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

OBJECTIVE: We 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). METHODS: Eleven 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. RESULTS: First, 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. CONCLUSIONS: Left 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. SIGNIFICANCE: STN-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.

Deep-Brain Subthalamic Nucleus Stimulation Enhances Food-Related Motivation by Influencing Neuroinflammation and Anxiety Levels in a Rat Model of Early-Stage Parkinson's Disease.

Deep-brain subthalamic nucleus stimulation (DBS-STN) has become a well-established therapeutic option for advanced Parkinson's disease (PD). While the motor benefits of DBS-STN are widely acknowledged, the neuropsychiatric effects are still being investigated. Beyond its immediate effects on neuronal circuits, emerging research suggests that DBS-STN might also modulate the peripheral inflammation and neuroinflammation. In this work, we assessed the effects of DBS-STN on food-related motivation, food intake pattern, and the level of anxiety and compared them with markers of cellular and immune activation in nigrostriatal and mesolimbic areas in rats with the 6-OHDA model of early PD. To evaluate the potential mechanism of observed effects, we also measured corticosterone concentration in plasma and leukocyte distribution in peripheral blood. We found that DBS-STN applied during neurodegeneration has beneficial effects on food intake pattern and motivation and reduces anxiety. These behavioral effects occur with reduced percentages of IL-6-labeled cells in the ventral tegmental area and substantia nigra pars compacta in the stimulated brain hemisphere. At the same brain structures, the cFos cell activations were confirmed. Simultaneously, the corticosterone plasma concentration was elevated, and the peripheral blood lymphocytes were reduced after DBS-STN. We believe that comprehending the relationship between the effects of DBS-STN on inflammation and its therapeutic results is essential for optimizing DBS therapy in PD.

Medication only improves limb movements while deep brain stimulation improves eye and limb movements during visually-guided reaching in Parkinson's disease.

Background: Antiparkinson medication and subthalamic nucleus deep brain stimulation (STN-DBS), two common treatments of Parkinson's disease (PD), effectively improve skeletomotor movements. However, evidence suggests that these treatments may have differential effects on eye and limb movements, although both movement types are controlled through the parallel basal ganglia loops. Objective: Using a task that requires both eye and upper limb movements, we aimed to determine the effects of medication and STN-DBS on eye and upper limb movement performance. Methods: Participants performed a visually-guided reaching task. We collected eye and upper limb movement data from participants with PD who were tested both OFF and ON medication (n = 34) or both OFF and ON bilateral STN-DBS while OFF medication (n = 11). We also collected data from older adult healthy controls (n = 14). Results: We found that medication increased saccade latency, while having no effect on reach reaction time (RT). Medication significantly decreased saccade peak velocity, while increasing reach peak velocity. We also found that bilateral STN-DBS significantly decreased saccade latency while having no effect on reach RT, and increased saccade and reach peak velocity. Finally, we found that there was a positive relationship between saccade latency and reach RT, which was unaffected by either treatment. Conclusion: These findings show that medication worsens saccade performance and benefits reaching performance, while STN-DBS benefits both saccade and reaching performance. We explore what the differential beneficial and detrimental effects on eye and limb movements suggest about the potential physiological changes occurring due to treatment.

Illness perceptions in pre-operative Parkinson's disease patients.

