Search

Electroconvulsive therapy (ECT) is one of the oldest and most effective forms of neurostimulation, wherein electrical current is used to elicit brief, generalized seizures under general anesthesia. When electrodes are positioned to target frontotemporal cortex, ECT is arguably the most effective treatment for severe major depression, with response rates and times superior to other available antidepressant therapies. Neuroimaging research has been pivotal in improving the field's mechanistic understanding of ECT, with a growing number of magnetic resonance imaging studies demonstrating hippocampal plasticity after ECT, in line with evidence of upregulated neurotrophic processes in the hippocampus in animal models. However, the precise roles of the hippocampus and other brain regions in antidepressant response to ECT remain unclear. Seizure physiology may also play a role in antidepressant response to ECT, as indicated by early positron emission tomography, single-photon emission computed tomography, and electroencephalography research and corroborated by recent magnetic resonance imaging studies. In this review, we discuss the evidence supporting neuroplasticity in the hippocampus and other brain regions during and after ECT, and their associations with antidepressant response. We also offer a mechanistic, circuit-level model that proposes that core mechanisms of antidepressant response to ECT involve thalamocortical and cerebellar networks that are active during seizure generalization and termination over repeated ECT sessions, and their interactions with corticolimbic circuits that are dysfunctional prior to treatment and targeted with the electrical stimulus.

People with schizophrenia spectrum disorders (SSDs) often experience persistent social cognitive impairments, associated with poor functional outcome. There are currently no approved treatment options for these debilitating symptoms, highlighting the need for novel therapeutic strategies. Work to date has elucidated differential social processes and underlying neural circuitry affected in SSDs, which may be amenable to modulation using neurostimulation. Further, advances in functional connectivity mapping and electric field modeling may be used to identify individualized treatment targets to maximize the impact of brain stimulation on social cognitive networks. Here, we review literature supporting a roadmap for translating functional connectivity biomarker discovery to individualized treatment development for social cognitive impairments in SSDs. First, we outline the relevance of social cognitive impairments in SSDs. We review machine learning approaches for dimensional brain-behavior biomarker discovery, emphasizing the importance of individual differences. We synthesize research showing that brain stimulation techniques, such as repetitive transcranial magnetic stimulation, can be used to target relevant networks. Further, functional connectivity-based individualized targeting may enhance treatment response. We then outline recent approaches to account for neuroanatomical variability and optimize coil positioning to individually maximize target engagement. Overall, the synthesized literature provides support for the utility and feasibility of this translational approach to precision treatment. The proposed roadmap to translate biomarkers of social cognitive impairments to individualized treatment is currently under evaluation in precision-guided trials. Such a translational approach may also be applicable across conditions and generalizable for the development of individualized neurostimulation targeting other behavioral deficits.

Spinal cord stimulation (SCS) is a popular neurostimulation therapy for severe chronic pain. To improve stimulation efficacy, multiple modes are now used clinically, including conventional, burst, and 10-kHz SCS. Clinical observations have produced speculation that these modes target different neural elements and/or work via distinct mechanisms of action. However, in humans, these hypotheses cannot be conclusively answered via experimental methods. Therefore, we utilized computational modeling to assess the response of primary afferents, interneurons, and projection neurons to conventional, burst, and 10-kHz SCS. We found that local cell thresholds were always higher than afferent thresholds, arguing against direct recruitment of these local cells. Furthermore, although we observed relative threshold differences between conventional, burst, and 10-kHz SCS, the recruitment order was the same. Finally, contrary to previous reports, axon collateralization produced complex changes in activation thresholds of primary afferents. These results motivate future work to contextualize clinical observations across SCS paradigms. PERSPECTIVE: This article presents the first computational modeling study to investigate neural recruitment during conventional, burst, and 10-kilohertz spinal cord stimulation for chronic pain within a single modeling framework. The results provide insight into these treatments' unknown mechanisms of action and offer context to interpreting clinical observations.

