Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

BACKGROUND: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies. METHODS: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months. RESULTS: Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. CONCLUSIONS: Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

Altered prefrontal beta oscillatory activity during removal of information from working memory in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is related to working memory impairment. Since patients with OCD have difficulty controlling their obsessive thoughts, removal of irrelevant information might be important in the pathophysiology of OCD. However, little is known about brain activity during the removal of information from working memory in patients with OCD. Our goal was to explore potential deficits in inhibitory function related to working memory processes in patients with OCD. METHODS: Sixteen OCD patients and 20 healthy controls (HCs) were recruited. We compared in prefrontal alpha and beta band activity derived from magnetoencephalography (MEG) between patients with OCD and HCs during multiple phases of information processing associated with working memory, especially in post-trial period of the visuospatial working memory task (the delayed matching-to-sample task), which is presumed to be related to the information removal process of working memory. RESULTS: Prefrontal post-trial beta power change (presumed to occur at high levels during the post-trial period) exhibited significant reductions in patients with OCD compared to HCs. In addition, the post-trial beta power change was negatively correlated with Obsessive-Compulsive Inventory-Revised total scores in patients with OCD. CONCLUSIONS: These findings suggest that impairment in the removal of information from working memory might be a key mechanism underlying the inability of OCD patients to rid themselves of their obsessions.

Advances in Technical Aspects of Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. SUMMARY: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.

One-year outcomes of deep brain stimulation in refractory Tourette syndrome.

AIM: Deep brain stimulation (DBS) is one option for treating refractory Tourette syndrome (TS); however, it remains unclear which preoperative factors are predictive of DBS outcomes. This study investigated the efficacy of DBS targeting the anteromedial globus pallidus internus and evaluated predisposing factors affecting the outcomes of DBS in a single center in Korea. METHOD: Twenty patients who had undergone DBS for refractory TS were reviewed retrospectively. Tic symptoms were followed up at 3-month intervals for up to 1 year after surgery. The Yale Global Tic Severity Scale was used to evaluate preoperative/postoperative tic symptoms. Scores from the Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory were also evaluated. RESULTS: Patients with refractory TS achieved improvement in tic symptoms within 1 year after DBS. Initial responders who achieved a 35% reduction in Yale Global Tic Severity Scale total score within the first 3 months after DBS showed larger treatment effects during 1-year follow-up. Although no clinical or demographic factors were predictive of initial responses, patients with serious self-injurious behaviors tended to show delayed responses. CONCLUSION: This is the first study to our knowledge to report the DBS outcomes of 20 patients with TS in a single center in Asia. Our study supports the efficacy of DBS targeting anteromedial globus pallidus internus in refractory TS with no evident serious adverse events. Initial responses after DBS seem to be a predictor of long-term outcomes after surgery.

Endogenous Neural Stem Cell Activation after Low-Intensity Focused Ultrasound-Induced Blood-Brain Barrier Modulation.

Endogenous neural stem cells (eNSCs) in the adult brain, which have the potential to self-renew and differentiate into functional, tissue-appropriate cell types, have raised new expectations for neurological disease therapy. Low-intensity focused ultrasound (LIFUS)-induced blood-brain barrier modulation has been reported to promote neurogenesis. Although these studies have reported improved behavioral performance and enhanced expression of brain biomarkers after LIFUS, indicating increased neurogenesis, the precise mechanism remains unclear. In this study, we evaluated eNSC activation as a mechanism for neurogenesis after LIFUS-induced blood-brain barrier modulation. We evaluated the specific eNSC markers, Sox-2 and nestin, to confirm the activation of eNSCs. We also performed 3'-deoxy-3'[18F] fluoro-L-thymidine positron emission tomography ([18F] FLT-PET) to evaluate the activation of eNSCs. The expression of Sox-2 and nestin was significantly upregulated 1 week after LIFUS. After 1 week, the upregulated expression decreased sequentially; after 4 weeks, the upregulated expression returned to that of the control group. [18F] FLT-PET images also showed higher stem cell activity after 1 week. The results of this study indicated that LIFUS could activate eNSCs and induce adult neurogenesis. These results show that LIFUS may be useful as an effective treatment for patients with neurological damage or neurological disorders in clinical settings.

A Single Injection of rAAV-shmTOR in Peripheral Nerve Persistently Attenuates Nerve Injury-Induced Mechanical Allodynia.

