Unilateral Magnetic Resonance-Guided Focused Ultrasound Lesion of the Subthalamic Nucleus in Parkinson's Disease: A Prospective Study.

BACKGROUND: Unilateral subthalamic nucleus (STN) ablation using magnetic resonance-guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD). OBJECTIVES: The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions. METHODS: This prospective, single-center, open-label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6-month follow-up. We also evaluated cognitive-neuropsychological changes, self-assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes. RESULTS: On the treated side, the MDS-UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow-up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive-neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS-UPDRS III and contralateral tremor scores (P < 0.05). CONCLUSION: Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pallidal Versus Subthalamic Deep-Brain Stimulation for Generalized Isolated Dystonia: A Retrospective Study.

Objectives: Deep-brain stimulation (DBS) has been used for the treatment of medically refractory dystonia with excellent results. In this study, we compared in detail the therapeutic advantages of two DBS targets for generalized isolated dystonia. Methods: In this retrospective study, we recruited 29 patients with generalized isolated dystonia who had undergone DBS treatment targeting either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) in the Department of Functional Neurosurgery at Tiantan Hospital, Beijing, China, between January 2016 and December 2021. The movement and disability subscales of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) were used to assess the severity of their dystonic symptoms and their activities of daily living, respectively. SF-36 was used to evaluate the patients' health-related quality of life. Results: The percentage improvement in the BFMDRS-M score at 6 months relative to the baseline score was clearly higher in the STN group (63.91%) than in the GPi group (38.36%). At the 3-, 6-, and 12-month follow-ups, the percentage improvement in arm symptoms was significantly higher after DBS of the STN (70.64%, 80.66%, and 76.89%, respectively) than after stimulation of the GPi (36.75%, 34.21%, and 38.47%, respectively). At 12 months after surgery, patient quality of life had improved on all SF-36 subscales in both groups. Conclusions: STN-DBS may have more advantages than GPi-DBS in patients with obvious arm dystonia. STN-DBS had a better clinical effect than GPi-DBS within 6 months after surgery.

STN-PFC circuit related to attentional fluctuations during non-movement decision-making.

Decision-making is a cognitive process, in which participants need to attend to relevant information and ignore the irrelevant information. Previous studies have described a set of cortical areas important for attention. It is unclear whether subcortical areas also serve a role. The subthalamic nucleus (STN), a part of basal ganglia, is traditionally considered a critical node in the cortico-basal ganglia-thalamus-cortico network. Given the location of the STN and its widespread connections with cortical and subcortical brain regions, the STN plays an important role in motor and non-motor cognitive processing. We would like to know if STN is also related to fluctuations in attentional task performance, and how the STN interacts with prefrontal cortical regions during the process. We examined neural activities within STN covaried with lapses of attention (defined as behavior error). We found that decreased neural activities in STN were associated with sustained attention. By examining connectivity across STN and various sub-regions of the prefrontal cortex (PFC), we found that decreased connectivity across areas was associated with sustained attention. Our results indicated that decreased STN activities were associated with sustained attention, and the STN-PFC circuit supported this process.

Accuracy of ultrasound-guided fine-needle aspiration cytology in evaluation of thyroid nodules using different ultrasonographic and cytological features.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a reliable method for preoperative evaluation of thyroid nodules particularly if ultrasound-guided (USG-FNAC). The main purpose of this study is to evaluate the efficacy of USG-FNAC and its accuracy. METHODS: We retrospectively studied 212 thyroidectomy cases with preoperative ultrasonography and FNAC data during the period 2015-2022 using TI-RADS for final ultrasound diagnosis and Bethesda system for cytological diagnosis. RESULTS: The studied cases were 200 females and 12 males. Thyroid cancer was more prevalent under 20 years old (78.5%). Papillary thyroid carcinoma comprises 84% of all cancer cases. Significant ultrasound features (p-value <0.05) favour malignancy were hypoechogenicity (66%), mixed echogenicity (84%), irregular border (61%), microcalcification (68%) and rim halo (63.6%). Malignancy was found in 21% of TI-RADS-2, 65% of TI-RADS-4 and 100% of TI-RADS-5. There is a significant difference between different categories of Bethesda system. All cases in Cat-VI were malignant (100%). Malignancy was also found in 81% of Cat-V, 20% of Cat-IV, 33% of Cat-III, 16% of Cat-II and 43% of Cat-I. Cytological features consistent with malignancy were as follows: grooving (94%), nuclear irregularities (89%), nuclear pseudoinclusion (89%) and little colloid (82%). In our study, USG-FNAC sensitivity was 83%, specificity 85%, PPV 85%, NPV 83% and accuracy 84%. CONCLUSION: Ultrasound features in favour of malignancy in thyroid nodules are hypoechoic or complex echogenicity, irregular border, punctuate calcification and presence of rim halo. Cytological features in favour of malignancy are grooving, nuclear irregularities, nuclear pseudoinclusion and little or absent colloid.