Spinal cord stimulation (SCS) consists of the application of electrical stimuli to the dorsal columns of the spinal cord or to the posterior nerve roots in order to modulate the pain signals carried by the ascending pain pathways to the brain. Two cases of SCS in patients with cauda equina syndrome after lumbar surgery are presented. They were treated for persistent neuropathic pain but also experienced improvement in their motor and urinary symptoms after this treatment. Although the primary indication for SCS is neuropathic pain control, its application can also lead to improvement of motor deficits, sensory disorders, and urinary incontinence, as shown in these two cases. SCS will likely play a fundamental role in rehabilitative therapies in different neurological diseases. Further investigation in the field is needed.

BackgroundTransdiagnostic clinical emotional dysregulation is a key component of psychopathology and offers an avenue to address multiple disorders with one transdiagnostic treatment. In the current study, we pilot a one-time intervention that combines cognitive restructuring (CR) with repetitive transcranial magnetic stimulation (rTMS), targeted using functional magnetic resonance imaging (fMRI).MethodsThirty-seven clinical adults with high emotional dysregulation were enrolled in this randomized, double-blind, placebo-controlled trial. fMRI was collected as participants were reminded of lifetime stressors and asked to downregulate their distress using CR tactics. fMRI BOLD data were analyzed to identify the cluster of voxels within the left dorsolateral prefrontal cortex (dlPFC) with the highest activation when participants attempted to downregulate, versus passively remember, distressing memories. Participants underwent active or sham rTMS (10 Hz) over the target while practicing CR following autobiographical emotional induction.ResultsReceiving active versus sham rTMS led to significantly higher high frequency heart rate variability during regulation, lower regulation duration, and higher likelihood to use CR during the week following the intervention. There were no differences between conditions when administering neurostimulation without CR compared to sham. Participants in the sham versus active condition experienced less distress the week after the intervention. There were no differences between conditions at the one-month follow up.ConclusionThis study demonstrated that combining active rTMS with emotion regulation training significantly enhances emotion regulation and augments the impact of training for as long as a week. These findings are a promising step towards a combined intervention for transdiagnostic emotion dysregulation.

Swallowing is a complex activity requiring a sophisticated system of neurological control from neurones within the brainstem, cerebral cortices and cerebellum. The cerebellum is a critical part of the brain responsible for the modulation of movements. It receives input from motor cortical and sensory areas and fine tunes these inputs to produce coordinated motor outputs. With respect to swallowing, numerous functional imaging studies have demonstrated increased activity in the cerebellum during the task of swallowing and damage to the cerebellum following differing pathological processes is associated with dysphagia. Single pulses of transcranial magnetic stimulation (TMS) have been applied to the cerebellum and have been shown to evoke motor responses in the pharynx. Moreover, repetitive TMS (rTMS) over the cerebellum can modulate cerebral motor (pharyngeal) cortical activity. Neurostimulation has allowed a better understanding of the connections that exist between the cerebellum and cerebral swallowing motor areas in health and provides a potential treatment for neurogenic dysphagia in illness. In this review we will examine what is currently known about the role of the cerebellum in the control of swallowing, explore new findings from neurostimulatory and imaging studies and provide an overview of the future clinical applications of cerebellar stimulation for treating dysphagia. ispartof: DYSPHAGIA vol:38 issue:2 pages:497-509 ispartof: location:United States status: published

Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment.At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Anterior thalamic deep brain stimulation is an effective therapeutic option for patients with drug-refractory focal epilepsy who are poor surgical candidates. Although the precise mechanism of action of thalamic neurostimulation is unknown, studies demonstrating increased efficacy over time have raised the possibility that therapeutic benefits are mediated by stimulation-related long-term neuroplastic changes. Adverse effects related to hardware malfunction have been previously described, and most commonly include local infection, sensory disturbances, and migration of leads. However, the withdrawal effect of sudden deep brain stimulation malfunction on seizure control is unclear. We present the case of a 21-year-old patient with intractable focal epilepsy who developed status epilepticus concurrently with unexpected deep brain stimulator battery failure, 21 months post implantation. This case demonstrates an unfamiliar possible adverse effect of anterior thalamic stimulation withdrawal and emphasizes the importance of stimulator hardware assessment in patients presenting with seizure worsening.

