Subthalamic Nucleus Deep Brain Stimulation Research Articles

Possible improvement of social adjustment after subthalamic deep brain stimulation in people with Parkinson's disease? A systematic review and meta-analysis.

Interactions with others need social adjustment (i.e., the constant accommodation to changing social situations). Mixed evidence indicates positive as well as negative changes in social adjustment after subthalamic nucleus deep brain stimulation (STN-DBS) in people with Parkinson's Disease (PwPD). To date, however, no meta-analysis of these changes exists. Thus, the study aim was to review evidence of the effects of STN-DBS on social adjustment in PwPD. For this purpose, a systematic literature search in MEDLINE was conducted. The meta-analysis was performed using a random effects model and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The MINORS tool was used to assess the methodological quality of the studies. The initial literature search identified 13,124 articles, of which 1,550 full texts were assessed for eligibility. Eight studies were finally included; for seven articles sufficient data for a meta-analysis was available. Most studies found mild impairment in social adjustment impairment pre-surgery. The meta-analysis revealed no significant changes but a statistical trend towards improvement in social adjustment up to six months (SMD = 0.25; 95%CI=-0.03,0.53; P = 0.08) and over 12 months (SMD = 0.26; 95%CI=-0.03,0.55; P = 0.07) post-surgery. Methodological quality was moderate in 87.5% of the studies and good in 12.5%. While mild impairment in social adjustment pre-surgery was reported in most studies, the data indicate that STN-DBS might yield beneficial effects toward this outcome. However, not enough data yet exists to draw firm conclusions. As a crucial skill for everyday functioning, social adjustment should be more often defined as an outcome in STN-DBS trials in PwPD and should be considered in clinical routines.

E.3 fMRI correlates of symptom-specific improvement in STN deep brain stimulation

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal symptoms of Parkinson’s disease (PD). However, the therapeutic mechanisms are incompletely understood. By leveraging patient-specific brain responses to DBS using functional magnetic resonance imaging (fMRI) acquired during stimulation, we identify and validate symptom-specific networks associated with clinical improvement. Methods: Forty PD patients with STN-DBS were enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. The four cardinal motor outcomes of PD were chosen a priori and measured using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRSIII): axial instability, tremor, rigidity, bradykinesia. Stimulation-dependent changes in blood oxygen level-dependent (BOLD) signal were correlated with each symptom. Results: The relationship between BOLD response and outcomes revealed significant networks of clinical response (p<0.001). Using BOLD responses from the network hubs, each symptom-specific model was significantly predictive of actual improvement: axial instability (R2=0.38, p=0.000026), bradykinesia (R2=0.29, p=0.00033), rigidity (R2=0.40, p=0.000013), tremor (R2=0.26, p=0.00073). Conclusions: Using patient-specific imaging, we provide evidence of an association between DBS-evoked fMRI response and individual symptom improvement. Brain networks associated with clinical improvement were different depending on the PD symptom examined, suggesting the presence of symptom-specific networks of efficacy which may allow personalization of DBS therapy.

Premotor cortical beta synchronization and the network neuromodulation of externally paced finger tapping in Parkinson's disease

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13–30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.

Disentangling Bradykinesia and Rigidity in Parkinson's Disease: Evidence from Short- and Long-Term Subthalamic Nucleus Deep Brain Stimulation.