Light-independent pathway of STN7 kinase activation under low temperature stress in runner bean (Phaseolus coccineus L.).

BACKGROUND: The phosphorylation of the Light-Harvesting Complex of photosystem II (LHCII) driven by STATE TRANSITION 7 (STN7) kinase is a part of one of the crucial regulatory mechanisms of photosynthetic light reactions operating in fluctuating environmental conditions, light in particular. There are evidenced that STN7 can also be activated without light as well as in dark-chilling conditions. However, the biochemical mechanism standing behind this complex metabolic pathway has not been deciphered yet. RESULTS: In this work, we showed that dark-chilling induces light-independent LHCII phosphorylation in runner bean (Phaseolus coccineus L.). In dark-chilling conditions, we registered an increased reduction of the PQ pool which led to activation of STN7 kinase, subsequent LHCII phosphorylation, and possible LHCII relocation inside the thylakoid membrane. We also presented the formation of a complex composed of phosphorylated LHCII and photosystem I typically formed upon light-induced phosphorylation. Moreover, we indicated that the observed steps were preceded by the activation of the oxidative pentose phosphate pathway (OPPP) enzymes and starch accumulation. CONCLUSIONS: Our results suggest a direct connection between photosynthetic complexes reorganization and dark-chilling-induced activation of the thioredoxin system. The proposed possible pathway starts from the activation of OPPP enzymes and further NADPH-dependent thioredoxin reductase C (NTRC) activation. In the next steps, NTRC simultaneously activates ADP-glucose pyrophosphorylase and thylakoid membrane-located NAD(P)H dehydrogenase-like complex. These results in starch synthesis and electron transfer to the plastoquinone (PQ) pool, respectively. Reduced PQ pool activates STN7 kinase which phosphorylates LHCII. In this work, we present a new perspective on the mechanisms involving photosynthetic complexes while efficiently operating in the darkness. Although we describe the studied pathway in detail, taking into account also the time course of the following steps, the biological significance of this phenomenon remains puzzling.

Structural Brain Connectivity Guided Optimal Contact Selection for Deep Brain Stimulation of the Subthalamic Nucleus.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy in ameliorating the motor symptoms of Parkinson disease. However, postoperative optimal contact selection is crucial for achieving the best outcome of deep brain stimulation of the subthalamic nucleus surgery, but the process is currently a trial-and-error and time-consuming procedure that relies heavily on surgeons' clinical experience. METHODS: In this study, we propose a structural brain connectivity guided optimal contact selection method for deep brain stimulation of the subthalamic nucleus. Firstly, we reconstruct the DBS electrode location and estimate the stimulation range using volume of tissue activated from each DBS contact. Then, we extract the structural connectivity features by concatenating fractional anisotropy and the number of streamlines features of activated regions and the whole brain regions. Finally, we use a convolutional neural network with convolutional block attention module to identify the structural connectivity features for the optimal contact selection. RESULTS: We review the data of 800 contacts from 100 patients with Parkinson disease for the experiment. The proposed method achieves promising results, with the average accuracy of 97.63%, average precision of 94.50%, average recall of 94.46%, and average specificity of 98.18%, respectively. Our method can provide the suggestion for optimal contact selection. CONCLUSIONS: Our proposed method can improve the efficiency and accuracy of DBS optimal contact selection, reduce the dependence on surgeons' experience, and has the potential to facilitate the development of advanced DBS technology.

