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Background and Objectives: Deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS) is an established treatment for medically refractory essential tremor. However, the effect of VIM-DBS on vocal tremor remains poorly understood, with results varying by method of vocal tremor assessment and stimulation laterality. This single-center study measures the effect of bilateral VIM-DBS on essential vocal tremor using blinded objective acoustic voice analysis., Methods: Ten patients with consecutive essential tremor with comorbid vocal tremor receiving bilateral VIM-DBS underwent voice testing before and after implantation of DBS in this prospective cohort study. Objective acoustic measures were extracted from the middle one second of steady-state phonation including cepstral peak prominence, signal-to-noise ratio, percentage voicing, tremor rate, extent of fundamental frequency modulation, and extent of intensity modulation. DBS surgery was performed awake with microelectrode recording and intraoperative testing. Postoperative voice testing was performed after stable programming., Results: Patients included 6 female and 4 male, with a mean age of 67 ± 6.7 years. The VIM was targeted with the following coordinates relative to the mid-anterior commissure:posterior commissure point: 13.2 ± 0.6 mm lateral, 6.2 ± 0.7 mm posterior, and 0.0 mm below. Mean programming parameters were amplitude 1.72.0 ± 0.6 mA, pulse width 63.0 ± 12.7 µs, and rate 130.6 ± 0.0 Hz. VIM-DBS significantly improved tremor rate from 4.43 ± 0.8 Hz to 3.2 ± 0.8 Hz ( P = .001) CI (0.546, 1.895), jitter from 1 ± 0.94 to 0.53 ± 0.219 ( P = .02) CI (-0.124, 1.038), cepstral peak prominence from 13.6 ± 3.9 to 18.8 ± 2.9 ( P = .016) CI (-4.100, -0.235), signal-to-noise ratio from 15.7 ± 3.9 to 18.5 ± 3.7 ( P = .02) CI (-5.598, -0.037), and articulation rate from 0.77 ± 0.2 to 0.82 ± .14 ( P = .04) CI (-0.097, 0.008). There were no major complications in this series., Conclusion: Objective acoustic voice analyses suggest that bilateral VIM-DBS effectively reduces vocal tremor rate and improves voicing. Further studies using objective acoustic analyses and laryngeal imaging may help refine surgical and stimulation techniques and evaluate the effect of laterality on vocal tremor., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: The aim of this study was to identify features of responsive neurostimulation (RNS) lead configuration and contact placement associated with greater seizure reduction in mesial temporal lobe epilepsy (MTLE)., Methods: A single-center series of patients with MTLE treated with RNS were retrospectively analyzed to assess the relationship between anatomical targeting and seizure reduction. Targeting was determined according to both the preoperatively conceived lead configuration and the actual placement of RNS contacts. Three lead configurations were used: 1) single bilateral, with 1 depth lead in each hippocampus; 2) single unilateral, with 1 hippocampal depth lead and another implant outside the mesial temporal lobe; and 3) dual unilateral, with 2 leads in 1 hippocampus. Contact placement on postoperative imaging was measured according to the number of hippocampal contacts per targeted hippocampus (contact density) and per patient (contact count), distribution throughout the hippocampus, and proximity to the anteromedial hippocampus., Results: Dual unilateral lead placement resulted in significantly higher hippocampal contact density compared with the single hippocampal approaches, but only showed a nonsignificant trend toward a higher rate of response. However, those patients with more than 4 contacts in a single hippocampus, achievable only with dual unilateral leads, had a significantly higher rate of response. The higher likelihood of response was poorly explained by more widespread hippocampal coverage, but well correlated with proximity to the anteromedial hippocampus., Conclusions: Dual unilateral hippocampal implantation increased RNS contact density in patients with unilateral MTLE, which contributed to improved outcomes, not by stimulating more of the hippocampus, but instead by being more likely to stimulate a latent subtarget in the anterior hippocampus. It remains to be explored whether a single electrode targeted selectively to this region would also result in improved outcomes.