Parkinson's disease (PD) is a neurodegenerative disease, that combines motor and non-motor disorders, and alters patients' autonomy. Even if subthalamic nucleus deep brain stimulation (STN-DBS) induces undisputable motor improvement, a post-operative social maladjustment was described by some patients. Our aim was to describe pre-operative illness perceptions in parkinsonian patients, and to determine the possible impact of cognitive restructuration over them. We analyzed 27 parkinsonian patient's candidates to DBS. The mean age was 59 ± 5.94 years, and mean disease duration was 9.89 ± 4.15 years. The patients had two pre-operative psychological interviews (DBS-45 days, DBS-25 days) and completed the Illness Perception Questionnaire-Revised (IPQ-R) before the first interview and at DBS-1 day. The CRTG group (n = 13) had cognitive restructuration during second interview, on dysfunctional cognitions about their perception of post-DBS life which emerged from the first interview. The PIG group (n = 14) benefited of two non-structured interviews. No significant differences were found between the visits (DBS-45 days, DBS-1 day) for IPQ-R dimensions, except for the perception of "personal control" over PD which appears significantly higher for CRTG than PIG group (p = .039) at DBS-1 day, whereas the scores were quite similar at DBS-45 days. Illness perceptions seem to be stable over time and mostly influenced by disease experience of PD. However, the perception of personal control over PD seemed to be modulated through cognitive restructuration, giving patients' control back over disease. Before DBS, illness perceptions investigation and restructuration constitute an interesting point to work on, to enhance perceived benefits of neurosurgery.Trial registration: Clinical Research Program, N°IDRCB 2008-A00655-50, approved by the local ethics committee (CPP EST III, N° CPP: 08.07.03, first version date: 04/01/2008), registered on the ClinicalTrials.gov website (NCT02893449).

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies? / ¿La estimulación cerebral profunda del núcleo subtalámico afecta el equilibrio estático en diferentes frecuencias?

Purpose To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. Materials and methods Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were ‘stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)’. These tests reported the centre of pressure data ‘ellipse area, perimeter, front/back and mediolateral standard deviations’. Results There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward–backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). Conclusion This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges (AU)

Propósito Investigar los efectos de la estimulación cerebral profunda del núcleo subtalámico bilateral (STN-DBS) con diferentes frecuencias de estimulación sobre el equilibrio estático. Materiales y métodos Se incluyó en el estudio a 20 pacientes (15 varones y 5 mujeres), con edades comprendidas entre 43 y 81 años (media: 60,05±7,4), que habían sido diagnosticados de enfermedad de Parkinson idiopática e intervenidos mediante cirugía STN-DBS. El equilibrio estático se evaluó con el sistema de rehabilitación TecnoBody en 4 frecuencias diferentes: 230, 130, 90 y 60Hz y sin estimulación. Las pruebas de equilibrio estático fueron: prueba estabilométrica, ojo cerrado/abierto bípedo comparado con estabilométrico, monopedal comparado con estabilométrico (pie derecho/izquierdo). Estas pruebas informaron el centro de datos de presión: área de elipse, perímetro, desviaciones estándar mediolateral y frontal/posterior. Resultados No hubo diferencias estadísticamente significativas entre los resultados de la prueba de equilibrio estático en cualquier frecuencia (p>0,05), pero los resultados fueron mejores con 90Hz. El resultado de la desviación estándar hacia adelante-atrás del ojo abierto bípedo comparado con el estabilométrico fue significativo entre la estimulación inactiva y 130Hz (p=0,04). La estimulación de diferente frecuencia afectó al porcentaje de categorías de equilibrio estático, sin significación estadística entre la estimulación inactiva y otras (todas p>0,05). Conclusión Este estudio mostró que STN-DBS no afectó negativamente al equilibrio estático. La estimulación de baja frecuencia mejoró el equilibrio estático. Los sistemas de posturografía darán resultados más precisos y cuantitativos en estudios similares con amplios rangos de frecuencia (AU)

Intraoperative microelectrode recording under general anesthesia guided subthalamic nucleus deep brain stimulation for Parkinson's disease: One institution's experience.

