Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson's Disease.

Deep brain stimulation (DBS) is effective for Parkinson's disease (PD), dystonia, and essential tremor (ET). While motor benefits are well documented, cognitive and psychiatric side effects from the subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS for PD are increasingly recognized. Underlying disease, medications, microlesions, and post-surgical stimulation likely all contribute to non-motor symptoms (NMS).

Invasive cortical stimulation.

The field of neuromodulation, at its essence, aims to apply electrical stimulation to the brain to ameliorate various pathology. Many methods of applying this stimulation exist, including invasive and non-invasive means. In the realm of invasive stimulation, stimulation of the cortex remains one of the earliest techniques investigated, yet one of the most underutilized today. Evidence for the efficacy of direct invasive cortical stimulation continues to mount, especially in recent years. In this chapter we will review the evidence for the use of invasive cortical stimulation as it applies to neuropathic pain, epilepsy, psychiatric disease, movement disorders, tinnitus, and post-stroke recovery, as well explore some potential mechanisms and future directions of the technique.

Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry.

The basal ganglia have been a target for neuromodulation surgery since Russell Meyers' pioneering works in the late 1930s. Contemporary movement disorder surgery on the brain has evolved from empiric observations on movement behavior after neurological lesions. So too has the development of psychiatric surgical procedures followed the observation of lesions in the brain on cognitive and affective behavior. Just as deep brain stimulation (DBS) has revolutionized the practice of movement disorder surgery, its application to psychiatric illness has become the cutting edge of functional and restorative neurosurgery. The fundamental concept of the cortico-striatal-pallido-thalamocortical loop will be explored in the context of psychiatric disorders. DBS targeting this circuitry appears from initial evidence in obsessive-compulsive disorder (OCD) to be a promising option for patients with neuropsychiatric illness resistant to conventional therapies. Further exploring the anatomic interconnectivity of the physiologically relevant cortical and subcortical areas will inevitably lead to better applications of DBS for the treatment of OCD, major depression (MD) and potentially for other psychiatric disorders. Implementing such therapies optimally will require the creation of treatment centers with specialized expertise in the psychiatric, neurosurgical, and ethical issues that arise with these populations.

Utilization of Quantitative Susceptibility Mapping for Direct Targeting of the Subthalamic Nucleus During Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) has demonstrated efficacy in improving motor disability in Parkinson's disease. The recently developed quantitative susceptibility mapping (QSM) technique, which can accurately map iron deposits in deep brain nuclei, promises precise targeting of the STN. OBJECTIVE: To demonstrate the use of QSM to target STN effectively by correlating with classical physiological-based targeting measures in a prospective study. METHODS: The precision and accuracy of direct targeting with QSM was examined in a total of 25 Parkinson's disease patients between 2013 and 2015 at our institution. QSM was utilized as the primary magnetic resonance imaging (MRI) method to perform direct STN targeting on a stereotactic planning station utilizing computed tomography/MR fusion. Intraoperative microelectrode recordings (MER) were obtained to confirm appropriate trajectory through the sensorimotor STN. RESULTS: Estimations of STN thickness between the MER and QSM methods appeared to be correlated. Mean STN thickness was 5.3 mm. Kinesthetic responsive cells were found in > 90% of electrode runs. The mean radial error (±SEM) was 0.54 ± 0.1 mm. Satisfactory clinical response as determined by Unified Parkinson's Disease Rating Scale (UPDRS III) was seen at 12 mo after surgery. CONCLUSION: Direct targeting of the sensorimotor STN using QSM demonstrates MER correlation and can be safely used for deep brain stimulation lead placement with satisfactory clinical response. These results imply that targeting based on QSM signaling alone is sufficient to obtain reliable and reproducible outcomes in the absence of physiological recordings.

Feasibility of auditory cortical stimulation for the treatment of tinnitus.

