ReviewThe nucleus accumbens: a target for deep brain stimulation in obsessive–compulsive- and anxiety-disorders
Introduction
Obsessive–compulsive disorder (OCD) is a chronic and disabling condition, which severely impairs personal, social and professional life. Patients with OCD suffer from recurrent obsessive thoughts and uncontrollable compulsive reactions, like repetitive behavioural or mental acts occurring in response to an obsession. OCD occurs frequently in combination with other anxiety- and depressive-disorders. It is notorious for both, chronicity and difficulty of treatment. In severe cases of treatment-refractory, OCD and anxiety-disorders neurosurgical procedures (cingulotomy, limbic leucotomy, subcaudate tractotomy and anterior capsulotomy) may be indicated (Jenike, 1998, Rauch et al., 2001). The best results have been obtained with bilateral anterior capsulotomy (Meyerson, 1998, Lippitz et al., 1999).
Electrical deep brain stimulation (DBS) at high-frequencies has a blocking effect on the stimulated area and mimics the effect of tissue lesioning (Benabid et al., 1991, Blond et al., 1992). DBS is reversible and has a much lower rate of side effects than lesioning with thermocoagulation (Schuurman et al., 2000). Thus, Nuttin and Cosyns (1999) used bilateral DBS of the anterior limb of the internal capsule, instead of lesioning, for treatment of severe OCD. Significant improvement of symptoms was achieved in four patients. However, unusually high stimulation amplitudes had to be used, which resulted in high energy consumption requiring frequent exchange of portable energy source.
Based on clinical observations as well as anatomical and pathophysiological considerations, we used the right nucleus accumbens as primary target for DBS in four patients with the diagnosis of severe, pharmaceutically resistant anxiety-disorders and OCD.
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Anatomy and pathophysiology
During the past three decades, basal forebrain areas, especially the ventral striatum, the nucleus accumbens and the rostral parts of the “extended amygdala” (Heimer et al., 1997, de Olmos and Heimer, 1999) have attracted growing interest of anatomists, pharmacologists and clinicians. The dopamine theory of schizophrenia has been focused on the nucleus accumbens and its role in psychiatric diseases (Stevens, 1973, Matthysse, 1973). The nucleus is located immediately underneath the anterior limb
Implications for psychiatric surgery
In the 1960s, Leksell and Talairach introduced anterior capsulotomy as treatment for severe OCD and anxiety-disorders. Fibre tracts, connecting the mediodorsal thalamus reciprocally with the prefrontal cortex were interrupted by thermo-coagulation or focussed stereotactic irradiation bilaterally in the anterior limb of the internal capsule (Meyerson, 1998, Lippitz et al., 1999). Significant reduction of OCD related behaviour, fear and anxiety has been achieved in the majority of the patients,
Target-selection and clinical findings
Considering the central position of the nucleus accumbens between the amygdaloid complex, basal ganglia, mediodorsal thalamic nucleus and prefrontal cortex which are all involved in the pathophysiology of anxiety-disorders (Shumyatsky et al., 2002) and OCD (Saxena and Rauch, 2000) the beneficial clinical effects of anterior capsulotomy might well be caused by blocking of amygdaloid-basal ganglia-prefrontal circuitry at the level of the shell region of the nucleus accumbens rather than by
Discussion
The significant improvement of symptoms due to severe anxiety- and OC-disorders obtained with unilateral high-frequency stimulation of the shell of the right accumbens indicates a major role for this nucleus as central relay between amygdaloid complex, basal ganglia, mediodorsal thalamus and the prefrontal cortex. The amygdaloid complex, especially the lateral nucleus, is well-known to be involved in anxiety and fear reactions (Le Doux, 2000; Shumyatsky et al., 2002). Disinhibition of the
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