scholarly journals Distributed Global Functional Connectivity Networks Predict Responsiveness to L-DOPA and Subthalamic Deep Brain Stimulation

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Chengyuan Wu ◽  
Thomas Foltynie ◽  
Patricia Limousin ◽  
Ludvic Zrinzo ◽  
Harith Akram
Keyword(s):  
Deep Brain Stimulation ◽  
Functional Connectivity ◽  
Brain Stimulation ◽  
Resting State ◽  
Visuomotor Control ◽  
Global Network ◽  
Resting State Functional Connectivity ◽  
Graph Metrics ◽  
Stn Dbs ◽  
Deep Brain

Abstract INTRODUCTION Brain circuit dysfunction in Parkinson's disease (PD) involves an extensive global network. A distinctive basal ganglia resting-state functional connectivity (rsFC) pattern has been linked with the ranked response to L-DOPA. We therefore sought to investigate global rsFC patterns associated with response to L-DOPA and to subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced PD. METHODS A total of 19 patients underwent 3-Tesla resting-state functional magnetic resonance imaging (rsfMRI) in the ON-medication state prior to STN DBS. Improvement in UPDRS-III hemibody scores were assessed following L-DOPA therapy and STN DBS. Global rsFC was measured between regions-of-interest (ROIs) defined by the Automated Anatomical Labeling (AAL) atlas and the Montreal Neurologic Institute (MNI) PD25 subcortical atlas. Seed- and network-level correlations were made with an FDR-P < .005. Graph theoretical analysis was performed with an analysis threshold of FDR-P < .005; and then looking at the top 15% of edges. RESULTS Response to L-DOPA and to DBS displayed cerebellar desynchronization with bilateral thalami and synchronization with bilateral ventromedial prefrontal cortices (vmPFC). L-DOPA response was additionally associated with desynchronization between the vmPFC and the fusiform gyrus. Meanwhile, DBS response was associated with more widespread areas, which have been implicated in visuomotor control and planning. Graph theory analysis revealed that DBS response was inversely related to global efficiency of the thalamus and putamen bilaterally. No significant graph metrics were found relative to L-DOPA response. CONCLUSION Response to DBS and to L-DOPA share similar characteristics, particularly in cerebello-thalamo-cortical circuits, including those that play a role in planning, learning, decision-making, and reward-based behavior. Preservation of distributed networks involved in visuomotor control and network integration of striatothalamocortical circuits appear to predict DBS response. These findings shed a light on the mechanism of action of DBS and L-DOPA and may help serve as useful treatment response biomarkers.

scholarly journals Deep brain stimulation modulates the dynamics of resting-state networks in patients with Parkinson’s Disease

2020 ◽  
Author(s):  
Maria T. Gomes ◽  
Henrique M. Fernandes ◽  
Joana Cabral
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Electric Field ◽  
Brain Stimulation ◽  
Resting State ◽  
Surgical Procedure ◽  
Resting State Networks ◽  
Stn Dbs ◽  
Deep Brain

ABSTRACTDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is increasingly used for the treatment of Parkinson’s Disease (PD), but despite its success, the neural mechanisms behind this surgical procedure remain partly unclear. As one working hypothesis, it was proposed that DBS works by restoring the balance of the brain’s resting-state networks (RSNs), which is reported to be disrupted in people with PD. Hence, to elucidate the effects that STN-DBS induces on disseminated networks, we analyzed an fMRI dataset of 20 PD patients at rest under DBS ON and OFF conditions. Moving beyond ‘static’ functional connectivity studies, we employ a recently developed fMRI analysis tool, the Leading Eigenvector Dynamic Analysis (LEiDA), to characterize the recurrence of brain-wide phase-locking patterns overlapping with known RSNs. Here, STN-DBS seems to increase the Default Mode Network (DMN) occurrence in individuals with PD. Since the DMN is usually disturbed in PD patients presenting deficits in cognition, our observation might be suggestive that STN-DBS contributes to a normalization of the PD-induced cognitive impairment.Moreover, we addressed the effects of DBS lead placement on RSNs balance, considering the overlap between the DBS-induced electric field and 3 STN subsections. We found that the Visual Network (VN) probability of occurrence increased proportionally to the electric field-limbic STN overlap. Our finding might be indicative that stimulation of the limbic STN is related to the stabilization of visual symptoms sometimes presented by PD patients, which are usually accompanied by VN disruption.Overall, this study offers new insights into the fine-grained temporal dynamics of brain states portraying the effects of STN-DBS in patients with PD, while at the same time trying to pave the way to improved planning strategies for this surgical procedure.