Objective: Microelectrode recording (MER) guided subthalamic nucleus deep brain stimulation (STN-DBS) under local anesthesia (LA) is widely applied in the management of advanced Parkinson's disease (PD). Whereas, awake DBS under LA is painful and burdensome for PD patients. We analyzed the influence of general anesthesia (GA) on intraoperative MER, to assess the feasibility and effectiveness of GA in MER guided STN-DBS. Methods: Retrospective analysis was performed on the PD patients, who underwent bilateral MER guided STN-DBS in Wuhan Union Hospital from July 2019 to December 2021. The patients were assigned to LA or GA group according to the anesthetic methods implemented. Multidimensional parameters, including MER signals, electrode implantation accuracy, clinical outcome and adverse events, were analyzed. Results: A total of 40 PD patients were enrolled in this study, including 18 in LA group and 22 in GA group. There were no statistically significant differences in patient demographics and baseline characteristics between two groups. Although, the parameters of MER signal, including frequency, inter-spike interval (ISI) and amplitude, were obviously interfered under GA, the waveforms of MER signals were recognizable and shared similar characteristics with LA group. Both LA and GA could achieve effective electrode implantation accuracy and clinical outcome. They also shared similar adverse events postoperatively. Conclusion: GA is viable and comparable to LA in MER guided STN-DBS for PD, regarding electrode implantation accuracy, clinical outcome and adverse events. Notably, GA is more friendly and acceptable to the patients who are incapable of enduring intraoperative MER under LA.

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies?

PURPOSE: To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. MATERIALS AND METHODS: Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were 'stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)'. These tests reported the centre of pressure data 'ellipse area, perimeter, front/back and mediolateral standard deviations'. RESULTS: There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward-backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). CONCLUSION: This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges.

Physical activity levels in people with Parkinson's disease treated by subthalamic nucleus deep brain stimulation.

PURPOSE: To explore the physical activity of people with Parkinson's disease (PD) with subthalamic nucleus deep brain stimulation (STN-DBS) and investigate factors associated with physical activity. METHODS: Twenty-four participants who had STN-DBS for one or more years were recruited. Eligibility criteria included Hoehn and Yahr stage ≤ 4, continuation of STN-DBS, living at home and able to provide informed consent. Physical activity was measured using the self-report physical activity scale for the elderly (PASE). Motor and non-factors that influence physical activity in PD, such as gait disturbance and mood, were recorded using clinical measures. RESULTS: Participants had long-standing PD of moderate severity, mean Hoehn and Yahr 2.3, and mild to moderate functional disability, MDS-UPDRS M-EDL mean 16.2. PASE scores were significantly lower compared to norms for adults ≤ 70 years (115.2 versus 143, p= 0.045). There was a significant negative correlation between PASE scores and falls history, fatigue, fear of falling (FOF) and quality of life (p < 0.05). CONCLUSIONS: This study provides further evidence that physical activity levels in PD with STN-DBS remain low compared to PASE norms for older adults. Future research investigating interventions to improve factors associated with low physical activity levels should be considered.Implications for RehabilitationDespite the benefits of deep brain stimulation (DBS) on motor function and activities of daily living, physical activity levels remain low in people with Parkinson's disease (PD) with subthalamic nucleus (STN)-DBS compared to norms for older adults.A history of falls, greater fear of falling (FOF) and higher levels of fatigue are associated with lower levels of physical activity in people with PD with STN-DBS.When planning rehabilitation interventions consideration should be given to strategies that promote and support regular physical activity for people with PD with STN-DBS.Rehabilitation clinicians should consider using falls prevention programmes and include strategies to decrease FOF for people with PD with STN-DBS.Consideration should be given to the presence of fatigue when planning the rehabilitation programme for the person with PD with STN-DBS.

Encoding type, medication, and deep brain stimulation differentially affect memory-guided sequential reaching movements in Parkinson's disease.