Clinical asymmetry in Parkinson's disease is characterized by prevalence of subthalamic pause-burst neurons and alpha-beta oscillations.

OBJECTIVE: We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry. METHODS: We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed. RESULTS: We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12-15 Hz. CONCLUSIONS: Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both. SIGNIFICANCE: Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology.

Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy.

Osteosarcoma is a type of bone cancer that primarily affects children and young adults. The overall 5-year survival rate for localized osteosarcoma is 70-75%, but it is only 20-30% for patients with relapsed or metastatic tumors. To investigate potential glycan-targeting structures for immunotherapy, we stained primary osteosarcomas with recombinant C-type lectin CD301 (MGL, CLEC10A) and observed moderate to strong staining on 26% of the tumors. NK92 cells expressing a CD301-CAR recognized and eliminated osteosarcoma cells in vitro. Cytotoxic activity assays correlated with degranulation and cytokine release assays. Combination with an inhibitory antibody against the immune checkpoint TIGIT (T-cell immunoreceptor with lg and ITIM domains) showed promising additional effects. Overall, this study showed, for the first time, the expression of CD301 ligands in osteosarcoma tissue and demonstrated their use as potential target structures for lectin-based immunotherapy.

Long-Term Medication Profiles in Parkinson's Disease under Subthalamic Deep Brain Stimulation: A Controlled Study.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking. OBJECTIVE: To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients. METHODS: We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities. RESULTS: In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists. CONCLUSION: In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

Investigation of the nonmotor symptoms in patients with STN-DBS therapy in comparison with those without STN-DBS.

The impact of STN-DBS on NMS remains rather as an underestimated topic. Besides, the significance of NMSs in QOL indexes of PD subjects with STN-DBS is unknown. We primarily aimed to evaluate the NMSs and their significance in QOL indexes in PD subjects comparatively with and without STN-DBS therapy. We enrolled all consecutive PD subjects with and without STN-DBS who applied to our movement disorders outpatient clinics between January/2023 and September/2023. We performed comprehensive assessments of the motor and nonmotor features including the clinical scales of Movement Disorder Society-sponsored revision of the MDS-UPDRS, NMSS, HAM-A, HAM-D, and the PDQ-39. Overall, 48 PD subjects with STN-DBS and 161 without STN-DBS treatment were included. The comparative analyses revealed that the sub-scores of the MDS-UPDRS-2, -3 and -4 were higher in the STN-DBS group. However, the MDS-UDPRS-1 and the total scores of the NMSS were similar between groups. Among eight subitems of the NMSS, only, the sub scores of the mood/cognition and the gastrointestinal tract differed. Remarkably, the significant correlations between the scores of the QOL and the NMSS scores in the STN-DBS (-) group, did not persist within the STN-DBS group. Remarkably, the correlations between the NMSS and PQQ-39 disappeared for most of the sub scores within the STN-DBS group. We found indirect evidence regarding the benefit of STN-DBS therapy on NMSs in our cross-sectional study. Besides, we found weaker impact of NMSs in QOL indexes in PD subjects with STN-DBS therapy.

Auditory oddball responses in the human subthalamic nucleus and substantia nigra pars reticulata.

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

Open-Set Recognition of Individual Cows Based on Spatial Feature Transformation and Metric Learning.

The automated recognition of individual cows is foundational for implementing intelligent farming. Traditional methods of individual cow recognition from an overhead perspective primarily rely on singular back features and perform poorly for cows with diverse orientation distributions and partial body visibility in the frame. This study proposes an open-set method for individual cow recognition based on spatial feature transformation and metric learning to address these issues. Initially, a spatial transformation deep feature extraction module, ResSTN, which incorporates preprocessing techniques, was designed to effectively address the low recognition rate caused by the diverse orientation distribution of individual cows. Subsequently, by constructing an open-set recognition framework that integrates three attention mechanisms, four loss functions, and four distance metric methods and exploring the impact of each component on recognition performance, this study achieves refined and optimized model configurations. Lastly, introducing moderate cropping and random occlusion strategies during the data-loading phase enhances the model's ability to recognize partially visible individuals. The method proposed in this study achieves a recognition accuracy of 94.58% in open-set scenarios for individual cows in overhead images, with an average accuracy improvement of 2.98 percentage points for cows with diverse orientation distributions, and also demonstrates an improved recognition performance for partially visible and randomly occluded individual cows. This validates the effectiveness of the proposed method in open-set recognition, showing significant potential for application in precision cattle farming management.

