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BACKGROUND Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. OBJECTIVES The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. METHODS We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. RESULTS NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P

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” targeting. The authors reviewed studies relating to direct MRI visualization of the most common functional neurosurgery targets (subthalamic nucleus, globus pallidus, and thalamus) and summarize sequence specifications for the various approaches described in this literature. METHODS The peer-reviewed literature on MRI visualization of the subthalamic nucleus, globus pallidus, and thalamus was obtained by searching MEDLINE. Publications examining direct MRI visualization of these deep brain stimulation targets were included for review. RESULTS A variety of specialized sequences and postprocessing methods for enhanced MRI visualization are in current use. These include susceptibility-based techniques such as quantitative susceptibility mapping, which exploit the amount of tissue iron in target structures, and white matter attenuated inversion recovery, which suppresses the signal from white matter to improve the distinction between gray matter nuclei. However, evidence confirming the superiority of these sequences over indirect targeting with respect to clinical outcome is sparse. Future targeting may utilize information about functional and structural networks, necessitating the use of resting-state functional MRI and diffusion-weighted imaging. CONCLUSIONS Specialized MRI sequences have enabled considerable improvement in the visualization of common deep brain stimulation targets. With further validation of their ability to improve clinical outcomes and advances in imaging techniques, direct visualization of targets may play an increasingly important role in preoperative planning.

Background The therapeutic challenge of glioblastoma (GBM) has catalyzed the development of clinical trials to evaluate novel interventions. With increased understanding of GBM biology and technological advances, the neurosurgeon's role in neuro-oncology has evolved. Objective To evaluate the current landscape of procedure-based clinical trials for GBM to characterize this evolution, gain insight into past failures, and accordingly outline implications for future research and practice that may inform future studies. Methods The ClinicalTrials.gov database was searched for surgical/procedural trials in individuals with GBM. Demographics, specific intervention, trial phase, and main outcome measures were abstracted. Results A total of 224 of 2311 GBM trials (9.7%) were identified as procedural, with the majority being based in the United States (155/224, 69.2%), single-center (155/224, 69.2%), and not randomized (176/224, 78.6%). Primary and recurrent GBMs were evenly addressed. The leading interventions were local delivery of therapeutics (50.0%), surgical techniques (33.9%), such as image-guided surgery, and novel device applications (14.3%). Phase I designs predominated (82/224, 36.6%). The top primary outcome was safety/tolerability/feasibility (88/224, 39.3%), followed by survival (46/224, 20.5%). Approximately 17% of studies were terminated, withdrawn, or suspended. Fifty-two linked publications were identified, among which 42 were classified as having a positive result. Conclusion Procedural interventions comprised ∼10% of all registered GBM trials. Local delivery of therapeutics, use of surgical imaging techniques and novel device applications, predominantly through phase I designs, represent the evolved role of the neurosurgeon in neuro-oncology. Improved reporting of trial designs, outcomes, and results are needed to better inform the field and increase efficiency.

Abstarct Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural 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 retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied—at multiple international centres—58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer’s disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation—including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear—were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

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 hyperintensity (as an indicator of sclerosis)—based on 2D coronal FLAIR sequences—in the hippocampus were manually segmented, independently and in duplicate; degree of segmentation agreement was confirmed using the DICE index. Segmented lesions were used for separate analyses. First, the correlation of cortical thickness with disease duration and seizure focus laterality was explored using linear model regression. Then, the relationship between the rostro-caudal location of the FLAIR hyperintense signal and seizure severity, based on the Cleveland Clinic seizure freedom score (ccSFS), was explored using probabilistic voxel-wise mapping and functional connectivity analysis from normative data. The mean DICE Index was 0.71 (range 0.60–0.81). A significant correlation between duration of epilepsy and decreased mean whole brain cortical thickness was identified, regardless of seizure laterality (p

Introduction Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback 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) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel‐wise VTA mapping to identify flashback‐associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback‐associated brain‐wide networks. Results A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback‐inducing stimulation exhibited greater functional connectivity to a network of memory‐evoking and autobiographical memory‐related sites. Discussion These results clarify the neuroanatomical substrates of stimulation‐evoked flashbacks.