Activation of mammalian target of rapamycin (mTOR) has been known as one of the contributing factors in nociceptive sensitization after peripheral injury. Its activation followed by the phosphorylation of downstream effectors causes hyperexcitability of primary sensory neurons in the dorsal root ganglion. We investigated whether a single injection of rAAV-shmTOR would effectively downregulate both complexes of mTOR in the long-term and glial activation as well. Male SD rats were categorized into shmTOR (n = 29), shCON (n = 23), SNI (n = 13), and Normal (n = 8) groups. Treatment groups were injected with rAAV-shmTOR or rAAV-shCON, respectively. DRG tissues and sciatic nerve were harvested for Western blot and immunohistochemical analyses. Peripheral sensitization was gradually attenuated in the shmTOR group, and it reached a peak on PID 21. Western blot analysis showed that both p-mTORC1 and p-mTORC2 were downregulated in the DRG compared to shCON and SNI groups. We also found decreased expression of phosphorylated p38 and microglial activation in the DRG. We first attempted a therapeutic strategy for neuropathic pain with a low dose of AAV injection by interfering with the mTOR signaling pathway, suggesting its potential application in pain treatment.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Potential optimization of focused ultrasound capsulotomy for obsessive compulsive disorder.

Obsessive-compulsive disorder is a debilitating and often refractory psychiatric disorder. Magnetic resonance-guided focused ultrasound is a novel, minimally invasive neuromodulatory technique that has shown promise in treating this condition. We investigated the relationship between lesion location and long-term outcome in patients with obsessive-compulsive disorder treated with focused ultrasound to discern the optimal lesion location and elucidate the efficacious network underlying symptom alleviation. Postoperative images of 11 patients who underwent focused ultrasound capsulotomy were used to correlate lesion characteristics with symptom improvement at 1-year follow-up. Normative resting-state functional MRI and normative diffusion MRI-based tractography analyses were used to determine the networks associated with successful lesions. Patients with obsessive-compulsive disorder treated with inferior thalamic peduncle deep brain stimulation (n = 5) and lesions from the literature implicated in obsessive-compulsive disorder (n = 18) were used for external validation. Successful long-term relief of obsessive-compulsive disorder was associated with lesions that included a specific area in the dorsal anterior limb of the internal capsule. Normative resting-state functional MRI analysis showed that lesion engagement of areas 24 and 46 was significantly associated with clinical outcomes (R = 0.79, P = 0.004). The key role of areas 24 and 46 was confirmed by (i) normative diffusion MRI-based tractography analysis, showing that streamlines associated with better outcome projected to these areas; (ii) association of these areas with outcomes in patients receiving inferior thalamic peduncle deep brain stimulation (R = 0.83, P = 0.003); and (iii) the connectedness of these areas to obsessive-compulsive disorder-causing lesions, as identified using literature-based lesion network mapping. These results provide considerations for target improvement, outlining the specific area of the internal capsule critical for successful magnetic resonance-guided focused ultrasound outcome and demonstrating that discrete frontal areas are involved in symptom relief. This could help refine focused ultrasound treatment for obsessive-compulsive disorder and provide a network-based rationale for potential alternative targets.

A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control.

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

A novel rat robot controlled by electrical stimulation of the nigrostriatal pathway.

OBJECTIVE: Artificial manipulation of animal movement could offer interesting advantages and potential applications using the animal's inherited superior sensation and mobility. Although several behavior control models have been introduced, they generally epitomize virtual reward-based training models. In this model, rats are trained multiple times so they can recall the relationship between cues and rewards. It is well known that activation of one side of the nigrostriatal pathway (NSP) in the rat induces immediate turning toward the contralateral side. However, this NSP stimulation-induced directional movement has not been used for the purpose of animal-robot navigation. In this study, the authors aimed to electrically stimulate the NSP of conscious rats to build a command-prompt rat robot. METHODS: Repetitive NSP stimulation at 1-second intervals was applied via implanted electrodes to induce immediate contraversive turning movements in 7 rats in open field tests in the absence of any sensory cues or rewards. The rats were manipulated to navigate from the start arm to a target zone in either the left or right arm of a T-maze. A leftward trial was followed by a rightward trial, and each rat completed a total of 10 trials. In the control group, 7 rats were tested in the same way without NSP stimulation. The time taken to navigate the maze was compared between experimental and control groups. RESULTS: All rats in the experimental group successfully reached the target area for all 70 trials in a short period of time with a short interstimulus interval (< 0.7 seconds), but only 41% of rats in the control group reached the target area and required a longer period of time to do so. The experimental group made correct directional turning movements at the intersection zone of the T-maze, taking significantly less time than the control group. No significant difference in navigation duration for the forward movements on the start and goal arms was observed between the two groups. However, the experimental group showed quick and accurate movement at the intersection zone, which made the difference in the success rate and elapsed time of tasks. CONCLUSIONS: The results of this study clearly indicate that a rat-robot model based on NSP stimulation can be a practical alternative to previously reported models controlled by virtual sensory cues and rewards.

