Thalamic stimulation modulated neural oscillations in central post-stroke pain: A case report.

The characterization of neural signatures within the somatosensory pathway is essential for elucidating the pathogenic mechanisms of central post-stroke pain (CPSP) and developing more effective treatments such as deep brain stimulation (DBS). We explored the characteristics of thalamic neural oscillations in response to varying pain levels under multi-day local field potential (LFP) recordings and examined the influences of continuous DBS on these thalamic activities. We recorded LFPs from the left ventral posterolateral thalamus (VPL) of a patient with CPSP in the resting state under both off- and on-stimulation conditions. We observed significant differences in the power spectral density (PSD) of different pain levels in the delta, theta and gamma frequency bands of the left VPL; 75Hz DBS significantly increased the PSD of delta and decreased the PSD of low-beta, while 130Hz DBS significantly reduced the PSD of theta and low-beta. Thalamic stimulation modulated the neural oscillations related to pain, and the changes in neural activities in response to stimulation could serve as quantitative indicators for pain relief.

Motor improvement of remote programming in patients with Parkinson's disease after deep brain stimulation: a 1-year follow-up.

Background: Remote programming (RP) is an emerging technology that enables the adjustment of implantable pulse generators (IPGs) via the Internet for people with Parkinson's disease (PwPD) who have undergone deep brain stimulation (DBS). Previous studies have not comprehensively explored the effectiveness of RP in managing motor symptoms, often omitting assessments such as the rigidity and retropulsion tests during the follow-up. This study evaluates the comprehensive improvements in motor performance and the potential cost benefits of RP for PwPD with DBS. Methods: A retrospective analysis was conducted on two groups of patients-those who received RP and those who received standard programming (SP). Clinical outcomes including motor improvement, quality of life, and daily levodopa dosage were compared between the groups during a 12 (± 3)-month in-clinic follow-up. Results: A total of 44 patients were included in the study, with 18 in the RP group and 26 in the SP group. No significant differences were observed in the frequency of programming sessions or clinical outcomes between the groups (p > 0.05). However, the RP group experienced significantly lower costs per programming session than the SP group (p < 0.05), despite patients in the former group living further from our center (p < 0.05). Conclusions: Our findings suggest that RP could significantly reduce the costs of programming for PwPD with DBS, especially without compromising the effectiveness of treatment across all motor symptoms in the short term.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

Background: Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD). Aims: The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD. Methods: Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations. Results: Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age. Conclusions: Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST-NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

Anterior capsulotomy combined with subthalamic nucleus deep brain stimulation for tardive dystonia.

BACKGROUND: Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients. METHODS: Six severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1-3 years post-operation. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively. RESULTS: After receiving the combination treatment for 25 ± 11.6 months (range, 12-41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems. CONCLUSION: Bilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.

Unlocking the potential: T1-weighed MRI as a powerful predictor of levodopa response in Parkinson's disease.

BACKGROUND: The efficacy of levodopa, the most crucial metric for Parkinson's disease diagnosis and treatment, is traditionally gauged through the levodopa challenge test, which lacks a predictive model. This study aims to probe the predictive power of T1-weighted MRI, the most accessible modality for levodopa response. METHODS: This retrospective study used two datasets: from the Parkinson's Progression Markers Initiative (219 records) and the external clinical dataset from Ruijin Hospital (217 records). A novel feature extraction method using MedicalNet, a pre-trained deep learning network, along with three previous approaches was applied. Three machine learning models were trained and tested on the PPMI dataset and included clinical features, imaging features, and their union set, using the area under the curve (AUC) as the metric. The most significant brain regions were visualized. The external clinical dataset was further evaluated using trained models. A paired one-tailed t-test was performed between the two sets; statistical significance was set at p < 0.001. RESULTS: For 46 test set records (mean age, 62 ± 9 years, 28 men), MedicalNet-extracted features demonstrated a consistent improvement in all three machine learning models (SVM 0.83 ± 0.01 versus 0.73 ± 0.01, XgBoost 0.80 ± 0.04 versus 0.74 ± 0.02, MLP 0.80 ± 0.03 versus 0.70 ± 0.07, p < 0.001). Both feature sets were validated on the clinical dataset using SVM, where MedicalNet features alone achieved an AUC of 0.64 ± 0.03. Key responsible brain regions were visualized. CONCLUSION: The T1-weighed MRI features were more robust and generalizable than the clinical features in prediction; their combination provided the best results. T1-weighed MRI provided insights on specific regions responsible for levodopa response prediction. CRITICAL RELEVANCE STATEMENT: This study demonstrated that T1w MRI features extracted by a deep learning model have the potential to predict the levodopa response of PD patients and are more robust than widely used clinical information, which might help in determining treatment strategy. KEY POINTS: This study investigated the predictive value of T1w features for levodopa response. MedicalNet extractor outperformed all other previously published methods with key region visualization. T1w features are more effective than clinical information in levodopa response prediction.