Introduction: Neuromodulation is an important treatment modality for patients with drug-resistant epilepsy who are not candidates for resective or ablative procedures. However, randomized controlled trials and real-world studies reveal that a subset of patients will experience minimal reduction or even an increase in seizure frequency after neuromodulation. We describe our experience with patients who undergo a second intracranial neuromodulation procedure after unsatisfactory initial response to intracranial neuromodulation., Methods: We performed a retrospective chart review to identify all patients who had undergone deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) or responsive neurostimulation (RNS), followed by additional intracranial neuromodulatory procedures, with at least 12 months of follow-up. Demographic and clinical data, including seizure frequencies, were collected., Results: All patients had temporal lobe epilepsy. Six patients were treated with concurrent ANT DBS and temporal lobe RNS, and 3 patients transitioned between neuromodulation systems. Of the patients treated concurrently with ANT DBS and temporal lobe RNS, 5 of the 6 patients experienced additional reduction in seizure frequency after adding a second neuromodulation system. Of the patients who switched between neuromodulation modalities, all patients experienced further reduction in seizure frequency., Conclusions: For patients who do not experience adequate benefit from initial therapy with ANT DBS or temporal lobe RNS, the addition of a neuromodulation system or switching to a different form of neuromodulation may allow for additional reduction in seizure frequency. Larger studies will need to be performed to understand whether the use of multiple systems concurrently leads to improved clinical results in patients who are initially treatment resistant to neuromodulation., (© 2024 S. Karger AG, Basel.)

Objective: Thalamic deep brain stimulation (DBS) is an effective therapeutic option in patients with drug-resistant epilepsy. Recent DBS devices with sensing capabilities enable chronic, outpatient local field potential (LFP) recordings. Whereas beta oscillations have been demonstrated to be a useful biomarker in movement disorders, the clinical utility of DBS sensing in epilepsy remains unclear. Our aim was to determine LFP features that distinguish ictal from inter-ictal states, which may aid in tracking seizure outcomes with DBS., Methods: Electrophysiology data were obtained from DBS devices implanted in the anterior nucleus (N = 12) or centromedian nucleus (N = 2) of the thalamus. Power spectra recorded during patient/caregiver-marked seizure events were analyzed with a method that quantitatively separates the oscillatory and non-oscillatory/aperiodic components of the LFP using non-parametric statistics, without the need for pre-specification of the frequency bands of interest. Features of the LFP parameterized using this algorithm were compared with those from inter-ictal power spectra recorded in clinic., Results: Oscillatory activity in multiple canonical frequency bands was identified from the power spectra in 86.48% of patient-marked seizure events. Delta oscillations were present in all patients, followed by theta (N = 10) and beta (N = 9). Although there were no differences in oscillatory LFP features between the ictal and inter-ictal states, there was a steeper decline in the 1/f slope of the aperiodic component of the LFP during seizures., Significance: Our work highlights the potential and shortcomings of chronic LFP recordings in thalamic DBS for epilepsy. Findings suggest that no single frequency band in isolation clearly differentiates seizures, and that features of aperiodic LFP activity may be clinically-relevant biomarkers of seizures., (© 2023 International League Against Epilepsy.)

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD) 1 . However, achieving stable recovery is unpredictable 2 , typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting 3 . We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment., (© 2023. The Author(s).)

Objective: Stereoelectroencephalography (SEEG)-guided radiofrequency ablation (RFA) is increasingly being used as a treatment for drug-resistant localization-related epilepsy. The aim of this study is to analyze the successes and failures using RFA and how response correlates with surgical epilepsy treatment outcomes., Methods: We retrospectively reviewed 62 patients who underwent RFA via SEEG electrodes. After excluding five, the remaining 57 were classified into subgroups based on procedures and outcomes. Forty patients (70%) underwent a secondary surgical procedure, of whom 32 were delayed: 26 laser interstitial thermal therapy (LITT), five resection, one neuromodulation. We determined the predictive value of RFA outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the transient time of seizure freedom after RFA were calculated for each patient., Results: Twelve of 49 patients (24.5%) who had RFA alone and delayed follow-up achieved Engel class I. Of the 32 patients who underwent a delayed secondary surgical procedure, 15 achieved Engel class I and nine Engel class II (24 successes), and eight were considered failures (Engel class III/IV). The transient time of seizure freedom after RFA was significantly longer in the success group (4 months, SD = 2.6) as compared to the failure group (.75 months, SD = 1.16; p < .001). Additionally, there was a higher portion of preoperative lesional findings in patients in the RFA alone and delayed surgical success group (p = .03) and a longer time to seizure recurrence in the presence of lesions (p < .05). Side effects occurred in 1% of patients., Significance: In this series, RFA provided a treatment during SEEG-guided intracranial monitoring that led to seizure freedom in ~25% of patients. Of the 70% who underwent delayed surgery, longer transient time of seizure freedom after RFA was predictive of the results of the secondary surgeries, 74% of which were LITT., (© 2023 International League Against Epilepsy.)

