**1. Introduction**

The term "psychosurgery" was coined by Egas Moniz in 1935 to indicate the set of surgical procedures performed on the brain to treat diseases and psychiatric symptoms. The goal is to change the behavioral—obviously pathological—aspects, placing not only clinically but also

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ethically complex problems. The entry into the neurosurgical practice of neuromodulation methods has opened up a new scenario due to their flexibility and reversibility in their possible application to the treatment of addiction, such as substance abuse, gambling and internet gaming. The term "addiction" generally indicates a model of persistent redundant behaviors despite adverse medical or psychological results. The common element is recurrent problematic behavior accompanied by a preoccupation with the behavior [1, 2]. It is attested that the development of addiction is not simply the effect of the acute impact of the substance or behavior [3–5] but instead represents a state of imbalance in the reward system [6]. Alterations in prefrontal, limbic and cortical areas seem to be involved in addiction and maladaptive behavior not only in animal models but also in human neuroimaging studies [7–9]. The areas most involved in the manifestations of addiction are represented by the dopaminergic connections between ventral tegmental area (VTA) and nucleus accumbens (NAcc), which modulates learning, memory and repetitive behaviors. Stimulation of NACC in animals has proven to control acquired behaviors as a result of alcohol and cocaine consumption [10–12].

therapeutics in a manner similar in some ways to addiction, a phenomenon known as dopamine dysregulation syndrome (DDS) [18]. Witjas et al. in 2005 described a reduction of the behavioral disorders as well as addiction to dopaminergic treatment in two PD patients who underwent subthalamic nucleus (STN)-DBS [19]. Subsequently, other studies confirmed the resolution of dopamine dysregulation syndrome following STN-DBS for PD [20–22]. In rat models it was demonstrated that lesions of the STN decrease motivation to take cocaine suggesting that STN-DBS might be a therapeutic option for addiction [23]. In 2007, during a DBS procedure of the nucleus accumbens (NAcc) in a heavy drinker patient with agoraphobia and panic attacks, a rapid reduction of the alcohol intake of the patient was observed [24]. Similarly, three additional patients receiving accumbens DBS for other indications were reported to have

Deep Brain Stimulation in Treatment-Refractory Addiction

http://dx.doi.org/10.5772/intechopen.73694

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The mechanism of action of DBS remains unclear. As to the anatomical organization of the nucleus accumbens, it is divided into two major subregions, the core and shell, which differ from each other both functionally and anatomically. The core receives projections from the anterior cingulate and dorsal prelimbic, while the shell receives projections from the infralimbic and ventral prelimbic cortices [26, 27]. DBS of the accumbens shell or core increased c-Fos immunoreactivity, a measure of neuronal activation in these nuclei. c-Fos study indicates that DBS of the accumbens shell activates the infralimbic cortex, which could have contributed to the DBSinduced activation of the shell [12]. DBS applied to either the accumbens core or shell reduced alcohol consumption [11]. In contrast, DBS of the medial accumbens shell, but not the accumbens core, attenuated cocaine priming-induced reinstatement of drug seeking [12]. Moreover, since enhancing neuronal activity in the nucleus accumbens actually promotes the reinstatement of cocaine seeking [28, 29], DBS-induced inactivation of the nucleus accumbens via depolarization inactivation and/or activation of inhibitory neurons may be responsible for the attenuation of cocaine reinstatement [30–32]. Electrophysiological studies showed that accumbens DBS attenuated the spontaneous activity of cortico-accumbal glutamatergic neurons but also stimulated cortical interneurons, apparently via recurrent inhibition [33]. However, GABA agonist-induced inactivation of the infralimbic cortex attenuated the reinstatement of cocaine seeking induced by a priming injection of cocaine [12], which is consistent with accumbens DBS indirectly activating GABAergic interneurons. These results suggested that DBS of the accumbens shell produced complex effects throughout the circuit in which the shell is embedded. It is generally agreed that cocaine self-administration results in aberrant activity in the cortico-accumbal system and it appears that normalization of this system is one of the main effects of accumbens DBS [34, 35].

The proposed target areas for DBS in treatment-refractory addiction are several but welldocumented rationale for the choice of the target is required in order to investigate the effec-

spontaneously quit smoking [25].

**4. Mechanism of action**

**5. Targets**

tiveness, safety and feasibility.