Bradykinesia and rigidity are considered closely related motor signs in Parkinson disease (PD), but recent neurophysiological findings suggest distinct pathophysiological mechanisms. This study aims to examine and compare longitudinal changes in bradykinesia and rigidity in PD patients treated with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). In this retrospective cohort study, the clinical progression of appendicular and axial bradykinesia and rigidity was assessed up to 15 years after STN-DBS in the best treatment conditions (ON medication and ON stimulation). The severity of bradykinesia and rigidity was examined using ad hoc composite scores from specific subitems of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III). Short- and long-term predictors of bradykinesia and rigidity were analyzed through linear regression analysis, considering various preoperative demographic and clinical data, including disease duration and severity, phenotype, motor and cognitive scores (eg, frontal score), and medication. A total of 301 patients were examined before and 1 year after surgery. Among them, 101 and 56 individuals were also evaluated at 10-year and 15-year follow-ups, respectively. Bradykinesia significantly worsened after surgery, especially in appendicular segments (p < 0.001). Conversely, rigidity showed sustained benefit, with unchanged clinical scores compared to preoperative assessment (p > 0.05). Preoperative motor disability (eg, composite scores from the UPDRS-III) predicted short- and long-term outcomes for both bradykinesia and rigidity (p < 0.01). Executive dysfunction was specifically linked to bradykinesia but not to rigidity (p < 0.05). Bradykinesia and rigidity show long-term divergent progression in PD following STN-DBS and are associated with independent clinical factors, supporting the hypothesis of partially distinct pathophysiology. ANN NEUROL 2024;96:234-246.

Impact of subthalamic nucleus deep brain stimulation at different frequencies on neurogenesis in a rat model of Parkinson's disease

Neurogenesis, play a vital role in neuronal plasticity of adult mammalian brains, and its dysregulation is present in the pathophysiology of Parkinson's disease (PD). While subthalamic nucleus deep brain stimulation (STN-DBS) at various frequencies has been proven effective in alleviating PD symptoms, its influence on neurogenesis remains unclear. This study aimed to investigate the effects of 1-week electrical stimulation at frequencies of 60Hz, 130Hz, and 180Hz on neurogenesis in the subventricular zone (SVZ) of PD rats. A hemiparkinsonian rat model was established using 6-hydroxydopamine and categorized into six groups: control, PD, sham stimulation, 60Hz stimulation, 130Hz stimulation, and 180Hz stimulation. Motor function was assessed using the open field test and rotarod test after one week of STN-DBS at different frequencies. Tyrosine hydroxylase (TH) expression in brain tissue was analyzed via Western blot and immunohistochemistry. Immunofluorescence analysis was conducted to evaluate the expression of BrdU/Sox2, BrdU/GFAP, Ki67/GFAP, and BrdU/DCX in bilateral SVZ and the rostral migratory stream (RMS). Our findings revealed that high-frequency STN-DBS improved motor function. Specifically, stimulation at 130Hz increased dopaminergic neuron survival in the PD rat model, while significantly enhancing the proliferation of neural stem cells (NSCs) and neuroblasts in bilateral SVZ. Moreover, this stimulation effectively facilitated the generation of new NSCs in the ipsilateral RMS and triggered the emergence of fresh neuroblasts in bilateral RMS, with notable presence within the lesioned striatum. Conversely, electrical stimulation at 60Hz and 180Hz did not exhibit comparable effects. The observed promotion of neurogenesis in PD rats following STN-DBS provides valuable insights into the mechanistic basis of this therapeutic approach for PD.

Mixed anxiety-depressive disorder in Parkinson's disease associated with worse resting state functional response to deep brain stimulation of subthalamic nucleus

BackgroundParkinson's disease (PD), even though generally perceived as a dominantly motor disorder, is associated with a wide range of non-motor symptoms, including mixed anxiety-depressive disorder (MADD). ObjectivesThe aim of the presented study was to determine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) brings the functional characteristics of non-motor networks closer to the condition detected in healthy population and whether pre-DBS presence of MADD in PD patients was associated with different reaction to this therapeutic modality. MethodsResting-state fMRI signature elicited by STN DBS activation and deactivation in 81 PD patients was compared against healthy controls, with the focus on measures of efficiency of information processing and localised subnetwork differences. ResultsWhile all the MRI metrics showed statistically significant differences between PD patients in DBS OFF condition and healthy controls, none were detected in such a comparison against DBS ON condition. Furthermore, in the post-DBS evaluation, PD patients with MADD in the pre-DBS stage showed no differences in depression scales compared to pre-DBS psychiatrically intact PD patients, but still exhibited lower DBS-related connectivity in a subnetwork encompassing anterior and posterior cingulate, dorsolateral prefrontal and medial temporal cortices. ConclusionsSTN DBS improved all the metrics of interest towards the healthy state, normalising the resting-state MRI signature of PD. Furthermore, pre-DBS presence of MADD, even though clinically silent at post-DBS MRI acquisition, was associated with lower DBS effect in areas highly relevant for depression. This finding points to a possibly latent nature of post-DBS MADD, calling for caution in further follow-up of these patients.