Objective: Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent randomized controlled trials have demonstrated efficacy of DBS of the anterior nucleus of the thalamus (ANT), particularly in frontal or temporal epilepsy, whereas DBS of the centromedian (CM) nucleus appears to be most suitable in well-defined generalized epilepsy syndromes. At the authors' institution, DBS candidates who did not fit the populations represented in these trials were managed with DBS of multiple distinct targets, which included ANT, CM, and less-studied nuclei-i.e., mediodorsal nucleus, pulvinar, and subthalamic nucleus. The goal of this study was to present the authors' experience with these types of cases, and to motivate future investigations that can determine the long-term efficacy of multitarget DBS., Methods: This single-center retrospective study of adult patients with drug-resistant epilepsy who underwent multitarget DBS was performed to demonstrate the feasibility and safety of this approach, and to present seizure outcomes. Patients in this cohort had epilepsy with features that were difficult to treat with DBS of the ANT or CM nucleus alone, including multifocal/multilobar, diffuse-onset, and/or posterior-onset seizures; or both generalized and focal seizures., Results: Eight patients underwent DBS of 2-3 distinct thalamic/subthalamic nuclei. DBS was performed with 2 electrodes in each hemisphere. All leads in each patient were implanted with either frontal or parietal trajectories. There were no surgical complications. Among those with > 6 months of follow-up (n = 5; range 7-21 months), all patients were responders in terms of overall seizure frequency and/or convulsive seizure frequency (i.e., ≥ 50% reduction). Two patients had adverse stimulation effects, which resolved with further programming., Conclusions: Multitarget DBS is a procedurally feasible and safe treatment strategy to maximize outcomes in patients with complex epilepsy. The authors highlight their approach to inform future studies that are sufficiently powered to assess its efficacy.

Electrical brain stimulation has become an essential treatment option for more than one third of epilepsy patients who are resistant to pharmacological therapy and are not candidates for surgical resection. However, currently approved stimulation paradigms achieve only moderate success, on average providing approximately 75% reduction in seizure frequency and extended periods of seizure freedom in nearly 20% of patients. Outcomes from electrical stimulation may be improved through the identification of novel anatomical targets, particularly those with significant anatomical and functional connectivity to the epileptogenic zone. Multiple studies have investigated the medial septal nucleus (i.e., medial septum) as such a target for the treatment of mesial temporal lobe epilepsy. The medial septum is a small midline nucleus that provides a critical functional role in modulating the hippocampal theta rhythm, a 4-7-Hz electrophysiological oscillation mechanistically associated with memory and higher order cognition in both rodents and humans. Elevated theta oscillations are thought to represent a seizure-resistant network activity state, suggesting that electrical neuromodulation of the medial septum and restoration of theta-rhythmic physiology may not only reduce seizure frequency, but also restore cognitive comorbidities associated with mesial temporal lobe epilepsy. Here, we review the anatomical and physiological function of the septohippocampal network, evidence for seizure-resistant effects of the theta rhythm, and the results of stimulation experiments across both rodent and human studies, to argue that deep brain stimulation of the medial septum holds potential to provide an effective neuromodulation treatment for mesial temporal lobe epilepsy. We conclude by discussing the considerations necessary for further evaluating this treatment paradigm with a clinical trial., (© 2022 International League Against Epilepsy.)

