Introduction – Deep Brain Stimulation is an established treatment for movement disorders. Data-driven approaches like probabilistic mapping and predictive modeling are being increasingly used to optimize stimulation parameter selection. However, it remains unclear whether intra-operative test data alone can reliably inform such models. Clarifying the predictive value of intra-operative data is essential, as it may influence data collection strategies and surgical and programming protocols. Objective – This study examined whether post-operative DBS effects can be accurately predicted using intra-operative data alone or if post-operative information is required. Methods – A dataset comprising 1117 intra-operative and 1553 post-operative stimulation tests from 35 patients (14 Essential Tremor, 21 Parkinson’s Disease) was analyzed. Volumes of tissue activated (VTAs) were simulated to generate probabilistic maps, from which mapping and target anatomy-related features were extracted to train predictive classification models (low and high improvement, side effects). Model performance was assessed across scenarios linking intra- and post-operative data. Results – Intra-operative data effectively identified regions associated with optimal stimulation, highlighting their utility in guiding parameter selection (predictive accuracy ~60%). However, the predictive relationship between VTAs, probabilistic maps, and clinical outcomes differed between intra- and post-operative contexts. When trained solely on intra-operative VTAs, the model performed at a near chance level (predictive accuracy ~35%). Discussion – The study demonstrates that while intra-operative data are useful for identifying optimal target regions, they are insufficient for accurately predicting post-operative DBS outcomes. Incorporating post-operative data remains crucial for reliable and clinically meaningful DBS effect prediction.
Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment providing long-term efficacy for motor symptoms in Parkinson’s disease (PD). However, the influence of patient expectations on freezing of gait (FOG), a complex and disabling axial symptom, has not been specifically reported. Methods A 64-year-old man with PD underwent bilateral STN-DBS for severe motor fluctuations and dyskinesias. STN-DBS electrodes were implanted under local anesthesia using MRI and electrophysiological targeting. After surgery, DBS programming was optimized and the motor symptoms, including FOG, were assessed clinically during DBS programming consultations. Results STN-DBS significantly improved motor symptoms, but several months post-surgery the patient developed recurrent and fluctuating FOG during ON stimulation. Notably, FOG improved not only after minimal stimulation adjustments (+0.1mA), but also after simulated changes based solely on verbal suggestion, without any objective modification of stimulation parameters. Conversely, simulated decreases in stimulation were associated with immediate worsening of gait. These observations were reproducible across multiple consultations. Conclusion This case suggests that FOG may represent a motor phenotype particularly sensitive to expectation, at the interface between neuromodulation and cognitive-affective processes. It supports a model in which STN-DBS establishes a permissive physiological state, while patient expectations and contextual cues influence the expression of locomotor function. Although these findings arise from a single-case observation, they highlight the potential impact of placebo and nocebo mechanisms on gait outcomes under STN-DBS and underscore the importance of considering non-specific effects during DBS programming and clinical follow-up.
Background Deep brain stimulation (DBS) is a promising treatment option for obsessive compulsive disorders (OCD). Here, we report the case of a young 19-year-old patient, diagnosed with severe OCD since the age of 12 and has exhibited contamination, accumulation and symmetry obsessions along with compulsions related to cleanliness and order since the age of 7. Methods DBS electrodes were implanted in the subthalamic nucleus (STN) under local anesthesia and electrophysiological targeting the antero-medial part of the nucleus. Results Before surgery, the score of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was 40/40, the Montgomery-Åsberg Depression Rating Scale (MADRS) was 38/63 and the Young Mania Rating Scale (YMRS) was 8/60. Despite multiple pharmacological treatments, psychotherapy and repetitive transcranial magnetic stimulation, no significant improvement was observed. However, DBS of the associative/limbic part of the STN improved OCD symptoms (45%), depression (79%) and mania (100%). At the start of programming, monopolar stimulation was associated with troublesome dyskinesias, which have previously been reported as persistent motor side effects of STN DBS in OCD patients, sometimes making optimal DBS programming impossible. In our patient, we resolved dyskinesia issue by switching to bipolar stimulation, which proved effective without inducing dyskinesia. Conclusion Our results further support the use of STN DBS for the treatment of refractory OCD and mood disorders. The transition to bipolar stimulation maximized therapeutic effects without motor side effects. The patient’s positive evolution confirms existing literature on the efficacy of this approach while underscoring the importance of a rigorous follow-up protocol and personalized stimulation parameter adjustments.