Delayed-onset seizures after subthalamic nucleus deep brain stimulation surgery for Parkinson’s disease

BackgroundDelayed-onset seizures after deep brain stimulation (DBS) surgery were seldom reported. This study summarized the clinical characteristics of delayed-onset seizures after subthalamic nucleus (STN) DBS surgery for Parkinson’s disease (PD) and analyzed risk factors. MethodsA single-center retrospective study containing consecutive STN-DBS PD patients from 2006 to 2021 was performed. Seizures occurred during the DBS surgery or within one month after DBS surgery were identified based on routine clinical records. Patients with postoperative magnetic resonance imaging (MRI) were included to further analyze the risk factors for postoperative seizures with univariate and multivariate statistical methods. Results341 consecutive PD patients treated with bilateral STN-DBS surgery wereidentified, and five patients experienced seizures after DBS surgery with an incidence of 1.47 %. All seizures of the five cases were characterized as delayed onset with average 12 days post-operatively. All seizures presented as generalized tonic-clonic seizures and didn’t recur after the first onset. In those seizures cases, peri-electrode edema was found in both hemispheres without hemorrhage and infarction. The average diameter of peri-electrode edema of patients with seizures was larger than those without seizures (3.15 ± 1.00 cm vs 1.57 ± 1.02 cm, p = 0.005). Multivariate risk factor analysis indicated that seizures were only associated with the diameter of peri-electrode edema (OR 4.144, 95 % CI 1.269–13.530, p = 0.019). ConclusionsDelayed-onset seizures after STN-DBS surgery in PD patients were uncommon with an incidence of 1.47 % in this study. The seizures were transient and self-limiting, with no developing into chronic epilepsy. Peri-electrode edema was a risk factor for delayed-onset seizures after DBS surgery. Patients with an average peri-electrode edema diameter > 2.70 cm had a higher risk to develop seizures.

General anesthesia versus local anesthesia for deep brain stimulation targeting of STN in Parkinson's disease: A systematic review and meta-analysis.

Subthalamic nucleus deep brain stimulation (STN-DBS) is a viable therapeutic for advanced Parkinson's disease. However, the efficacy and safety of STN-DBS under local anesthesia (LA) versus general anesthesia (GA) remain controversial. This meta-analysis aims to compare them using an expanded sample size. The databases of Embase, Cochrane Library and Medline were systematically searched for eligible cohort studies published between 1967 and 2023. Clinical efficacy was assessed using either Unified Parkinson's Disease Rating Scale (UPDRS) section III scores or levodopa equivalent dosage requirements. Subgroup analyses were performed to assess complications (adverse effects related to stimulation, general neurological and surgical complications, and hardware-related complications). Fifteen studies, comprising of 13 retrospective cohort studies and 2 prospective cohort studies, involving a total of 943 patients were included in this meta-analysis. The results indicate that there were no significant differences between the 2 groups with regards to improvement in UPDRS III score or postoperative levodopa equivalent dosage requirement. However, subgroup analysis revealed that patients who underwent GA with intraoperative imaging had higher UPDRS III score improvement compared to those who received LA with microelectrode recording (MER) (P = .03). No significant difference was found in the improvement of UPDRS III scores between the GA group and LA group with MER. Additionally, there were no notable differences in the incidence rates of complications between these 2 groups. Our meta-analysis indicates that STN-DBS performed under GA or LA have similar clinical outcomes and complications. Therefore, GA may be a suitable option for patients with severe symptoms who cannot tolerate the procedure under LA. Additionally, the GA group with intraoperative imaging showed better clinical outcomes than the LA group with MER. A more compelling conclusion would require larger prospective cohort studies with a substantial patient population and extended long follow-up to validate.