Memory-guided movements, vital to daily activities, are especially impaired in Parkinson's disease (PD). However, studies examining the effects of how information is encoded in memory and the effects of common treatments of PD, such as medication and subthalamic nucleus deep brain stimulation (STN-DBS), on memory-guided movements are uncommon and their findings are equivocal. We designed two memory-guided sequential reaching tasks, peripheral-vision or proprioception encoded, to investigate the effects of encoding type (peripheral-vision vs. proprioception), medication (on- vs. off-), STN-DBS (on- vs. off-, while off-medication), and compared STN-DBS vs. medication on reaching amplitude, error, and velocity. We collected data from 16 (analyzed n = 7) participants with PD, pre- and post-STN-DBS surgery, and 17 (analyzed n = 14) healthy controls. We had four important findings. First, encoding type differentially affected reaching performance: peripheral-vision reaches were faster and more accurate. Also, encoding type differentially affected reaching deficits in PD compared to healthy controls: peripheral-vision reaches manifested larger deficits in amplitude. Second, the effect of medication depended on encoding type: medication had no effect on amplitude, but reduced error for both encoding types, and increased velocity only during peripheral-vision encoding. Third, the effect of STN-DBS depended on encoding type: STN-DBS increased amplitude for both encoding types, increased error during proprioception encoding, and increased velocity for both encoding types. Fourth, STN-DBS was superior to medication with respect to increasing amplitude and velocity, whereas medication was superior to STN-DBS with respect to reducing error. We discuss our findings in the context of the previous literature and consider mechanisms for the differential effects of medication and STN-DBS.

The effect of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation in Parkinson's disease patients.

BACKGROUND: Previous studies have reported the effects of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation (STN-DBS) of Parkinson's disease (PD) patients. However, available data involving these issues are not consistent. In particular, the effect of age and disease duration on the initial efficacy of STN-DBS has not been established. METHODS: A total of 51 patients with PD treated with bilateral STN-DBS were involved in the present study. They received clinical symptom evaluation during the preoperative, initial, and chronic stages of surgery. The correlations between age when undergoing surgery/age at disease onset/disease duration and outcomes of STN-DBS were measured. RESULTS: The preoperative levodopa response was negatively associated with age. During the initial stage, the age when undergoing surgery and age at disease onset were negatively correlated with the effect on bradykinesia, with better symptom control of general symptoms in long-term disease patients. Similarly, patients with an early time of surgery and disease onset and long-term disease duration showed better control of bradykinesia and axial symptoms at the chronic stage. Furthermore, a long-term disease duration and early disease onset benefited from an increase of therapeutic efficacy in general, rigid, and axial symptoms with STN-DBS after a long period. Nevertheless, patients with late disease onset achieved a better relief of stigma. CONCLUSION: Age and disease durations played a unique role in controlling the symptoms of PD patients treated with STN-DBS. These results may contribute to patient selection and adjustments of expectations of surgery, based on the age, disease duration, and different symptoms.

Investigation of the changes in the presynaptic inhibition in association with the subthalamic nucleus stimulation in Parkinson's disease.

BACKGROUND AND PURPOSE: Presynaptic inhibition (PSI) is a critical spinal inhibitory mechanism for modulating muscle coordination by adjusting both supraspinal motor commands and sensory feedback at the spinal level. The literature data regarding the role of PSI in the efficiency of STN-DBS therapy in Parkinson's disease (PD) are limited. We aimed to investigate the possible alteration in this pathway in association with the STN stimulation (STIM) within the very early period after the STIM is off. METHODS: We performed the H-reflex investigation on 8 PD subjects with STN-DBS who applied to our polyclinic for routine clinical evaluations. The investigations were initially performed at the STIM-on period and repeated after the STIM set is off for 5 min. A within-subjects ANOVA was used to test for a significant difference between the STIM-on and -off states for the variables of (repeated measures) H-latency, H amplitude, M amplitude, H/M amplitude, H threshold, and M threshold. RESULTS: The results of the analyses did not reveal marked changes in the variables of the H-reflex between the STIM-on and -off states. CONCLUSION: PSI do not alter in the very early period after the STIM is off. Taken together with the related literature data and our study results, it can be hypothesized that the PSI might involve in the DBS efficiency in the later phase of the STIM as a compensatory mechanism. Further prospective studies including a larger number of patients with serial electrophysiological recordings to investigate the temporal course of the underlying dynamics are required to clarify these discussions.

