Search

Objective: This retrospective analysis assessed regression-based reliable change (RC) of cognition in a sample of essential tremor (ET) patients who underwent unilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS). Method: Thirty patients (mean age at pre-evaluation = 70.4 ± 6.3 years) underwent neuropsychological evaluation pre- and post-unilateral VIM-DBS placement (mean time between pre and post-evaluation = 13.1 ± 4.0 months). Paired samples t -tests and RC analyses were employed. Results: No significant within-group differences were observed when cognitive scores were compared between evaluations. The vast majority of patients demonstrated stability across pre-and post-surgical evaluations (i.e. 29 out of 30); however, those with high-risk co-morbid medical conditions may be vulnerable to post-surgical cognitive decline as indicated by RC measures. Conclusions: The use of regression-based RC indices to assess individual cognitive changes between pre and post-surgical evaluations control for systematic and measurement errors that can occur over repeated evaluations, and may be able to identify cognitive changes that evade detection in traditional within-group comparisons.

Surgical neuromodulation has witnessed significant progress in recent decades. Notably, deep brain stimulation (DBS), delivered precisely within therapeutic targets, has revolutionized the treatment of medication-refractory movement disorders and is now expanding for refractory psychiatric disorders, refractory epilepsy, and post-stroke motor recovery. In parallel, the advent of incisionless treatment with focused ultrasound ablation (FUSA) can offer patients life-changing symptomatic relief. Recent research has underscored the potential to further optimize DBS and FUSA outcomes by conceptualizing the therapeutic targets as critical nodes embedded within specific brain networks instead of strictly anatomical structures. This paradigm shift was facilitated by integrating two imaging modalities used regularly in brain connectomics research: diffusion MRI (dMRI) and functional MRI (fMRI). These advanced imaging techniques have helped optimize the targeting and programming techniques of surgical neuromodulation, all while holding immense promise for investigations into treating other neurological and psychiatric conditions. This review aims to provide a fundamental background of advanced imaging for clinicians and scientists, exploring the synergy between current and future approaches to neuromodulation as they relate to dMRI and fMRI capabilities. Focused research in this area is required to optimize existing, functional neurosurgical treatments while serving to build an investigative infrastructure to unlock novel targets to alleviate the burden of other neurological and psychiatric disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vibhor Krishna reports financial support was provided by National Institutes of Health. Vibhor Krishna reports a relationship with Medtronic Inc that includes: board membership and consulting or advisory. N/A If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals., Competing Interests: Competing interests statement:The authors declare no competing interest.

The current white matter connectivity analyses of the subthalamic region have focused on the motor effects of deep brain stimulation. We investigate white matter connectivity associated with the stimulation-induced non-motor acute clinical effects in three domains: mood changes, dizziness, and sweating. We performed whole-brain probabilistic tractography seeded from the domain-specific stimulation volumes. The resultant connectivity maps were statistically compared across patients. The cortical voxels associated with each non-motor domain were compared with stimulation-induced motor improvements in a multivariate model. The resulting voxel maps were thresholded for false discovery (FDR q < 0.05) and clustered using a multimodal atlas. We also performed a group-level parcellation of stimulation volumes to identify the local pathways associated with each non-motor domain. The non-motor effects were rarely observed during stimulation titration: from 1100 acute clinical effects, mood change was observed in 14, dizziness in 23, and sweating in 20. Distinct cortical clusters were associated with each domain; notably, mood change was associated with voxels in the salience network and dizziness with voxels in the visual association cortex. The subthalamic parcellation yielded a mediolateral gradient, with the motor parcel being lateral and the non-motor parcels medial. We also observed an anteroposterior organization in the medial non-motor clusters with mood changes being anterior, followed posteriorly by dizziness, and sweating. We interpret these findings based on the literature and foresee these to be useful in guiding DBS programming., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Deep brain stimulation (DBS) is an effective treatment for medically refractory Parkinson's disease (PD). During DBS surgery, intraoperative testing is performed to confirm optimal lead placement by determining the stimulation thresholds for symptom improvement and side effects. However, the reliability of intraoperative testing in predicting distant postoperative thresholds is unknown. In this study, we hypothesized that intraoperative testing reliably estimates postoperative thresholds for both symptom improvement and side effects., Methods: We retrospectively analyzed a prospective database with intraoperative and postoperative thresholds for symptom improvement and side effects from a cohort of 66 PD patients who underwent STN DBS. We recorded the stimulation locations relative to the mid-commissural point. Within-patient stimulation pairs were generated by clustering the intraoperative stimulation locations closest to the DBS contacts. We computed the distance between stimulation locations and atlas-based pyramidal tract (PT) and medial lemniscus (ML) masks. A leave-one-out cross-validation analysis was performed to determine the reliability of intraoperative testing in predicting postoperative thresholds while controlling for the distance from the relevant tracks., Results: Intraoperative testing reliably predicted (area under ROC >0.8) postoperative thresholds for tremor and rigidity improvements, as well as stimulation-induced motor contractions and paresthesias. The reliability was poor for improvement in bradykinesia., Conclusion: Intraoperative testing reliably predicts postoperative thresholds. These results are relevant during the informed consent process and patient counseling for DBS surgery. These will also guide the development of future methods for intraoperative feedback, especially during asleep DBS., (© 2019 International Neuromodulation Society.)