Effects of Unilateral High Frequency Stimulation of the Subthalamic Nucleus on Risk-avoidant Behavior in a Partial 6-hydroxydopamine Model of Parkinson's Disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.

Deep Brain Stimulation Modulates the Visual Pathway to Improve Freezing of Gait in Parkinson's Disease Patients

ObjectiveTo investigate the involvement of the visual cortex in improving freezing of gait (FoG) after subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD) patients using whole-brain seed-based functional connectivity. MethodsA total of 66 PD patients with FoG who underwent bilateral STN-DBS were included in our study. Patients were divided into a FoG responder group (FoG-R) and an FoG non-responder group (FoG-nonR) according to whether FoG improved one year after DBS. We compared the differences in clinical characteristics, brain structural imaging and seed-based functional connectivity between the two groups. The locations of active contacts were further analyzed. ResultsAll PD patients benefited from STN-DBS. No significant differences in the baseline characteristics or brain structures were found between the two groups. Seed-based functional connectivity analysis revealed that better connectivity in bilateral primary visual areas was associated with better clinical improvement in FoG (p < 0.05 familywise error [FWE] corrected). Further analysis revealed that this disparity was associated with the location of the active contacts within the rostral region of the sensorimotor subregion in the FoG-R group, in contrast to the findings in the FoG-nonR group. ConclusionThis study suggested that DBS in the rostral region of the STN sensorimotor subregion may alleviate FoG by strengthening functional connectivity in primary visual areas, which has significant implications for guiding surgical strategies for FoG in the future.

Rescue Lead Implantation After Deep Brain Stimulation for Parkinson's Disease: A Single-Center Experience and Case Series.

Despite the well-established efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's Disease (PD), there remains a subset of patients with only a moderate improvement in symptoms even with appropriate lead placement and optimal programming. In patients with persistent tremor or dyskinesias, one consideration is the addition of a second "rescue lead" to provide dual stimulation to primary and secondary targets to address the refractory component. This study aimed to assess all "rescue lead" cases from our institution and characterize the patients and their outcomes. Records of all patients with PD treated at our institution between 2005 and 2023 were retrospectively reviewed. Clinical data of all patients treated with a second rescue lead to supplement a positive but inadequate initial DBS response were collected and reviewed. Of 670 patients with PD treated at our institution during the study period, 7 were managed with a rescue lead. All 7 were initially treated with STN DBS with a partial improvement in underlying symptoms, had confirmed appropriate lead placement, and underwent thorough programming. Four patients underwent rescue with a globus pallidus interna lead for persistent dyskinesias, all with subsequent improvement in their dyskinesias. Three patients had persistent tremors that were treated with a rescue ventrointermediate thalamus stimulation with subsequent improvement in tremor scores. There were no operative complications, and all patients tolerated dual stimulation. For a small subset of patients with PD with persistent dyskinesias or tremors after STN DBS despite optimized lead parameters and adequate lead placement, rescue lead placement offers an effective treatment option.

