Effect of deep brain stimulation on brain network and white matter integrity in Parkinson's disease.
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ABSTRACT: Aims
The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS.Methods
Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics.Results
Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores.Conclusion
STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.
SUBMITTER: Huang LC
PROVIDER: S-EPMC8673709 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: The objective of this study was to use functional connectivity and graphic indicators to investigate the abnormal brain network topological characteristics caused by Parkinson's disease (PD) and the effect of acute deep brain stimulation (DBS) on those characteristics in patients with PD. Methods: We recorded high-density EEG (256 channels) data from 21 healthy controls (HC) and 20 patients with PD who were in the DBS-OFF state and DBS-ON state during the resting state with eyes closed. A high-density EEG source connectivity method was used to identify functional brain networks. Power spectral density (PSD) analysis was compared between the groups. Functional connectivity was calculated for 68 brain regions in the theta (4-8 Hz), alpha (8-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz) frequency bands. Network estimates were measured at both the global (network topology) and local (inter-regional connection) levels. Results: Compared with HC, PSD was significantly increased in the theta (p = 0.003) frequency band and was decreased in the beta1 (p = 0.009) and beta2 (p = 0.04) frequency bands in patients with PD. However, there were no differences in any frequency bands between patients with PD with DBS-OFF and DBS-ON. The clustering coefficient and local efficiency of patients with PD showed a significant decrease in the alpha, beta1, and beta2 frequency bands (p < 0.001). In addition, edgewise statistics showed a significant difference between the HC and patients with PD in all analyzed frequency bands (p < 0.005). However, there were no significant differences between the DBS-OFF state and DBS-ON state in the brain network, except for the functional connectivity in the beta2 frequency band (p < 0.05). Conclusion: Compared with HC, patients with PD showed the following characteristics: slowed EEG background activity, decreased clustering coefficient and local efficiency of the brain network, as well as both increased and decreased functional connectivity between different brain areas. Acute DBS induces a local response of the brain network in patients with PD, mainly showing decreased functional connectivity in a few brain regions in the beta2 frequency band.
| S-EPMC8551554 | biostudies-literature
Project description:Deep brain stimulation (DBS) has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD) and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN), other investigators reported on improvements of distinct parameters of oral control and voice. Though, these ameliorations of single speech modalities were not always accompanied by an improvement of overall speech intelligibility. On the other hand, there are also indications for an induction of dysarthria as an adverse effect of STN-DBS occurring at least in some patients with PD. Since a deterioration of speech function has more often been observed under high stimulation amplitudes, this phenomenon has been ascribed to a spread of current-to-adjacent pathways which might also be the reason for the sporadic observation of an onset of dysarthria under DBS of other basal ganglia targets (e.g., globus pallidus internus/GPi or thalamus/Vim). The aim of this paper is to review and evaluate reports in the literature on the effects of DBS on speech function in PD.
| S-EPMC3512320 | biostudies-other
Project description:ObjectiveDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established neurosurgical treatment for the motor symptoms of Parkinson's disease (PD). While often highly effective, DBS does not always yield optimal therapeutic outcomes, and stimulation-induced adverse effects, including paresthesia, muscle contractions, and nausea/lightheadedness, commonly occur and can limit the efficacy of stimulation. Currently, objective metrics do not exist for monitoring neural changes associated with stimulation-induced therapeutic and adverse effects.MethodsIn the present study, the authors combined intraoperative functional MRI (fMRI) with STN DBS in 20 patients with PD to test the hypothesis that stimulation-induced blood oxygen level-dependent signals contained predictive information concerning the therapeutic and adverse effects of stimulation.ResultsAs expected, DBS resulted in blood oxygen level-dependent activation in myriad motor regions, including the primary motor cortex, caudate, putamen, thalamus, midbrain, and cerebellum. Across the patients, DBS-induced improvements in contralateral Unified Parkinson's Disease Rating Scale tremor subscores correlated with activation of thalamic, brainstem, and cerebellar regions. In addition, improvements in rigidity and bradykinesia subscores correlated with activation of the primary motor cortex. Finally, activation of specific sensorimotor-related subregions correlated with the presence of DBS-induced adverse effects, including paresthesia and nausea (cerebellar cortex, sensorimotor cortex) and unwanted muscle contractions (caudate and putamen).ConclusionsThese results suggest that DBS-induced activation patterns revealed by fMRI contain predictive information with respect to the therapeutic and adverse effects of DBS. The use of fMRI in combination with DBS therefore may hold translational potential to guide and improve clinical stimulator optimization in patients.
