Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

Background: Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year.

Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression.

Ventral intermediate thalamic deep brain stimulation is a standard therapy for the treatment of medically refractory essential tremor and tremor-dominant Parkinson's disease. Despite the therapeutic benefits, the mechanisms of action are varied and complex, and the pathophysiology and genesis of tremor remain unsubstantiated. This intraoperative study investigated the effects of high frequency microstimulation on both neuronal firing and tremor suppression simultaneously.

Subthalamic Nucleus Visualization on Routine Clinical Preoperative MRI Scans: A Retrospective Study of Clinical and Image Characteristics Predicting Its Visualization.

Background: The visualization of the subthalamic nucleus (STN) on magnetic resonance imaging (MRI) is variable. Studies of the contribution of patient-related factors and intrinsic brain volumetrics to STN visualization have not been reported previously.

Objective: To assess the visualization of the STN during deep brain stimulation (DBS) surgery in a clinical setting.

Fornical Closed-Loop Stimulation for Alzheimer's Disease.

Pharmacological neuromodulation strategies have shown limited efficacy in treating memory deficits related to Alzheimer's disease (AD). Despite encouraging results from a few preclinical studies, clinical trials investigating open-loop deep brain stimulation (DBS) for AD have not been successful. Recent refinements in understanding the various phases of memory processes, animal studies investigating phase-specific modulation of hippocampal activity during memorization, and clinical studies using closed-loop DBS strategies to treat patients with movement disorders, all point to the need to investigate closed-loop fornical DBS strategies to better understand memory dynamics and potentially treat memory deficits in AD preclinical models.

Skull bone marrow injury caused by MR-guided focused ultrasound for cerebral functional procedures.

Objective: One patient for whom an MR-guided focused ultrasound (MRgFUS) pallidotomy was attempted was discovered to have multiple new skull lesions with the appearance of infarcts on the MRI scan 3 months after his attempted treatment. The authors conducted a retrospective review of the first 30 patients treated with MRgFUS to determine the incidence of skull lesions in patients undergoing these procedures and to consider possible causes.

Methods: A retrospective review of the MRI scans of the first 30 patients, 1 attempted pallidotomy and 29 ventral intermediate nucleus thalamotomies, was conducted.

Conflict monitoring mechanism at the single-neuron level in the human ventral anterior cingulate cortex.

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task.

Eight-hours adaptive deep brain stimulation in patients with Parkinson disease.

Objectives: To assess the feasibility and clinical efficacy of local field potentials (LFPs)-based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study.

Methods: We monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power.

Neuromodulation for the treatment of eating disorders and obesity.

Eating disorders and obesity adversely affect individuals both medically and psychologically, leading to reduced life expectancy and poor quality of life. While there exist a number of treatments for anorexia, morbid obesity and bulimia, many patients do not respond favorably to current behavioral, medical or bariatric surgical management. Neuromodulation has been postulated as a potential treatment for eating disorders and obesity.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

Objective: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials.

Pallidal deep brain stimulation modulates cortical excitability and plasticity.

Objective: Internal globus pallidus (GPi) deep brain stimulation (DBS) relieves symptoms in dystonia patients. However, the physiological effects produced by GPi DBS are not fully understood. In particular, how a single-pulse GPi DBS changes cortical circuits has never been investigated.

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

Importance: Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.

Objective: To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.

Design, Setting, And Participants: The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.

Current and Expected Advances in Deep Brain Stimulation for Movement Disorders.

Deep brain stimulation (DBS) has become an established treatment for medically refractory movement disorders including Parkinson's disease, essential tremor, and dystonia. The field of DBS continues to evolve with advances in patient selection, target identification, electrode and pulse generator technology, and the development of more effective stimulation paradigms such as closed-loop stimulation. Furthermore, as the safety and efficacy of DBS improves through better hardware design and deeper understanding of its mechanisms of action, the indications for DBS will continue to expand to cover a wider range of disorders.

Characterizing the effects of deep brain stimulation with magnetoencephalography: A review.

Background: Deep brain stimulation (DBS) is an important form of neuromodulation that is being applied to patients with motor, mood, or cognitive circuit disorders. Despite the efficacy and widespread use of DBS, the precise mechanisms by which it works remain unknown. Over the last decade, magnetoencephalography (MEG) has become an important functional neuroimaging technique used to study DBS.

Predictors of deep brain stimulation outcome in tremor patients.

Background: Deep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown.

Methods: We retrospectively investigated the clinical, pharmacological, electrophysiological and anatomical features that might predict the initial response and preservation of benefit in all patients who underwent deep brain stimulation for tremor. Data were collected at the following time points: baseline (preoperative), one-year post-surgery, and most recent visit.

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.

Chronic deep brain stimulation in an Alzheimer's disease mouse model enhances memory and reduces pathological hallmarks.

Background: Alzheimer's disease (AD) is a progressive degenerative disorder that currently remains extremely disabling. Recent work has shown that deep brain stimulation (DBS) has promising effects in AD patients. In parallel to the clinical trials, we investigated the impact of chronic DBS in 3xTg mice, a well-established animal model of AD.

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical.

The changing landscape of surgery for Parkinson's Disease.

Neurosurgical interventions have been used to treat PD for over a century. We examined the changing landscape of surgery for PD to appraise the value of various procedures in the context of advances in our understanding and technology. We assessed the number of articles published on neurosurgical procedures for PD over time as an albeit imprecise surrogate for their usage level.

Stopping and slowing manual and spoken responses: Similar oscillatory signatures recorded from the subthalamic nucleus.

Response control in the forms of stopping and slowing responses is thought to be implemented by a frontal-subcortical network, which includes the subthalamic nucleus (STN). For manual control, stopping is linked to STN beta (13-30 Hz) and slowing responses are linked to lower frequencies (<12 Hz). Whether similar STN oscillatory activities are associated with the control of spoken responses is not clear.

Gamma oscillations in the somatosensory thalamus of a patient with a phantom limb: case report.

The amputation of an extremity is commonly followed by phantom sensations that are perceived to originate from the missing limb. The mechanism underlying the generation of these sensations is still not clear although the development of abnormal oscillatory bursting in thalamic neurons may be involved. The theory of thalamocortical dysrhythmia implicates gamma oscillations in phantom pathophysiology although this rhythm has not been previously observed in the phantom limb thalamus.