Evaluation of Predictors of Treatment Response in Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease Using Connectomics and Wearable Sensors (P1-3.010)

Evaluation of Predictors of Treatment Response in Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease Using Connectomics and Wearable Sensors (P1-3.010)

Exploring Outcome Differences of a Rhythmic Auditory Stimulation-enhanced Walking Program for Veterans with Parkinson’s Disease with and Without Subthalamic Nucleus Deep Brain Stimulation (P1-3.008)

Exploring Outcome Differences of a Rhythmic Auditory Stimulation-enhanced Walking Program for Veterans with Parkinson’s Disease with and Without Subthalamic Nucleus Deep Brain Stimulation (P1-3.008)

Assessment of lmage-guided Programming (IGP) on Bilateral STN and GPi Deep Brain Stimulation Programming Time (P1-3.003)

Assessment of lmage-guided Programming (IGP) on Bilateral STN and GPi Deep Brain Stimulation Programming Time (P1-3.003)

Subthalamic Nucleus DBS Sub-harmonic Oscillatory Activity Reflect Presence or Absence of DBS Responsiveness (P1-3.013)

Subthalamic Nucleus DBS Sub-harmonic Oscillatory Activity Reflect Presence or Absence of DBS Responsiveness (P1-3.013)

490 Unilateral Subthalamic Nucleus Deep Brain Stimulation Improves Motor Symptoms Without Neurocognitive Worsening in Parkinsons Disease

INTRODUCTION: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical intervention for patients with medically refractory Parkinson’s disease (PD). Numerous reports have described adverse nonmotor side effects, such as declines in verbal fluency and working memory, following bilateral implantation. Unilateral STN DBS is a possible alternative; however, it remains unclear whether unilateral implantation meaningfully reduces harmful effects on cognition. METHODS: This retrospective cohort study utilized chart review to collect pre- and postoperative Unified Parkinson’s Disease Rating Scale (UPDRS)-III, Levodopa Equivalent Daily Dosage (LEDD), imaging, and neurocognitive test results from 32 patients (unilateral, n = 12; bilateral, n = 20). For all statistical comparisons, p-values less than or equal to 0.05 were considered statistically significant. Student’s unpaired and paired T-tests were used to assess for differences between groups and within groups, respectively. RESULTS: There was no difference across 17 preoperative neurocognitive tests. Both unilateral and bilateral STN DBS resulted in significant decreases in postoperative UPDRS-III and LEDD (unilateral: p &lt; 0.0001; bilateral: p &lt; 0.0001) scores. There were no differences in the absolute decreases in UPDRS (p=0.055) and LEDD (p=0.120) scores between the groups. The bilateral STN DBS group had a significant deterioration in verbal fluency (COWAT FAS, p = 0.002; COWAT Animals, p = 0.014) and attention/executive function (Trails A, p=0.049 and Trails B, p = 0.011) compared to the unilateral group. CONCLUSIONS: Unilateral STN DBS is an effective and safe treatment option for patients with advanced PD. Particularly for patients with asymmetric motor symptoms, unilateral implantation provides a meaningful improvement in motor symptoms and reductions in dopaminergic medications without the risk of neurocognitive decline seen in bilateral implantation.

Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Benefits of subthalamic nucleus deep brain stimulation on visually-guided saccades depend on stimulation side and classic paradigm in Parkinson’s disease

ObjectiveWe aimed to gain further insight into previously reported beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on visually-guided saccades by examining the effects of unilateral compared to bilateral stimulation, paradigm, and target eccentricity on saccades in individuals with Parkinson’s disease (PD). MethodsEleven participants with PD and STN-DBS completed the visually-guided saccade paradigms with OFF, RIGHT, LEFT, and BOTH stimulation. Rightward saccade performance was evaluated for three paradigms and two target eccentricities. ResultsFirst, we found that BOTH and LEFT increased gain, peak velocity, and duration compared to OFF stimulation. Second, we found that BOTH and LEFT stimulation decreased latency during the gap and step paradigms but had no effect on latency during the overlap paradigm. Third, we found that RIGHT was not different compared to OFF at benefiting rightward saccade performance. ConclusionsLeft unilateral and bilateral stimulation both improve the motor outcomes of rightward visually-guided saccades. Additionally, both improve latency, a cognitive-motor outcome, but only in paradigms when attention does not require disengagement from a present stimulus. SignificanceSTN-DBS primarily benefits motor and cognitive-motor aspects of visually-guided saccades related to reflexive attentional shifting, with the latter only evident when the fixation-related attentional system is not engaged.