Objective: Neuromodulation of the centromedian nucleus of the thalamus (CM) has unclear effectiveness in the treatment of drug-resistant epilepsy. Prior reports suggest that it may be more effective in the generalized epilepsies such as Lennox-Gastaut syndrome (LGS). The objective of this study was to determine the outcome of CM deep brain stimulation (DBS) at the authors' institution., Methods: Retrospective chart review was performed for all patients who underwent CM DBS at Emory University, which occurred between December 2018 and May 2021. CM DBS electrodes were implanted using three different surgical methods, including frame-based, robot-assisted, and direct MRI-guided. Seizure frequency, stimulation parameters, and adverse events were recorded from subsequent clinical follow-up visits., Results: Fourteen patients underwent CM DBS: 9 had symptomatic generalized epilepsy (including 5 with LGS), 3 had primary or idiopathic generalized epilepsy, and 2 had bifrontal focal epilepsy. At last follow-up (mean [± SEM] 19 ± 5 months, range 4.1-33 months, ≥ 6 months in 11 patients), the median seizure frequency reduction was 91%. Twelve patients (86%) were considered responders (≥ 50% decrease in seizure frequency), including 10 of 12 with generalized epilepsy and both patients with bifrontal epilepsy. Surgical adverse events were rare and included 1 patient with hardware breakage, 1 with a postoperative aspiration event, and 1 with a nonclinically significant intracranial hemorrhage., Conclusions: CM DBS was an effective treatment for drug-resistant generalized and bifrontal epilepsies. Additional studies and analyses may investigate whether CM DBS is best suited for specific epilepsy types, and the relationship of lead location to outcome in different epilepsies.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is a promising intervention for treatment-resistant depression (TRD). Despite the failure of a clinical trial, multiple case series have described encouraging results, especially with the introduction of improved surgical protocols. Recent evidence further suggests that tractography targeting and intraoperative exposure to stimulation enhances early antidepressant effects that further evolve with ongoing chronic DBS. Accelerating treatment gains is critical to the care of this at-risk population, and identification of intraoperative electrophysiological biomarkers of early antidepressant effects will help guide future treatment protocols. Eight patients underwent intraoperative electrophysiological recording when bilateral DBS leads were implanted in the SCC using a connectomic approach at the site previously shown to optimize 6-month treatment outcomes. A machine learning classification method was used to discriminate between intracranial local field potentials (LFPs) recorded at baseline (stimulation-naïve) and after the first exposure to SCC DBS during surgical procedures. Spectral inputs (theta, 4-8 Hz; alpha, 9-12 Hz; beta, 13-30 Hz) to the model were then evaluated for importance to classifier success and tested as predictors of the antidepressant response. A decline in depression scores by 45.6% was observed after 1 week and this early antidepressant response correlated with a decrease in SCC LFP beta power, which most contributed to classifier success. Intraoperative exposure to therapeutic stimulation may result in an acute decrease in symptoms of depression following SCC DBS surgery. The correlation of symptom improvement with an intraoperative reduction in SCC beta power suggests this electrophysiological finding as a biomarker for treatment optimization., (© 2021. The Author(s).)

Objective. Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) but its success depends on a time-consuming process of trial-and-error to identify the optimal stimulation settings for each individual patient. Data-driven optimization algorithms have been proposed to efficiently find the stimulation setting that maximizes a quantitative biomarker of symptom relief. However, these algorithms cannot efficiently take into account stimulation settings that may control symptoms but also cause side effects. Here we demonstrate how multi-objective data-driven optimization can be used to find the optimal trade-off between maximizing symptom relief and minimizing side effects. Approach. Cortical and motor evoked potential data collected from PD patients during intraoperative stimulation of the subthalamic nucleus were used to construct a framework for designing and prototyping data-driven multi-objective optimization algorithms. Using this framework, we explored how these techniques can be applied clinically, and characterized the design features critical for solving this optimization problem. Our two optimization objectives were to maximize cortical evoked potentials, a putative biomarker of therapeutic benefit, and to minimize motor potentials, a biomarker of motor side effects. Main Results. Using this in silico design framework, we demonstrated how the optimal trade-off between two objectives can substantially reduce the stimulation parameter space by 61 ± 19%. The best algorithm for identifying the optimal trade-off between the two objectives was a Bayesian optimization approach with an area under the receiver operating characteristic curve of up to 0.94 ± 0.02, which was possible with the use of a surrogate model and a well-tuned acquisition function to efficiently select which stimulation settings to sample. Significance. These findings show that multi-objective optimization is a promising approach for identifying the optimal trade-off between symptom relief and side effects in DBS. Moreover, these approaches can be readily extended to newly discovered biomarkers, adapted to DBS for disorders beyond PD, and can scale with the development of more complex DBS devices., (© 2021 IOP Publishing Ltd.)

