Effects Of Deep Brain Stimulation Research Articles

Opposite effects of low and high frequency deep brain stimulation of lateral hypothalamus on arousal and temperature in a monkey pilot study.

Deep brain stimulation is a well-established treatment for improving motor symptoms in Parkinson's disease. However, persistent non-motor symptoms, such as excessive daytime sleepiness, remain a significant challenge and necessitate further investigation. In this study, we conducted repeated measurements of daytime sleepiness using a modified multiple sleep latency test in a healthy monkey (macaca fascicularis), which was later rendered parkinsonian through MPTP administration. Deep brain stimulation targeting the lateral hypothalamic area revealed frequency-dependent modulation of both sleepiness level and core body temperature. High-frequency stimulation (80Hz) increased sleepiness in the healthy state, while low-frequency stimulation (20Hz) promoted wakefulness in the parkinsonian state. These findings suggest a promising therapeutic approach for addressing sleep/wake disturbances, not only in Parkinson's disease but also in other severe sleep disorders.

Subthalamic nucleus deep brain stimulation modulates speech graphs in patients with Parkinson’s disease

Graph theory enables a direct quantification of topological properties of any arbitrary network. Its application in neuroscience has unveiled topological changes of brain networks associated with various neurodegenerative diseases. This study used the graph theory to understand speech deficits in patients with Parkinson’s disease (PD). In particular, this study investigated the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the topology of speech graphs. Sixty patients with PD completed a standard semantic fluency test with DBS switched ON and OFF. A control group of sixty matched nonsurgical PD patients completed the test once. All verbal responses were recorded, transcripted, and transformed into directed speech graphs. Volumes of tissue activated (VTA) were estimated for three STN subregions, including sensorimotor, associative, and limbic parts. First, the patients with DBS OFF produced smaller and denser speech graphs than nonsurgical patients, showing fewer nodes, higher density, shorter diameter, and shorter average shortest path. Second, DBS partially reversed the effect of surgery, leading to larger and sparser speech graphs with more nodes, lower density, longer diameter, and longer average shortest path (ON versus OFF). Third, however, the left associative VTA negatively correlated with the DBS-induced diameter and average shortest path changes (ON versus OFF), suggesting that the patients with greater left associative STN stimulation tended to produce smaller and denser speech graphs. This study demonstrates that STN-DBS can partially restore the topological structure of speech graphs in PD patients. However, stimulating the left associative STN appears to disrupt speech graphs.

Directional Subthalamic Deep Brain Stimulation Better Improves Gait and Balance Disorders in Parkinson's Disease Patients: A Randomized Controlled Study.

To investigate the effects of directional subthalamic deep brain stimulation (STN-dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD). We included 10 participants who underwent STN-DBS and presented severe preoperative FOG, in a randomized, double-blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non-directional (ring-mode) STN-DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre-operative structural and diffusion-weighted imaging to model individual VTAs and to examine cortico-subthalamic connectivity. We used linear mixed-effects models to contrast the effects of central STN-dDBS, posterior STN-dDBS, and ring-mode STN-DBS. Central STN-dDBS produced significantly better improvement in gait and balance control compared to posterior STN-dDBS (p = 0.027), with fewer FOG episodes (p < 0.001). Conversely, ring-mode STN-DBS resulted in worsened postural control compared to central STN-dDBS (p = 0.009). The cortico-subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico-STN connectivity with ring-mode STN-DBS. Central STN-dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN-DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2024.

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial.

Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD. A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores. Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported. STN or GPi DBS are ineffective on dystonia related to WD.