Introduction: Optimal placement of Deep Brain Stimulation (DBS) lead is critical to ensure an adequate therapeutic benefit and minimize stimulation-induced side effects., Methods: We reviewed data from 2004 to 2018 of all cases of essential tremor treated with thalamic DBS at the University of Cincinnati. All procedures were performed with the patient awake. Change in parallel trajectory was classified as major repositioning, whereas a change in depth of electrode classified as minor repositioning. The following data were compared between groups (no vs. minor vs. major repositioning): age at surgery, sex, AC-PC length, third ventricle width, cerebral atrophy, small vessel disease burden, and intraoperative tremor control. Univariate and multivariate analyses were conducted to identify factors associated with intraoperative repositioning., Results: Of the 127 encounters with essential tremor, 71 required repositioning (33 major and 38 minor). Comparing procedures with major, minor, and no repositioning, mean number of changes per procedure (4 vs. 1.2 vs 0; p < 0.001) and AC-PC length (26 vs. 27 vs. 27.2 mm; p = 0.021) differed between the three groups. Older age at surgery (OR 1.04, p = 0.042), left side (OR 2.56, p = 0.04) and decrease in AC-PC length (OR 1.33, p = 0.026) were associated with greater odds of any (minor or major) repositioning. A decrease in AC-PC length was associated with greater odds of major repositioning (OR 1.37, p = 0.009)., Conclusion: Intraoperative functional testing may be critical to ensure the accuracy of thalamic DBS targeting based on neuroimaging data, particularly in patients with reduced AC-PC length., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The selection of optimal deep brain stimulation (DBS) parameters is time-consuming, experience-dependent, and best suited when acute effects of stimulation can be observed (e.g., tremor reduction)., Objectives: To test the hypothesis that optimal stimulation location can be estimated based on the cortical connections of DBS contacts., Methods: We analyzed a cohort of 38 patients with Parkinson's disease (24 training, and 14 test cohort). Using whole-brain probabilistic tractography, we first mapped the cortical regions associated with stimulation-induced efficacy (rigidity, bradykinesia, and tremor improvement) and side effects (paresthesia, motor contractions, and visual disturbances). We then trained a support vector machine classifier to categorize DBS contacts into efficacious, defined by a therapeutic window ≥2 V (threshold for side effect minus threshold for efficacy), based on their connections with cortical regions associated with efficacy versus side effects. The connectivity-based classifications were then compared with actual stimulation contacts using receiver-operating characteristics (ROC) curves., Results: Unique cortical clusters were associated with stimulation-induced efficacy and side effects. In the training dataset, 42 of the 47 stimulation contacts were accurately classified as efficacious, with a therapeutic window of ≥3 V in 31 (66%) and between 2 and 2.9 V in 11 (24%) electrodes. This connectivity-based estimation was successfully replicated in the test cohort with similar accuracy (area under ROC = 0.83)., Conclusions: Cortical connections can predict the efficacy of DBS contacts and potentially facilitate DBS programming. The clinical utility of this paradigm in optimizing DBS outcomes should be prospectively tested, especially for directional electrodes., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: Disturbances in the reward network of the brain underlie addiction, depression, and obsessive-compulsive disorder. The ventral capsule/ventral striatum and nucleus accumbens (NAc) region is a clinically approved target for deep brain stimulation for obsessive-compulsive disorder., Methods: We performed a comprehensive literature review to define clinically relevant anatomy and connectivity of the ventral capsule/ventral striatum and NAc region to guide target selection for deep brain stimulation., Results: Architecturally and functionally, the NAc is divided into the core and the shell, with each area having different connections. The shell primarily receives limbic information, and the core typically receives information from the motor system. In general, afferents from the prefrontal cortex, hippocampus, and amygdala are excitatory. The dopaminergic projections to the NAc from the ventral tegmental area modulate the balance of these excitatory inputs. Several important inputs to the NAc converge at the junction of the internal capsule (IC) and the anterior commissure (AC): the ventral amygdalofugal pathways that run parallel to and underneath the AC, the precommissural fornical fibers that run anterior to the AC, axons from the ventral prefrontal cortex and medial orbitofrontal cortex that occupy the most ventral part of the IC and embedding within the NAc and AC, and the superolateral branch of the medial forebrain bundle located parallel to the anterior thalamic radiation in the IC., Conclusions: The caudal part of the NAc passing through the IC-AC junction may be an effective target for deep brain stimulation to improve behavioral symptoms associated with obsessive-compulsive disorder., (Copyright © 2019. Published by Elsevier Inc.)

