scholarly journals The structural connectivity of subthalamic deep brain stimulation correlates with impulsivity in Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2235-2254 ◽  
Author(s):  
Philip E Mosley ◽  
Saee Paliwal ◽  
Katherine Robinson ◽  
Terry Coyne ◽  
Peter Silburn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Side Effects ◽  
Brain Stimulation ◽  
Orbitofrontal Cortex ◽  
Stimulation Site ◽  
Neuropsychiatric Side Effects ◽  
Stn Dbs ◽  
Deep Brain

Abstract Subthalamic deep brain stimulation (STN-DBS) for Parkinson’s disease treats motor symptoms and improves quality of life, but can be complicated by adverse neuropsychiatric side-effects, including impulsivity. Several clinically important questions remain unclear: can ‘at-risk’ patients be identified prior to DBS; do neuropsychiatric symptoms relate to the distribution of the stimulation field; and which brain networks are responsible for the evolution of these symptoms? Using a comprehensive neuropsychiatric battery and a virtual casino to assess impulsive behaviour in a naturalistic fashion, 55 patients with Parkinson’s disease (19 females, mean age 62, mean Hoehn and Yahr stage 2.6) were assessed prior to STN-DBS and 3 months postoperatively. Reward evaluation and response inhibition networks were reconstructed with probabilistic tractography using the participant-specific subthalamic volume of activated tissue as a seed. We found that greater connectivity of the stimulation site with these frontostriatal networks was related to greater postoperative impulsiveness and disinhibition as assessed by the neuropsychiatric instruments. Larger bet sizes in the virtual casino postoperatively were associated with greater connectivity of the stimulation site with right and left orbitofrontal cortex, right ventromedial prefrontal cortex and left ventral striatum. For all assessments, the baseline connectivity of reward evaluation and response inhibition networks prior to STN-DBS was not associated with postoperative impulsivity; rather, these relationships were only observed when the stimulation field was incorporated. This suggests that the site and distribution of stimulation is a more important determinant of postoperative neuropsychiatric outcomes than preoperative brain structure and that stimulation acts to mediate impulsivity through differential recruitment of frontostriatal networks. Notably, a distinction could be made amongst participants with clinically-significant, harmful changes in mood and behaviour attributable to DBS, based upon an analysis of connectivity and its relationship with gambling behaviour. Additional analyses suggested that this distinction may be mediated by the differential involvement of fibres connecting ventromedial subthalamic nucleus and orbitofrontal cortex. These findings identify a mechanistic substrate of neuropsychiatric impairment after STN-DBS and suggest that tractography could be used to predict the incidence of adverse neuropsychiatric effects. Clinically, these results highlight the importance of accurate electrode placement and careful stimulation titration in the prevention of neuropsychiatric side-effects after STN-DBS.

Psychiatric morbidity in patients with Parkinson’s disease following bilateral subthalamic deep brain stimulation: literature review

2008 ◽  
Vol 20 (4) ◽  
pp. 182-192 ◽  
Author(s):  
Linton J. Meagher ◽  
Ralf Ilchef ◽  
Paul Silberstein ◽  
Raymond J. Cook ◽  
Daniel Wasson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Side Effects ◽  
Effective Treatment ◽  
Brain Stimulation ◽  
Psychiatric Morbidity ◽  
Motor Symptoms ◽  
Stn Dbs ◽  
Deep Brain

Objective:To provide a comprehensive review and evaluation of the literature pertaining to the psychiatric sequelae of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson’s disease (PD).Methods:A structured search of the EMBASE, PsychINFO and MEDLINE databases was performed on articles published since the first use of STN DBS in 1993 for PD until March 2007. Non-human studies were excluded, along with studies reporting on unilateral DBS and studies reporting on the use of STN DBS for indications other than idiopathic PD. Ninety-seven articles were selected for inclusion in the review.Results:Patients with advanced PD have a high rate of psychiatric morbidity. STN DBS has been shown to be an effective treatment for the control of motor symptoms in advanced PD. Neurobehavioural side-effects are, however, relatively common following STN DBS. Side-effects include impaired executive function and verbal fluency, depression, hypomania, apathy, postoperative delirium, anxiety disorders and psychotic symptoms, especially hallucinations. The alteration in dopaminergic medication following surgery as well as the direct effect of STN stimulation both appear to contribute to the short-term and long-term postoperative psychiatric complications. Methodological issues that limit the applicability of the current literature in this field are highlighted.Conclusions:STN DBS is an effective treatment for the motor symptoms of advanced PD. However, further research is needed to assess the extent to which STN DBS contributes to or exacerbates psychiatric morbidity over and above that associated with advanced PD. Careful neuropsychiatric evaluation and monitoring are required in this patient group.