Deciphering the effects of STN DBS on neuropsychiatric fluctuations in Parkinson’s disease

The impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on neuropsychiatric fluctuations in Parkinson´s disease (PD) remains unclear. The Neuropsychiatric Fluctuations Scale (NFS) can help to fill this gap, directly measuring fluctuations between the OFF- and ON-medication conditions. The NFS provides NFS-plus (hyperdopaminergic) and NFS-minus (hypodopaminergic) sub-scores. Based on these, the NFS global scores express the overall magnitude of neuropsychiatric symptoms in both the OFF- and ON-medication states. The total fluctuation score (TFS) represents the difference between ON- vs. OFF-medication NFS global scores, thus assessing fluctuations amplitude. The NFS was used to evaluate changes in neuropsychiatric fluctuations between the OFF- and ON-medication conditions before and 1-year after bilateral STN-DBS in 45 PD patients (32 males; mean age, 61.3 ± 7.2 years; PD duration, 10.2 ± 3.0 years). After surgery, the amplitude of neuropsychiatric fluctuations was significantly reduced (p < 0.001), confirming the efficacy of STN-DBS on these symptoms.

Deep brain stimulation for Parkinson's disease: bibliometric analysis of the top 100 cited literature.

Deep Brain Stimulation (DBS) has been widely applied and accepted in the treatment of neurological and psychiatric disorders. Despite numerous studies exploring the effects of DBS on the progression of neurodegenerative diseases and the treatment of advanced Parkinson's disease (PD), there is a limited number of articles summarizing this research. The purpose of this study is to investigate the current trends, hot topics, and potential in research surrounding DBS therapy for PD, as well as to anticipate the challenges of such research. We searched the Web of Science Core Collection database (WoSCC) for DBS research literature related to PD published from January 2014 to January 2024, utilized CiteSpace, VOS viewer, the bibliometric online analysis platform, Scimago Graphica, Microsoft Excel 2021, and R software version 4.2.3 for data analysis. And we conducted quantitative research on publications, citations, journals, authors, countries, institutions, keywords, and references, visualized the results in network graphs. From 2014 to 2024, papers from 39 journals from 11 countries were among the top 100 cited. Most papers were published in Neurology, with the highest average citations per paper in Nature Neuroscience. The United States (US) contributed the most publications, followed by the United Kingdom (UK) and Germany. In terms of total publications, University College London (UCL) contributed the most papers. The primary classifications of articles were Clinical Neurology, Neurosciences, and Surgery. The top five keywords were subthalamic nucleus, DBS, PD, medical therapy, and basal ganglia. Cluster analysis indicates that DBS research focus on improving quality of life and applying computational models. Through bibliometric analysis, researchers could quickly and clearly understand the hotspots and boundaries of their research field, thus guiding their research direction and scope to improve research efficiency and the quality of outcomes. Although studies indicate that DBS is currently a crucial method for treating advanced PD, in the long run, creating a personalized, low-cost treatment regimen with precise targeting and long-term efficacy poses a challenge.

Modulation of Cerebellar Oscillations with Subthalamic Stimulation in Patients with Parkinson's Disease.

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson's disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations. To observe the effects of STN-DBS on cerebellar oscillations in patients with PD. We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity. In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions. While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD.

Exploring adverse effects of deep brain stimulation: the need for personalized care and long-term monitoring.

Deep Brain Stimulation (DBS), an FDA-approved treatment for movement disorders such as Parkinson's Disease (PD), is increasingly used for various neurological and neuropsychiatric conditions. A recent systematic review and meta-analysis by Bahadori et al. highlighted a significant increase in Body Mass Index (BMI) among patients post-DBS, with most participants having PD. The study, however, noted moderate heterogeneity (I² = 67.566%) without thoroughly addressing its potential causes or proposing strategies to mitigate it. The review's limited patient diversity and short follow-up period also challenge its generalizability and long-term implications. In addition to BMI changes, DBS has been linked to motor, cognitive, and psychiatric side effects. Patients undergoing subthalamic nucleus (STN) stimulation, for example, face risks of motor complications, including speech and gait issues, while cognitive declines, particularly in verbal fluency and executive function, are also concerning. Psychiatric side effects such as depression, anxiety, and psychosis further complicate treatment outcomes. These findings underscore the importance of personalized treatment strategies, preoperative assessments, and ongoing patient education to minimize adverse effects and optimize the therapeutic potential of DBS.

In Reply: Adverse Effects of Deep Brain Stimulation for Treatment-Resistant Depression: A Scoping Review.