Background: Deep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown., Methods: We retrospectively investigated the clinical, pharmacological, electrophysiological and anatomical features that might predict the initial response and preservation of benefit in all patients who underwent deep brain stimulation for tremor. Data were collected at the following time points: baseline (preoperative), one-year post-surgery, and most recent visit. Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale and/or the Unified Parkinson's Disease Rating Scale., Results: A total of 52 patients were included in the final analysis: 31 with essential tremor, 15 with cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long-term success (mean follow-up duration 34.7 months, range 1.7-121.1 months) was reported in 63.5%. Predictors of long-term benefit were: underlying tremor etiology (best outcome in Parkinson's disease, worst outcome in cerebellar tremor); age at surgery (the older the better); baseline tremor severity (the greater the better); lack of response to benzodiazepines; a more anterior electrode placement and single-unit beta power (the greater the better)., Conclusions: Specific patients' features (including single unit beta activity) and electrode locations may predict the short- and long-term benefit of thalamic stimulation for tremor. Future prospective studies enrolling a much larger sample of patients are needed to substantiate the associations detected by this retrospective study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Thalamic deep brain stimulation (DBS) is an effective strategy for treatment of essential tremor (ET). With limitations of imaging modalities, targeting largely relies on indirect methods. This study was designed to determine the optimal target for DBS in ET and construct a targeting method based on probabilistic maps., Methods: Patients with ET who had sustained tremor reduction at 1 year and optimal microelectrode recordings were selected. Stimulation volume was individually modeled in standard space, and a final optimal region was derived for the whole population. A fornix (FX) targeting method was developed to determine the location of the optimal stimulation site relative to the FX and posterior commissure (PC) in the anteroposterior plane, the border between the thalamus and internal capsule in the mediolateral plane, and the anterior commissure (AC)-PC (AC-PC) plane in the dorsoventral axis. Following comparative analyses with other standard indirect methods (25% of AC-PC and PC + 6 mm), the FX method was studied in relation to diffusion tensor imaging., Results: Using the FX method, the optimal stimulation site was at the intersection of two thirds and one third of the PC-FX distance (mean of 28% ± 1.5 AC-PC length) and 4 mm medial to the lateral border of the thalamus. Compared with previously used methods, there was a significant reduction in variability of the optimal stimulation site with the FX method. The target defined using this strategy was found to be within the boundaries of the dentatorubrothalamic tract., Conclusions: The FX method may be an additional targeting strategy in patients undergoing thalamic DBS surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