Drug-resistant epilepsy, characterized by ongoing seizures despite appropriate trials of anti-seizure medications, affects approximately one-third of people with epilepsy. Brain stimulation has recently become available as an alternative treatment option to reduce symptomatic seizures in short and long-term follow-up studies. Several questions remain on how to optimally develop patient-specific treatments and manage therapy over the long term. This review aims to discuss the clinical use and mechanisms of action of Responsive Neural Stimulation and Deep Brain Stimulation in the treatment of epilepsy and highlight recent advances that may both improve outcomes and present new challenges. Finally, a rational approach to device selection is presented based on current mechanistic understanding, clinical evidence, and device features.

BACKGROUND Refractory chronic migraine (rCM) is a highly disabling condition for which novel safe and effective treatments are needed. Safety and long-term efficacy of paresthesia-free high cervical 10 kHz spinal cord stimulation (SCS) were here prospectively evaluated for the treatment of rCM. MATERIALS AND METHODS Twenty adults with rCM (mean numbers of preventive treatments failed: 12.2 ± 3.1) were enrolled in this single-center, open-label, prospective study and implanted with a 10 kHz SCS system (Senza™ system, Nevro Corp.), with the distal tip of the lead(s) positioned epidurally at the C2 vertebral level. Safety and effectiveness outcomes, such as adverse events, headache and migraine reductions, responder rates, Migraine Disability Assessment (MIDAS), Headache Impact Test-6 (HIT-6), and Migraine-Specific Quality-of-Life (MSQ), were captured up to 52 weeks after implantation. RESULTS Compared to baseline, at 52 weeks postimplantation, there was a significant reduction of mean monthly migraine days (MMD) by 9.3 days (p

Rationale: Mechanical ventilation (MV) is associated with hippocampal apoptosis and inflammation, and it is important to study strategies to mitigate them. Objectives: Explore whether temporary tra...

Febrile infection-related epilepsy syndrome (FIRES) is a rare, life-threatening complication of febrile illness in previously healthy individuals followed by super-refractory status epilepticus. Deep brain stimulation (DBS) has been demonstrated to be a promising therapy for the treatment of intractable epilepsy. Here, we present a pediatric patient with FIRES whose seizures were mitigated by acute DBS of the bilateral centromedian thalamic nucleus (CMTN). This is a previously healthy 11-year-old female who presented emergently with altered mental status, fever, and malaise after 1 week of lethargy, anorexia, fever, and abdominal pain. The patient began having seizures shortly after admission. After thorough workup for encephalitis and other potential etiologies, this patient was diagnosed with FIRES due to super-refractory status epilepticus. Status epilepticus persisted despite pharmacologic management, immunotherapy, and vagus nerve stimulation. DBS of the bilateral CMTN (CM-DBS) was pursued after 56 days of hospitalization, and she demonstrated considerable improvement in baseline mental status 30 days after DBS insertion. This report highlights application of CM-DBS for super-refractory status epilepticus in FIRES. This region is a diffusely connected brain region and has been shown to modulate neural networks contributing to seizure propagation and consciousness; therefore, neurostimulation is a potential therapeutic intervention for patients with super-refractory status epilepticus.

The prefrontal cortex is appreciated as a key neurobiological player in human eating behavior. A special focus is herein dedicated to the dorsolateral prefrontal cortex (DLPFC), which is critically involved in executive function such as cognitive control over eating. Persons with obesity display hypoactivity in this brain area, which is linked to overconsumption and food craving. Contrary to that, higher activity in the DLPFC is associated with successful weight-loss and weight-maintenance. Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation tool used to enhance self-control and inhibitory control. The number of studies using tDCS to influence eating behavior rapidly increased in the last years. However, the effectiveness of tDCS is still unclear, as studies show mixed results and individual differences were shown to be an important factor in the effectiveness of non-invasive brain stimulation. Here, we describe the current state of research of human studies using tDCS to influence food intake, food craving, subjective feeling of hunger and body weight. Excitatory stimulation of the right DLPFC seems most promising to reduce food cravings to highly palatable food, while other studies provide evidence that stimulating the left DLPFC shows promising effects on weight loss and weight maintenance, especially in multisession approaches. Overall, the reported findings are heterogeneous pointing to large interindividual differences in tDCS responsiveness.