In Reply: Adverse Effects of Deep Brain Stimulation for Treatment-Resistant Depression: A Scoping Review.

Letter: Adverse Effects of Deep Brain Stimulation for Treatment-Resistant Depression: A Scoping Review.

Letter: Adverse Effects of Deep Brain Stimulation for Treatment-Resistant Depression: A Scoping Review.

The effect of subthalamic nucleus deep brain stimulation on speech performance: a prospective clinical and tractography study.

Speech changes significantly impact the quality of life for Parkinson's disease (PD) patients. Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) is a standard treatment for advanced PD, but its effects on speech remain unclear. This study aimed to investigate the relationship between STN-DBS and speech changes in PD patients using comprehensive clinical assessments and tractography. Forty-seven PD patients underwent STN-DBS, with preoperative and 3-month postoperative assessments. Speech analyses included acoustic measurements, auditory-perceptual evaluations, and fluency-intelligibility tests. On the other hand, structures within the volume tissue activated (VTA) were identified using MRI and DTI. The clinical and demographic data and structures associated with VTA (Corticospinal tract, Internal capsule, Dentato-rubro-thalamic tract, Medial forebrain bundle, Medial lemniscus, Substantia nigra, Red nucleus) were compared with speech analyses. The majority of patients (36.2-55.4% good, 29.7-53.1% same) exhibited either improved or unchanged speech quality following STN-DBS. Only a small percentage (8.5-14.9%) experienced deterioration. Older patients and those with worsened motor symptoms postoperatively were more likely to experience negative speech changes (p < 0.05). Interestingly, stimulation of the right Substantia Nigra correlated with improved speech quality (p < 0.05). No significant relationship was found between other structures affected by VTA and speech changes. This study suggests that STN-DBS does not predominantly negatively impact speech in PD patients, with potential benefits observed, especially in younger patients. These findings underscore the importance of individualized treatment approaches and highlight the need for further long-term studies to optimize therapeutic outcomes and better understand the effects of STN-DBS on speech.

Unveiling the Dominant Factors in Subthalamic Stimulation for Improving Depression in Parkinson's Disease.

Currently, the conclusions of studies on subthalamic nucleus (STN) deep brain stimulation (DBS) for improving Parkinson's disease (PD) with depression are inconsistent, and the reasons for improvement or deterioration remain unclear. The aim was to investigate the prognosis of PD with depression after bilateral STN-DBS and the factors related to the improvement in depression. The local and network effects of DBS on depression in PD (DPD) were further explored based on the volume of tissue activation (VTA). The study analyzed 80 primary PD patients who had undergone bilateral STN-DBS, comprising 47 patients with improved depression and 33 patients without improvement. Two groups of clinical profiles and stimulation parameters were compared, and the network models for improving depression were constructed. The improvement in depression was closely associated with improvement in anxiety (odd rate [OR] = 1.067, P = 0.006) and the standardized space left y-coordinate (OR = 0.253, P = 0.005). The VTA overlapping with the left motor STN subregion is most significantly associated with improvement in depression (RSpearman = 0.53, P < 0.001; RPearson = 0.43, P < 0.001). The y-coordinates in the improvement group were closer to the optimal stimulation site for improving motor symptoms. Finally, both the structural and functional network models indicate a positive correlation between depression improvement and the connectivity of the sensorimotor cortex. The amelioration of DPD is primarily attributed to the stimulation of bilateral motor STN, particularly on the left. However, this stimulatory effect manifests as an indirect influence.

Non-invasive temporal interference brain stimulation reduces preference on morphine-induced conditioned place preference in rats