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

Four-year follow-up results of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Following the emergence of magnetic resonance-guided focused ultrasound as a promising tool for movement disorder surgery, thalamotomy for essential tremor using this technique has become a useful tool based on its efficacy and lack of adverse effects. Here, we summarize the 4-year results of previous reports focusing on the durability of effectiveness of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. METHODS: From October 2013 to August 2014, 15 patients with intractable essential tremor were enrolled. Twelve of them completed clinical assessment through 4 years of postoperative follow-up. Tremor severity, task performance, and disability were measured using the Clinical Rating Scale of Tremor. RESULTS: The mean age of the 12 patients was 61.7 ± 8.1 years. Maximally delivered energy was 15,552.4 ± 6574.1 joules. The mean number of sonications was 17.3 ± 1.6. The mean postoperative lesion volume was 82.6 ± 29.023 mm3 and in 1 year was a mean of 9.667 ± 8.573 mm3 . Four years postoperatively, improvement of the hand tremor score was 56%, that of the disability score was 63%, that of the postural score was 70%, and that of the action score was 63% compared with baseline; all improvements were significant and sustained over the 4-year period after thalamotomy. There was no permanent adverse effect throughout the 4-year follow-up period. CONCLUSIONS: Magnetic resonance-guided focused ultrasound thalamotomy exhibits sustained clinical efficacy 4 years after the treatment of intractable essential tremor. Adverse events are generally transient. A large cohort of patients who have undergone magnetic resonance-guided focused ultrasound thalamotomy with longer follow-up is needed to confirm our findings. © 2019 International Parkinson and Movement Disorder Society.

Optimization of Medial Forebrain Bundle Stimulation Parameters for Operant Conditioning of Rats.

BACKGROUND: The medial forebrain bundle (MFB) is involved in the integration of pleasure and reward. Previous studies have used various stimulation parameters for operant conditioning, though the effectiveness of these parameters has not been systematically studied. OBJECTIVES: The purpose of the present study was to investigate the optimal MFB stimulation parameters for controlling the conditioned behavior of rats. METHODS: We evaluated four factors, including intensity, frequency, pulse duration, and train duration, to determine the effect of each on lever pressure applied by animals. We further compared burst and tonic stimulation in terms of learning and performance abilities. RESULTS: The number of lever presses increased with each factor. Animals in the burst stimulation group exhibited more lever presses. Furthermore, the average speed in the maze among burst stimulation group subjects was higher. CONCLUSION: We determined the optimal parameters for movement control of animals in operant conditioning and locomotor tasks by adjusting various electrical stimulation parameters. Our results reveal that a burst stimulation is more effective than a tonic stimulation for increasing the moving speed and number of lever presses. The use of this stimulation technique also allowed us to minimize the training required to control animal behavior.

The long-term effects of microvascular decompression on social phobia and health-related quality of life in patients with hemifacial spasm: a 3-year prospective study.

BACKGROUND: Although not a life-threatening condition, hemifacial spasm (HFS) frequently leads to social phobia because it causes significant facial disfigurement and consequently reduces health-related quality of life (HRQoL). The purpose of the current study was to examine the long-term effects of MVD on psychological aspects and HRQoL in HFS patients with social anxiety over a 36-month follow-up. METHODS: Thirty patients with HFS who underwent MVD from January 2015 to May 2015 were included in this prospective study. Clinical data, including standardized measures of general anxiety and depression (Hospital Anxiety Depression Scale (HADS)), social anxiety (Liebowitz Social Anxiety Scale (LSAS)), and the severity of HFS, were collected postoperatively, and 6 months and 36 months after MVD. Likewise, data on HRQoL were collected at baseline, and 6 months and 36 months after MVD using the Korean version of the Short Form 36 (SF-36). RESULTS: Twenty-two patients who completed the 36-month follow-up were classified into social phobia group and non-social phobia group based on the LSAS total scores of 60. Repeated measures analysis of variance demonstrated significant differences between the two groups over time for the total LSAS score (p < 0.001), anxiety subscale score of the HADS (p = 0.002), and the Mental Component Summary (MCS) (p = 0.046) of the SF-36. A comparison of these two groups in terms of differences observed in their scales at 6 months after MVD has shown that the improvements of the social phobia group in HADS anxiety subscale (p = 0.010), LSAS total score (p = 0.008), and MCS (p = 0.040) were significantly more improved than the those of non-social phobia group. And at 36 months after surgery, the improvement of the scales mentioned above was maintained, and additionally Vitality (p = 0.040) and Mental Health (p = 0.040) dimensions showed a statistically significant improvement. CONCLUSIONS: The improvements previously observed in psychological aspects and HRQoL over a short-term follow-up after MVD in HFS patients with social phobia were maintained for at least 36 months after MVD.

Carbon-Fiber Based Microelectrode Array Embedded with a Biodegradable Silk Support for In Vivo Neural Recording.

