Rapid advancements in neurostimulation technologies are providing relief to an unprecedented number of patients affected by debilitating neurologic and psychiatric disorders. Neurostimulation ...therapies include invasive and noninvasive approaches that involve the application of electrical stimulation to drive neural function within a circuit. This review focuses on established invasive electrical stimulation systems used clinically to induce therapeutic neuromodulation of dysfunctional neural circuitry. These implantable neurostimulation systems target specific deep subcortical, cortical, spinal, cranial, and peripheral nerve structures to modulate neuronal activity, providing therapeutic effects for a myriad of neuropsychiatric disorders. Recent advances in neurotechnologies and neuroimaging, along with an increased understanding of neurocircuitry, are factors contributing to the rapid rise in the use of neurostimulation therapies to treat an increasingly wide range of neurologic and psychiatric disorders. Electrical stimulation technologies are evolving after remaining fairly stagnant for the past 30 years, moving toward potential closed-loop therapeutic control systems with the ability to deliver stimulation with higher spatial resolution to provide continuous customized neuromodulation for optimal clinical outcomes. Even so, there is still much to be learned about disease pathogenesis of these neurodegenerative and psychiatric disorders and the latent mechanisms of neurostimulation that provide therapeutic relief. This review provides an overview of the increasingly common stimulation systems, their clinical indications, and enabling technologies.
We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ ...by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.
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•Noninvasive TI stimulation electrically stimulates neurons at depth selectively•Neurons are stimulated by interference between multiple electric fields•Neurons in mouse hippocampus can be stimulated without affecting the overlying cortex
A noninvasive method for deep-brain stimulation may be a new approach for the treatment of neuropsychiatric diseases.
Background:
The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines ...remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.
Methods:
Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Neurostimulation Treatments” is the fourth of six sections of the 2016 guidelines.
Results:
Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance.
Conclusions:
There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments.
Over the past 30 years, the field of neuromodulation has witnessed remarkable advancements. These developments encompass a spectrum of techniques, both non-invasive and invasive, that possess the ...ability to both probe and influence the central nervous system. In many cases neuromodulation therapies have been adopted into standard care treatments. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial ultrasound stimulation (TUS) are the most common non-invasive methods in use today. Deep brain stimulation (DBS), spinal cord stimulation (SCS), and vagus nerve stimulation (VNS), are leading surgical methods for neuromodulation. Ongoing active clinical trials using are uncovering novel applications and paradigms for these interventions.
Transcranial magnetic stimulation is an increasingly popular FDA-approved treatment for resistant depression, migraines, and OCD. Research is also underway for its use in various other psychiatric ...and medical disorders. Although rare, seizures are a potential adverse event of TMS treatment. In this article, we discuss TMS-related seizures with the various coils used to deliver TMS, the risk factors associated with seizures, the differential diagnosis of its presentations, the effects of sleep deprivation and alcohol use on seizures, as well as seizure risks with protocols for traditional TMS, theta-burst stimulation, and accelerated TMS. A discussion is presented comparing the potential risk of seizures with various psychotropic medications versus TMS. Included are case reports of TMS seizures in the child/adolescent patient, bipolar disorder patients, patients with a history of a traumatic brain injury, and those with epilepsy. Reports are also shared on TMS use without seizures in patients with a history of head injuries and TMS's continued use if patients have a seizure during their TMS treatment. Findings generated in this review suggest the following. Seizures, if present, are usually self-limiting. Most treatment recommendations for TMS-related seizures are supportive in nature. The risk of TMS-related seizures is <1% overall. TMS has successfully been used in patients with epilepsy, traumatic brain injuries, and those with a prior TMS-related seizure. The rate of TMS-related seizures is comparable to that of most psychotropic medications. While having a seizure is a rare but serious adverse effect of TMS, the benefits of treating refractory depression with TMS may outweigh the risk of suicidal ideation and other significant complications of depression.
Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent ...developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field.
•This is an overview of the state of tES/TMS applied in drug addictions.•Neuroscience will be translated into tES/TMS tools for clinical practice in addiction.•Heterogeneity of methods and outcome ...measures in the literature are addressed.•This article provides guidelines for best practices in tES/TMS addiction research.
There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.
The effective treatment of many diseases requires the use of multiple treatment strategies among which neuromodulation is playing an increasingly important role. Neuromodulation devices that act to ...normalize or modulate nerve activity through the targeted delivery of electrical stimuli will be the focus of this review. These devices encompass deep brain stimulators, vagus nerve stimulators, spinal cord simulators and sacral nerve stimulators. Already neuromodulation has proven successful in the treatment of a broad range of conditions from Parkinson's disease to chronic pain and urinary incontinence. Many of these approaches seek to exploit the activities of the autonomic nervous system, which influences organ function through the release of neurotransmitters and associated signalling cascades. This review will outline existing and emerging applications for each of these neuromodulation devices, proposed mechanisms of action and clinical studies evaluating both their safety and therapeutic efficacy.
Highlights • A review of technical aspects of transcranial electrical stimulation (tES) techniques. • Recommendations for safe and replicable application of tDCS and other tES methods. • Discussion ...of state-of-the-art methodology and design considerations in tES.
Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial ...electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.
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