Prediction of subthalamic stimulation efficacy on isolated dystonia via support vector regression.

Introduction: Deep brain stimulation (DBS) of subthalamic nucleus (STN) has been well-established and increasingly applied in patients with isolated dystonia. Nevertheless, the surgical efficacy varies among patients. This study aims to explore the factors affecting clinical outcomes of STN-DBS on isolated dystonia and establish a well-performed prediction model. Methods: In this prospective study, thirty-two dystonia patients were recruited and received bilateral STN-DBS at our center. Their baseline characteristics and up to one-year follow-up outcomes were assessed. Implanted electrodes of each subject were reconstructed with their contact coordinates and activated volumes calculated. We explored correlations between distinct clinical characteristics and surgical efficacy. Those features were then trained for the model in outcome prediction via support vector regression (SVR) algorithm and testified through cross-validation. Results: Patients demonstrated an average clinical improvement of 56 ± 25 % after STN-DBS, significantly affected by distinct symptom forms and activated volumes. The optimal targets and activated volumes were concentratedly located at the dorsal posterior region to STN. Most patients had a rapid response to STN-DBS, and their motor score improvement within one week was highly associated with long-term outcomes. The trained SVR model, contributed by distinct weights of features, could reach a maximum prediction accuracy with mean errors of 11 ± 7 %. Conclusion: STN-DBS demonstrated significant and rapid therapeutic effects in patients with isolated dystonia, by possibly affecting the pallidofugal fibers. Early improvement highly indicates the ultimate outcomes. SVR proves valid in outcome prediction. Patients with predominant phasic and generalized symptoms, shorter disease duration, and younger onset age may be more favorable to STN-DBS in the long run.

Spinal cord stimulation for postural abnormalities in Parkinson's disease: 1-year prospective pilot study.

BACKGROUND: Postural abnormalities (PA) are common in the advanced stages of Parkinson's disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. METHODS: T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. RESULTS: Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. CONCLUSIONS: Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

Superior cerebellar peduncle deep brain stimulation for cerebral palsy.

OBJECTIVE: Patients with coexisting spastic cerebral palsy (CP) and dystonia have limited treatment options. In this study, the authors aimed to evaluate the efficacy of deep brain stimulation (DBS) targeting the superior cerebellar peduncles (SCPs) in adults with CP. METHODS: Five patients with CP and medically refractory dystonia and spasticity underwent SCP DBS. Assessments included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), modified Ashworth scale (mAS), and tests of cognition, mental status, and quality of life preoperatively and at 3, 6, and 12 months postoperatively (in both DBS ON and OFF states, double blinded). Active contacts and fiber bundles were examined. RESULTS: Four patients completed follow-up. The BFMDRS motor score decreased from 74 to 52 at 12 months postoperatively (30%, p = 0.008). The mean mAS score indicated significant spasticity reduction (from 2.9 ± 0.9 to 1.9 ± 0.6 after 12 months, p = 0.0454). Quality of life improved (p < 0.01), while cognition remained unaffected. Active contacts were found within the dentato-rubro-thalamic tract, with variable efficiency in decussating and nondecussating portions. CONCLUSIONS: In this pilot trial, SCP DBS showed promise as a well-tolerated treatment for CP, improving dystonic symptoms, spasticity, quality of life, and functional capacities. However, caution is needed when interpreting the results given the small sample size and heterogeneous motor outcomes.

Iron and neuromelanin imaging in basal ganglia circuitry in Parkinson's disease with freezing of gait.

OBJECTIVE: This study aimed to examine the structural alterations of the deep gray matter (DGM) in the basal ganglia circuitry of Parkinson's disease (PD) patients with freezing of gait (FOG) using quantitative susceptibility mapping (QSM) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI). METHODS: Twenty-five (25) PD patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 30 age- and sex-matched healthy controls (HCs) underwent 3-dimensional multi-echo gradient recalled echo and NM-MRI scanning. The mean volume and susceptibility of the DGM on QSM data and the relative contrast (NMRC-SNpc) and volume (NMvolume-SNpc) of the substantia nigra pars compacta on NM-MRI were analyzed among groups. A multiple linear regression analysis was performed to explore the associations of FOG severity with MRI measurements and disease stage. RESULTS: The PD-FOG group showed higher susceptibility in the bilateral caudal substantia nigra (SN) compared to the HC group. Both the PD-FOG and PD-nFOG groups showed lower volumes than the HC group in the bilateral caudate and putamen as determined from the QSM data. The NMvolume-SNpc on NM-MRI in the PD-FOG group was significantly lower than in the HC and PD-nFOG groups. Both the PD-FOG and PD-nFOG groups showed significantly decreased NMRC-SNpc. CONCLUSIONS: The PD-FOG patients showed abnormal neostriatum atrophy, increases in iron deposition in the SN, and lower NMvolume-SNpc. The structural alterations of the DGM in the basal ganglia circuits could lead to the abnormal output of the basal ganglia circuit to trigger the FOG in PD patients.

Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression.

BACKGROUND: Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. METHODS: Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. RESULTS: Depression and anxiety symptoms improved after 3-6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LIMITATIONS: This study was limited to the small sample size and lack of a healthy control group. CONCLUSIONS: Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

Telemedicine in patients with obsessive-compulsive disorder after deep brain stimulation: a case series.

Background: Patients suffering from refractory obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS) surgery require repeated in-person programming visits. These sessions could be labor-intensive and may not always be feasible, particularly when in-person hospital visits are restricted. Telemedicine is emerging as a potential supplementary tool for post-operative care. However, its reliability and feasibility still require further validation due to the unconventional methods of interaction. Methods: A study was conducted on three patients with refractory OCD who had undergone DBS. Most of their programming sessions were completed via a remote programming system. These patients were recruited and monitored for a year. Changes in their clinical symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II), the Hamilton Anxiety Scale-14 (HAMA), the Hamilton Depression Scale-17 (HAMD), and the Short Form 36 Health Survey Questionnaire (SF-36). The scores from these assessments were reported. Results: At the last follow-up, two out of three patients were identified as responders, with their Y-BOCS-II scores improving by more than 35% (P1: 51%, P3: 42%). These patients also experienced some mood benefits. All patients observed a decrease in travel expenses during the study period. No severe adverse events were reported throughout the study. Conclusion: The group of patients showed improvement in their OCD symptoms within a 1-year follow-up period after DBS surgery, without compromising safety or benefits. This suggests that telemedicine could be a valuable supplementary tool when in-person visits are limited.

Preoperative Attention/Memory Problem Affects the Quality of Life of Parkinson's Disease Patients after Deep Brain Stimulation: A Cohort Study.

Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively. Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (ß = 0.869, P < 0.001) and the preoperative attention/memory subscore (ß = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL). Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.

Parameter-based analysis of clinical efficacy of combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

OBJECTIVE: Treatment-resistant depression (TRD) is a severely disabling psychiatric condition that responds poorly to conventional treatments. Deep brain stimulation (DBS) has been proposed for the treatment of patients with TRD in numerous studies. Several deep brain nuclei are considered as potential targets for TRD-DBS, but their clinical efficacy needs further validation. This study carried out dual-target combined stimulation of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) to investigate the effectiveness of the treatment for TRD patients. METHODS: An 8-contact DBS electrode was used in the study with a surgical path that crossed the BNST and NAc targets. Stimulation parameters and the corresponding severity of symptoms evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17) and other scales were obtained at each follow-up. The accuracy of electrode positions, the effect of combined stimulation, and the corresponding stimulation parameters were evaluated. Sweet spot prediction models were used to assess the effective stimulation sites in the treatment. RESULTS: The study included 23 TRD patients undergoing DBS at a single center from March 2021 to May 2023. At the last follow-up (range 4-24 months), 14 patients had responded to the treatment (HAMD-17 score improved ≥ 50%), 7 of whom had achieved clinical remission (HAMD-17 score ≤ 7). Electrode position analysis suggested that the BNST may be more important for the improvement of depressive symptoms than the NAc. Overlapped volumes of volume of tissue activated (VTA) and BNST were significantly correlated with absolute (ρleft = -0.377, p < 0.001; ρright = -0.251, p < 0.001) and percent (ρleft = -0.249, p < 0.001; ρright = -0.098, p = 0.102) changes in HAMD-17 score. The sweet spot model of HAMD-17 improvement also suggested that the VTA overlap with the dorsal side of BNST was associated with the impact on depressive symptoms (t = -4.10, p < 0.05). CONCLUSIONS: Combined BNST-NAc stimulation of TRD can effectively improve depressive symptoms, in which the BNST seems to have a dominant therapeutic effect. The results of this study not only help to optimize the DBS programming parameters, but also offer an opportunity to further understand the differences between the two targets. In the future, larger prospective cohorts are needed to verify the results of combined BNST-NAc DBS.

Optimizing Deep Brain Stimulation in Essential Tremor: A Randomized Controlled Trial for Target Consideration.