OBJECTIVE The aim of this study was to evaluate the safety of 3-T MRI in patients with implanted deep brain stimulation (DBS) systems. METHODS This study was performed in 2 phases. In an initial phantom study, a Lucite phantom filled with tissue-mimicking gel was assembled. The system was equipped with a single DBS electrode connected to an internal pulse generator. The tip of the electrode was coupled to a fiber optic thermometer with a temperature resolution of 0.1°C. Both anatomical (T1- and T2-weighted) and functional MRI sequences were tested. A temperature change within 2°C from baseline was considered safe. After findings from the phantom study suggested safety, 10 patients with implanted DBS systems targeting various brain areas provided informed consent and underwent 3-T MRI using the same imaging sequences. Detailed neurological evaluations and internal pulse generator interrogations were performed before and after imaging. RESULTS During phantom testing, the maximum temperature increase was registered using the T2-weighted sequence. The maximal temperature changes at the tip of the DBS electrode were < 1°C for all sequences tested. In all patients, adequate images were obtained with structural imaging, although a significant artifact from lead connectors interfered with functional imaging quality. No heating, warmth, or adverse neurological effects were observed. CONCLUSIONS To the authors' knowledge, this was the first study to assess the clinical safety of 3-T MRI in patients with a fully implanted DBS system (electrodes, extensions, and pulse generator). It provided preliminary data that will allow further examination and assessment of the safety of 3-T imaging studies in patients with implanted DBS systems. The authors cannot advocate widespread use of this type of imaging in patients with DBS implants until more safety data are obtained.

Freezing of gait (FOG) is a common and debilitating, but largely mysterious, symptom of Parkinson disease. In this review, we will discuss the cerebral substrate of FOG focusing on brain physiology and animal models. Walking is a combination of automatic movement processes, afferent information processing, and intentional adjustments. Thus, normal gait requires a delicate balance between various interacting neuronal systems. To further understand gait control and specifically FOG, we will discuss the basic physiology of gait, animal models of gait disturbance including FOG, alternative etiologies of FOG, and functional magnetic resonance studies investigating FOG. The outcomes of these studies point to a dynamic network of cortical areas such as the supplementary motor area, as well as subcortical areas such as the striatum and the mesencephalic locomotor region including the pedunculopontine nucleus (PPN). Additionally, we will review PPN (area) stimulation as a possible treatment for FOG, and ponder whether PPN stimulation truly is the right step forward. Ann Neurol 2016;80:644-659., (© 2016 American Neurological Association.)

Background: Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) at standard frequency (>100 Hz) often develop gait impairment, postural instability and speech difficulties. Low frequency stimulation (<100 Hz, LFS) can improve such axial symptoms, but there are concerns that improvement may be transient., Objective: To identify long-term outcome and predictors of low-frequency subthalamic stimulation in Parkinson's disease., Methods: Through a chart review we identified 85 out of 324 STN DBS patients who received a trial of LFS and describe their characteristics and outcome predictors., Results: Patients were switched to LFS (<100 Hz) 3.8 ± 3.3 years after surgery. Most patients (64%) attained a subjective improvement of gait, speech or balance for 2.0 ± 1.9 years. Motor scores improved within the first year after the stimulation change and showed a slower progression over time when compared to patients switched back to high frequency stimulation. UPDRS III axial score on medication before surgery and the y-axis coordinate of the active contact were independent predictors of LFS retention., Conclusions: This report provides evidence that the use of LFS yields an enduring benefit in a considerable percentage of patients who develop axial motor symptoms during conventional stimulation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The effect of the variability of electrode placement on outcomes after bilateral deep brain stimulation of subthalamic nucleus has not been sufficiently studied, especially with respect to the sequence of hemisphere implantation., Methodology: We retrospectively analysed the clinical and radiographic data of all the consecutive patients with Parkinson's disease who underwent surgery at our centre and completed at least 1 year follow-up. The dispersion in electrode location was calculated by the square of deviation from population mean, and the direction of deviation was analysed by comparing the intended and final implantation coordinates. Linear regression analysis was performed to analyse the predictors of postoperative improvement of the motor condition, also controlling for the sequence of implanted hemisphere., Results: 76 patients (mean age 58±7.2 years) were studied. Compared with the first side, the second side electrode tip had significantly higher dispersion as an overall effect (5.6±21.6 vs 2.2±4.9 mm(2), p=0.04), or along the X-axis (4.1±15.6 vs 1.4±2.4 mm(2), p=0.03) and Z-axis (4.9±11.5 vs 2.9±3.6 mm(2), p=0.02); the second side stimulation was also associated with a lower threshold for side effects (contact 0, p<0.001 and contact 3, p=0.004). In the linear regression analysis, the significant predictors of outcome were baseline activities of daily living (p=0.010) and dispersion of electrode on the second side (p=0.005)., Conclusions: We observed a higher dispersion for the electrode on the second implanted side, which also resulted to be a significant predictor of motor outcome at 1 year., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The most common anesthetic technique for patients undergoing insertion of deep brain stimulators (DBS) is local anesthesia with or without conscious sedation as this facilitates intraoperative microelectrode recordings (MERs) for target localization. However, general anesthesia (GA) may be needed in some of the patients especially those with dystonia. The purpose of our study was to determine the effects of GA on MERs from pallidal neurons in patients with dystonia undergoing DBS implantation surgery., Methods: After IRB approval, we retrospectively reviewed the medical records of all patients who had insertion of DBS from January 2009 to December 2013. Data collected and analyzed included demographics, indications for DBS, targets of insertion, MER, and anesthetic management. From the records we identified patients with dystonia who received GA for DBS insertion. We then compared the MER data under GA with the data from patients who had surgery under local anesthesia only during the same time period. Because of the small sample size, the effects of various anesthetic regiments on MER and localization of target nuclei were compared qualitatively., Results: Of the 435 patients who underwent DBS insertion during the study period, 20 (4.3%) patients had GA for the procedure. Dystonia was the most common indication for GA (16/20 patients, 80%). Good-quality MER data obtained from 10 patients with dystonia under GA was compared with 8 patients who had no sedation for the procedure. Administration of GA made target localization difficult due to suppression of both spontaneous and evoked neuronal discharges from internal globus pallidus. Although not studied systematically, propofol (>100 mcg/kg/min) seemed to suppress pallidal discharges more than GA with a lower dose of propofol (<75 mcg/kg/min), remifentanil, and 0.2% to 0.4% end-tidal sevoflurane or desflurane., Conclusions: Our retrospective review suggests that there was a difference in spontaneous and evoked neuronal discharges with MER performed under GA compared with no sedation. MER recordings during GA appeared most robust during a combination of anesthetics including low-dose propofol infusion, remifentanil, and a low concentration of either sevoflurane or desflurane. Our findings can inform a power analysis to determine the sample size that would be required to prospectively test the hypothesis that there is a difference in spontaneous and evoked neuronal discharges with MER performed under GA compared with no sedation.

