eye movement toward the mirror position (anti-saccade). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior. However, the precise role of different components in generation of anti-saccade behavior is still uncertain. Parkinson’s disease patients with implanted deep brain stimulation (DBS) in subthalamic nucleus (STN) provide us with a unique opportunity to investigate the role of STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinson’s disease patients on anti- and pro-saccade tasks ON and OFF STN DBS and ON and OFF dopaminergic medication. We made three main observations. First, STN DBS increases the anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, there is an interaction between dopamine replacement therapy and STN DBS. More specifically, L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS can induce different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.

scholarly journals Subthalamic stimulation affects homophone meaning generation in Parkinson's disease

2008 ◽  
Vol 14 (5) ◽  
pp. 890-894 ◽  
Author(s):  
JOANNA E. CASTNER ◽  
DAVID A. COPLAND ◽  
PETER A. SILBURN ◽  
TERRY J. COYNE ◽  
FELICITY SINCLAIR ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Verbal Fluency ◽  
Neurologically Impaired ◽  
Stimulation Condition ◽  
Subthalamic Stimulation ◽  
Stn Dbs ◽  
Generation Test ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in individuals with Parkinson's disease (PD) has often been associated with reduced verbal fluency performance. This study aimed to directly assess semantic switching as a function of STN stimulation in PD participants with the Homophone Meaning Generation Test (HMGT). Seventeen participants with PD who had received STN DBS completed the HMGT in on and off stimulation conditions. Twenty-one non-neurologically impaired participants acted as controls. PD participants (in both on and off stimulation conditions) generated significantly fewer meanings than control participants and consistent with the previous reports of verbal fluency impairment, PD participants produced fewer definitions in the on stimulation condition. PD participants (in both on and off stimulation conditions) also had greater difficulty generating definitions for nonhomographic homophones compared with homographic homographs. The results of this study indicate that STN stimulation exacerbates impairment in semantic switching. (JINS, 2008, 14, 890–894.)

scholarly journals Role of TLR4 in the gut-brain axis in Parkinson’s disease: a translational study from men to mice

Gut ◽  
2018 ◽  
Vol 68 (5) ◽  
pp. 829-843 ◽  
Author(s):  
Paula Perez-Pardo ◽  
Hemraj B Dodiya ◽  
Phillip A Engen ◽  
Christopher B Forsyth ◽  
Andrea M Huschens ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Motor Dysfunction ◽  
Brain Inflammation ◽  
Translational Study ◽  
Colonic Biopsy ◽  
Rotenone Treatment

ObjectiveRecent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible role of the gut-brain axis in neurodegenerative diseases. Given the prominence of dysbiosis and colonic dysfunction in patients with Parkinson’s disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal dysfunction could contribute to intestinal and central inflammation in PD-related neurodegeneration.DesignTo test this hypothesis we performed studies in both human tissue and a murine model of PD. Inflammation, immune activation and microbiota composition were measured in colonic samples from subjects with PD and healthy controls subjects and rotenone or vehicle-treated mice. To further assess the role of the TLR4 signalling in PD-induced neuroinflammation, we used TLR4-knockout (KO) mice in conjunction with oral rotenone administration to model PD.ResultsPatients with PD have intestinal barrier disruption, enhanced markers of microbial translocation and higher pro-inflammatory gene profiles in the colonic biopsy samples compared with controls. In this regard, we found increased expression of the bacterial endotoxin-specific ligand TLR4, CD3+ T cells, cytokine expression in colonic biopsies, dysbiosis characterised by a decrease abundance of SCFA-producing colonic bacteria in subjects with PD. Rotenone treatment in TLR4-KO mice revealed less intestinal inflammation, intestinal and motor dysfunction, neuroinflammation and neurodegeneration, relative to rotenone-treated wild-type animals despite the presence of dysbiotic microbiota in TLR4-KO mice.ConclusionTaken together, these studies suggest that TLR4-mediated inflammation plays an important role in intestinal and/or brain inflammation, which may be one of the key factors leading to neurodegeneration in PD.

scholarly journals Subthalamic stimulation breaks the balance between distal and axial signs in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cyril Atkinson-Clement ◽  
Émilie Cavazzini ◽  
Alexandre Zénon ◽  
Thierry Legou ◽  
Tatiana Witjas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Impairments ◽  
Vowel Production ◽  
Treatment Conditions ◽  
Subthalamic Stimulation ◽  
The Difference ◽  
Stn Dbs ◽  
Deep Brain

AbstractIn Parkinson’s disease (PD), the effects of both Ldopa and subthalamic deep brain stimulation (STN-DBS) are known to change cost-valuation. However, this was mostly studied through reward-effort task involving distal movements, while axial effort, less responsive to treatments, have been barely studied. Thus, our objective was to compare the influence of both Ldopa and STN-DBS on cost-valuation between two efforts modalities: vowel production (as an example of axial movement) and hand squeezing (as an example of distal movement). Twelve PD patients were recruited to participate in this study. The task consisted in deciding whether to accept or reject trials based on a reward-effort trade-off. Participants performed two blocks with hand squeezing, and two with vowel production, in the four treatment conditions (LdopaOn/Off; STN-DBS On/Off). We found that STN-DBS changed the ratio difference between hand and phonation efforts. Vowel production effort was estimated easier to perform with STN-DBS alone, and harder when associated with Ldopa. The difference between hand and phonation efforts was correlated with quality of life in Off/Off and On Ldopa alone conditions, and with impulsive assessment On STN-DBS alone. We highlighted that STN-DBS could introduce an imbalance between the actual motor impairments and their subjective costs. With this finding, we also suggest paying particular attention to the different treatment effects that should be expected for axial and distal movement dysfunctions.

Modulation of motor cortex by subthalamic stimulation in Parkinson's disease

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
B Haslinger ◽  
K Kalteis ◽  
F Alesch ◽  
H Boecker ◽  
AO Ceballos-Baumann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Subthalamic Stimulation
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