Clemens Neudorfer

Massachusetts General Hospital | MGH · Department of Neurosurgery

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used...

Background Recent imaging studies identified a brain network associated with clinical improvement following deep brain stimulation (DBS) in Parkinson's disease (PD), the PD response network. Objectives This study aimed to assess the impact of neuromodulation on PD motor symptoms by targeting this network noninvasively using multifocal transcranial...

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson’s disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the...

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfull...

Deep brain stimulation is a viable and efficacious treatment option for dystonia. While the internal pallidum serves as the primary target, more recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its complex surroundings have not been studied in depth. Indeed, multiple...

Importance Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia. Objective To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit. Design This case-control study mapped functional connections of published cases of lesions causi...

Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric...

Mapping circuits for DBS. Within the enigmatic depths of an aquatic universe, divers use flashlights to reveal the hidden contours of an uncharted seabed that teems with wondrous vegetation. In an analogous exploration, Hollunder et al. describe how invasive brain stimulation delivered to deep-seated brain nuclei may act as a beacon. Using deep br...

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By anal...

The advent of next-generation technology has significantly advanced the implementation and delivery of Deep Brain Stimulation (DBS) for Essential Tremor (ET), yet controversies persist regarding optimal targets and networks responsible for tremor genesis and suppression. This review consolidates key insights from anatomy, neurology, electrophysiolo...

Background: Deep brain stimulation (DBS) is a promising treatment option for treatment- refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum (VC/VS). However, the precise target within this region remains a matter of debate. Me...

Speaking evokes modulation of neuronal activity in the subthalamic nucleus (STN), a basal ganglia node that receives both mono- and polysynaptic inputs from cortex and subcortex. Indeed, speech provides a rich context for exploring interactions within human cortical-basal ganglia circuits, but direct intracranial recordings are rare. Here, we synch...

Objective: To describe relationships between electrode localization and motor outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot trial. Methods: To determine anatomical and network correlates associated with motor outcomes for subjects randomized to early DBS (n=14), voxel-wise...

INTRODUCTION Parkinson’s disease (PD) patients with deep brain stimulation (DBS) implantation to the subthalamic nucleus (STN) often have neurocognitive side effects, but the modulated networks associated with their occurrence are largely unknown. METHODS We localized electrodes and investigated brain connectivity seeding from stimulation volumes...

Following its introduction in 2014 and with support of a broad international community, the open-source toolbox Lead-DBS has evolved into a comprehensive neuroimaging platform dedicated to localizing, reconstructing, and visualizing electrodes implanted in the human brain, in the context of deep brain stimulation (DBS) and epilepsy monitoring. Expa...

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neur...

Deep brain stimulation (DBS) to the fornix is an investigational treatment option for patients with mild Alzheimer's disease. Outcomes from randomised clinical trials have shown that cognitive function improved in some patients but deteriorated in others. One reason could be variance in electrode placement leading to differential engagement of neur...

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulatio...

Background: Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) or local field potential recordings (LFP) can be used to extend neuroanatomical information (defined by magnetic resonance imaging) with neurophysio...

Introduction: Tremor is defined as an involuntary, rhythmic oscillatory movement of a body part and represents one of the most common symptoms in movement disorders, existing across several diseases. Particularly, in advanced states of tremor-related diseases such as Parkinson’s disease (PD) and Essential tremor syndrome (ET), response to pharmacot...

Stereotactic neurosurgery is a minimally invasive procedure with high accuracy for diagnosis and treatment of intracranial pathologies. While surgery is typically performed with mechanical aiming devices, the increasing indication spectrum coupled with a growing demand for fast, reliable, and accurate treatment has instigated the search for alterna...

Objective: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their br...

Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed ‘lesion network mapping’ to interr...

At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite “optimal” electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-cen...

Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS allow to pre-select a set of potentially optimal stimulation parameters. If efficacious, they could further carry insight into the mechanism of action of DBS and foster the development of more efficient stimulation approac...

Objective: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their bro...

At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite "optimal" electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-cen...

The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson’s disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common functional network. To tes...

Subcallosal cingulate deep brain stimulation produces long-term clinical improvement in approximately half of patients with severe treatment-resistant depression. We hypothesized that both structural and functional brain attributes may be important in determining responsiveness to this therapy. In a treatment-resistant depression subcallosal cingul...

Obsessive-compulsive disorder is a debilitating and often refractory psychiatric disorder. Magnetic resonance-guided focused ultrasound is a novel, minimally invasive neuromodulatory technique that has shown promise in treating this condition. We investigated the relationship between lesion location and long-term outcome in patients with obsessive-...

Objective Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. The functional and structural consequences of this intervention on brain circuitry are poorly understood, however. We investigated structural changes that occur in brain circuits following mesial temporal lobe resection for refractory epilep...

Due to its involvement in a wide variety of cardiovascular, metabolic, and behavioral functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospec...

OBJECTIVE Historically, preoperative planning for functional neurosurgery has depended on the indirect localization of target brain structures using visible anatomical landmarks. However, recent technological advances in neuroimaging have permitted marked improvements in MRI-based direct target visualization, allowing for refinement of “first-pass”...

Deep brain stimulation of the subthalamic nucleus has become a standard therapy for Parkinson’s disease. Despite extensive experience, however, the precise target of optimal stimulation and the relationship between site of stimulation and alleviation of individual signs remains unclear. We examined whether machine learning could predict the benefit...