OBJECTIVES A recent approach to treatment of cluster headaches (CH) employs a microstimulator device for on-demand neuromodulation of the sphenopalatine ganglion (SPG) during an acute CH attack. A precise anatomical localization of the SPG within the pterygopalatine fossa (PPF) is optimal in order to position the SPG electrode array. This study aims to investigate a novel approach for SPG localization using computed tomography angiographic studies (CTA). MATERIALS AND METHODS Two independent observers identified the location of the SPG on 54 computed tomography angiographic studies (CTA) and measured its position relative to the vidian canal (VC). The qualitative confidence of identification, morphology, position within the PPF and its relation to vascular structures were also recorded. RESULTS The SPG was detectable in 88% of cases with a variable position. The most frequent positions were superior (56%) and lateral (99%) relative to the VC with a mean (±SD) craniocaudal distance of 0.34 mm (±1.38) and a mean mediolateral distance of 3.04 mm (±1.2). However, in a considerable proportion of cases, the SPG was identified inferiorly to the VC (33%). Interobserver and intraobserver agreement for SPG location were moderate and strong respectively. CONCLUSIONS Since localization of SPG on CTAs is feasible and reproducible, it has future clinical potential to aid placement, optimal positioning and individualized programming of the electrode array.

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea. Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction or STAR trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, obstructive sleep apnea phenotypes, individual health status, psychological conditions, and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This article presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel. CITATION: Suurna MV, Jacobowitz O, Chang J, et al. Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum. J Clin Sleep Med. 2021;17(12):2477–2487.

OBJECTIVES Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI). MATERIALS AND METHODS This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively. RESULTS The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p

OBJECTIVES Different anesthesia techniques are used for surgical implantation of paddle lead electrodes for neurostimulation through a laminectomy. We wanted to evaluate the use of dexmedetomidine as sedative for this procedure in a series of patients. Second, we wanted to verify whether the stimulation pattern and position of the electrode had to be changed during the procedure guided by the patient's feedback. MATERIAL AND METHODS Twenty-five consecutive patients received surgical implantation of a spinal cord stimulation electrode under conscious sedation using dexmedetomidine and local anesthesia. We evaluated the effects of the administered drug, the patient comfort, and the adequacy of the stimulation pattern. RESULTS Twenty-four patients completed the procedure with only dexmedetomidine and local anesthetic. Infusion was started on average 55 minutes (sd 29) prior to incision. The mean dose of lidocaine was 430 mg (sd 95). There were no significant hemodynamic changes. Median time to reach Modified Aldrete's score postoperative was 67 minutes (sd 38). In 46% of the patients, the position of the electrode was changed guided by the feedback of the patient. More than half of the patients remember most details of the procedure. Only four patients mentioned substantial discomfort and only three would definitely not want to undergo this procedure again. CONCLUSIONS Implantation of spinal cord stimulation electrodes through a surgical laminectomy using dexmedetomidine is a safe and feasible procedure with adequate comfort for patient and surgeon. This way of working increases the optimal position of the electrode resulting in the most convenient stimulation pattern and avoiding revisions.

Objectives Translingual neurostimulation (TLNS) with adjunct physical rehabilitation is used to treat balance and gait deficits in several chronic neurological conditions. The purpose of this review is to summarize and appraise the evidence currently available on the portable TLNS device and to assess its potential clinical application. Materials and methods In this narrative review, MEDLINE, EMBASE, Web of Science, and Google Scholar were searched for primary research investigating the use of portable TLNS devices on any neurologic condition. Data were extracted, reviewed, and appraised with respect to study design, conduct, and reporting. Results Five randomized controlled trials (RCTs), three quasi-experimental trials, and seven case reports/series were found. Most studies demonstrated improvements in balance and gait deficits secondary to traumatic brain injury and multiple sclerosis, but evidence is also present to a lesser degree for stroke and balance disorder patients. In these studies, the feasibility and safety of TLNS have been convincingly demonstrated. Functional magnetic resonance studies have also suggested a plausible neuroplastic therapeutic mechanism. However, the efficacy of TLNS remains unclear due to bias and confounding within studies, and heterogeneity of results between studies. Conclusions TLNS is a promising treatment modality for various chronic neurological conditions that are often refractory to conventional therapy. However, TLNS technology remains largely investigational as high-quality RCTs are still required to elucidate efficacy, optimal dosages, necessary treatment durations, and treatment durability. Further research to develop an appropriate control group is needed for scientifically valid comparisons of TLNS.