BACKGROUND: Recently, carbon fibers have been utilized to develop a depth-type microelectrode array for chronic neural recording. Since the diameter of carbon fibers is smaller than the conventional electrodes made of metal wires or microfabricated silicon, the carbon fiber electrodes showed an improved capability for chronic neural recording with less tissue damages. However, the carbon fiber based microelectrodes have a limitation of short insertion depth due to a low stiffness. METHODS: We proposed a carbon fiber based microelectrode array embedded with a mechanical support structure to facilitate the penetration into the deeper brain. The support is made of biodegradable silk fibroin to reduce the reactive tissue responses. The 4-channel carbon fiber based microelectrode arrays were fabricated and accessed in terms of electrochemical impedance, recording capability for 1-month implantation in rat hippocampi. The electrodes with tungsten supports were fabricated and tested as a control group. Immunohistochemical analysis was performed to identify the reactive glial responses. RESULTS: The carbon fiber based electrode arrays with silk supports showed about 2-fold impedance increase 2 weeks after implantation while the number of active electrodes decreased simultaneously. However, after 1 month, the electrode impedance decreased back to its initial value and the percentage of active electrodes also increased above 70%. Immunohistochemical staining clearly showed that the electrodes with silk supports induced less reactive glial responses than that with tungsten supports. CONCLUSION: The proposed carbon fiber based microelectrode array is expected to be used for long-term in vivo neural recording from deep brain regions with the minimized reactive tissue response.

Interbrain phase synchronization during turn-taking verbal interaction-a hyperscanning study using simultaneous EEG/MEG.

Recently, neurophysiological findings about social interaction have been investigated widely, and hardware has been developed that can measure multiple subjects' brain activities simultaneously. These hyperscanning studies have enabled us to discover new and important evidences of interbrain interactions. Yet, very little is known about verbal interaction without any visual input. Therefore, we conducted a new hyperscanning study based on verbal, interbrain turn-taking interaction using simultaneous EEG/MEG, which measures rapidly changing brain activities. To establish turn-taking verbal interactions between a pair of subjects, we set up two EEG/MEG systems (19 and 146 channels of EEG and MEG, respectively) located ∼100 miles apart. Subjects engaged in verbal communication via condenser microphones and magnetic-compatible earphones, and a network time protocol synchronized the two systems. Ten subjects participated in this experiment and performed verbal interaction and noninteraction tasks separately. We found significant oscillations in EEG alpha and MEG alpha/gamma bands in several brain regions for all subjects. Furthermore, we estimated phase synchronization between two brains using the weighted phase lag index and found statistically significant synchronization in EEG and MEG data. Our novel paradigm and neurophysiological findings may foster a basic understanding of the functional mechanisms involved in human social interactions. Hum Brain Mapp 39:171-188, 2018. © 2017 Wiley Periodicals, Inc.

Functional lesional neurosurgery for tremor: a systematic review and meta-analysis.

BACKGROUND: This work evaluates the consistency, effect size and incidence of persistent side effects of lesional neurosurgical interventions in the treatment of tremor due to Parkinson's disease (PD), essential tremor (ET), multiple sclerosis (MS) and midbrain lesions. METHODS: Systematic review and meta-analysis according to PRISMA-P guidelines. Random effects meta-analysis of standardised mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049). RESULTS: From 1249 abstracts screened, 86 peer-reviewed studies reporting 102 cohorts homogeneous for tremor aetiology, surgical target and technique were included.Effect on PD tremor was better when targeted at the ventral intermediate nucleus (V.im.) by radiofrequency ablation (RF) (Hedge's g: -4.15;) over V.im. by Gamma Knife (GK) (-2.2), subthalamic nucleus (STN) by RF (-1.12) and globus pallidus internus (GPi) by RF (-0.89). For ET MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (-2.35) and V.im. (-2.08) showed similar mean tremor reductions to V.im. ablation by RF (-2.42) or GK (-2.13). In MS V.im. ablation by GK (-1.96) and RF (-1.63) were similarly effective.Mean rates of persistent side effects after unilateral lesions in PD were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0% (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7% (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral tremor 30.3% (RF V.im.). CONCLUSION: This meta-analysis quantifies safety, consistency and efficacy of lesional neurosurgical interventions for tremor by target, technique and aetiology.

Functional lesional neurosurgery for tremor: back to the future?

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson's disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article.

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

BACKGROUND: Recently, a new thermal lesioning approach using magnetic resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS: Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS: After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS: The main limitations of this study were the small sample size and the open-label design. CONCLUSION: Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

BACKGROUND: Recently, a new thermal lesioning approach using magnetic-resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS: Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS: After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS: The main limitations of this study were the small sample size and the open-label design. CONCLUSION: Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.