OBJECTIVE The objective of this study was to report the authors’ experience with deep brain stimulation (DBS) of the internal globus pallidus (GPi) as a treatment for pediatric dystonia, and to elucidate substrates underlying clinical outcome using state-of-the-art neuroimaging techniques. METHODS A retrospective analysis was conducted in 11 pedia...

Background Electrical stimulation in the kilohertz-frequency range has gained interest in the field of neuroscience. The mechanisms underlying stimulation in this frequency range, however, are poorly characterized to date. Objective/Hypothesis To summarize the manifold biological effects elicited by kilohertz-frequency stimulation in the context o...

Abstract In mesial temporal lobe epilepsy (mTLE), the correlation between disease duration, seizure laterality, and rostro-caudal location of hippocampal sclerosis has not been examined in the context of seizure severity and global cortical thinning. In this retrospective study, we analyzed structural 3 T MRI from 35 mTLE subjects. Regions of FLAIR...

Background: Large hypothalamic hamartomas (HH) are often associated with difficult-to-treat, refractory seizures. Although magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a useful tool to treat these challenging lesions, postoperative outcomes are variable and potentially related to differences in surgical targ...

Introduction: Fornix deep brain stimulation (fx-DBS) is under investigation for treatment of Alzheimer’s disease (AD). We investigated the anatomic correlates of flash-back phenomena that were reported previously during acute diencephalic stimulation. Methods: Thirty-nine patients with mild AD who took part in a prior fx-DBS trial (NCT01608061) wer...

Background Mesial temporal sclerosis (MTS) is the most common cause of temporal lobe epilepsy (TLE). While MTS is associated with a high cure rate after temporal lobectomy (TL), postoperative neurocognitive deficits are common, and a subset of patients may continue to have refractory seizures. Objective To use magnetic resonance (MR) volumetry to...

Treating brain disorders with the aim of modulating brain connections or networks has been a concept since before 1900. However, with the introduction of the human connectome in 2005, a more formal way of analyzing whole-brain connectivity measures was introduced. Shortly after, the concept of connectomic surgery was proposed, harnessing the power...

Deep brain stimulation (DBS) of the subthalamic nucleus, pallidum, and thalamus is an established therapy for various movement disorders. Limbic targets have also been increasingly explored for their application to neuropsychiatric and cognitive disorders. The brainstem constitutes another DBS substrate, although the existing literature on the indi...

Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multi‐disorder DBS dataset assembled over 15 years at our institution (ntotal=482 patients; nParkins...

Background: Spinal cord stimulation (SCS) is a neuromodulation technology widely used in the treatment of intractable chronic pain syndromes. SCS is now being applied more broadly as a possible therapy for a range of indications, including neurological, cardiac, and gastrointestinal disorders. Ongoing research in this field is critical in order to...

Deep brain stimulation (DBS) is a neurosurgical intervention that allows probing and recalibration of dysfunctional brain circuits using electrical current delivered via implanted electrodes. While predominantly used in the treatment of Parkinson’s disease and other movement disorders, DBS is increasingly being studied for its application to psychi...

Background Endovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date. Objective To establish the relationships betw...

The study of the hypothalamus and its topological changes provides valuable insights into underlying physiological and pathological processes. Owing to technological limitations, however, in vivo atlases detailing hypothalamic anatomy are currently lacking in the literature. In this work we aim to overcome this shortcoming by generating a high-reso...

MRI is a valuable clinical and research tool for patients undergoing deep brain stimulation (DBS). However, risks associated with imaging DBS devices have led to stringent regulations, limiting the clinical and research utility of MRI in these patients. The main risks in patients with DBS devices undergoing MRI are heating at the electrode tips, in...

Background Mechanisms of deep brain stimulation (DBS) remain controversial, and spatiotemporal control of brain-wide circuits remains elusive. Adeno-associated viral (AAV) vectors have emerged as vehicles for spatiotemporal expression of exogenous transgenes in several tissues, including specific nuclei in the brain. Coupling DBS with viral vectors...

Essential tremor (ET) is a disabling movement disorder that is most prevalent among the elderly. While deep brain stimulation surgery targeting the ventral intermediate nucleus of the thalamus is commonly used to treat ET, the most elderly patients or those with multiple medical comorbidities may not qualify as surgical candidates. Magnetic resonan...

Abstract Parkinson’s disease is a progressive neurodegenerative disorder characterised by the accumulation of misfolded α-synuclein in selected brain regions, including the substantia nigra pars compacta (SNpc), where marked loss of dopaminergic neurons is also observed. Yet, the relationship between misfolded α-synuclein and neurotoxicity currentl...

Objective: Spinal Cord Stimulation (SCS) overlaps painful areas with paresthesia to alleviate pain. Ten kHz High-Frequency SCS (HF10 cSCS) constitutes a treatment option that can provide pain relief without inducing paresthesia. In this retrospective, open-label study, we evaluated the efficacy of HF10 cSCS in chronic neck and/or upper limb pain....

Background: The employment of the O-arm for intraoperative localization of deep brain stimulation (DBS) leads has been shown to be feasible and effective. However, partial volume artifacts impede the determination of individual electrode contacts and thus allow only an indirect approximation of each contact's localization. Objective: To reduce t...

Objectives Despite its efficacy in tremor‐suppression, the ventral intermediate thalamic (VIM) nucleus has largely been neglected in deep brain stimulation (DBS) for tremor‐dominant Parkinson's disease (tdPD). The employment of a parietal approach, however, allows stimulation of VIM and subthalamic nucleus (STN) using one trajectory only and thus c...