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310

Nowadays there are two types of electrical treatment of functional disorders of micturition—electrical neurostimulation and electrical neuromodulation.

BACKGROUND: Newer “closed-loop” neurostimulation devices in development could, in theory, induce changes to patients’ personalities and self-perceptions. Empirically, however, only limited data of patient and family experiences exist. Responsive neurostimulation (RNS) as a treatment for refractory epilepsy is the first approved and commercially available closed-loop brain stimulation system in clinical practice, presenting an opportunity to observe how conceptual neuroethical concerns manifest in clinical treatment. METHODS: We conducted ethnographic research at a single academic medical center with an active RNS treatment program and collected data via direct observation of clinic visits and in-depth interviews with 12 patients and their caregivers. We used deductive and inductive analyses to identify the relationship between these devices and patient changes in personality and self-perception. RESULTS: Participants generally did not attribute changes in patients’ personalities or self-perception to implantation of or stimulation using RNS. They did report that RNS affected patients’ experiences and conceptions of illness. In particular, the capacity to store and display electrophysiological data produced a common frame of reference and a shared vocabulary among patients and clinicians. DISCUSSION: Empirical experiences of a clinical population being treated with closed-loop neuromodulation do not corroborate theoretical concerns about RNS devices described by neuroethicists and technology developers. However, closed-loop devices demonstrated an ability to change illness experiences. Even without altering identify and self-perception, they provided new cultural tools and metaphors for conceiving of epilepsy as an illness and the process of diagnosis and treatment. These findings call attention to the need to situate neuroethical concerns in the broader contexts of patients’ illness experiences and social circumstances.

Background. Spastic diplegia (Little’s disease) is the most common form of infantile cerebral palsy (ICP), leading to persistent motor and functional impairments. One promising area of rehabilitation is a combination of physical therapy with methods of stimulation of various parts of the nervous system, among which functional electrical stimulation of muscles and nerves is the most prominent.Objective. To study structural changes of cerebral white matter conduction pathways in patients with spastic diplegia after translingual neurostimulation using magnetic resonance tractography.Materials and Methods. An open single center-controlled study was conducted. A total of 18 children were examined. All patients underwent comprehensive MRI in two time points, before and after a course of translingual neurostimulation, on a tomograph with magnetic field induction 3.0 Tesla, which included a traditional protocol in 3 mutually perpendicular planes), and diffusion-weighted imaging — DWI (Diffusion-Weight Imaging).Results. All patients after neurostimulation showed clinical improvement of movement coordination and decrease of muscle tone with formation of new motor skills, improvement of limb motor function. Statistically significant decrease of spasticity index was revealed up to 17% for arms and 23% for legs, improvement of motor skills on all three scales.Conclusion. Translingual neurostimulation allows to affect all components of motor activity, as a result of which neuroplasticity processes are activated and the brain of patients with spastic diplegia becomes more receptive to motor rehabilitation aimed at restoration of motor control and formation of new motor skills.

This article summarizes and critiques the evidence for use of available pharmacotherapies (vasoactive, psychoactive, and hormonal medications) and energy-based therapies (laser, radiofrequency, shockwave, and neurostimulation) for treatment of female sexual dysfunction. The enthusiasm with which energy-based treatments for sexual dysfunction have been adopted is disproportionate to the amount of data currently available to support their clinical use. Pharmacotherapy for female sexual dysfunction has considerably more research evidence to justify its use. Patients must be empowered to make an informed, autonomous determination as to whether the risk/reward ratio favors the use of pharmacotherapy, energy-based therapy, or some other treatment intervention.