| S-EPMC10193504 | biostudies-literature
Project description:Patients aged 65 years and older are not traditionally considered optimal candidates for subthalamic deep brain stimulation (STN-DBS), mainly for their presumed increased incidence of surgical complications. The aim of this study was to assess STN-DBS surgery safety in relation to age.A total of 107 consecutive patients undergoing bilateral STN-DBS at our institution between 2002 and 2014 were retrospectively stratified according to age in two groups (Young group < 65 years old; Elderly group ≥ 65 years old;). Rate of short-term surgical complications (within 90 days) was reviewed and compared between the two groups.Pre-operative baseline data were comparable between the two groups. The 90-days post-operative mortality rate was 0%. Overall incidence of complications related to surgery was 6,54%. In the Elderly group we observed 3 post-operative intra-cerebral haematomas (7,89%), 1 requiring urgent surgical evacuation. In the Young group we observed 2 post-operative asymptomatic intra-cerebral haematomas (2,89%) and 2 wound infections (2,89%), 1 requiring system removal. No others surgical complications were noticed in both groups.Chronological age ≥ 65 years old should not be considered alone as exclusion criteria to STN-DBS surgery.
| S-EPMC4595247 | biostudies-other
Project description:Deep brain stimulation (DBS) is considered a safe and well tolerated surgical procedure to alleviate Parkinson's disease (PD) and other movement disorders symptoms along with some psychiatric conditions. Over the last few decades DBS has been shown to provide remarkable therapeutic effect on carefully selected patients. Although its precise mechanism of action is still unknown, DBS improves motor functions and therefore quality of life. To date, two main targets have emerged in PD patients: the globus pallidus pars interna and the subthalamic nucleus. Two other targets, the ventralis intermedius and zona incerta have also been selectively used, especially in tremor-dominant PD patients. The main indications for PD DBS have traditionally been motor fluctuations, debilitating medication induced dyskinesias, unpredictable "off time" state, and medication refractory tremor. Medication refractory tremor and intolerable dyskinesia are potential palliative indications. Besides aforementioned targets, the brainstem pedunculopontine nucleus (PPN) is under investigation for the treatment of ON-state freezing of gait and postural instability. In this article, we will review the most recent literature on DBS therapy for PD, including cutting-edge advances and data supporting the role of DBS in advanced neural-network modulation.
| S-EPMC4529685 | biostudies-literature
Project description:Introduction Subthalamic Deep Brain Stimulation (STN-DBS) is a safe and well-established therapy for the management of motor symptoms refractory to best medical treatment in patients with Parkinson's disease (PD). Early intervention is discussed especially for Early-onset PD (EOPD) patients that present with an age of onset ≤ 45–50 years and see themselves often confronted with high psychosocial demands. Methods We retrospectively assessed the effect of STN-DBS at 12 months follow-up (12-MFU) in 46 EOPD-patients. Effects of stimulation were evaluated by comparison of disease-specific scores for motor and non-motor symptoms including impulsiveness, apathy, mood, quality of life (QoL), cognition before surgery and in the stimulation ON-state without medication. Further, change in levodopa equivalent dosage (LEDD) after surgery, DBS parameter, lead localization, adverse and serious adverse events as well as and possible additional clinical features were assessed. Results PD-associated gene mutations were found in 15% of our EOPD-cohort. At 12-MFU, mean motor scores had improved by 52.4 ± 17.6% in the STIM-ON/MED-OFF state compared to the MED-OFF state at baseline (p = 0.00; n = 42). These improvements were accompanied by a significant 59% LEDD reduction (p < 0.001), a significant 6.6 ± 16.1 points reduction of impulsivity (p = 0.02; n = 35) and a significant 30 ± 50% improvement of QoL (p = 0.01). At 12-MFU, 9 patients still worked full- and 6 part-time. Additionally documented motor and/or neuropsychiatric features decreased from n = 41 at baseline to n = 14 at 12-MFU. Conclusion The present study-results demonstrate that EOPD patients with and without known genetic background benefit from STN-DBS with significant improvement in motor as well as non-motor symptoms. In line with this, patients experienced a meaningful reduction of additional neuropsychiatric features. Physicians as well as patients have an utmost interest in possible predictors for the putative DBS outcome in a cohort with such a highly complex clinical profile. Longitudinal monitoring of DBS-EOPD-patients over long-term intervals with standardized comprehensive clinical assessment, accurate phenotypic characterization and documentation of clinical outcomes might help to gain insights into disease etiology, to contextualize genomic information and to identify predictors of optimal DBS candidates as well as those in danger of deterioration and/or non-response in the future.
| S-EPMC9713840 | biostudies-literature
Project description:ObjectiveWe used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson's disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer's disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance.MethodsThis study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group.ResultsPatients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities.ConclusionsIn early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD.
