A randomized, crossover trial of deep brain stimulation of the ventral anterior limb of the internal capsule in depression

Object Deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease is often very effective for treatment of debilitating motor symptoms. Nevertheless, the small size of the STN and its proximity to axonal projections results in multiple side effects during high-frequency stimulation. Contralateral eye deviation is produced in a small percentage of patients, but the precise mechanism of this side effect is at present poorly understood. Methods Contralateral eye deviation was produced by high-frequency stimulation of 22 contact sites in nine patients undergoing deep brain stimulation of the STN. The precise locations of these contacts were calculated and compiled in order to locate the stimulated structure responsible for eye deviation. Results The mean x, y, and z coordinates associated with contralateral eye deviation were found to be 11.57, 2.03, and 3.83 mm lateral, posterior, and inferior to the anterior commissure–posterior commissure midpoint, respectively. The point described by these coordinates is located within the lateral anterosuperior border of the STN. Conclusions Given that stimulation of frontal eye field cortical regions produces similar contralateral conjugate eye deviation, these results are best explained by electrical current spread to nearby frontal eye field axons coursing lateral to the STN within the internal capsule. Thus, placement of the implanted electrode in a more medial, posterior, and inferior position may bring resolution of these symptoms by reducing the amount of current spread to internal capsule axons.

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Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in Sapap3 Mutant Mice

Biological Psychiatry ◽

10.1016/j.biopsych.2018.05.011 ◽

2018 ◽

Vol 84 (12) ◽

pp. 917-925 ◽

Cited By ~ 14

Author(s):

Cindy M. Pinhal ◽

Bastijn J.G. van den Boom ◽

Fabiana Santana-Kragelund ◽

Lizz Fellinger ◽

Pol Bech ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Internal Capsule ◽

Mutant Mice ◽

Differential Effects ◽

Excessive Grooming ◽

Deep Brain ◽

Stimulation Of

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Deep brain stimulation modulates directional limbic connectivity in obsessive-compulsive disorder

Brain ◽

10.1093/brain/awaa100 ◽

2020 ◽

Vol 143 (5) ◽

pp. 1603-1612 ◽

Cited By ~ 4

Author(s):

Egill Axfjord Fridgeirsson ◽

Martijn Figee ◽

Judy Luigjes ◽

Pepijn van den Munckhof ◽

P Richard Schuurman ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Obsessive Compulsive Disorder ◽

Brain Stimulation ◽

Internal Capsule ◽

Connectivity Analysis ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

The Impact ◽

Deep Brain ◽

Stimulation Of

Abstract Deep brain stimulation is effective for patients with treatment-refractory obsessive-compulsive disorder. Deep brain stimulation of the ventral anterior limb of the internal capsule rapidly improves mood and anxiety with optimal stimulation parameters. To understand these rapid effects, we studied functional interactions within the affective amygdala circuit. We compared resting state functional MRI data during chronic stimulation versus 1 week of stimulation discontinuation in patients, and obtained two resting state scans from matched healthy volunteers to account for test-retest effects. Imaging data were analysed using functional connectivity analysis and dynamic causal modelling. Improvement in mood and anxiety following deep brain stimulation was associated with reduced amygdala-insula functional connectivity. Directional connectivity analysis revealed that deep brain stimulation increased the impact of the ventromedial prefrontal cortex on the amygdala, and decreased the impact of the amygdala on the insula. These results highlight the importance of the amygdala circuit in the pathophysiology of obsessive-compulsive disorder, and suggest a neural systems model through which negative mood and anxiety are modulated by stimulation of the ventral anterior limb of the internal capsule for obsessive-compulsive disorder and possibly other psychiatric disorders.

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Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression

JAMA Psychiatry ◽

10.1001/jamapsychiatry.2016.0152 ◽

2016 ◽

Vol 73 (5) ◽

pp. 456 ◽

Cited By ~ 106

Author(s):

Isidoor O. Bergfeld ◽

Mariska Mantione ◽

Mechteld L. C. Hoogendoorn ◽

Henricus G. Ruhé ◽

Peter Notten ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Internal Capsule ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Resistant Depression ◽

Deep Brain ◽

Stimulation Of

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Directed stimulation of the dentato-rubro-thalamic tract for deep brain stimulation in essential tremor: a blinded clinical trial

The Neuroradiology Journal ◽

10.1177/19714009211036689 ◽

2021 ◽

pp. 197140092110366

Author(s):

Erik H Middlebrooks ◽

Lela Okromelidze ◽

Rickey E Carter ◽

Ayushi Jain ◽

Chen Lin ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Brain Stimulation ◽

Crossover Trial ◽

Standard Of Care ◽

Rating Score ◽

Percentage Improvement ◽

Deep Brain ◽

Stimulation Of ◽

Care Programming

Objective Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. Methods A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn–Tolosa–Marín tremor rating score compared to the preoperative baseline. Results Among the six patients, tremor rating scores differed significantly among the three experimental conditions ( P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R2=0.24; P=0.04). No significant adverse events were encountered. Conclusions Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

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