Background: Subthalamic deep brain stimulation (DBS) is an effective surgical treatment for Parkinson's disease and continues to advance technologically with an enormous parameter space. As such, in-silico DBS modeling systems have become common tools for research and development, but their underlying methods have yet to be standardized and validated., Objective: Evaluate the accuracy of patient-specific estimates of neural pathway activations in the subthalamic region against intracranial, cortical evoked potential (EP) recordings., Methods: Pathway activations were modeled in eleven patients using the latest advances in connectomic modeling of subthalamic DBS, focusing on the hyperdirect pathway (HDP) and corticospinal/bulbar tract (CSBT) for their relevance in human research studies. Correlations between pathway activations and respective EP amplitudes were quantified., Results: Good model performance required accurate lead localization and image fusions, as well as appropriate selection of fiber diameter in the biophysical model. While optimal model parameters varied across patients, good performance could be achieved using a global set of parameters that explained 60% and 73% of electrophysiologic activations of CSBT and HDP, respectively. Moreover, restricted models fit to only EP amplitudes of eight standard (monopolar and bipolar) electrode configurations were able to extrapolate variation in EP amplitudes across other directional electrode configurations and stimulation parameters, with no significant reduction in model performance across the cohort., Conclusions: Our findings demonstrate that connectomic models of DBS with sufficient anatomical and electrical details can predict recruitment dynamics of white matter. These results will help to define connectomic modeling standards for preoperative surgical targeting and postoperative patient programming applications., Competing Interests: Declaration of competing interest Bryan Howell is a paid consultant for Abbott Laboratories. Robert E. Gross is a paid consultant for Medtronic, PLC and Abbot Laboratories. Philip A: Starr has research supported by Medtronic, PLC and Boston Scientific, Co. Jon T. Willie is a paid consultant for Medtronic, PLC and Neuropace, Inc. Cameron C. McIntyre is a paid consultant for Boston Scientific, Co., receives royalties from Hologram Consultants, Neuros Medical, and Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, CereGate, Autonomic Technologies, Cardionomic, Enspire DBS. All other authors have no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames., Methods: The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms., Results: Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20-49 years), the median duration of epilepsy was 21 years (range 9-48 years), and median postablation follow-up was 20 months (range 4-44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%-80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2-2.0 mm) versus 2.4 mm (range 0.6-6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique., Conclusions: This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