OBJECTIVES: To investigate the feasibility and safety of an implantable epidural cortical stimulator for the treatment of severe tinnitus. STUDY DESIGN: Prospective, controlled, single-blinded study of cortical stimulation for 4 weeks, and then an open-label stimulation period. SETTING: Tertiary care referral center. PATIENTS: Adults (n = 8) with constant tinnitus of at least 1 year with a tinnitus reaction questionnaire score greater than 33. Tinnitus was predominantly unilateral with a frequency less than 8,000 Hz. INTERVENTIONS: Surgical implantation of an investigational epidural electrode over the posterior superior temporal gyrus using functional magnetic resonance imaging targeting. A 2-week stimulation period alternated with a 2-week sham period in random order to which subjects were blinded. This was followed by continuous stimulation with parameter adjustments to maximize tinnitus suppression. MAIN OUTCOME MEASURE: Subjective rating of tinnitus severity, loudness, and device efficacy. Objective measures of hearing thresholds, tinnitus frequency, loudness, and minimum masking levels. Outcome measures using the Tinnitus Handicap Questionnaire, Tinnitus Reaction Questionnaire, and Beck Depression Inventory. RESULTS: There were no effects of stimulation during the 4-week blinded period. With continuous chronic stimulation, 2 patients had persistent reduction of pure-tone tinnitus, and 6 patients had short periods of total tinnitus suppression. Significant improvements in the Beck Depression Inventory and tinnitus questionnaires were found, although objective measures of tinnitus loudness remained fairly stable. No surgical or stimulation-related complications were noted. CONCLUSION: Chronic electrical stimulation of the secondary auditory cortex seems safe and warrants further investigation as a potential therapeutic intervention for the suppression of tinnitus.

The Adjunctive Use of Vancomycin Powder Appears Safe and May Reduce the Incidence of Surgical-Site Infections After Deep Brain Stimulation Surgery.

BACKGROUND: Postoperative surgical-site infections (SSIs) are a common complication after deep brain stimulation (DBS) surgery, occurring at a quoted rate of approximately 1%-9%. Intraoperative vancomycin powder has demonstrated efficacy in reducing SSIs after cranial and spinal surgery; however, its use during DBS surgery has yet to be established. In this study, we describe the senior author's experience with the use of intraoperative vancomycin powder to prevent SSIs after DBS surgery. METHODS: We retrospectively examined the incidence of SSI in 297 patients who underwent DBS surgery at the Mount Sinai Health System from September 2012 to December 2015. All patients underwent a uniform perioperative antiseptic protocol, including thorough skin cleansing, intravenous anticephalosporin antibiotics, copious irrigation, and the application of topical vancomycin powder (1 g) before skin closure. Patient information was obtained through a review of electronic medical records. Primary outcome was the incidence of SSI, which was defined per the standards of the Centers for Disease Control and Prevention and confirmed with wound cultures. RESULTS: Four patients developed clinical signs and symptoms of SSI (1.3%); all were men with Parkinson disease. The primary organism responsible was Staphylococcus aureus (75%). Two patients presented with neurostimulator infections, and 2 presented with parietal connector-site infections between 2 months and 1 year after initial surgery. No patients in our series developed topical or systemic reactions attributable to the use of vancomycin powder. CONCLUSIONS: In our experience, vancomycin powder has demonstrated safety and efficacy as an adjunct medication for infection prophylaxis after DBS surgery. Further prospective studies with larger patient cohorts are warranted.

Case Study of Image-Guided Deep Brain Stimulation: Magnetic Resonance Imaging-Based White Matter Tractography Shows Differences in Responders and Nonresponders.

BACKGROUND: The caudal zona incerta (cZI) is an increasingly popular deep brain stimulation (DBS) target for the treatment of tremor-predominant disease. The dentatorubrothalamic tract (DRTT) is a white matter fiber bundle that traverses the cZI and can be identified using diffusion-weighted magnetic resonance imaging fiber tractography to ascertain its precise course. In this report, we compare 2 patient cases of cZI DBS, a responder and a nonresponder. CASE DESCRIPTION: Patient 1 (responder) is a 65-year-old man with medically refractory Parkinson disease who underwent bilateral DBS lead placement in the cZI. Postoperatively he demonstrated >90% reduction in baseline tremor and was not limited by stimulation side effects. Postoperative imaging showed correct lead placement in the cZI. Tractography revealed a DRTT within the field of stimulation, bilaterally. Patient 2 (nonresponder) is a 61-year-old man with medically refractory Parkinson disease who also underwent bilateral DBS lead placement in the cZI. He initially demonstrated >90% reduction in baseline tremor but developed disabling dystonia of his left leg and significant slurring of his speech in the months after surgery. Postoperative imaging showed bilateral lead placement in the cZI. Right-sided electrode revision was recommended and resulted in relief of tremor and reduced dystonic side effects. Tractography analysis of the original leads revealed a DRTT with an atypical anterior trajectory and a location outside the field of stimulation. Tractography analysis of the revised lead showed a DRTT within the field of stimulation. CONCLUSIONS: Preoperative diffusion-weighted magnetic resonance imaging fiber tractography imaging of the DRTT has the potential to improve and individualize DBS planning.