Sweets for my sweet: modulation of the limbic system drives salience for sweet foods after deep brain stimulation in Parkinson’s disease

2021 ◽  
pp. jnnp-2021-326280
Author(s):  
Julia Steinhardt ◽  
Henrike Hanssen ◽  
Marcus Heldmann ◽  
Alexander Neumann ◽  
Alexander Münchau ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Deep Brain Stimulation ◽  
Functional Connectivity ◽  
Brain Stimulation ◽  
Sweet Food ◽  
Local Impact ◽  
Stn Dbs ◽  
Deep Brain

BackgroundAn increase in body weight is observed in the majority of patients with Parkinson’s disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear.ObjectivesTo identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations.MethodsWe acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated.ResultsSTN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images.ConclusionsOur findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated.

scholarly journals The rostro-caudal gradient in the prefrontal cortex and its modulation by subthalamic deep brain stimulation in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
F. Konrad Schumacher ◽  
Lena V. Schumacher ◽  
Florian Amtage ◽  
Andreas Horn ◽  
Karl Egger ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Prefrontal Cortex ◽  
Deep Brain Stimulation ◽  
Side Effects ◽  
Functional Connectivity ◽  
Brain Stimulation ◽  
Cognitive Functions ◽  
Stn Dbs ◽  
Deep Brain

AbstractDeep brain stimulation of the subthalamic nucleus (STN-DBS) alleviates motor symptoms in Parkinson’s disease (PD) but also affects the prefrontal cortex (PFC), potentially leading to cognitive side effects. The present study tested alterations within the rostro-caudal hierarchy of neural processing in the PFC induced by STN-DBS in PD. Granger-causality analyses of fast functional near-infrared spectroscopy (fNIRS) measurements were used to infer directed functional connectivity from intrinsic PFC activity in 24 PD patients treated with STN-DBS. Functional connectivity was assessed ON stimulation, in steady-state OFF stimulation and immediately after the stimulator was switched ON again. Results revealed that STN-DBS significantly enhanced the rostro-caudal hierarchical organization of the PFC in patients who had undergone implantation early in the course of the disease, whereas it attenuated the rostro-caudal hierarchy in late-implanted patients. Most crucially, this systematic network effect of STN-DBS was reproducible in the second ON stimulation measurement. Supplemental analyses demonstrated the significance of prefrontal networks for cognitive functions in patients and matched healthy controls. These findings show that the modulation of prefrontal functional networks by STN-DBS is dependent on the disease duration before DBS implantation and suggest a neurophysiological mechanism underlying the side effects on prefrontally-guided cognitive functions observed under STN-DBS.

scholarly journals Fully Automated Targeting Using Nonrigid Image Registration Matches Accuracy and Exceeds Precision of Best Manual Approaches to Subthalamic Deep Brain Stimulation Targeting in Parkinson Disease

Neurosurgery ◽  
2015 ◽  
Vol 76 (6) ◽  
pp. 756-765 ◽  
Author(s):  
Srivatsan Pallavaram ◽  
Pierre-François D'Haese ◽  
Wendell Lake ◽  
Peter E. Konrad ◽  
Benoit M. Dawant ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Image Registration ◽  
Parkinson Disease ◽  
Brain Stimulation ◽  
Red Nucleus ◽  
Nonrigid Image Registration ◽  
Direct Targeting ◽  
Fully Automatic ◽  
Stn Dbs ◽  
Deep Brain

Abstract BACKGROUND: Finding the optimal location for the implantation of the electrode in deep brain stimulation (DBS) surgery is crucial for maximizing the therapeutic benefit to the patient. Such targeting is challenging for several reasons, including anatomic variability between patients as well as the lack of consensus about the location of the optimal target. OBJECTIVE: To compare the performance of popular manual targeting methods against a fully automatic nonrigid image registration-based approach. METHODS: In 71 Parkinson disease subthalamic nucleus (STN)-DBS implantations, an experienced functional neurosurgeon selected the target manually using 3 different approaches: indirect targeting using standard stereotactic coordinates, direct targeting based on the patient magnetic resonance imaging, and indirect targeting relative to the red nucleus. Targets were also automatically predicted by using a leave-one-out approach to populate the CranialVault atlas with the use of nonrigid image registration. The different targeting methods were compared against the location of the final active contact, determined through iterative clinical programming in each individual patient. RESULTS: Targeting by using standard stereotactic coordinates corresponding to the center of the motor territory of the STN had the largest targeting error (3.69 mm), followed by direct targeting (3.44 mm), average stereotactic coordinates of active contacts from this study (3.02 mm), red nucleus-based targeting (2.75 mm), and nonrigid image registration-based automatic predictions using the CranialVault atlas (2.70 mm). The CranialVault atlas method had statistically smaller variance than all manual approaches. CONCLUSION: Fully automatic targeting based on nonrigid image registration with the use of the CranialVault atlas is as accurate and more precise than popular manual methods for STN-DBS.

scholarly journals Resting‐State Functional Connectivity Predicts STN DBS Clinical Response