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Project description:Mechanisms of deep brain stimulation (DBS) on cortical networks were explored mainly by fMRI. Advanced analysis of high-density EEG is a source of additional information and may provide clinically useful biomarkers. The presented study evaluates EEG microstates in Parkinson's disease and the effect of DBS of the subthalamic nucleus (STN). The association between revealed spatiotemporal dynamics of brain networks and changes in oscillatory activity and clinical examination were assessed. Thirty-seven patients with Parkinson's disease treated by STN-DBS underwent two sessions (OFF and ON stimulation conditions) of resting-state EEG. EEG microstates were analyzed in patient recordings and in a matched healthy control dataset. Microstate parameters were then compared across groups and were correlated with clinical and neuropsychological scores. Of the five revealed microstates, two differed between Parkinson's disease patients and healthy controls. Another microstate differed between ON and OFF stimulation conditions in the patient group and restored parameters in the ON stimulation state toward to healthy values. The mean beta power of that microstate was the highest in patients during the OFF stimulation condition and the lowest in healthy controls; sources were localized mainly in the supplementary motor area. Changes in microstate parameters correlated with UPDRS and neuropsychological scores. Disease specific alterations in the spatiotemporal dynamics of large-scale brain networks can be described by EEG microstates. The approach can reveal changes reflecting the effect of DBS on PD motor symptoms as well as changes probably related to non-motor symptoms not influenced by DBS.
| S-EPMC10110608 | biostudies-literature
Project description:The effect of the surgical site of DBS on balance and gait in Parkinson's Disease (PD) is uncertain. This is the first double-blind study of subjects randomized to either the STN (N = 14) or GPi (N = 14) who were assessed on a range of clinical balance measures.Balance testing occurred before and 6 months postsurgery. A control PD group was tested over the same period without surgery (N = 9). All subjects were tested on and off medication and DBS subjects were also tested on and off DBS. The Postural Instability and Gait Disability items of the UPDRS and additional functional tests, which we call the Balance and Gait scale, were assessed. Activities of Balance Confidence and Activities of Daily Living questionnaires were also recorded.Balance was not different between the best-treated states before and after DBS surgery for both sites. Switching DBS on improved balance scores, and scores further improved with medication, compared to the off state. The GPi group showed improved performance in the postsurgery off state and better ratings of balance confidence after surgery, compared to the STN group.Clinical measures of balance function for both the STN and GPi sites showed that balance did not improve beyond the best medically treated state before surgery. Both clinical balance testing in the off/off state and self-reported balance confidence after surgery showed better performance in the GPi than the STN group.
| S-EPMC4057940 | biostudies-literature
Project description:BackgroundPrevious studies investigated the risk of suicide in patients with Parkinson's disease (PD) but reported discrepant results. Deep brain stimulation (DBS) is an effective therapy for PD, while its effect on suicide risk has seldom been researched. This meta-analysis aimed to estimate the risk of suicide and/or suicidal ideation in PD patients and in PD patients who underwent DBS.MethodsRelevant articles published in the PubMed or EMBASE or CNKI database from 1990 to December 2019 were sourced, and the combined standardized mortality rate (SMR) or odds ratio (OR) was pooled.ResultA total of 1070 articles were found. After screening, 4 cross-sectional studies, 4 cohort studies, 2 randomized controlled trial studies, and 2 case-control studies were included in this meta-analysis. Pooled data indicated that PD patients may have increased risk of suicide (lnSMR, 0.459; 95% confidence interval (CI), 0.286 to 0.632; p < 0.001). No significant difference was found in the risk of suicide when comparing PD patients who underwent DBS with PD patients who received only drug therapy (OR = 2.844, 95%CI: 0.619 to 13.072, p=0.179). DBS may increase the risk of suicide and/or suicidal ideation in PD patients compared with general population (lnSMR = 3.383, 95%CI: 2.839 to 3.927, p < 0.001).ConclusionPD patients have higher risk of suicide and/or suicidal ideation compared with controls, while PD patients who received DBS tend to have an increased risk of suicide or suicidal ideation. Psychological evaluation is needed in PD patients, and pre- and post-operation evaluations are necessary for PD patients who underwent DBS.
| S-EPMC7537696 | biostudies-literature