Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder

J Neurosurg 139:1376–1385, 2023

Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD.

METHODS Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAcALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG.

RESULTS The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude.

CONCLUSIONS These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD.

Nucleus accumbens: a systematic review of neural circuitry and clinical studies in healthy and pathological states

J Neurosurg 138:337–346, 2023

The nucleus accumbens (NAcc) of the ventral striatum is critically involved in goal- and reward-based behavior. Structural and functional abnormalities of the NAcc or its associated neural systems are involved in neurological and psychiatric disorders. Studies of neural circuitry have shed light on the subtleties of the structural and functional derangements of the NAcc across various diseases. In this systematic review, the authors sought to identify human studies involving the NAcc and provide a synthesis of the literature on the known circuity of the NAcc in healthy and diseased states, as well as the clinical outcomes following neuromodulation.

METHODS A systematic review was conducted using the PubMed, Embase, and Scopus databases. Neuroimaging studies that reported on neural circuitry related to the human NAcc with sample sizes greater than 5 patients were included. Demographic data, aim, design and duration, participants, and clinical and neurocircuitry details and outcomes of the studies were extracted.

RESULTS Of 3591 resultant articles, 123 were included. The NAcc and its corticolimbic connections to other brain regions, such as the prefrontal cortex, are largely involved in reward and pain processes, with distinct functional circuitry between the shell and core in healthy patients. There is heterogeneity between clinical studies with regard to the NAcc indirect targeting coordinates, methods for postoperative confirmation, and blinded trial design. Neuromodulation studies provided promising clinical results in the context of addiction and substance misuse, obsessive-compulsive disorder, and mood disorders. The most common complications were impaired memory or concentration, and a notable serious complication was hypomania.

CONCLUSIONS The functional diversity of the NAcc highlights the importance of studying the NAcc in healthy and pathological states. The results of this review suggest that NAcc neuromodulation has been attempted in the management of diverse psychiatric indications. There is promising, emerging evidence that the NAcc may be an effective target for specific reward- or pain-based pathologies with a reasonable risk profile.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Deep Brain Stimulations for Obsessive-Compulsive Disorder: Update of the 2014 Guidelines

 Neurosurgery 88:710–712, 2021

In 2020, the Guidelines Task Force conducted another systematic review of the relevant literature on deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) to update the original 2014 guidelines to ensure timeliness and accuracy for clinical practice.

OBJECTIVE: To conduct a systematic review of the literature and update the evidencebased guidelines on DBS for OCD.

METHODS: The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies as used to search PubMed and Embase for relevant literature. The updated search included studies published between 1966 and December 2019. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed and relevant full-text articles were retrieved and graded. Of 864 articles, 10 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update.

RESULTS: Seven studies were included in the original guideline, reporting the use of bilateral DBS as more effective in improving OCD symptoms than sham treatment. An additional 10 studies were included in this update: 1 class II and 9 class III.

CONCLUSION: Based on the data published in the literature, the following recommendations can be made: (1) It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD (level I). (2) Cliniciansmay use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patientswithmedically refractory OCD (level II). There is insufficient evidence to make a recommendation for the identification of themost effective target. The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelinesdetail/ deep-brain-stimulation-obsessive-compulsive-disord.

Improved Function After Deep Brain Stimulation for Chronic, Severe Traumatic Brain Injury

Improved Function After Deep Brain Stimulation for Chronic, Severe Traumatic Brain Injury

Neurosurgery 79:204–211, 2016

Severe traumatic brain injury (TBI) damages the frontal lobes and connecting networks, which impairs executive functions, including the ability to selfregulate. Despite significant disabling effects, there are few treatment options in the chronic phase after injury.

OBJECTIVE: To investigate the safety and potential effectiveness of deep brain stimulation (DBS) for individuals with chronic, disabling TBI and problems of behavioral and emotional self-regulation.

METHODS: This study was an open-label, prospective design with serial assessments of behavioral outcomes and positron emission tomography 2 years after DBS implantation. Four participants 6 to 21 years after severe TBIs from automobile crashes were included. Although alert and volitional, all experienced significant executive impairments, including either impulsivity or reduced initiation. DBS implants were placed bilaterally in the nucleus accumbens and anterior limb of the internal capsule to modulate the prefrontal cortex.

RESULTS: The procedure was safe, and all participants had improved functional outcomes. Two years after implantation, 3 met a priori criteria for improvement on the Mayo-Portland Adaptability Inventory-4. Improvement was due largely to better emotional adjustment, although 1 participant showed marked increases in multiple domains. Significant improvement in a composite score of functional capacity indicated improved independence in self-care and activities of daily living. The pattern of change in cognition corresponded with changes in activation of the prefrontal cortex observed in serial scanning.