Background Gout treatment is not optimized globally, often due to therapeutic inertia by physicians or poor adherence to urate-lowering medications by patients. A patient decision aid (PDA) to facilitate shared decision making (SDM) in gout treatment may overcome these physician-patient barriers. Objective The study explored the views of physicians and patients on a novel locally designed gout treatment PDA prototype. Design Qualitative descriptive design was used to gather data from in-depth-interviews (IDI) and focus group discussions (FGD). Data analysis was via thematic analysis. Emergent themes shaped a revised version of the PDA. Setting and participants Adult Asian patients with recent acute gout exacerbations and local Primary Care Physicians (PCP) in Singapore were purposefully chosen. 15 patients with gout and 11 PCPs participated across three IDIs and six FGDs, with the investigators exploring their views of a prototype gout treatment PDA. Results Patients and physicians generally concurred with the content and design of the PDA prototype. However, while patients preferred fewer treatment details, the PCPs desired more information. Patients preferred the display of statistics, while PCPs felt that numbers were not relevant to patients. The latter were hesitant to include treatment options that were unavailable in primary care. Both stakeholders indicated that they would use the PDA during a consultation. PCPs would need further training in SDM, given a lack of understanding of it. Conclusion and patient contribution Patients will be the prime users of the PDA. While their views differed partially from the physicians, both have jointly developed the novel gout treatment PDA.

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 between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS. Methods Neuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed. Results Six out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue. Conclusions While several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.

Deep brain stimulation (DBS) is becoming increasingly central in the treatment of patients with Parkinson's disease and other movement disorders. Recent developments in DBS lead and implantable pulse generator design provide increased flexibility for programming, potentially improving the therapeutic benefit of stimulation. Directional DBS leads may increase the therapeutic window of stimulation by providing a means of avoiding current spread to structures that might give rise to stimulation-related side effects. Similarly, control of current to individual contacts on a DBS lead allows for shaping of the electric field produced between multiple active contacts. The following review aims to describe the recent developments in DBS system technology and the features of each commercially available DBS system. The advantages of each system are reviewed, and general considerations for choosing the most appropriate system are discussed.

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, induced currents, implantable pulse generator dysfunction, and mechanical forces. Phantom model studies indicate that electrode tip heating remains the most serious risk for modern DBS devices. The absence of adverse events in patients imaged under DBS vendor guidelines for MRI demonstrates the general safety of MRI for patients with DBS devices. Moreover, recent work indicates that—given adequate safety data—patients may be imaged outside these guidelines. At present, investigators are primarily focused on improving DBS device and MRI safety through the development of tools, including safety simulation models. Existing guidelines provide a standardized framework for performing safe MRI in patients with DBS devices. It also highlights the possibility of expanding MRI as a tool for research and clinical care in these patients going forward. © RSNA, 2020 Online supplemental material is available for this article.

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 resonance-guided focused ultrasound (MRgFUS) constitutes a less invasive modality that may be used to perform thalamotomy without the need for a burr hole craniotomy. Here, we report on 2 patients over the age of 90 years who benefited significantly from MRgFUS thalamotomy to relieve their symptoms and improve their quality of life. The procedure was well tolerated and performed safely in both patients. We conclude that age should not be a limiting factor in the treatment of patients with MRgFUS.

Commonly used for Parkinson’s disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming., Deep brain stimulation programming for Parkinson’s disease entails the assessment of a large number of possible simulation settings, requiring numerous clinic visits after surgery. Here, the authors show that patterns of functional MRI can predict the optimal stimulation settings.

Objective Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) has shown promise as a treatment for medically refractory epilepsy. To better understand the mechanism of this intervention, we used functional magnetic resonance imaging (fMRI) to map the acute blood oxygen level-dependent (BOLD) response pattern to thalamic DBS in fully implanted patients with epilepsy. Methods Two patients with epilepsy implanted with bilateral ANT-DBS devices underwent four fMRI acquisitions each, during which active left-sided monopolar stimulation was delivered in a 30-s DBS-ON/OFF cycling paradigm. Each fMRI acquisition featured left-sided stimulation of a different electrode contact to vary the locus of stimulation within the thalamus and to map the brain regions modulated as a function of different contact selection. To determine the extent of peri-electrode stimulation and the engagement of local structures during each fMRI acquisition, volume of tissue activated (VTA) modeling was also performed. Results Marked changes in the pattern of BOLD response were produced with thalamic stimulation, which varied with the locus of the active contact in each patient. BOLD response patterns to stimulation that directly engaged at least 5% of the anterior nuclear group by volume were characterized by changes in the bilateral putamen, thalamus, and posterior cingulate cortex, ipsilateral middle cingulate cortex and precuneus, and contralateral medial prefrontal and anterior cingulate. Significance The differential BOLD response patterns associated with varying thalamic DBS parameters provide mechanistic insights and highlight the possibilities of fMRI biomarkers of optimizing stimulation in patients with epilepsy.

Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. However, the functional and structural consequences of this intervention on brain circuitry are poorly understood. We investigated structural changes that occur in brain circuits after mesial temporal lobe resection for refractory epilepsy. Specifically, we used neuroimaging techniques to evaluate changes in 1) contralesional hippocampal and bilateral mammillary body volume and 2) brain-wide cortical thickness.Serial T1-weighted brain magnetic resonance images were acquired before and after surgery (1.6 ± 0.5 year interval) in 21 patients with temporal lobe epilepsy (9 women, 12 men; mean age, 39.4 ± 11.5 years) who had undergone unilateral temporal lobe resection (14 anterior temporal lobectomy; 7 selective amygdalohippocampectomy). Blinded manual segmentation of the unresected hippocampal formation and bilateral mammillary bodies was performed using the Pruessner and Copenhaver protocols, respectively. Brain-wide cortical thickness estimates were computed using the CIVET pipeline.Surgical resection was associated with a 5% reduction in contralesional hippocampal volume (P0.01) and a 9.5% reduction in mammillary body volume (P = 0.03). In addition, significant changes in cortical thickness were observed in contralesional anterior and middle cingulate gyrus and insula (PThese results indicate that mesial temporal lobe resection is associated with both volume loss in spared Papez circuitry and changes in cortical thickness across the brain.

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 cingulate deep brain stimulation cohort, we retrospectively examined baseline and longitudinal differences in MRI-derived brain volume (n = 65) and 18F-fluorodeoxyglucose-PET glucose metabolism (n = 21) between responders and non-responders. Support vector machines were subsequently trained to classify patients’ response status based on extracted baseline imaging features. A machine learning model incorporating preoperative frontopolar, precentral/frontal opercular and orbitofrontal local volume values classified binary response status (12 months) with 83% accuracy [leave-one-out cross-validation (LOOCV): 80% accuracy] and explained 32% of the variance in continuous clinical improvement. It was also predictive in an out-of-sample subcallosal cingulate deep brain stimulation cohort (n = 21) with differing primary indications (bipolar disorder/anorexia nervosa; 76% accuracy). Adding preoperative glucose metabolism information from rostral anterior cingulate cortex and temporal pole improved model performance, enabling it to predict response status in the treatment-resistant depression cohort with 86% accuracy (LOOCV: 81% accuracy) and explain 67% of clinical variance. Response-related patterns of metabolic and structural post-deep brain stimulation change were also observed, especially in anterior cingulate cortex and neighbouring white matter. Areas where responders differed from non-responders—both at baseline and longitudinally—largely overlapped with depression-implicated white matter tracts, namely uncinate fasciculus, cingulum bundle and forceps minor/rostrum of corpus callosum. The extent of patient-specific engagement of these same tracts (according to electrode location and stimulation parameters) also served as an independent predictor of treatment-resistant depression response status (72% accuracy; LOOCV: 70% accuracy) and augmented performance of the volume-based (88% accuracy; LOOCV: 82% accuracy) and combined volume/metabolism-based support vector machines (100% accuracy; LOOCV: 94% accuracy).Taken together, these results indicate that responders and non-responders to subcallosal cingulate deep brain stimulation exhibit differences in brain volume and metabolism, both pre- and post-surgery. Moreover, baseline imaging features predict response to treatment (particularly when combined with information about local tract engagement) and could inform future patient selection and other clinical decisions.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5-12 Hz) are important in cognition. METHODS: We tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients' peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation. RESULTS: Acute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions. CONCLUSION: Here, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes. ispartof: BRAIN STIMULATION vol:14 issue:4 pages:754-760 ispartof: location:United States status: published

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 benefits in specific Parkinsonian signs when informed by precise locations of stimulation. We studied 275 Parkinson’s disease patients who underwent subthalamic nucleus deep brain stimulation between 2003 and 2018. We selected pre-deep brain stimulation and best available post-deep brain stimulation scores from motor items of the Unified Parkinson's Disease Rating Scale (UPDRS-III) to discern sign-specific changes attributable to deep brain stimulation. Volumes of tissue activated were computed and weighted by (i) tremor, (ii) rigidity, (iii) bradykinesia and (iv) axial signs changes. Then, sign-specific sites of optimal (‘hot spots’) and suboptimal efficacy (‘cold spots’) were defined. These areas were subsequently validated using machine learning prediction of sign-specific outcomes with in-sample and out-of-sample data (n = 51 subthalamic nucleus deep brain stimulation patients from another institution). Tremor and rigidity hot spots were largely located outside and dorsolateral to the subthalamic nucleus whereas hot spots for bradykinesia and axial signs had larger overlap with the subthalamic nucleus. Using volume of tissue activated overlap with sign-specific hot and cold spots, support vector machine classified patients into quartiles of efficacy with ≥92% accuracy. The accuracy remained high (68–98%) when only considering volume of tissue activated overlap with hot spots but was markedly lower (41–72%) when only using cold spots. The model also performed poorly (44–48%) when using only stimulation voltage, irrespective of stimulation location. Out-of-sample validation accuracy was ≥96% when using volume of tissue activated overlap with the sign-specific hot and cold spots. In two independent datasets, distinct brain areas could predict sign-specific clinical changes in Parkinson’s disease patients with subthalamic nucleus deep brain stimulation. With future prospective validation, these findings could individualize stimulation delivery to optimize quality of life improvement., Boutet and Germann et al. examined whether machine learning could predict clinical benefits in specific Parkinsonian signs when informed by the precise location of stimulation. They report that machine learning modelling using distinct brain areas could predict sign-specific clinical changes in Parkinson’s disease patients with subthalamic nucleus deep brain stimulation., Graphical Abstract Graphical Abstract