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 Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

2021 ◽  
Vol 15 ◽  
Author(s):  
Lila H. Levinson ◽  
David J. Caldwell ◽  
Jeneva A. Cronin ◽  
Brady Houston ◽  
Steve I. Perlmutter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Evoked Potentials ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Therapeutic Effects ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

Comparison of Subthalamic Nucleus and Globus Pallidus Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Azari H ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Adverse Effects ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Stn Dbs ◽  
Deep Brain

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

scholarly journals Adaptive deep brain stimulation as advanced Parkinson’s disease treatment (ADAPT study): protocol for a pseudo-randomised clinical study

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e029652 ◽  
Author(s):  
Dan Piña-Fuentes ◽  
Martijn Beudel ◽  
Simon Little ◽  
Peter Brown ◽  
D L Marinus Oterdoom ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Clinical Study ◽  
Side Effects ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Motor Symptoms ◽  
Internal Globus Pallidus ◽  
Deep Brain

IntroductionAdaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson’s disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.Methods and analysisThis protocol describes a single-centre clinical study in which aDBS will be tested in 12 patients with PD undergoing battery replacement, with electrodes implanted in the STN, and as a proof of concept in the internal globus pallidus. Patients included will be allocated in a pseudo-randomised fashion to a three-condition (no stimulation/cDBS/ aDBS), cross-over design. A battery of tests will be conducted and recorded during each condition, which aim to measure the severity of motor symptoms and side effects. These tests include a tablet-based tapping test, a subscale of the Movement Disorder Society-unified Parkinson’s disease rating scale (subMDS-UPDRS), the Speech Intelligibility Test (SIT) and a tablet-based version of the Stroop test. SubMDS-UPDRS and SIT recordings will be blindly assessed by independent raters. Data will be analysed using a linear mixed-effects model.Ethics and disseminationThis protocol was approved by the Ethical Committee of the University Medical Centre Groningen, where the study will be carried out. Data management and compliance to research policies and standards of our centre, including data privacy, storage and veracity, will be controlled by an independent monitor. All the scientific findings derived from this protocol are aimed to be made public through publication of articles in international journals.Trial registration numberNTR 5456; Pre-results.

Clinical outcomes following awake and asleep deep brain stimulation for Parkinson disease

2018 ◽  
Vol 130 (1) ◽  
pp. 109-120 ◽  
Author(s):  
Tsinsue Chen ◽  
Zaman Mirzadeh ◽  
Kristina M. Chapple ◽  
Margaret Lambert ◽  
Holly A. Shill ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Clinical Outcomes ◽  
Brain Stimulation ◽  
Stn Dbs ◽  
Deep Brain

OBJECTIVERecent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, and historical cohorts undergoing “awake” DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution.METHODSPD patients undergoing awake or asleep bilateral GPi or STN DBS were prospectively monitored. The primary outcome measure was stimulation-induced change in motor function off medication 6 months postoperatively, measured using the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Secondary outcomes included change in quality of life, measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), change in levodopa equivalent daily dosage (LEDD), stereotactic accuracy, stimulation parameters, and adverse events.RESULTSSix-month outcome data were available for 133 patients treated over 45 months (78 GPi [16 awake, 62 asleep] and 55 STN [14 awake, 41 asleep]). UPDRS-III score improvement with stimulation did not differ between awake and asleep groups for GPi (awake, 20.8 points [38.5%]; asleep, 18.8 points [37.5%]; p = 0.45) or STN (awake, 21.6 points [40.3%]; asleep, 26.1 points [48.8%]; p = 0.20) targets. The percentage improvement in PDQ-39 and LEDD was similar for awake and asleep groups for both GPi (p = 0.80 and p = 0.54, respectively) and STN cohorts (p = 0.85 and p = 0.49, respectively).CONCLUSIONSIn PD patients, bilateral GPi and STN DBS using the asleep method resulted in motor, quality-of-life, and medication reduction outcomes that were comparable to those of the awake method.