Background: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is the surgical method of choice to treat the canonical symptoms of Parkinson disease, occasionally surgical sites become infected or the hardware erodes, necessitating explantation. Usual practice is to remove and reimplant replacement leads after tissue healing, leaving patients without the clinical benefits of DBS for several months, and at risk for DBS withdrawal in some, and some patients are no longer good surgical candidates for reimplantation. Radiofrequency ablation through the DBS lead is an option for these patients., Methods: We performed a retrospective chart review of all patients who underwent radiofrequency ablation of the STN or GPi through indwelling DBS leads performed before hardware removal at our institution. We generated patient-specific anatomic models to determine lesion locations and volumes., Results: Six patients underwent radiofrequency ablation of the STN (n = 4) and GPi (n = 2) through indwelling DBS leads. All 6 of these patients initially showed comparable motor symptom relief to that experienced with DBS before lesioning, with 4 patients sustaining meaningful long-term (≥2 years) improvement. Better outcomes were achieved in those patients with a higher percentage of the planned target lesioned., Conclusions: Radiofrequency ablation through indwelling DBS leads before explantation could be considered a viable alternative to subsequent reimplantation or stereotactic lesion in patients with Parkinson disease in whom hardware explantation is necessary, if the patient achieved substantive symptom relief with DBS. This approach avoids symptom exacerbation while awaiting revision surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Deep brain stimulation (DBS) lead placement is increasingly performed with the patient under general anesthesia by surgeons using intraoperative MRI (iMRI) guidance without microelectrode recording (MER) or macrostimulation. The authors assessed the accuracy of lead placement, safety, and motor outcomes in patients with Parkinson disease (PD) undergoing DBS lead placement into the globus pallidus internus (GPi) using iMRI or MER guidance., Methods: The authors identified all patients with PD who underwent either MER- or iMRI-guided GPi-DBS lead placement at Emory University between July 2007 and August 2016. Lead placement accuracy and adverse events were determined for all patients. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor scores for patients completing 12 months of follow-up. The authors also assessed the levodopa-equivalent daily dose (LEDD) and stimulation parameters., Results: Seventy-seven patients were identified (MER, n = 28; iMRI, n = 49), in whom 131 leads were placed. The stereotactic accuracy of the surgical procedure with respect to the planned lead location was 1.94 ± 0.21 mm (mean ± SEM) (95% CI 1.54-2.34) with frame-based MER and 0.84 ± 0.007 mm (95% CI 0.69-0.98) with iMRI. The rate of serious complications was similar, at 6.9% for MER-guided DBS lead placement and 9.4% for iMRI-guided DBS lead placement (RR 0.71 [95% CI 0.13%-3.9%]; p = 0.695). Fifty-seven patients were included in clinical outcome analyses (MER, n = 16; iMRI, n = 41). Both groups had similar characteristics at baseline, although patients undergoing MER-guided DBS had a lower response on their baseline levodopa challenge (44.8% ± 5.4% [95% CI 33.2%-56.4%] vs 61.6% ± 2.1% [95% CI 57.4%-65.8%]; t = 3.558, p = 0.001). Greater improvement was seen following iMRI-guided lead placement (43.2% ± 3.5% [95% CI 36.2%-50.3%]) versus MER-guided lead placement (25.5% ± 6.7% [95% CI 11.1%-39.8%]; F = 5.835, p = 0.019). When UPDRS III motor scores were assessed only in the contralateral hemibody (per-lead analyses), the improvements remained significantly different (37.1% ± 7.2% [95% CI 22.2%-51.9%] and 50.0% ± 3.5% [95% CI 43.1%-56.9%] for MER- and iMRI-guided DBS lead placement, respectively). Both groups exhibited similar reductions in LEDDs (21.2% and 20.9%, respectively; F = 0.221, p = 0.640). The locations of all active contacts and the 2D radial distance from these to consensus coordinates for GPi-DBS lead placement (x, ±20; y, +2; and z, -4) did not differ statistically by type of surgery., Conclusions: iMRI-guided GPi-DBS lead placement in PD patients was associated with significant improvement in clinical outcomes, comparable to those observed following MER-guided DBS lead placement. Furthermore, iMRI-guided DBS implantation produced a similar safety profile to that of the MER-guided procedure. As such, iMRI guidance is an alternative to MER guidance for patients undergoing GPi-DBS implantation for PD.