Conditional Depletion of STN1 in Mouse Embryonic Fibroblasts.

The CTC1-STN1-TEN1 (CST) complex is a single-strand DNA-binding protein complex that plays an important role in genome maintenance in various model eukaryotes. Dysfunction of CST is the underlying cause of the rare genetic disorder known as Coats plus disease. In addition, down regulation of STN1 promotes colorectal cancer development in mice. While prior studies have utilized RNAi to knock down CST components in mammalian cells, this approach is associated with off-target effects. Attempts to employ CRISPR/Cas9-based knockout of CST components in somatic cell lines have been unsuccessful due to CST's indispensable role in DNA replication and cell proliferation. To address these challenges, we outline a novel approach utilizing a Cre-loxP-based conditional knockout in mouse embryonic fibroblasts (MEFs). This method offers an alternative means to investigate the function and characteristics of the CST complex in mammalian systems, potentially shedding new light on its roles in genome maintenance. Key features • Conditional depletion of mammalian STN1 using mouse embryonic fibroblast (MEFs). • Analysis of oxidative damage sensitivity using STN1-depleted MEFs. • This protocol requires Stn1flox/flox mice.

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

BACKGROUND: Delayed-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. METHODS: A 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. RESULTS: 341 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). CONCLUSIONS: Delayed-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.

Effectiveness of Deep Brain Stimulation in Improving Balance in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance dysfunction is a debilitating feature of advanced Parkinson's disease (PD), potentially improved by deep brain stimulation (DBS). This systematic review and meta-analysis pooled evidence from randomized controlled trials (RCTs) on DBS effectiveness in improving balance in PD. METHODS: A systematic search was conducted to identify eligible RCTs investigating the effectiveness of DBS on improving balance in people with PD. Meta-analysis was performed using random effects models and reported as mean difference and 95% confidence intervals. Risk of bias was assessed using Cochrane's ROB-2 tool. RESULTS: Seventeen RCTs were eligible (n = 333), utilizing a range of stimulation sites, parameters, reporting tools for balance outcomes, and control/comparator groups, making the identification of clear trends and recommendations difficult. Eleven studies were deemed as having some risk of bias, 4 having low risk of bias and 2 having high risk of bias. One small meta-analysis was conducted and found no significant difference in balance outcomes. Most studies reported no significant improvement in Timed Up-and-Go scores, Berg Balance Scale scores, frequency of falls, and balance-related items of the Movement Disorder Society's Unified Parkinson's Disease Rating Scales. Some studies reported improvements in the Tinetti balance test, posturography readings, and reduction in falls though these were not supported by other studies due to a lack of reporting on these items or conflicting findings. CONCLUSIONS: Current research suggests that DBS results in no significant improvement in balance dysfunction for people with PD, though such assertions require larger RCTs with clear reporting methods using validated reporting tools.

Deep brain stimulation of the subthalamic nucleus increases the risk of sialorrhea in patients with advanced Parkinson's disease.