Several neuroimaging studies have shown that a distributed network of brain regions is involved in our ability to appraise the emotions we experience in daily life. In particular, scholars suggested that the dorsal anterior cingulate cortex (dACC) may play a role in the appraisal of emotional stimuli together with subcortical regions, especially when stimuli are negatively valenced, and the dorsolateral prefrontal cortex (dlPFC) may play a role in regulating emotions. However, proofs of the causal role of these regions are lacking. In the present study, we aim at testing this model by stimulating both the dACC and the left dlPFC via cathodal tDCS. Twenty-four participants were asked to attend and rate the arousal and valence of negative and neutral emotional stimuli (pictures and words) in three different experimental sessions: cathodal stimulation of dACC, left dlPFC, or sham. In addition to the experimental task, the baseline affective state was measured before and after the stimulation to further assess the effect of stimulation over the baseline affective state after the experimental session. Results showed that cathodal stimulation of dACC, but not the left dlPFC, was associated with reduced arousal ratings of emotional stimuli, both compared with the sham condition. Moreover, cathodal stimulation of left dlPFC decreased participant's positive affective state after the session. These findings suggest for the first time, a dissociation between the dACC and dlPFC, with the former more involved in emotion appraisal, and the latter more involved in mood modulation.

We present findings of a 10-year retrospective study, analysing the reasons for rejection of neurosurgical intervention (deep brain stimulation or DBS) in patients with Parkinson’s disease, who were referred to an extrapyramidal movement disorders clinic and then to a neurosurgery centre. It was found that after screening, 78.6% of patients referred as candidates for neurosurgical treatment to an extrapyramidal movement disorders clinic were rejected, while 21.4% of patients were referred to a neurosurgery centre, where 12% underwent surgery. The main reasons for rejecting potential DBS candidates were: “early referral”, “inadequate pharmacotherapy”, “levodopa-resistant symptoms”, “atypical/secondary Parkinsonism”, “cognitive reasons”, “psychological reasons”, “comorbidity”, “abnormal MRI”, “poor response to levodopa medication” and “declined surgery”. Furthermore, the number of self-referrals decreased, the number of patients referred by neurologists increased, the number of rejections of ‘unsuitable’ DBS candidates decreased, and the number of ‘suitable’ candidates referred to the extrapyramidal centre increased during the time period of 10 years. In addition, the number of patients who were referred to the neurosurgery centre and underwent surgery there increased, which suggests greater awareness of the selection criteria among doctors, as well increased knowledge and experience among neurologists in both primary healthcare and specialized centres.

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such as excitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of the pathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer’s disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.

Introduction Spinal cord stimulation (SCS) is a commonly utilized therapy for the treatment of neuropathic pain conditions. The Neurostimulation Appropriateness Consensus Committee (NACC) has recommended that the placement of percutaneous SCS leads be performed in an awake patient capable of providing feedback. It is not currently known how commonly this recommendation is adhered to by physicians in clinical practice. This article presents the findings of a survey designed to answer this important question. Methods We conducted a survey of the active membership of the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the Spine Intervention Society (SIS) regarding practice patterns with SCS therapy. We analyzed the percent of respondents who indicated that they use deep sedation and general anesthesia during SCS placement as well as any reported complications. Results Many practitioners frequently utilize deep sedation as well as general anesthesia when performing SCS implants. Our findings demonstrate that 77% of physicians reported that they utilize deep sedation for permanent SCS implants at times, and 45% of physicians reported the use of general anesthesia for 10 kHz implants. Additionally, 94% of physicians reported that they have never had a complication related to the use of general anesthesia for a spinal cord stimulator placement. Conclusions This survey provides initial data on SCS practices among a large cohort of clinicians who utilize SCS. SCS lead placement under deep sedation and general anesthesia appears to be common practice for many physicians who perform implants. This survey should stimulate further research on this topic, given that the current safety guidelines and the rate of physicians reporting the use of deep sedation and general anesthesia for spinal cord stimulator placement remain at odds.