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 of the currently existing literature and provide a mechanistic framework for the neural responses observed in this frequency range. Methods A comprehensive search of the peer-reviewed literature was conducted across electronic databases. Relevant computational, clinical, and mechanistic studies were selected for review. Results The effects of kilohertz-frequency stimulation on neural tissue are diverse and yield effects that are distinct from conventional stimulation. Broadly, these can be divided into 1) subthreshold, 2) suprathreshold, 3) synaptic and 4) thermal effects. While facilitation is the dominating mechanism at the subthreshold level, desynchronization, spike-rate adaptation, conduction block, and non-monotonic activation can be observed during suprathreshold kilohertz-frequency stimulation. At the synaptic level, kilohertz-frequency stimulation has been associated with the transient depletion of the available neurotransmitter pool – also known as synaptic fatigue. Finally, thermal effects associated with extrinsic (environmental) and intrinsic (associated with kilohertz-frequency stimulation) temperature changes have been suggested to alter the neural response to stimulation paradigms. Conclusion The diverse spectrum of neural responses to stimulation in the kilohertz-frequency range is distinct from that associated with conventional stimulation. This offers the potential for new therapeutic avenues across stimulation modalities. However, stimulation in the kilohertz-frequency range is associated with distinct challenges and caveats that need to be considered in experimental paradigms.

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 indications for and the effects of brainstem stimulation remains comparatively sparse. The objective of this review was to provide a comprehensive overview of the pertinent anatomy, indications, and reported stimulation-induced acute and long-term effects of existing white and grey matter brainstem DBS targets. We systematically searched the published literature, reviewing clinical trial articles pertaining to DBS brainstem targets. Overall, 164 studies describing brainstem DBS were identified. These studies encompassed 10 discrete structures: periaqueductal/periventricular grey (n = 63), pedunculopontine nucleus (n = 48), ventral tegmental area (n = 22), substantia nigra (n = 9), mesencephalic reticular formation (n = 7), medial forebrain bundle (n = 8), superior cerebellar peduncles (n = 3), red nucleus (n = 3), parabrachial complex (n = 2), and locus coeruleus (n = 1). Indications for brainstem DBS varied widely and included central neuropathic pain, axial symptoms of movement disorders, headache, depression, and vegetative state. The most promising results for brainstem DBS have come from targeting the pedunculopontine nucleus for relief of axial motor deficits, periaqueductal/periventricular grey for the management of central neuropathic pain, and ventral tegmental area for treatment of cluster headaches. Brainstem DBS has also acutely elicited numerous motor, limbic, and autonomic effects. Further work involving larger, controlled trials is necessary to better establish the therapeutic potential of DBS in this complex area.

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 identify features of the mesial temporal lobe in patients with MTS that correlate with seizure and neurocognitive outcome after temporal lobectomy. Methods Thirty-five patients with unilateral MTS, high-resolution MR imaging, and at least one year of postoperative assessments were retrospectively examined. Volumetric analysis of the hippocampus, parahippocampal gyrus (PHG) and FLAIR hyperintensity of the affected temporal lobe was performed. TL resections were manually segmented, and resection heat maps reflecting seizure outcome were produced. The degree of preoperative atrophy of the affected mesial structures relative to the unaffected side were related to preoperative and postoperative component scores of verbal and visuospatial memory as well as confrontation naming. Results Greater FLAIR hyperintense volume was associated with favorable seizure outcome at one year and last follow-up. Resections extending most medial and posteriorly were associated with favorable seizure outcome. In patients with left MTS, less atrophy of the affected PHG was predictive of higher preoperative naming scores and greater postoperative naming deficit, while less hippocampal atrophy was predictive of higher preoperative verbal memory component scores. Conclusion Greater hippocampal FLAIR volume is associated with favorable surgical outcome. Hippocampal volume correlates with preoperative verbal memory, while PHG volume is implicated in confrontation naming ability.