Effects of Bilateral Subthalamic Nucleus Stimulation on Depressive Symptoms and Cerebral Glucose Metabolism in Parkinson's Disease: A 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography Study.

Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor symptoms in Parkinson's disease (PD), as well as potentially improving otherwise intractable comorbid depressive symptoms. To address the latter issue, we evaluated the severity of depressive symptoms along with the severity of motor symptoms in 18 PD patients (mean age, 58.4 ± 5.4 years; 9 males, 9 females; mean PD duration, 9.4 ± 4.4 years) with treatment-resistant depression (TRD) before and after approximately 1 year of STN-DBS treatment. Moreover, to gain more insight into the brain mechanism mediating the therapeutic action of STN-DBS, we utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess cerebral regional glucose metabolism in the patients at baseline and 1-year follow-up. Additionally, the baseline PET data from patients were compared with PET data from an age- and sex-matched control group of 16 healthy volunteers. Among them, 12 PD patients underwent post-operative follow-up PET scans. Results showed that the severity of both motor and depressive symptoms in patients with PD-TRD was reduced significantly at 1-year follow-up. Also, patients used significantly less antiparkinsonian medications and antidepressants at 1-year follow-up, as well as experiencing improved daily functioning and a better quality of life. Moreover, relative to the PET data from healthy controls, PD-TRD patients displayed widespread abnormalities in cerebral regional glucose metabolism before STN-DBS treatment, which were partially recovered at 1-year follow-up. Additionally, significant correlations were observed between the patients' improvements in depressive symptoms following STN-DBS and post-operative changes in glucose metabolism in brain regions implicated in emotion regulation. These results support the view that STN-DBS provides a promising treatment option for managing both motor and depressive symptoms in patients who suffer from PD with TRD. However, the results should be interpreted with caution due to the observational nature of the study, small sample size, and relatively short follow-up.

The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. OBJECTIVES: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. METHODS: Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. RESULTS: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) ~3.8 mm. CONCLUSIONS: The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predict initial subthalamic nucleus stimulation outcome in Parkinson's disease with brain morphology.

AIM: Subthalamic nucleus deep brain stimulation (STN-DBS) has been reported to be effective in treating motor symptoms in Parkinson's disease (PD), which may be attributed to changes in the brain network. However, the association between brain morphology and initial STN-DBS efficacy, as well as the performance of prediction using neuroimaging, has not been well illustrated. Therefore, we aim to investigate these issues. METHODS: In the present study, 94 PD patients underwent bilateral STN-DBS, and the initial stimulation efficacy was evaluated. Brain morphology was examined by magnetic resonance imaging (MRI). The volume of tissue activated in the motor STN was measured with MRI and computed tomography. The prediction of stimulation efficacy was achieved with a support vector machine, using brain morphology and other features, after feature selection and hyperparameter optimization. RESULTS: A higher stimulation efficacy was correlated with a thicker right precentral cortex. No association with subcortical gray or white matter volumes was observed. These morphological features could estimate the individual stimulation response with an r value of 0.5678, an R2 of 0.3224, and an average error of 11.4%. The permutation test suggested these predictions were not based on chance. CONCLUSION: Our results indicate that changes in morphology are associated with the initial stimulation motor response and could be used to predict individual initial stimulation-related motor responses.

StimFit-A Data-Driven Algorithm for Automated Deep Brain Stimulation Programming.