Background: Anterior nucleus (AN) deep brain stimulation (DBS) is a palliative treatment for medically refractory epilepsy. The long-term efficacy and the optimal target localization for AN DBS are not well understood., Objective: To analyze the long-term efficacy of AN DBS and its predictors., Methods: We performed a retrospective review of 16 patients who underwent AN DBS. We selected only patients with reliable seizure frequency data and at least a 1-year follow-up. We studied the duration of the seizure reduction after DBS insertion and before stimulation (the insertional effect) and its association with long-term outcome. We modeled the volume of activation using the active contacts, stimulation parameters, and postoperative imaging. The overlap of this volume was plotted in Montreal Neurological Institute 152 space in 7 patients with significant clinical efficacy., Results: Nine patients reported a decrease in seizure frequency immediately after electrode insertion (insertional or microthalamotomy effect). The duration of insertional effect varied from 2 to 4 months. However, 1 patient had a long-term insertional effect of 36 months. Altogether, 11 patients reported >50% decrease in seizure frequency with long-term stimulation. The most common pattern of seizure control was immediate and sustained stimulation benefit (n = 8). In patients with long-term stimulation benefit, the efficacious target was localized in the anteroventral AN in close proximity to the mammillothalamic tract., Conclusion: AN DBS is efficacious in the control of seizure frequency in selected patients. An insertional effect is commonly observed (56%). The most efficacious site of stimulation appears to be the anteroventral AN., Abbreviations: AN, anterior nucleusDBS, deep brain stimulationMNI, Montreal Neurological InstituteMRE, medical refractory epilepsyMT, mammillothalamic tractSANTE, Stimulation of the Anterior Nucleus of the Thalamus for EpilepsyVNS, vagal nerve stimulation.

Several palliative neuromodulation treatment modalities are currently available for adjunctive use in the treatment of medically intractable epilepsy. Over the past decades, a variety of different central and peripheral nervous system sites have been identified, clinically and experimentally, as potential targets for chronic, nonresponsive therapeutic neurostimulation. Currently, the main modalities in clinical use, from most invasive to least invasive, are anterior thalamus deep brain stimulation, vagus nerve stimulation, and trigeminal nerve stimulation. Significant reductions in seizure frequency have been demonstrated in clinical trials using each of these neuromodulation therapies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The article discusses the use of automated motion sensor-based functional mapping (SBFM) to improve deep brain stimulation (DBS) programming efficiency for patients with Parkinson's disease. A randomized trial compared SBFM programming with standard-of-care (SoC) programming and found that SBFM reduced the number of settings tested and showed similar clinical outcomes. While SBFM was not significantly faster than SoC, integrating the SBFM system with the DBS programmer could enhance programming efficiency in the future. The study suggests that SBFM can extend expert programming strategies to populations without access to specialized DBS centers, with potential for further improvements in future research. [Extracted from the article]