CONCLUSION: This first study of DBS to this target for severe TBI supports its safety and suggests potential effectiveness to improve function years after injury. The primary impact was on behavioral and emotional adjustment, which in turn improved functional independence.

Deep Brain Stimulation in Gilles de la Tourette Syndrome

Deep Brain Stimulation in Gilles de la Tourette Syndrome

Neurosurgery 78:91–100, 2016

Gilles de la Tourette syndrome (GTS) is a severe neuropsychiatric disorder with childhood onset, characterized by disabling motor and vocal tics lasting for more than 1 year and associated with a wide range of psychiatric comorbidities. Pharmacological treatment is indicated for moderate to severe GTS patients. However, when GTS is refractory to conventional medical and behavioral treatments, deep brain stimulation (DBS) can be considered as a last resort therapeutic avenue.

OBJECTIVE: To evaluate the efficacy of DBS and its comorbidities in the largest pool of GTS patients to date.

METHODS: Our cohort study was based on 48 patients’ refractory to conventional treatment who underwent DBS for GTS at Galeazzi Institute, Milan, Italy. An exhaustive preoperative and a follow-up battery of tests was performed including the Yale Global Tic Severity Rating Scale, the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Subjective Social Impairment on a 10-point Visual Analogue Scale tests.

RESULTS: Eleven patients in whom the device was removed for inflammatory complications or for poor compliance were excluded from final analysis. Twenty-seven of the remaining 37 patients had a Yale Global Tic Severity Rating Scale score at the last follow-up that was less than 35. Of the 37 patients, in 29 cases (78%) a reduction of more than 50% of the Yale Global Tic Severity Rating Scale score was observed.

CONCLUSION: The clinical efficacy of DBS in GTS is promising. Although DBS is associated with risks, as is any surgical intervention, DBS should be considered as a last resort therapeutic option in carefully selected GTS patients.

Three dimensional anatomy of the human nucleus accumbens

Three dimensional anatomy of the human nucleus accumbens

Acta Neurochir (2013) 155:2389–2398

The Nucleus accumbens (Acc) is the main structure of the ventral striatum. It acts as a motor-limbic interface, being involved in emotional and psychomotor functions, frequently disturbed in neuropsychiatric disorders such as obsessive compulsive disorder and addiction. Most of the studies concerning the Acc were made in animals and those performed in humans are contradictory. Nevertheless, it has become a target for stereotactic deep brain stimulation for some of those diseases, when refractory to medical treatment. Previous studies performed by our group have established the localization, limits and dimensions of the human Acc and its stereotactic coordinates. Now it is our purpose to perform the Acc anatomical three-dimensional (3D) reconstruction in order to clarify its shape and topography and to render this nucleus a safer target for stereotactic procedures.

Methods Anatomical coronal slicing of ten Acc from human brains was performed, perpendicular to the anterior commissure-posterior commissure line and to the midline; then the Acc contours were traced and its dimensions and 3D stereotactic coordinates measured, on each slice. Finally a 3D computerized model was created.

Results The human Acc was identified as a distinct brain structure, with clear-cut limits on its posterior half. It lies parallel to the midline, descends caudally, and progresses from a globose to a flattened and dorsolateral concave shape. Its main expression is subcomissural.

Conclusion This study defined more accurately the 3D anatomy of the human Acc, providing new tools for stereotactic procedures.

Expanding applications of deep brain stimulation: a potential therapeutic role in obesity and addiction management

Acta Neurochir (2011) 153:2293–2306. DOI 10.1007/s00701-011-1166-3

The indications for deep brain stimulation (DBS) are expanding, and the feasibility and efficacy of this surgical procedure in various neurologic and neuropsychiatric disorders continue to be tested.

This review attempts to provide background and rationale for applying this therapeutic option to obesity and addiction. We review neural targets currently under clinical investigation for DBS—the hypothalamus and nucleus accumbens—in conditions such as cluster headache and obsessive-compulsive disorder. These brain regions have also been strongly implicated in obesity and addiction. These disorders are frequently refractory, with very high rates of weight regain or relapse, respectively, despite the best available treatments.

Methods We performed a structured literature review of the animal studies of DBS, which revealed attenuation of food intake, increased metabolism, or decreased drug seeking. We also review the available radiologic evidence in humans, implicating the hypothalamus and nucleus in obesity and addiction.

Results The available evidence of the promise of DBS in these conditions combined with significant medical need, support pursuing pilot studies and clinical trials of DBS in order to decrease the risk of dietary and drug relapse.

Conclusions Well-designed pilot studies and clinical trials enrolling carefully selected patients with obesity or addiction should be initiated.