Objective: Lead placement for deep brain stimulation (DBS) using intraoperative MRI (iMRI) relies solely on real-time intraoperative neuroimaging to guide electrode placement, without microelectrode recording (MER) or electrical stimulation. There is limited information, however, on outcomes after iMRI-guided DBS for dystonia. The authors evaluated clinical outcomes and targeting accuracy in patients with dystonia who underwent lead placement using an iMRI targeting platform., Methods: Patients with dystonia undergoing iMRI-guided lead placement in the globus pallidus pars internus (GPi) were identified. Patients with a prior ablative or MER-guided procedure were excluded from clinical outcomes analysis. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores were assessed preoperatively and at 6 and 12 months postoperatively. Other measures analyzed include lead accuracy, complications/adverse events, and stimulation parameters., Results: A total of 60 leads were implanted in 30 patients. Stereotactic lead accuracy in the axial plane was 0.93 ± 0.12 mm from the intended target. Nineteen patients (idiopathic focal, n = 7; idiopathic segmental, n = 5; DYT1, n = 1; tardive, n = 2; other secondary, n = 4) were included in clinical outcomes analysis. The mean improvement in BFMDRS score was 51.9% ± 9.7% at 6 months and 63.4% ± 8.0% at 1 year. TWSTRS scores in patients with predominant cervical dystonia (n = 13) improved by 53.3% ± 10.5% at 6 months and 67.6% ± 9.0% at 1 year. Serious complications occurred in 6 patients (20%), involving 8 of 60 implanted leads (13.3%). The rate of serious complications across all patients undergoing iMRI-guided DBS at the authors' institution was further reviewed, including an additional 53 patients undergoing GPi-DBS for Parkinson disease. In this expanded cohort, serious complications occurred in 11 patients (13.3%) involving 15 leads (10.1%)., Conclusions: Intraoperative MRI-guided lead placement in patients with dystonia showed improvement in clinical outcomes comparable to previously reported results using awake MER-guided lead placement. The accuracy of lead placement was high, and the procedure was well tolerated in the majority of patients. However, a number of patients experienced serious adverse events that were attributable to the introduction of a novel technique into a busy neurosurgical practice, and which led to the revision of protocols, product inserts, and on-site training.

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact. SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function., (Copyright © 2018 the authors 0270-6474/18/389129-13$15.00/0.)

A fundamental aspect of behavior in many animal species is 'social facilitation', the positive effect of the mere presence of conspecifics on performance. To date, the neuronal counterpart of this ubiquitous phenomenon is unknown. We recorded the activity of single neurons from two prefrontal cortex regions, the dorsolateral part and the anterior cingulate cortex in monkeys as they performed a visuomotor task, either in the presence of a conspecific (Presence condition) or alone. Monkeys performed better in the presence condition than alone (social facilitation), and analyses of outcome-related activity of 342 prefrontal neurons revealed that most of them (86%) were sensitive to the performance context. Two populations of neurons were discovered: 'social neurons', preferentially active under social presence and 'asocial neurons', preferentially active under social isolation. The activity of these neurons correlated positively with performance only in their preferred context (social neurons under social presence; asocial neurons under social isolation), thereby providing a potential neuronal mechanism of social facilitation. More generally, the fact that identical tasks recruited either social or asocial neurons depending on the presence or absence of a conspecific also brings a new look at the social brain hypothesis., (© The Author (2017). Published by Oxford University Press.)

While neuroscience research has tremendously advanced our knowledge about the neural mechanisms of individual learning, i.e. through trial-and-error, it is only recently that neuroscientists have begun to study observational learning, and thus little is known about its neural mechanisms. One limitation is that observational learning has been addressed under unconstrained experimental conditions, not compatible with neuronal recordings. This study examined observational learning in macaque monkeys under the constraining conditions of behavioral neurophysiology. Two animals sat in primate chairs facing each other, with their head fixed. A touch screen was placed face up between the chairs at arm's reach, and the monkeys were trained on an abstract visuomotor associative task. In one experiment, the monkeys alternated the roles of "actor" and "observer". The actor learned to associate visual cues with reaching targets, while the observer "watched" freely. Then, the observer was given the same cue-target associations just performed by the actor, or had to learn new, not previously observed ones. The results show that learning performance is better after observation. In experiment 2, one monkey learned from a human actor who performed the task with errors only, or with successes only in separate blocks. The monkey's gain in performance was higher after observation of errors than after successes. The findings suggest that observational learning can occur even under highly constraining conditions, and open the way for investigating the neuronal correlates of social learning using the methods of behavioral neurophysiology., (Copyright © 2015 Elsevier B.V. All rights reserved.)