BACKGROUND AND OBJECTIVES: The thalamic ventral intermediate nucleus (VIM) is a well-established target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). Increasing data indicate that the posterior subthalamic area (PSA) may be superior, but high-level evidence is limited. We aimed at further comparing the intraindividual efficacy and side effect profile of PSA vs VIM DBS in ET. METHODS: In this randomized, double-blind, crossover trial, 4-contact DBS leads were bilaterally implanted with single-trajectory covering the VIM and PSA. Patients were randomized postsurgery to 2 groups, receiving VIM stimulation (4-7 months) and then PSA stimulation (8-11 months) or vice versa. The primary end point was the difference in improvement from baseline to the end of the VIM vs PSA DBS period in the total score of the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). RESULTS: Ten patients with medically refractory ET were enrolled, and 9 completed the study. The difference between reduction of FTM-TRS total score in the PSA vs VIM DBS period was -7.4 (95% CI: -28.5 to 13.7, P = .328). Clinical benefit was achieved at significantly lower stimulation intensity under PSA DBS. Furthermore, PSA DBS provided greater improvement in head tremor subscore of FTM-TRS (PSA vs VIM: -2.2, P = .020) and disease-specific quality of life (PSA vs VIM: -13.8, P = .046) and induced fewer speech (Dysphonia Severity Index score: P = .043; diadochokinetic rate: P = .007; VDI score: P = .005) and gait disturbances compared with VIM DBS. Seven patients remained with PSA DBS after the crossover phase. CONCLUSION: Our study confirms that PSA-DBS is comparable with VIM-DBS in suppressing tremors, superior in improving disease-specific quality of life, and possibly more effective in reducing head tremor.

Impaired night-time mobility in patients with Parkinson's disease: a systematic review.

Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson's disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients' caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient's nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM's symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients' suffering.

Corrigendum: Fixed-life or rechargeable battery for deep brain stimulation: preference and satisfaction in Chinese patients with Parkinson's disease.

[This corrects the article DOI: 10.3389/fneur.2021.668322.].

Subacute alpha frequency (10Hz) subthalamic stimulation for emotional processing in Parkinson's disease.

BACKGROUND: Psychiatric comorbidities are common in Parkinson's disease (PD) and may change with high-frequency stimulation targeting the subthalamic nucleus. Numerous accounts indicate subthalamic alpha-frequency oscillation is implicated in emotional processing. While intermittent alpha-frequency (10Hz) stimulation induces positive emotional effects, with more ventromedial contacts inducing larger effects, little is known about the subacute effect of ventral 10Hz subthalamic stimulation on emotional processing. OBJECTIVE/HYPOTHESIS: To evaluate the subacute effect of 10Hz stimulation at bilateral ventral subthalamic nucleus on emotional processing in PD patients using an affective task, compared to that of clinical-frequency stimulation and off-stimulation. METHODS: Twenty PD patients with bilateral subthalamic deep brain stimulation for more than six months were tested with the affective task under three stimulation conditions (10Hz, 130Hz, and off-stimulation) in a double-blinded randomized design. RESULTS: While 130Hz stimulation reduced arousal ratings in all patients, 10Hz stimulation increased arousal selectively in patients with higher depression scores. Furthermore, 10Hz stimulation induced a positive shift in valence rating to negative emotional stimuli in patients with lower apathy scores, and 130Hz stimulation led to more positive valence to emotional stimuli in the patients with higher apathy scores. Notably, we found correlational relationships between stimulation site and affective rating: arousal ratings increase with stimulation from anterior to posterior site, and positive valence ratings increase with stimulation from dorsal to ventral site of the ventral subthalamic nucleus. CONCLUSIONS: Our findings highlight the distinctive role of 10Hz stimulation on subjective emotional experience and unveil the spatial organization of the stimulation effect.

Time-locked acute alpha-frequency stimulation of subthalamic nuclei during the evaluation of emotional stimuli and its effect on power modulation.

Introduction: Deep brain stimulation (DBS) studies in Parkinson's Disease (PD) targeting the subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8-12 Hz) event-related de-synchronization (ERD) (reduced power) has been demonstrated. The time-locked stimulation of STN relative to stimuli onset has shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation on power modulation have not been investigated. We aim to investigate effects of acute stimulation of the right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous study, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation would be also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation was to be associated with enhanced alpha power given the shift in behavioral valence ratings. Methods: Twenty-four subjects with STN DBS underwent emotional picture-viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 or 130 Hz. Power of signals was estimated relative to the baseline and subjected to non-parametric statistical testing. Results: As hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative vs. neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects. Conclusion: Acute alpha-specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time-locked stimulation has the potential to provide causal insights into the spectral frequencies and temporal dynamics of emotional processing.