INTRODUCTION: Sialorrhea is a common neurological manifestation of Parkinson's disease (PD). No specifically designed prospective study has tested the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on sialorrhea in patients with advanced PD. We focused on the effect of STN-DBS on the incidence of sialorrhea in patients with PD. METHODS: This multicenter, prospective, non-randomized concurrent clinical trial analyzed the incidence of sialorrhea during long-term follow-up in 170 patients with advanced PD (84 patients with STN-DBS and 86 patients with medication therapy). RESULTS: After STN-DBS, 58.1% of patients presented with sialorrhea (Drooling Rating Scale (DRS) > 5) compared with 39.3% of patients with medication therapy (P < 0.001). STN-DBS stimulation demonstrated a significant increase in DRS and Drooling Severity and Frequency Scale (DSFS) compared with the patients with medication therapy (P < 0.001). At follow-up, the onabotulinumtoxin-A (BTX-A) injection ratio was significantly higher in the STN-DBS group (29.8% vs. 11.9%, P = 0.0057) compared with the patients with medication therapy. CONCLUSIONS: STN-DBS increased the risk of sialorrhea in patients with advanced PD. TRIAL REGISTRATION: clinicaltrials. gov (NCT06090929).

Enhancing Attentional Performance in Parkinson's Disease: The Impact of Combined Deep Brain Stimulation of the Substantia Nigra Pars Reticulata and the Subthalamic Nucleus.

OBJECTIVE: The concomitant stimulation of the subthalamic nucleus and the substantia nigra pars reticulata is a promising approach to improve treatment of refractory axial symptoms in Parkinson's disease. While dual stimulation of the subthalamic nucleus and the substantia nigra pars reticulata has previously shown beneficial effects on gait, the role of the substantia nigra, a crucial component of the basal ganglia circuitry, in cognitive functions such as attention and executive control remains underexplored. This study aimed to investigate the impact of selective substantia nigra pars reticulata stimulation on attentional performance in patients receiving standard deep brain stimulation of the subthalamic nucleus. METHODS: Twelve patients with bilateral subthalamic nucleus stimulation underwent computerized assessment of attention using a simple reaction time task. Reaction times were assessed under standard stimulation of the subthalamic nucleus versus simultaneous stimulation of the subthalamic nucleus and the substantia nigra pars reticulata. RESULTS: The results revealed a significant improvement in reaction times during the simple reaction time task when patients received dual stimulation compared to standard stimulation. CONCLUSIONS: Our findings provide further evidence for the pivotal role of the substantia nigra pars reticulata in cognitive functions such as attention. Despite the limitations of the study, including a small sample size, our results suggest potential benefits of simultaneous deep brain stimulation of the subthalamic nucleus and the substantia nigra pars reticulata on attentional performance in patients with Parkinson's disease. Further research with larger cohorts is warranted to confirm these findings and better understand the underlying mechanisms.

Physiological effects of dual target DBS in an individual with Parkinson's disease and a sensing-enabled pulse generator.

INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus (GP) is an established therapy for Parkinson's disease (PD). Novel DBS devices can record local field potential (LFP) physiomarkers from the STN or GP. While beta (13-30 Hz) and gamma (40-90 Hz) STN and GP LFP oscillations correlate with PD motor severity and with therapeutic effects of treatments, STN-GP interactions in electrophysiology in patients with PD are not well characterized. METHODS: Simultaneous bilateral STN and GP LFPs were recorded in a patient with PD who received bilateral STN-DBS and GP-DBS. Power spectra in each target and STN-GP coherence were assessed in various ON- and OFF-levodopa and DBS states, both at rest and with voluntary movement. RESULTS: OFF-levodopa and OFF-DBS, beta peaks were present at bilateral STN and GP, coincident with prominent STN-GP beta coherence. Levodopa and dual-target-DBS (simultaneous STN-DBS and GP-DBS) completely suppressed STN-GP coherence. Finely-tuned gamma (FTG) activity at half the stimulation frequency (62.5 Hz) was seen in the STN during GP-DBS at rest. To assess the effects of movement on FTG activity, we recorded LFPs during instructed movement. We observed FTG activity in bilateral GP and bilateral STN during contralateral body movements while on GP-DBS and ON-levodopa. No FTG was seen with STN-DBS or dual-target-DBS. CONCLUSION: Dual-target-DBS and levodopa suppressed STN-GP coherence. FTG throughout the basal ganglia was induced by GP-DBS in the presence of levodopa and movement. This bilateral STN-FTG and GP-FTG corresponded with the least severe bradykinesia state, suggesting a pro-kinetic role for FTG.