The anterior limb of the internal capsule (ALIC) is a major target for deep brain stimulation (DBS) in obsessive-compulsive disorder and other treatment-resistant psychiatric disorders. Although anatomical studies have demonstrated a highly organized topography of prefrontal pathways within the ALIC, it remains unclear whether these organizational principles are preserved in treatment-resistant psychiatric patients and whether they predict stimulation-induced network engagement. We applied anatomically informed diffusion tractography to patients with treatment-resistant obsessive-compulsive disorder (n=18) and treatment-resistant depression (n=5) undergoing ALIC DBS. To assess functional network engagement, we analyzed cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse stimulation of ALIC DBS contacts while recording from ventral prefrontal cortex (vPFC) electrodes in depression patients. Diffusion tractography demonstrated preservation of established ALIC topography in treatment-resistant psychiatric patients, including the dorsoventral organization of prefrontal projections and the mediolateral organization of subcortical pathways. CCEP analyses revealed a corresponding functional organization: ventral ALIC stimulation preferentially engaged medial vPFC sites, whereas dorsal stimulation preferentially engaged lateral vPFC sites in the left hemisphere. These findings demonstrate that stimulation-induced network responses follow known anatomical principles of ALIC organization, and outcome that will support more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.
Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease in patients who have developed complications of levodopa therapy. Suppression of beta oscillations in the STN is associated with improvement of rigidity and bradykinesia. Newer implantable pulse generators can detect local field potentials (LPF) in the STN, and stimulation modulation allows the suppression of beta oscillations with resulting symptomatic improvement. This effect is thought to occur at the actively adjusted STN; LPF suppression can be monitored during routine DBS programming in the clinic. In this exploratory, retrospective analysis, we performed spectral analysis of the effects of current increase in both the actively adjusted and unadjusted STN in 26 patients from two different cohorts. We found that an ipsilateral current increase resulted in concurrent power reduction in both the ipsilateral and contralateral STN in the low-beta (13–22.5 Hz) and high beta (23–30.5 Hz) ranges in 77% of patients. The relative level of bilateral power reduction was more pronounced in the low beta-range (35%) than in the high beta range (19%). In the gamma range (31–125 Hz), 46% of patients showed a bilateral power reduction while 19% showed a bilateral power increase. These cross-hemispheric effects were not significantly associated with demographic, clinical or stimulation parameters, or GBA1 status. To determine whether this phenomenon has clinical significance and, potentially, to inform stimulation algorithms, new methodologies that allow for chronic concurrent monitoring of bilateral LFP suppression during unilateral stimulation adjustment need to be developed and assessed in longitudinal, prospective studies.
Chronic pain is one of the most common causes for patients to seek medical aid, but the currently available therapeutic interventions fail to meet the needs of many patients. Deep brain stimulation (DBS) has been proposed for years as an alternative treatment for chronic pain, though data supporting the use of the technique is mixed. This narrative review summarizes the current state of DBS as a treatment for chronic pain, including recent experiments in both humans and animal models. First, we summarize the current understanding of the interconnected networks in the brain responsible for the experience of pain and the impact of chronic pain on key regions in these networks. Next, a brief history of DBS and its uses in relation to chronic pain provide context for contemporary applications. Important technical considerations including stimulation parameters, anatomical targets, and cohort selection are summarized and reviewed in terms of efficacy and reliability. To improve future work, we also explore the role of placebo analgesia in DBS studies and provide recommendations. Altogether, this review provides an overview on the current state of DBS in the chronic pain field and proposes how future research may confirm the efficacy of DBS as a treatment for chronic pain.
Deep brain stimulation (DBS) has progressed from modulation of single-site nuclei into an adopted therapy for distributed network neuromodulation, with expanding indications spanning movement disorders, psychiatry, pain, epilepsy, and cognition. However, dominant DBS paradigms remain anchored to single-site assumptions, fixed stimulation parameters, and unimodal biomarker control, which increasingly limit selectivity and scalability as indications grow more dimensionally complex. This review proposes that the next critical advance for DBS is network-based, state-based control, in which stimulation is designed around modulating network dynamics as they evolve over time rather than targeting functionally isolated anatomical nodes. We trace the progression from nucleus-centric targeting toward connectivity-informed strategies, identifying three emerging architectural paradigms: single nodal hubs, tract and intersecting bundle targets, and multi-nodal configurations. We then examine how control policies, including continuous, adaptive, and patterned stimulation, must be matched to the temporal and functional properties of the targeted networks to achieve effective modulation. Finally, we argue that advancing beyond single-biomarker adaptive DBS toward multimodal, multi-feature state estimation is essential for capturing the heterogeneous symptom profiles characteristic of multi-network disorders. This requires integrating connectomic structural mapping, electrophysiological decoding from cortical and subcortical recordings, and behavioral kinematics to estimate symptom vectors rather than scalar severity measures. Together, the requirements of structural network mapping, network-aligned control policies, and robust state decoding constitute a principled framework for scalable, personalized neuromodulation capable of addressing circuit dysfunction across neurological and psychiatric conditions.
