Deep brain stimulation of the nucleus accumbens

DBS seems to be a promising technique in resistant major depressive disorder MDD treatment 1).

Sturm et al. choose the shell region of the right nucleus accumbens as a target for deep brain stimulation (DBS) in a pilot series of four patients with severe obsessive-compulsive disorder and anxiety disorders. A significant reduction in the severity of symptoms has been achieved in three of four patients treated. Clinical results as well as a 15-O-H(2)O-PET study, performed in one patient during stimulation, speak in favor of the following hypothesis. As a central relay structure between the amygdala, basal ganglia, mesolimbic dopaminergic areas, mediodorsal thalamus, and prefrontal cortex, the accumbens nucleus seems to play a modulatory role in information flow from the amygdaloid complex to the latter areas. If disturbed, imbalanced information flow from the amygdaloid complex could yield obsessive-compulsive- and anxiety disorders, which can be counteracted by blocking the information flow within the shell region of the accumbens nucleus by deep brain stimulation 2).

Options for eating disorders are limited and new approaches are desired. An interesting approach is the application of deep brain stimulation (DBS). The nucleus accumbens (NAcc) is part of the food reward system. A pilot study reported that DBS of the NAcc shell modulates food intake and body weight in rats. Underlying mechanisms such as the food intake microstructure are unknown so far. Normal-weight female Sprague-Dawley rats were equipped with a custom-made DBS electrode placed unilaterally in the NAcc shell. Biphasic stimulation was performed for seven days. Body weight and food intake including the microstructure were assessed over the experimental period. Behavior was monitored manually. DBS tended to increase body weight gain (28.1 ± 5.4 g) compared to sham-stimulated controls (16.7 ± 3.4, P = 0.05) without affecting daily food intake (P > 0.05). Further analyses showed that light phase food intake was stimulated, whereas dark-phase food intake was decreased in the DBS group (P < 0.05). During the light phase bout frequency (+50%), bout duration (+64%), meal duration (+71%) and overall time spent in meals (+92%) were increased in DBS rats (P < 0.05), while during the dark phase no alterations were observed (P > 0.05). Behavior did not show differences regarding overall eating and drinking behavior (including food/water approach), grooming or locomotion (P > 0.05). Summarized, although overall food intake was not changed by DBS, light phase food intake was stimulated likely via a reduction of satiation 3).

The use of DBS in treatment-resistant anorexia nervosa should be evaluated in carefully designed, early-phase feasibility trials 4).

Results of a study revealed that ablation of the NAc can increase the anorexia nervosa (AN) patients' physiological drive to eat. Furthermore, there were no severe and/or life-influencing complications associated with the treatment 5).

A 42 years old Autistic lady suffering from OCD and aggression was offered Deep brain stimulation of the nucleus accumbens (NAc DBS) for her comorbidities of OCD and aggression. NAc was targeted using standard stereotactic methods and the postoperative scans confirmed the position of the active electrode to be within the NAc. The patient had significant relief of her symptoms. At a one-year follow-up the Yale-Brown obsessive-compulsive scale (YBOCS) score for OCD, excluding items 1-5 of YBOCS, improved from 19 to 5. Her Hamilton depression and anxiety scores similarly improved from 20 to 15 and from 30 to 18. Social communication questionnaire - current autism score improved from 26 to 16, the subscores for reciprocal social interaction improved from 13 to 8, for communication from 5 to 4, and for the restricted, repetitive and stereotyped patterns of behavior 6 to 3.

This case reports illustrates the role of NAc in OCD and aggression in an autistic patient 6).

Nauczyciel C, Robic S, Dondaine T, Verin M, Robert G, Drapier D, Naudet F, Millet B. The nucleus accumbens: a target for deep brain stimulation in resistant major depressive disorder. J Mol Psychiatry. 2013 Oct 23;1:17. doi: 10.1186/2049-9256-1-17. eCollection 2013. Review. PubMed PMID: 26019865; PubMed Central PMCID: PMC4445576.
Sturm V, Lenartz D, Koulousakis A, Treuer H, Herholz K, Klein JC, Klosterkötter J. The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders. J Chem Neuroanat. 2003 Dec;26(4):293-9. Review. PubMed PMID: 14729131.
Prinz P, Kobelt P, Scharner S, Goebel-Stengel M, Harnack D, Faust K, Winter Y, Rose M, Stengel A. Deep brain stimulation alters light phase food intake microstructure in rats. J Physiol Pharmacol. 2017 Jun;68(3):345-354. PubMed PMID: 28820391.
Lipsman N, Woodside B, Lozano AM. Evaluating the potential of deep brain stimulation for treatment-resistant anorexia nervosa. Handb Clin Neurol. 2013;116:271-6. doi: 10.1016/B978-0-444-53497-2.00022-X. Review. PubMed PMID: 24112901.
Wang J, Chang C, Geng N, Wang X, Gao G. Treatment of intractable anorexia nervosa with inactivation of the nucleus accumbens using stereotactic surgery. Stereotact Funct Neurosurg. 2013;91(6):364-72. doi: 10.1159/000348278. Epub 2013 Oct 9. PubMed PMID: 24108066.
Doshi PK, Hegde A, Desai A. Nucleus Accumbens (NAc) DBS for obsessive compulsive disorder and aggression in an autistic patient: a case report and hypothesis of the role of NAc in autism and co-morbid symptoms. World Neurosurg. 2019 Feb 21. pii: S1878-8750(19)30431-0. doi: 10.1016/j.wneu.2019.02.021. [Epub ahead of print] PubMed PMID: 30797934.
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