scholarly journals Depression and Anxiety Following Deep Brain Stimulation in Parkinson’s Disease: Systematic Review and Meta-Analysis

2014 ◽  
Vol 27 (3) ◽  
pp. 372 ◽  
Author(s):  
Maria Inês Couto ◽  
Ana Monteiro ◽  
Ana Oliveira ◽  
Nuno Lunet ◽  
João Massano
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Depressive Symptoms ◽  
Deep Brain Stimulation ◽  
Medical Treatment ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Short Term ◽  
Stn Dbs ◽  
Deep Brain

<p><strong>Introduction:</strong> Deep brain stimulation (DBS) is effective in advanced Parkinson’s disease (PD), improving motor symptoms, fluctuations and quality of life. However, adverse psychiatric outcomes have been reported, albeit variably and in an unstandardized fashion. We aimed to summarize the published evidence on the outcomes of anxiety and depressive symptoms in Parkinson’s disease patients following DBS, through systematic review and meta-analysis.<br /><strong>Material and Methods:</strong> PubMed was searched until May 2012 to identify studies assessing anxiety and depressive symptoms in PD patients who underwent bilateral DBS of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Random effects metaanalyses were conducted for groups of at least three studies that were homogeneous regarding the design and the instruments used.<br /><strong>Results:</strong> 63 references were selected; 98.4% provided data on depression, and 38.1% on anxiety assessment scales. Two studies did not discriminate the target; from the remaining 61 references, short-term evaluation was performed in 37 (60.7%), mid-term in 36 (59.0%) and long-term in 5 (8.2%). Data on pre to postop variation was available in 57 (93.4%) reports and 16 (26.2%) presented STNDBS versus different comparison groups: GPi-DBS (n = 4 studies, 25.0%), eligible for surgery (n = 6, 37.5%), and medical treatment (n = 7, 43.8%).<br /><strong>Discussion:</strong> Improvement of depression and anxiety is apparent after DBS, more pronounced in the short-term, an effect that seems to wane in later assessments. Concerning depression, STN-DBS shows superiority against medical treatment, but not when compared to eligible for surgery control groups. The opposite is apparent for anxiety, as results favor medical treatment over STN-DBS, and STNDBS over eligible for surgery control group. Superiority of one target over the other is not evident from the results, but data slightly favors GPi for both outcomes.<br /><strong>Conclusion:</strong> The pattern and course of depressive symptoms and anxiety following DBS in PD is not clear, although both seem to improve in the short-term, especially depression following STN-DBS. Results are highly heterogeneous. Efforts should be carried out to standardize assessment procedures across centers.<br /><strong>Keywords:</strong> Parkinson’s Disease; Deep Brain Stimulation; Anxiety; Depression; Meta-Analysis.</p>

Apathy in patients with Parkinson’s disease following deep brain stimulation of the subthalamic nucleus

CNS Spectrums ◽  
2016 ◽  
Vol 21 (3) ◽  
pp. 258-264 ◽  
Author(s):  
Isabel Hindle Fisher ◽  
Hardev S. Pall ◽  
Rosalind D. Mitchell ◽  
Jamilla Kausar ◽  
Andrea E. Cavanna
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Control Group ◽  
Stn Dbs ◽  
Deep Brain ◽  
Stimulation Of

ObjectiveApathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson’s disease (PD) who underwent STN-DBS, as well as the effects of apathy on quality of life (QOL).MethodsAll patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS), and the Parkinson’s Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone.ResultsThere were no significant differences in the prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p<0.001) and the AS (p=0.021). PD-related disability also correlated with both apathy ratings (p<0.001 and p=0.017, respectively).ConclusionOur findings suggest that STN-DBS is not necessarily associated with apathy in the PD population; however, more severe apathy appears to be associated with a higher level of disability due to PD and worse QOL, but no other clinico-demographic characteristics.

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