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Deep brain stimulation (DBS) has been successfully used to treat movement disorders, such as Parkinson's disease, for more than 25 years and heralded the advent of electrical neuromodulation to treat diseases with dysregulated neuronal circuits. DBS is now superseding ablative techniques, such as stereotactic radiofrequency lesions. While serendipity has played a role in developing DBS as a therapy, research during the past two decades has shown that electrical neuromodulation is far more than a functional lesion that can be switched on and off. This understanding broadens the field to enable new types of stimulation, clinical indications, and research. This review highlights the complex effects of DBS from the single cell to the neuronal network. Specifically, we examine the electrical, cellular, molecular, and neurochemical mechanisms of DBS as applied to Parkinson's disease and other emerging applications. Graphical Abstract For over 25 years, deep brain stimulation (DBS) has been successfully used to treat movement disorders, i.e. Parkinson's disease. With high precision stereotactic implantation of electrodes, DBS is fast becoming a powerful tool for studying and treating the brain against many different diseases.

The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. As the most prevalent cause of dementia, Alzheimer’s disease (AD) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. As an established treatment for movement disorders, deep brain stimulation (DBS) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in AD by modulating fornix activity. Optimal target and stimulation parameters to potentially rescue memory deficits have yet to be determined. The aim of this review is to consolidate the structural and functional aspects of the fornix in the context of neuromodulation for memory deficits. We first present an anatomical and functional overview of the fibres and structures interconnected by the fornix. Recent evidence from preclinical models suggests that the fornix is subdivided into two distinct functional axes: a septohippocampal pathway and a subiculothalamic pathway. Each pathway’s target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. Overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal DBS strategies. It is not yet known whether driving fornix activity can enhance cognition—optimal target and stimulation parameters to rescue memory deficits have yet to be determined.

Essential tremor is the most common movement disorder and is often refractory to medical treatment. Surgical therapies, using lesioning and deep brain stimulation in the thalamus, have been used to treat essential tremor that is disabling and resistant to medication. Although often effective, these treatments have risks associated with an open neurosurgical procedure. MR-guided focused ultrasound has been developed as a non-invasive means of generating precisely placed focal lesions. We examined its application to the management of essential tremor. Our study was done in Toronto, Canada, between May, 2012, and January, 2013. Four patients with chronic and medication-resistant essential tremor were treated with MR-guided focused ultrasound to ablate tremor-mediating areas of the thalamus. Patients underwent tremor evaluation and neuroimaging at baseline and 1 month and 3 months after surgery. Outcome measures included tremor severity in the treated arm, as measured by the clinical rating scale for tremor, and treatment-related adverse events. Patients showed immediate and sustained improvements in tremor in the dominant hand. Mean reduction in tremor score of the treated hand was 89·4% at 1 month and 81·3% at 3 months. This reduction was accompanied by functional benefits and improvements in writing and motor tasks. One patient had postoperative paraesthesias which persisted at 3 months. Another patient developed a deep vein thrombosis, potentially related to the length of the procedure. MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor. If larger trials validate the safety and ascertain the efficacy and durability of this new approach, it might change the way that patients with essential tremor and potentially other disorders are treated. Focused Ultrasound Foundation.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation and has become a standard of care in a range of movement disorders. This Review discusses the evolution and current status of DBS technology and anticipates future advances.

In 2013, Nir Lipsman and colleagues reported a proof-of-concept study including four patients with essential tremor in whom MR-guided focused ultrasound was used to successfully and safely conduct unilateral thalamotomy. 1 Now, over a decade after this pioneering study, The Lancet Neurology publishes a Personal View on MR-guided focused ultrasound, covering the many developments of this technology in the field of movement disorders. 2 In their Personal View, Martínez-Fernández and colleagues 2 also describe the experimental application of low-intensity ultrasound to transiently open the blood–brain barrier or neuromodulate brain structures with a spatial and temporal accuracy that is not possible with other non-invasive methods. Science Photo Library MR-guided focused ultrasound is an incisionless procedure able to thermoablate discrete brain regions using ultrasound beams converging in the targeted area, and guided with MRI real-time monitoring of tissue temperature and anatomical imaging. 1 Several randomised controlled trials in patients with essential tremor or Parkinson's disease, as well as case series in other tremor and dystonia syndromes, have been conducted focusing on the classic targets of functional neurosurgery—ie, the ventral intermediate nucleus of the thalamus for tremor syndromes, and the subthalamus, globus pallidus pars interna, and pallidothalamic tract for Parkinson's disease. [...]the health-care delivery pathway of MR-guided focused ultrasound needs to be addressed. [...]MR-guided focused ultrasound for movement disorders has now entered a mature phase.

The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders. Despite the success and rapid adoption of DBS, crucial questions remain, including which brain areas should be targeted and in which patients. This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet challenges and future directions in the DBS field. Determining the next steps in DBS science will help to define the future role of this technology in the development of novel therapeutics for the most challenging disorders affecting the human brain.Over the past 20 years, deep brain stimulation (DBS) has transformed the treatment of movement disorders. Now, new therapeutic possibilities for DBS are emerging for other neurological and psychiatric disorders. This Review considers the clinical and scientific advances facilitated by DBS and the crucial questions, challenges and opportunities that face this technology.

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%–90%), RS (range, 48%–63%) and FUS thalamotomy (range, 35%–75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%–78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET.

Brain stimulation is a powerful treatment for an increasing number of psychiatric and neurological diseases, but it is unclear why certain stimulation sites work or where in the brain is the best place to stimulate to treat a given patient or disease. We found that although different types of brain stimulation are applied in different locations, targets used to treat the same disease most often are nodes in the same brain network. These results suggest that brain networks might be used to understand why brain stimulation works and to improve therapy by identifying the best places to stimulate the brain. Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation.

Within the last decade, ultrasound has been “rediscovered” as a technique for brain therapies. Modern technologies allow focusing ultrasound through the human skull for highly focal tissue ablation, clinical neuromodulatory brain stimulation, and targeted focal blood‐brain‐barrier opening. This article gives an overview on the state‐of‐the‐art of the most recent application: ultrasound neuromodulation as a new brain therapy. Although research centers have existed for decades, the first treatment centers were not established until 2020, and clinical applications are spreading rapidly. Ultrasound has been “rediscovered” as a technique for brain therapies within the last decade. This article gives an overview on the state‐of‐the‐art of the most recent application: ultrasound neuromodulation as a new brain therapy. Although research centers have existed for decades, the first treatment centers were not established until 2020, and clinical applications are spreading rapidly.

The COVID-19 pandemic has changed our world and impacted multiple layers of our society. All frontline workers and in particular those in direct contact with patients have been exposed to major risk. To mitigate pathogen spread and protect healthcare workers and patients, medical services have been largely restricted, including cancellation of elective surgeries, which has posed a substantial burden for patients and immense economic loss for various hospitals. The integration of a robot as a shielding layer, physically separating the healthcare worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes. In this Perspective, we outline detailed scenarios in the pre-, intra- and postoperative care, in which the use of robots and artificial intelligence can mitigate infectious contamination and aid patient management in the surgical environment during times of immense patient influx. We also discuss cost-effectiveness and benefits of surgical robotic systems beyond their use in pandemics. The current pandemic creates unprecedented demands for hospitals. Digitization and machine intelligence are gaining significance in healthcare to combat the virus. Their legacy may well outlast the pandemic and revolutionize surgical performance and management. Robots could play an important part in transforming healthcare to cope with the COVID-19 pandemic. This Perspective highlights how robotic technology integrated in a range of tasks in the surgical environment could help to ensure a continuation of medical services while reducing the risk of infection.