Background Deep brain stimulation (DBS), particularly targeting the subthalamic nucleus (STN), is an advanced therapy for Parkinson’s disease (PD). However, abrupt reduction of dopaminergic therapy or sudden interruption of stimulation may precipitate severe withdrawal syndromes. These include dopaminergic withdrawal syndrome (DWS), parkinsonism-hyperpyrexia syndrome (PHS)-like presentations and STN-DBS withdrawal syndrome (DBS-WS). Objective This narrative review summarizes reported cases of withdrawal syndromes in PD patients treated with STN-DBS, focusing on triggers, clinical presentation, management, and outcomes. Methods PubMed and Web of Science were searched for English-language reports published between 2007 and May 2024. Case reports and case series describing dopaminergic withdrawal, PHS-like presentations, dopamine agonist withdrawal syndrome (DAWS), or DBS-WS in PD patients treated with STN-DBS were reviewed descriptively. Results Dopaminergic withdrawal/PHS-like syndromes were mainly triggered by abrupt perioperative reduction or discontinuation of dopaminergic medications. Reported manifestations included hyperthermia, severe rigidity, autonomic instability, altered consciousness, elevated creatine kinase, seizures, renal failure, and multi-organ failure. Among six reported cases, three were fatal. DBS-WS was most commonly triggered by implantable pulse generator (IPG) depletion, hardware infection, device failure, or hardware removal. Twenty-three cases were identified. Patients typically developed rapid worsening of parkinsonism, akinesia, dysphagia, autonomic instability, hyperthermia, and systemic deterioration. Escalation of dopaminergic therapy was often insufficient, whereas IPG replacement, stimulation reactivation, or hardware reimplantation frequently led to rapid improvement. Conclusion Dopaminergic withdrawal/PHS-like syndromes and DBS-WS are rare but life-threatening emergencies in STN-DBS-treated PD patients. Early recognition, prevention of abrupt dopaminergic withdrawal, close IPG monitoring, urgent restoration of stimulation, and multidisciplinary emergency management are essential to reduce morbidity and mortality.
Objective Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is an incisionless neurosurgical procedure to treat essential tremor (ET) and tremor-dominant Parkinson’s disease (TDPD). While MRgHIFU is an effective neurosurgical procedure to suppress tremor in ET and TDPD, recurrence of tremor symptoms after a first MRgHIFU ablative procedure have been reported. We present 3 cases to report the utilization of deterministic tractography and digitized stereotactic atlases to identify variables that contribute to recurrent tremor and to plan retreatment MRgHIFU thalamotomies. Methods 2 patients with ET and 1 patient with TDPD initially underwent a successful and complication-free MRgHIFU thalamotomy procedure with standard indirect targeting. All 3 patients had recurrent tremor at 1-6 months post-ablation. Following this period, all patients received postoperative magnetic resonance imaging (MRI) scans with dentato-rubro-thalamic-tract (DRTT) two-tensor deterministic tracking (FT2) and a computerized stereotactic atlas superimposed onto the lesion site of thermoablation. Results In the TDPD patient, the DRTT was shown to be anterior to the high-intensity focused ultrasound lesion (HIFU) from the first ablation. Retreatment with anterior targeting permanently suppressed tremor. In 2 patients, the DRTT partially or fully reconstituted after the first ablation. The original target was retreated with increased-temperature sonications, resulting in permanent tremor suppression. Conclusions Postoperative image processing with DRTT deterministic tractography and computerized stereotactic atlases is an effective way to plan MRgHIFU thalamotomies for recurrent tremor. The target for TDPD may be anterior to the standard ventral intermediate nucleus (VIM) thalamotomy coordinates.
Background and hypothesis With a typical clinical onset in late adolescence and early adulthood, schizophrenia is a severe illness and one of the top ten global causes of disability. Despite improvements in the pharmacological treatment available, 30 % of patients have chronic symptoms and disability, the unemployment rate is at 80–90 %, and patients' life expectancy is reduced by 10–20 years. Deep brain stimulation (DBS) has proven to be effective for different neuropsychiatric diseases, and there is an increased commitment to advanced invasive neuromodulation options for this severe disease. Study design We performed a translational review of the efficacy and adverse effect profile of DBS in patients with schizophrenia using medical subject headings related to DBS and schizophrenia in MEDLINE (OVID interface), Web of Science, and Cochrane Central Register of Controlled Trials. There were no restrictions on study design, outcome, or language. We then performed a narrative review of the neuroscientific understanding of brain networks involved in schizophrenia, and how this may inform target location and explain outcomes observed in the reviewed studies. Study results Following the PRISMA guidelines, 6 studies involving 11 patients who received DBS in the substantia nigra pars reticulata, subgenual anterior cingulate cortex, nucleus accumbens, and habenula were included in the review. None of the studies were sham-controlled and all were open-label. Overall, progressive improvements in the negative symptoms and auditory hallucinations have been reported. Despite an initial improvement, one patient worsened, and two patients presented complications related to the surgery. Conclusion This systematic review presents emerging data regarding the possible utility of DBS in patients with refractory schizophrenia. Nonetheless, the available data have a high risk of bias, and multicenter trials are required to further refine the ability of DBS to target neural networks affected by schizophrenia.