Long-term use of opioid drugs such as morphine can induce addiction in the central nervous system through dysregulation of the reward system of the brain. Deep brain stimulation (DBS) is a non-pharmacological technique capable of attenuating behavioral responses associated with opioid drug consumption and possesses the capability to selectively activate and target localized brain regions with a high spatial resolution. However, long-term implantation of electrodes in brain tissue may limit the effectiveness of DBS due to changes in impedance, position, and shape of the tip of the stimulation electrode and the risk of infection of nerve tissue around the implanted electrode. The main objective of the current study is to evaluate the effect of temporal interference (TI) brain stimulation on addictive behaviors of morphine-induced conditioned place preference (CPP) in rats. TI stimulation is a non-invasive technique used transcranially to modulate neural activity within targeted brain regions. It involves applying two high-frequency currents with slightly different frequencies, resulting in interference and targeted stimulation of different brain areas with the desired spatial resolution. The results indicated that TI stimulation with the amplitude of I1=I2=0.5\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{I}}_{1}{ = }{\ ext{I}}_{2}{ = 0.5}$$\\end{document} mA, carrier frequency of 2 kHz, frequency difference of 25 Hz, ON–OFF stimulation frequency of 0.25 Hz, and total duration of 10 min in three consecutive days resulted in a significant reduction of morphine preference in the morphine-stimulation group in comparison with the morphine group (p < 0.001). These findings highlight the potential of TI stimulation as a modulatory intervention in mitigating the addictive properties of morphine and provide valuable insights into the therapeutic implications of this stimulation paradigm for treatment of opioid drugs in human subjects.

Carry-Over Effect of Deep Cerebellar Stimulation-Mediated Motor Recovery in a Rodent Model of Traumatic Brain Injury

Background We previously demonstrated that deep brain stimulation (DBS) of lateral cerebellar nucleus (LCN) can enhance motor recovery and functional reorganization of perilesional cortex in rodent models of stroke or TBI. Objective Considering the treatment-related neuroplasticity observed at the perilesional cortex, we hypothesize that chronic LCN DBS-enhanced motor recovery observed will carry-over even after DBS has been deactivated. Methods Here, we directly tested the enduring effects of LCN DBS in male Long Evans rats that underwent controlled cortical impact (CCI) injury targeting sensorimotor cortex opposite their dominant forepaw followed by unilateral implantation of a macroelectrode into the LCN opposite the lesion. Animals were randomized to DBS or sham treatment for 4 weeks during which the motor performance were characterize by behavioral metrics. After 4 weeks, stimulation was turned off, with assessments continuing for an additional 2 weeks. Afterward, all animals were euthanized, and tissue was harvested for further analyses. Results Treated animals showed significantly greater motor improvement across all behavioral metrics relative to untreated animals during the 4-week treatment, with functional gains persisting across 2-week post-treatment. This motor recovery was associated with the increase in CaMKIIα and BDNF positive cell density across perilesional cortex in treated animals. Conclusions LCN DBS enhanced post-TBI motor recovery, the effect of which was persisted up to 2 weeks beyond stimulation offset. Such evidence should be considered in relation to future translational efforts as, unlike typical DBS applications, treatment may only need to be provided until such time as a new function plateau is achieved.

What Should be the Anatomical Target in Deep Brain Stimulatıon in an Essential Tremor Plus Rest Tremor Case? Technical Case Report of Deep Brain Stimulation

While Deep Brain Stimulation (DBS) of Subthalamic Nucleus (STN) is effective on resting tremors, but its effectiveness on postural and kinetic tremors is limited. DBS of the Ventral Intermediate Nucleus (VIM) is effective on many types of tremors, especially postural and kinetic tremors, but its effect is weak on motor symptoms in Parkinson’s disease (PD). Although there is a consensus in the literature about where the anatomical target should be in essential tremor (ET) and PD, there are only case reports about where the anatomical target should be in Essential Tremor Plus Rest Tremor (ET+RT) cases.In this article, we aimed to reveal the effectiveness of STN DBS in a case-diagnosed with ET+RT. The patient had action tremors in both upper extremities for 21 years and developed rest tremors in both upper and lower extremities for the last six years. Rest tremor was effectively controlled with bilateral STN DBS. Postural tremor in the right upper extremity was continued, although it decreased.STN may be an appropriate choice when choosing an anatomical target in DBS in cases of resting, postural, and kinetic tremor.

Deep brain stimulation for Parkinson’s disease: systematic review with meta-analysis and trial sequential analysis

ObjectiveTo assess the benefits and harms of deep brain stimulation for Parkinson’s disease.DesignSystematic review with meta-analysis and trial sequential analysis.Data sourcesCochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, Latin...