BACKGROUND: Finding the optimal deep brain stimulation (DBS) parameters from a multitude of possible combinations by trial and error is time consuming and requires highly trained medical personnel. OBJECTIVE: We developed an automated algorithm to identify optimal stimulation settings in Parkinson's disease (PD) patients treated with subthalamic nucleus (STN) DBS based on imaging-derived metrics. METHODS: Electrode locations and monopolar review data of 612 stimulation settings acquired from 31 PD patients were used to train a predictive model for therapeutic and adverse stimulation effects. Model performance was then evaluated within the training cohort using cross-validation and on an independent cohort of 19 patients. We inverted the model by applying a brute-force approach to determine the optimal stimulation sites in the target region. Finally, an optimization algorithm was established to identify optimal stimulation parameters. Suggested stimulation parameters were compared to the ones applied in clinical practice. RESULTS: Predicted motor outcome correlated with observed outcome (R = 0.57, P < 10-10 ) across patients within the training cohort. In the test cohort, the model explained 28% of the variance in motor outcome differences between settings. The stimulation site for maximum motor improvement was located at the dorsolateral border of the STN. When compared to two empirical settings, model-based suggestions more closely matched the setting with superior motor improvement. CONCLUSION: We developed and validated a data-driven model that can suggest stimulation parameters leading to optimal motor improvement while minimizing the risk of stimulation-induced side effects. This approach might provide guidance for DBS programming in the future. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BDNF rs6265 Genotype Influences Outcomes of Pharmacotherapy and Subthalamic Nucleus Deep Brain Stimulation in Early-Stage Parkinson's Disease.

INTRODUCTION: The efficacy of pharmacotherapy and deep brain stimulation of the subthalamic nucleus in treating Parkinson's disease motor symptoms is highly variable and may be influenced by patient genotype. The relatively common (prevalence about one in three) and protein-altering rs6265 single nucleotide polymorphism (C > T) in the gene BDNF has been associated with different clinical outcomes with levodopa. OBJECTIVE: We sought to replicate this reported association in early-stage Parkinson's disease subjects and to examine whether a difference in clinical outcomes was present with subthalamic nucleus deep brain stimulation. MATERIALS AND METHODS: Fifteen deep brain stimulation and 13 medical therapy subjects were followed for 24 months as part of the Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152, FDA IDE #G050016). Primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39. RESULTS: Outcomes with drug therapy in subjects carrying the rs6265 T allele were significantly worse following 12 months of treatment compared to C/C subjects (UPDRS: +20 points, p = 0.019; PDQ-39: +16 points, p = 0.018). In contrast, rs6265 genotype had no effect on overall motor response to subthalamic nucleus deep brain stimulation at any time point; further, rs6265 C/C subjects treated with stimulation were associated with worse UPDRS part II scores at 24 months compared to medical therapy. CONCLUSIONS: Genotyping for the rs6265 polymorphism may be useful for predicting long-term response to drug therapy and counseling Parkinson's disease patients regarding whether to consider earlier subthalamic nucleus deep brain stimulation. Validation in a larger cohort of early-stage Parkinson's disease subjects is warranted.

Instability of speech in Parkinson disease patients with subthalamic nucleus deep brain stimulation.

INTRODUCTION: The impact of deep brain stimulation (DBS) on speech rhythm and its mechanism remains unclear. We investigated speech rhythm characteristics of patients with Parkinson's disease (PD) treated with subthalamic nucleus (STN) DBS to understand the underlying pathophysiology better. METHODS: We enrolled a total of 105 participants and evaluated speech rhythm performances among patients with PD who had undergone STN-DBS (the PD-DBS group), patients with PD treated only with medication (the PD-Med group), patients with cerebellar ataxia (the CA group), and healthy controls (the HC group). Each participant was asked to repeat the syllable/pa/at a comfortable self-chosen steady pace. A widely-used software (the Motor Speech Profile) program performed an acoustic analysis. RESULTS: Compared to the PD-Med and HC groups, speech rate instability (DDKjit) was significantly higher in the PD-DBS and CA groups (p < 0.01). However, after DBS was turned off, the DDKjit of the PD-DBS group improved to a level comparable to that of the PD-Med and HC groups. In contrast to the significantly higher variability of speech volume (DDKcvi) in the CA group, the PD-DBS group showed similar DDKcvi to the PD-Med and HC groups. CONCLUSIONS: STN-DBS affects the speech rate stability of patients with PD. Speech rhythm disorders caused by STN-DBS were phenotypically similar to that in CA in terms of interval variability but different regarding amplitude variability. Further studies are warranted to elucidate the underlying pathophysiology of speech rhythm disorders in PD patients treated with DBS.