As understanding of neurophysiology has progressed from individual neurons to large-scale brain networks, deep brain stimulation (DBS) has been established as a major intervention for neurological and psychiatric diseases. Here we review (1) the clinical implementation of intraoperative neurophysiological monitoring, focusing on invasive approaches including local field potential (LFP) and microelectrode recordings (MER), and (2) the insights gained from neurophysiological recordings during deep brain stimulation (DBS) into the mechanisms underlying human neurophysiology and behavior. By integrating fundamental neuroscience with clinical practice, this review bridges the gap between core neuroscience and clinical application, demonstrating how DBS serves as both a therapeutic tool and a means to explore human brain function.
Chronic pain is a major public health issue, and despite advances in understanding its pathophysiology, current treatments remain insufficient, significantly affecting patients' quality of life. Existing therapies, including opioids, antidepressants and non-steroidal anti-inflammatory drugs, target specific mechanisms but fail to address the multifactorial nature of chronic pain, which is often accompanied by comorbidities like depression and anxiety. In cases like neuropathic pain, where pharmacological treatments are ineffective, alternatives such as deep brain stimulation (DBS) have gained attention. Although widely used for movement disorders, particularly in Parkinson's disease, DBS has the potential to treat pain by targeting identified deep brain structures while minimizing side effects. Neuropathic pain is linked to changes in several brain networks making up the so-called pain matrix, which includes the thalamus, the cornerstone of sensory, emotional and cognitive dimensions. This review focuses on the use of DBS of the thalamus and closely associated brain structures, such as the periaqueductal and periventricular gray, anterior cingulate cortex and insula, to treat pain.
Chapter 9 reviews the rapidly expanding applications of deep brain stimulation (DBS) beyond movement disorders. With advancements in biomarkers, tractography, and brain mapping, DBS has gained approval for conditions like epilepsy and obsessive-compulsive disorder. Advancing clinical trials also are investigating the efficacy of DBS for depression and Tourette syndrome, among many other medical and neuropsychiatric conditions. This chapter discusses the diverse clinical syndromes that respond best to DBS, along with current research trials and patient factors including individual differences, neuropsychological profiles, and DBS eligibility considerations. Additional discussion is dedicated to a review of DBS trials that are in early yet ongoing stages of research.
Cultural competence and humility are vital for providing effective care to individuals from diverse cultural backgrounds, including those who are candidates for deep brain stimulation (DBS). In Chapter 12, we review health disparities in DBS candidate selection and health outcomes, as well as global care access and utilization for DBS populations. In-depth discussion of culturally competent DBS neuropsychological assessments is provided, with an emphasis on optimizing patient autonomy and nonmaleficence and navigating cultural influences. A critical perspective regarding the availability and use of culturally sensitive assessment tools and engagement of interpreters is offered, followed by a case study to provide further perspective of the consequential impact that cultural competence has on DBS outcome and prognosis.
Deep brain stimulation (DBS) targets specific brain regions to modulate abnormal neural activity, restoring balance to these circuits. Chapter 4 delves into the neuroanatomy of deep brain structures, providing a foundational understanding of how functional neuroanatomy and neuropathology inform DBS. The chapter explores the basal ganglia, thalamus, cerebellum, and other key interconnected brain structures that form complex neural circuits involved in motor control, cognition, and behavior. A comprehensive overview of basal ganglia pathways, including direct and indirect pathways, is presented. The chapter emphasizes the interconnected nature of these deep brain regions and their influence on widespread brain networks, which is crucial for understanding DBS.
Chapter 7 explores the crucial role that genetics plays in the onset, progression, and response to treatments like deep brain stimulation (DBS) among people with Parkinson’s disease. While the exact mechanisms are complex, studies have identified specific gene mutations influencing disease course and surgical outcomes. The chapter highlights genetic mutations associated with Parkinson’s disease, such as GBA, LRRK2, PRKN, and SNCA, and their varying impact on disease progression, cognition, and DBS efficacy. Genetic testing is increasingly important for personalized treatment plans; however, challenges remain, including ethical considerations about genetic testing in DBS decision-making, emphasizing the need for better clinical guidelines and genetic counseling access.