Deep brain stimulation for psychiatric disorders.

Over the last decade, deep brain stimulation (DBS) has revolutionized the practice of neurosurgery, particularly in the realm of movement disorders. It is no surprise that DBS is now being studied in the treatment of refractory psychiatric disease. Deep brain stimulation has inherent advantages over previous lesioning procedures. It is fully reversible, and stimulation can be adjusted according to a patient's changing symptoms and disease progression. Coupled with the fact that the stimulation can generally be turned on or off without the patient's awareness, DBS provides a unique opportunity for double-blinding studies. To undertake DBS for psychiatric conditions, appropriate surgical targets must be chosen. What is most strongly supported is the role of cortico-striato-thalamocortical (CSTC) loops in the pathophysiology of psychiatric symptoms. Recent functional imaging studies have consistently found evidence that corroborate this model of psychiatric symptom pathogenesis. Based on the psychiatric and cognitive effects seen in recent movement disorder surgery, it is apparent that modulation of neural systems subserving psychiatric phenomenon can be accomplished by DBS. The few published studies on DBS for obsessive-compulsive disorder (OCD) suggest that this can be done safely. While efficacy data are still uncertain, initial data are promising.

Psychiatric neurosurgery: a historical perspective.

Psychosurgery. Psychiatric neurosurgery. Neurosurgery for psychiatric disorders. Whatever the name, each of these refers to the surgical treatment of mental disease. Indeed, as many have pointed out, the most common term, "psychosurgery," is itself a misnomer, because the target of these procedures is not the "mind" or "psyche" but the neural substrates of higher cognitive function.

Use of cortical stimulation in neuropathic pain, tinnitus, depression, and movement disorders.

Medical treatment must strike a balance between benefit and risk. As the field of neuromodulation develops, decreased invasiveness, in combination with maintenance of efficacy, has become a goal. We provide a review of the history of cortical stimulation from its origins to the current state. The first part discusses neuropathic pain and the nonpharmacological treatment options used. The second part covers transitions to tinnitus, believed by many to be another deafferentation disorder, its classification, and treatment. The third part focuses on major depression. The fourth section concludes with the discussion of the use of cortical stimulation in movement disorders. Each part discusses the development of the field, describes the current care protocols, and suggests future avenues for research needed to advance neuromodulation.

Epidural cortical stimulation of the left dorsolateral prefrontal cortex for refractory major depressive disorder.

BACKGROUND: A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated. OBJECTIVE: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study. METHODS: Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest. RESULTS: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥ 40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study. CONCLUSION: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.

Neuromagnetic source imaging of abnormal spontaneous activity in tinnitus patient modulated by electrical cortical stimulation.

Electrical cortical stimulation (CS) of the auditory cortices has been shown to reduce the severity of debilitating tinnitus in some patients. In this study, we performed MEG source imaging of spontaneous brain activity during concurrent CS of the left secondary auditory cortex of a volunteer suffering from right unilateral tinnitus. CS produced MEG artifacts which were successfully sorted and removed using a combination of sensor and source level signal separation and classification techniques. This contribution provides the first proof of concept reporting on analysis of MEG data with concurrent CS. Effects of CS on ongoing brain activity were revealed at the MEG sensor and source levels and indicate CS significantly reduced ongoing brain activity in the lower frequency range (<40Hz), and emphasized its higher (>40Hz), gamma range components. Further, our results show that CS increased the spectral correlation across multiple frequency bands in the low and high gamma ranges, and between the alpha and beta bands of the MEG. Finally, MEG sources localized in the auditory cortices and nearby regions exhibited abnormal spectral activity that was suppressed by CS. These results provide promising evidence in favor of the Thalamocortical Dysrhytmia (TCD) hypothesis of tinnitus, and suggest that CS may prove to be an effective treatment of tinnitus when targeted to brain regions exhibiting abnormal spontaneous activity.