Individual Structural Covariance Network Predicts Long-Term Motor Improvement in Parkinson Disease with Subthalamic Nucleus Deep Brain Stimulation.

The efficacy of long-term chronic subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson disease (PD) exhibits substantial variability among individuals. The preoperative identification of suitable deep brain stimulation (DBS) candidates through predictive means becomes crucial. Our study aims to investigate the predictive value of characterizing individualized structural covariance networks for long-term efficacy of DBS, offering patients a precise and cost-effective preoperative screening tool. We included 138 patients with PD and 40 healthy controls. We developed individualized structural covariance networks from T1-weighted images utilizing network template perturbation, and computed the networks' topological characteristics. Patients were categorized according to their long-term motor improvement following STN-DBS. Intergroup analyses were conducted on individual network edges and topological indices, alongside correlation analyses with long-term outcomes for the entire patient cohort. Finally, machine learning algorithms were employed for regression and classification to predict post-DBS motor improvement. Among the patients with PD, 6 edges (left middle frontal and left caudate nucleus, right olfactory and right insula, left superior medial frontal gyrus and right insula, right middle frontal and left paracentral lobule, right middle frontal and cerebellum, left lobule VIIb of the cerebellum and the vermis of the cerebellum) exhibited significant results in intergroup comparisons and correlation analyses. Increased degree centrality and local efficiency of the cerebellum, parahippocampal gyrus, and postcentral gyrus were associated with DBS improvement. A regression model constructed from these 6 edges revealed a significant correlation between predicted and observed changes in the unified PD rating scale (R = 0.671, P < .001) and receiver operating characteristic analysis demonstrated an area under the curve of 0.802, effectively distinguishing between patients with good and moderate improvement post-DBS. Our findings reveal the link between individual structural covariance network fingerprints in patients with PD and long-term motor outcome following STN-DBS. Additionally, binary and continuous cerebellum-basal ganglia-frontal structural covariance network edges have emerged as potential predictive biomarkers for DBS motor outcome.

Effects of subthalamic nucleus deep brain stimulation using different frequency programming paradigms on axial symptoms in advanced Parkinson's disease.

In advanced Parkinson's disease (PD), axial symptoms are common and can be debilitating. Although deep brain stimulation (DBS) significantly improves motor symptoms, conventional high-frequency stimulation (HFS) has limited effectiveness in improving axial symptoms. In this study, we investigated the effects on multiple axial symptoms after DBS surgery with three different frequency programming paradigms comprising HFS, low-frequency stimulation (LFS), and variable-frequency stimulation (VFS). This study involved PD patients who had significant preoperative axial symptoms and underwent bilateral subthalamic nucleus (STN) DBS. Axial symptoms, motor symptoms, medications, and quality of life were evaluated preoperatively (baseline). One month after surgery, HFS was applied. At 6months post-surgery, HFS assessments were performed, and HFS was switched to LFS. A further month later, we conducted LFS assessments and switched LFS to VFS. At 8months after surgery, VFS assessments were performed. Of the 21 PD patients initially enrolled, 16 patients were ultimately included in this study. Regarding HFS, all axial symptoms except for the Berg Balance Scale (p < 0.0001) did not improve compared with the baseline (all p > 0.05). As for LFS and VFS, all axial symptoms improved significantly compared with both the baseline and HFS (all p < 0.05). Moreover, motor symptoms and medications were significantly better than the baseline (all p < 0.05) after using LFS and VFS. Additionally, the quality of life of the PD patients after receiving LFS and VFS was significantly better than at the baseline and with HFS (all p < 0.0001). Our findings indicate that HFS is ineffective at improving the majority of axial symptoms in advanced PD. However, both the LFS and VFS programming paradigms exhibit significant improvements in various axial symptoms.