Background Cognitive deficits are prevalent in bipolar disorder and are a significant contributor to negative patient-reported outcomes. Herein we conducted a pilot study of repetitive transcranial magnetic stimulation (rTMS) to improve cognitive function in adults with bipolar disorder. Methods The study was a triple-blinded, randomized, placebo-control trial. Participants (aged 18 to 60) with a diagnosis of DSM-5-defined bipolar disorder (I or II) were recruited and randomized (N=36) to receive either a sham treatment (n=20) or an active rTMS treatment (n=16). Patients completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at baseline and 1-2 weeks after the rTMS intervention. Results A significant group by time interaction was observed in the Hopkins Verbal Learning Test-Revised (HVLT-R), (F (1, 34) = 17.0, p Limitations The study was conducted in a small sample . Conclusion This pilot study, which was intended to establish feasibility, suggests that rTMS may offer benefit in select domains of cognitive functioning in bipolar disorder. None of the measures across subdomains revealed a dyscognitive effect.

Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far—from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED.

Purpose In recent years, neuromodulation has experienced a renaissance. Novel waveforms and anatomic targets show potential improvements in therapy that may signify substantial benefits. New innovations in peripheral nerve stimulation and dorsal root ganglion stimulation have shown prospective evidence and sustainability of results. Sub-perception physiologic bursting, high-frequency stimulation and feedback loop mechanisms provide significant benefits over traditional tonic spinal cords stimulation (SCS) in peer reviewed investigations. We reviewed the themes associated with novel technology in the context of historical stalwart publications. Findings New innovations have led to better nerve targeting, improvements in disease-based treatment, and opioid alternatives for those in chronic pain. In addition, new neural targets from both structural and cellular perspectives have changed the field of Neurostimulation. Summary For many years, tonic SCS was representative of neuromodulation, but as this review examines, the progression of the field in the past decade has reshaped patient options.

Background Insomnia is a widespread symptom of many psychiatric and neurological disorders, but can also be a clinically relevant disorder of its own. The application of low-dose electricity as a treatment for both has had a long history, dating back to the 19th century, but has seen somewhat of a renaissance in therapies such as tDCS. Objective The aim of this publication was to identify and present original works from the second half of the 19th century as well as contemporary studies that investigated the therapeutic value of electricity in treating sleep disorders. Methods While the nine historical sources identified mostly presented impressive successes in treatment, the nine modern publications had much more heterogeneous and moderate results. Results The discussion of these differences refers to the scientific discourse of the late 19th century about the placebo-effect and the role of suggestibility in the therapeutic process and outcome. Conclusion In conclusion profound parallels can be seen between treatment innovations and methodological discussions in the 1880–1890s and nowadays.

Introduction Low back pain impacts most people throughout the course of their lives and contributes significantly to the global burden of disease. In some patients, symptoms resolve with little intervention, while others are amenable to surgical intervention, some cases are intractable to current care paradigms. Restorative neurostimulation is an emerging therapy for chronic mechanical low back pain. Methods We conducted a prospective post-market follow-up of 42 patients treated for longstanding chronic mechanical low back pain with restorative neurostimulation. Patients were followed up at 45, 90, and 180 days and 1 and 2 years following activation of the device. Pain, disability, and health-related quality of life were recorded. Results Among the 37 patients completing 2-year follow-up, numerical rating scale (NRS) pain scores improved from 7.0 ± 0.2 to 3.5 ± 0.3 (p, Plain Language Summary The goal of this study was to examine the effectiveness of restorative neurostimulation for the treatment of patients with chronic mechanical low back pain. This technique has been studied in a clinical trial setting and been shown to be both safe and effective. This study reports on the real-world experience from five sites in the United Kingdom. Patients with a history of severe low back pain that lasted on average for more than 13 years were implanted with a nerve stimulation device that targets the nerves that control important spinal stabilising muscles. All of the patients were asked to perform two stimulation sessions per day for 30 min each. Over the next 2 years, patients reported substantial reductions in pain and disability and an improvement in health-related quality of life. The safety profile of the therapy was excellent when compared to similar minimally invasive therapies for different spine pathologies. In this difficult-to-treat patient population who have few remaining therapeutic options, restorative neurostimulation is a valuable tool in the clinician’s armamentarium.