2020 ◽  
Author(s):  
John R. Younce ◽  
Meghan C. Campbell ◽  
Tamara Hershey ◽  
Aaron B. Tanenbaum ◽  
Mikhail Milchenko ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Clinical Response ◽  
Resting State ◽  
Resting State Functional Connectivity ◽  
Stn Dbs

scholarly journals Dynamic Network Connectivity Reveals Markers of Response to Deep Brain Stimulation in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Chengyuan Wu ◽  
Caio Matias ◽  
Thomas Foltynie ◽  
Patricia Limousin ◽  
Ludvic Zrinzo ◽  
...  
Keyword(s):  
Graph Theory ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Theory Analysis ◽  
Whole Brain ◽  
Network Properties ◽  
Brain States ◽  
Graph Theory Analysis ◽  
Stn Dbs ◽  
Deep Brain

Background: Neuronal loss in Parkinson’s Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the rs-fMRI. FC between ICs was calculated across the entire time series and for dynamic brain states. Graph theory analysis was performed to investigate whole brain network topography in static and dynamic states.Results: Dynamic analysis identified two unique brain states: a relative hypoconnected state and a relative hyperconnected state. Time spent in a state, dwell time, and number of transitions were not correlated with DBS response. There were no significant FC findings, but graph theory analysis demonstrated significant relationships with STN-DBS response only during the hypoconnected state – STN-DBS was negatively correlated with network assortativity.Conclusion: Given the widespread effects of dopamine depletion in PD, analysis of whole brain networks is critical to our understanding of the pathophysiology of this disease. Only by leveraging graph theoretical analysis of dynamic FC were we able to isolate a hypoconnected brain state that contained distinct network properties associated with the clinical effects of STN-DBS.

scholarly journals A Meta-Analysis of the Effect of Subthalamic Nucleus-Deep Brain Stimulation in Parkinson's Disease-Related Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Yu Diao ◽  
Yutong Bai ◽  
Tianqi Hu ◽  
Zixiao Yin ◽  
Huangguang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Motor Symptom ◽  
Stn Dbs ◽  
Deep Brain

Pain from Parkinson's disease (PD) is a non-motor symptom affecting the quality of life and has prevalence of 20–80%. However, it is unclear whether subthalamic nucleus deep brain stimulation (STN–DBS), a well-established treatment for PD, is effective forPD-related pain. Thus, the objective of this meta-analysis was to investigate the efficacy of STN-DBS on PD-related pain and explore how its duration affects the efficacy of STN-DBS. A systematic search was performed using PubMed, Embase, and the Cochrane Library. Nine studies included numerical rating scale (NRS), visual analog scale (VAS), or non-motor symptom scale (NMSS) scores at baseline and at the last follow-up visit and therefore met the inclusion criteria of the authors. These studies exhibited moderate- to high-quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. Random effect meta-analysis revealed a significant change in PD-related pain as assessed by NMSS, NRS, and VAS (P &lt;0.01). Analysis of the short and long follow-up subgroups indicated delayed improvement in PD-related pain. These findings (a) show the efficacy of STN-DBS on PD-related pain and provide higher-level evidence, and (b) implicate delayed improvement in PD-related pain, which may help programming doctors with supplement selecting target and programming.Systematic Review Registration: This study is registered in Open Science Framework (DOI: 10.17605/OSF.IO/DNM6K).

scholarly journals Resolution of tardive tremor after bilateral subthalamic nucleus deep brain stimulation placement

2020 ◽  
Vol 11 ◽  
pp. 444
Author(s):  
Samir Kashyap ◽  
Rita Ceponiene ◽  
Paras Savla ◽  
Jacob Bernstein ◽  
Hammad Ghanchi ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Orofacial Dyskinesia ◽  
Major Depressive ◽  
History Of ◽  
Stn Dbs ◽  
Common Manifestation ◽  
Tardive Syndrome ◽  
Deep Brain

Background: Tardive tremor (TT) is an underrecognized manifestation of tardive syndrome (TS). In our experience, TT is a rather common manifestation of TS, especially in a setting of treatment with aripiprazole, and is a frequent cause of referrals for the evaluation of idiopathic Parkinson disease. There are reports of successful treatment of tardive orofacial dyskinesia and dystonia with deep brain stimulation (DBS) using globus pallidus interna (GPi) as the primary target, but the literature on subthalamic nucleus (STN) DBS for tardive dyskinesia (TD) is lacking. To the best of our knowledge, there are no reports on DBS treatment of TT. Case Description: A 75-year-old right-handed female with the medical history of generalized anxiety disorder and major depressive disorder had been treated with thioridazine and citalopram from 1980 till 2010. Around 2008, she developed orolingual dyskinesia. She was started on tetrabenazine in June 2011. She continued to have tremors and developed Parkinsonian gait, both of which worsened overtime. She underwent DBS placement in the left STN in January 2017 with near-complete resolution of her tremors. She underwent right STN implantation in September 2017 with similar improvement in symptoms. Conclusion: While DBS-GPi is the preferred treatment in treating oral TD and dystonia, DBS-STN could be considered a safe and effective target in patients with predominating TT and/or tardive Parkinsonism. This patient saw a marked improvement in her symptoms after implantation of DBS electrodes, without significant relapse or recurrence in the years following implantation.

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