One side effect: two networks? Lateral and posteromedial stimulation spreads induce dysarthria in subthalamic deep brain stimulation for Parkinson’s disease

BackgroundStimulation-induced dysarthria (SID) is a troublesome and potentially therapy-limiting side effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson’s disease (PD). To date, the origin...

Surgicogenomics: The Role of Genetics in Deep Brain Stimulation in Parkinson's Disease Patients.

Parkinson's disease (PD) is the second-most common neurodegenerative disease, affecting 1% of people aged over 60. Currently, there is only symptomatic relief for PD patients, with levodopa being the gold standard of PD treatment. Deep brain stimulation (DBS) is a surgical option to treat PD patients. DBS improves motor functions and may also allow a significant reduction in dopaminergic medication. Important parameters for DBS outcomes are the disease duration, the age of disease onset, responsiveness to levodopa and cognitive or psychiatric comorbidities. Emerging data also highlight the need to carefully consider the genetic background in the preoperative assessment of PD patients who are candidates for DBS, as genetic factors may affect the effectiveness of DBS in these patients. This review article discusses the role of genetics in DBS for PD patients, in an attempt to better understand inter-individual variability in DBS response, control of motor PD symptoms and appearance of non-motor symptoms, especially cognitive decline.

Deep brain stimulation targeted at lateral hypothalamus-medial forebrain bundle reverses depressive-like symptoms and related cognitive deficits in rat: Role of serotoninergic system

The aim of the study is to understand the rationale behind the application of deep brain stimulation (DBS) in the treatment of depression. Male Wistar rats, rendered depressive with chronic unpredictable mild stress (CUMS) were implanted with electrode in the lateral hypothalamus-medial forebrain bundle (LH-MFB) and subjected to deep brain stimulation (DBS) for 4 h each day for 14 days. DBS rats, as well as controls, were screened for a range of parameters indicative of depressive state. Symptomatic features noticed in CUMS rats like the memory deficit, anhedonia, reduction in body weight and 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in mPFC and elevated plasma corticosterone were reversed in rats subjected to DBS. DBS arrested CUMS induced degeneration of 5-HT cells in interfascicular region of dorsal raphe nucleus (DRif) and fibers in LH-MFB and induced dendritic proliferation in mPFC neurons. MFB is known to serve as a major conduit for the DRif-mPFC serotoninergic pathway. While the density of serotonin fibers in the LH-MFB circuit was reduced in CUMS, it was upregulated in DBS-treated rats. Furthermore, microinjection of 5-HT1A receptor antagonist, WAY100635 into mPFC countered the positive effects of DBS like the antidepressant and memory-enhancing action. In this background, we suggest that DBS at LH-MFB may exercise positive effect in depressive rats via upregulation of the serotoninergic system. While these data drawn from the experiments on rat provide meaningful clues, we suggest that further studies aimed at understanding the usefulness of DBS at LH-MFB in humans may be rewarding.

Number of serotonergic neurons in the subthalamic nucleus and globus pallidus internus could influence the effects of deep brain stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is a standard treatment for Parkinson's disease (PD), with both regions exhibiting similar treatment effectiveness. However, posttreatment neuropsychiatric side effects, such as severe depression, are common, primarily due to the loss of serotonergic cells. Identifying a region with fewer serotonergic neurons could potentially reduce these side effects. This study aimed to quantify the number of serotonergic neurons in the STN and GPi. Both regions were analyzed using hematoxylin and eosin staining and immunohistochemistry. The GPi exhibited a significantly lower number and H-score of serotonergic neurons than the STN. Within the STN, the number and H-score of serotonergic neurons were higher in the medial aspect than in the lateral aspect. Three different types of neurons, large and small, were observed. In STN, large neurons were concentrated in the center and small neurons in the periphery. This distribution was not observed in GPi. In addition, the concentration of the serotonergic neurons is less in GPi. These findings suggest that the GPi may be a safer target region, potentially reducing the incidence of post-DBS depression.