Over the last few years, while expanding its clinical indications from movement disorders to epilepsy and psychiatry, the field of deep brain stimulation (DBS) has seen significant innovations. Hardware developments have introduced directional leads to stimulate specific brain targets and sensing electrodes to determine optimal settings via feedback from local field potentials. In addition, variable-frequency stimulation and asynchronous high-frequency pulse trains have introduced new programming paradigms to efficiently desynchronize pathological neural circuitry and regulate dysfunctional brain networks not responsive to conventional settings. Overall, these innovations have provided clinicians with more anatomically accurate programming and closed-looped feedback to identify optimal strategies for neuromodulation. Simultaneously, software developments have simplified programming algorithms, introduced platforms for DBS remote management via telemedicine, and tools for estimating the volume of tissue activated within and outside the DBS targets. Finally, the surgical accuracy has improved thanks to intraoperative magnetic resonance or computerized tomography guidance, network-based imaging for DBS planning and targeting, and robotic-assisted surgery for ultra-accurate, millimetric lead placement. These technological and imaging advances have collectively optimized DBS outcomes and allowed "asleep" DBS procedures. Still, the short- and long-term outcomes of different implantable devices, surgical techniques, and asleep vs. awake procedures remain to be clarified. This expert review summarizes and critically discusses these recent innovations and their potential impact on the DBS field. [ABSTRACT FROM AUTHOR]

Object: A real-time functional magnetic resonance imaging (fMRI) feedback during ventral intermediate nucleus (VIM) deep brain stimulation (DBS) under general anesthesia (or "asleep" DBS) does not exist. We hypothesized that it was feasible to acquire a reliable and responsive fMRI during asleep VIM DBS surgery. Methods: We prospectively enrolled 10 consecutive patients who underwent asleep DBS for the treatment of medication-refractory essential tremor. Under general anesthesia, we acquired resting-state functional MRI immediately before and after the cannula insertion. Reliability was determined by a temporal signal-to-noise-ratio >100. Responsiveness was determined based on the fMRI signal change upon insertion of the cannula to the VIM. Results: It was feasible to acquire reliable fMRI during asleep DBS surgery. The fMRI signal was responsive to the brain cannula insertion, revealing a reduction in the tremor network's functional connectivity, which did not reach statistical significance in the group analysis. Conclusions: It is feasible to acquire a reliable and responsive fMRI signal during asleep DBS. The acquisition steps and the preprocessing pipeline developed in these experiments will be useful for future investigations to develop fMRI-based feedback for asleep DBS surgery. [ABSTRACT FROM AUTHOR]

Device titration is a major challenge when using deep brain stimulation (DBS) to treat behavioral disorders. Unlike in movement disorders, there is no reliable real-time clinical feedback for changes in complex behaviors resulting from DBS. Here, a female patient receiving DBS of the nucleus accumbens for the treatment of morbid obesity underwent cognitive testing via the flanker task alongside traditional methods of device titration. One set of stimulation parameters administered during titration resulted in acute cognitive improvement (p = 0.033) and increased frontal engagement as measured by electroencephalography (left anterior: p = 0.007, right anterior: p = 0.005) relative to DBS-OFF. The same parameters resulted in the most weight-loss during long-term continuous stimulation (47.8 lbs lost in 129 days) compared to the results of other stimulation settings. Diffusion tensor imaging analyses showed increased connectivity to dorsal attention networks and decreased connectivity to the default mode network for optimal parameters (p < 0.01). Our results provide evidence that targeted cognitive testing is a potentially useful tool for capturing acute effects of DBS stimulation during titration and predicting long-term treatment outcomes. Clinical Trial Registration: www.ClinicalTrials.gov , identifier: NCT01512134. [ABSTRACT FROM AUTHOR]

Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in the hierarchical organization of interregional neuronal communication and is also expressed by epileptogenic cortex during seizures. Here, we sought to characterize patterns of cfPAC expression in the anterior thalamic nuclei during seizures by studying extra-operative recordings in patients implanted with deep brain stimulation electrodes for intractable epilepsy. Nine seizures from two patients were analyzed in the peri-ictal period. CfPAC was calculated using the modulation index and interregional functional connectivity was indexed using the phase-locking value. Statistical analysis was performed within subjects on the basis of nonparametric permutation and corrected with Gaussian field theory. Five of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC occurred during the pre-ictal and ictal periods in three seizures, as well as the postictal windows in four seizures. The preferred phase at which cfPAC occurred differed 1) in space, between the thalami of the epileptogenic and nonepileptogenic hemispheres; and 2) in time, at seizure termination. The anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered interregional phase-locking synchrony concurrent with the expression of cfPAC. By analyzing extraoperative recordings from the anterior thalamic nuclei, we show that cfPAC associated with altered interregional phase synchrony is lateralized to the thalamus of the epileptogenic hemisphere during seizures. Electrophysiological differences in cfPAC, including preferred phase of oscillatory interactions may be further investigated as putative targets for individualized neuromodulation paradigms in patients with drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucleus ( STN) deep-brain stimulation ( DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesised that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analysed microelectrode recording ( MER) data from patients with Parkinson's disease who underwent STN DBS. A 'Dex bolus' group (dexmedetomidine bolus prior to MER; 27 cells from seven patients) was compared with a 'no sedation' group (29 cells from 11 patients). We also performed within-patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analysed using the Kaneoke-Vitek methodology and local field potential ( LFP) oscillatory activity was also investigated. Dexmedetomidine was associated with a slight increase in firing rate (41.1 ± 9.9 vs. 34.5 ± 10.6 Hz, P = 0.02) but a significant decrease in burstiness (number of bursts, P = 0.02; burst index, P < 0.001; percentage of spikes in burst, P = 0.002) of dorsal but not ventral STN neurons. This was not associated with modulation of beta oscillations in the spike-oscillations analysis(beta peak, P = 0.4; signal-to-noise ratio in the beta range for spikes and bursts, P = 0.3 and P = 0.5, respectively) and LFP analysis (Beta power, P = 0.17). As bursting pattern is often used to identify STN and guide electrode placement, we recommend that high-dose dexmedetomidine should be avoided during DBS surgery. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic targeting of ventral intermediate nucleus (VIM) relies on formulaic methods due to the limitations of current imaging sequences. Tractography-based VIM (T-VIM) targeting may address these limitations. We prospectively targeted T-VIM in consecutive patients undergoing deep brain stimulation (DBS) for essential tremor (ET) and tremor-dominant Parkinson's disease (PD). Here we report the short-term clinical outcomes using this technique. Methodology: All patients underwent imaging with structural (3D T1) and diffusion weighted sequences (60 diffusion directions, 2 mm isovoxel). The images were processed using streamline tractography (Stealth Viz, Medtronic Inc.) with a methodology described previously. Besides visualizing T-VIM, this method also localizes the pyramidal tract and medial lemniscus for avoiding off-target side effects. A T-VIM object was overlaid on the DICOM images for stereotactic targeting (Framelink, Medtronic Inc.). The composite tremor scores (for ET - rest, posture, action, handwriting & Archimides spiral and for PD - tremor scores from UPDRS-III, rated on a 5-points scale each) were compared before and after surgery. The T-VIM coordinates, stimulation parameters were also analyzed. Results: Eight patients (7ET and 1 PD) successfully underwent T-VIM targeting (n=9 hemispheres). We performed DBS implantations both in awake patients with MER guidance (n=5) and in asleep patients with intraoperative MRI guidance (n=4). TVIM was more medial (12.5±1.5 vs. 14.3±0.6) and anterior (7.7±1.5 vs. 6.6±0.4 in relation to PC) than the standard coordinates. During a mean follow-up of 5 months (range 2-12 months) tremor improved significantly (treated side: 80.1±17.7%, overall: 58.1±12.8%). Monopolar stimulation was most commonly used at contact 1 with a mean voltage of 2.8±0.9 Volts. Tremor medications were decreased in 4 patients and maintained at baseline in 2 others (2 patients were not on medications at baseline). Conclusion: The short-term clinical results are satisfactory in both awake and asleep T-VIM DBS implantations. Long-term tremor outcomes are being assessed to determine the usefulness of this technique. [ABSTRACT FROM AUTHOR]