Prediction of Deep Brain Stimulation Outcome in Parkinson's Disease With Connectome Based on Hemispheric Asymmetry.

Parkinson's disease (PD) is a neurodegenerative disease that is associated with motor and non-motor symptoms and caused by lack of dopamine in the substantia nigra of the brain. Subthalamic nucleus deep brain stimulation (STN-DBS) is a widely accepted therapy of PD that mainly inserts electrodes into both sides of the brain. The effect of STN-DBS was mainly for motor function, so this study focused on the recovery of motor function for PD after DBS. Hemispherical asymmetry in the brain network is considered to be a potential indicator for diagnosing PD patients. This study investigated the value of hemispheric brain connection asymmetry in predicting the DBS surgery outcome in PD patients. Four types of brain connections, including left intra-hemispheric (LH) connection, right intra-hemispheric (RH) connection, inter-hemispheric homotopic (Ho) connection, and inter-hemispheric heterotopic (He) connection, were constructed based on the resting state functional magnetic resonance imaging (rs-fMRI) performed before the DBS surgery. We used random forest for selecting features and the Ridge model for predicting surgical outcome (i.e., improvement rate of motor function). The functional connectivity analysis showed that the brain has a right laterality: the RH networks has the best correlation (r = 0.37, p = 5.68E-03) between the predicted value and the true value among the above four connections. Moreover, the region-of-interest (ROI) analysis indicated that the medioventral occipital cortex (MVOcC)-superior temporal gyrus (STG) and thalamus (Tha)-precentral gyrus (PrG) contributed most to the outcome prediction model for DBS without medication. This result provides more support for PD patients to evaluate DBS before surgery.

Preexisting Bipolar Disorder Influences the Subsequent Phenotype of Parkinson's Disease.

BACKGROUND: Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). OBJECTIVE: The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. METHODS: Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. RESULTS: Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. CONCLUSIONS: BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson's Disease and Bilateral Subthalamic Nuclei Deep Brain Stimulation: Beneficial Effects of Preoperative Cognitive Restructuration Therapy on Postoperative Social Adjustment.

BACKGROUND: Bilateral subthalamic nucleus deep brain stimulation improves motor symptoms and treatment-related complications in patients with Parkinson's disease. However, some patients have trouble adjusting socially after successful neurosurgery, in part because of "unrealistic" expectations and psychiatric disorders. Preoperative psychological interventions focusing on these aspects could be beneficial for such patients. METHODS: We compared the outcomes of 2 psychosocial approaches-1 based on cognitive restructuration and 1 consisting of 2 interviews-with those of a control group without preoperative preparation. All patients underwent a psychometric evaluation 2 months before surgery (M-2) and again at 3 (M+3) and 6 months (M+6) after surgery. The psychometric evaluation focused on social adjustment using the social adjustment scale-self-report. The psychiatric profile of the patients was also assessed. RESULTS: Of 73 patients initially enrolled, 62 performed the initial inclusion visit (M-2) and the 2 postoperative visits (M+3, M+6). For these 62 patients (52% male), the overall mean age was 59 ± 6.13 years, and the mean disease duration was 9.44 ± 3.62 years. No specific differences were observed for social adjustment between the groups or visits (M-2, M+3, M+6); however, an interaction was found in the cognitive restructuration group at M+6 for the family dimension of the social adjustment scale-self-report. CONCLUSION: Our results suggest that even if no overall increase in the social adjustment score was observed, patients with Parkinson's disease eligible for neurosurgery should undergo preoperative psychosocial therapy to define their expectations and help them in their psychological restructuration. This type of therapy, complementary to psychoeducation, could represent an opportunity to prevent postoperative deception and social maladjustment.