MDD is among the most common psychiatric conditions, with a lifetime prevalence of up to 16 % in the general adult population (Kessler et al. 2003). The condition is highly heterogeneous, and encompasses much more than just depressed mood. Patients often endorse varying degrees of amotivation, apathy, and anhedonia, as well as lack of energy, and sleep and appetite disturbances. The involvement of multiple ‘systems’ including mood, cognitive, perceptual and vegetative functions suggests broad circuit dysfunction involving several, primarily limbic, networks. It is not possible, therefore, to ascribe MDD to dysfunction of a specific structure, but instead MDD should be viewed as a network disorder, much like Parkinson’s disease. Similarly, it is not possible to link MDD to dysfunction in one neurotransmitter system, such as serotonin. Indeed, neurobiological models suggest that dopaminergic and noradrenergic dysfunction contribute in important ways to MDD, as evidenced, in part, by the successful use of anti-depressants that target these systems (Lam et al. 2009). An improved understanding of MDD aetiology, and the development of novel therapies, would therefore need to account for its heterogeneous clinical and neurobiological picture.

Much of the progress in elucidating MDD circuitry has been driven by advances in neuroimaging, and particularly functional imaging which permits a real-time view of the active brain. These studies have identified critical ‘nodes’ in primarily limbic circuits that are dysfunctional in the pathologically depressed state. For example, metabolic imaging with fluorodeoxyglucose (FDG)-PET has shown that the subcallosal cingulate (SCC) region is hyperactive in unmedicated depressed patients as well as in healthy subjects experiencing sadness (Kennedy et al. 2007; Mayberg 1997; Mayberg et al. 1999). This hyperactivity normalizes with remission of the depression following medical, psychotherapeutic or DBS treatment (Kennedy et al. 2001, 2007; Mayberg et al. 2005). Other regions implicated in depression include those involved in reward- and decision-making pathways, such as the nucleus accumbens and dorsolateral prefrontal cortex (DLPFC) (Price and Drevets 2010). Anhedonia, or the lack of pleasure in typically pleasurable activities, is a major component of depression, and has been linked to dysfunction in the nucleus accumbens (NAcc) in patients and pre-clinical models (Bewernick et al. 2010; Price and Drevets 2010). The DLPFC participates in decision-making and has reciprocal projections with both anterior cingulate and medial prefrontal cortical regions, which participate in affect- or reward-guided decisions, both dysfunctional in MDD. The DLPFC is also a TMS target in depression, where its modulation is linked to improvements in mood (Lipsman et al. 2013a). All of these structures, and the SCC in particular, project widely in the brain, along pathways subserving many of MDD’s cardinal symptoms. The SCC, for example, projects to amygdala and the insula, which participate in vegetative and homeostatic control, as well as to the medial prefrontal and anterior cingulate region, which participate in decision-making (Hamani et al. 2011). In this way, dysfunction in SCC can be linked to several key MDD symptoms. More broadly, such work can identify specific regions for DBS targeting, which can further be tailored according to the predominant clinical picture.

Several brain targets for the management of treatment-refractory MDD with DBS are currently under investigation. These include SCC, NAcc, ventral caudate/ventral striatum (VC/VS), inferior thalamic peduncle (ITP), lateral habenula (Hab), and medial forebrain bundle (MFB) (Table 13.1). Below we review the targets that have accumulated the most experience to date.

OCD is among the most common anxiety disorders, with a population prevalence of up to 2–3 % (Lipsman et al. 2007). The condition is marked by obtrusive, repetitive and anxiogenic thoughts (obsessions), as well as time-consuming, disproportionate, and anxiolytic behaviours (compulsions). Although obsessions and compulsions can occur in the same patient, some suffer only from obsessions or compulsions. For example, whereas some patients will have contamination obsessions and/or compulsions (i.e. ‘washers’) others will have compulsions to count (i.e. ‘checkers’). Heterogeneity in OCD is the rule, although it appears that activation of fear and anxiety circuitry is a common thread.

OCD exists at the interface between psychiatry and neurology given the prominence of physical behaviours that patients believe are ‘outside of their control’. Behaviours, or compulsions, that are meant to relieve anxiety become reinforcing, leading to a vicious cycle of thoughts and actions. Current treatment strategies include medications targeting primarily the serotonergic system, and psychotherapeutic treatments that attempt to break the cycle by altering pathological cognitions. As in depression, a substantial proportion of patients, often up to a third, remain significantly disabled, despite optimal guideline-concordant care. For these patients, novel treatment strategies, including neurosurgery, are being investigated.

Similar to mood disorders, advances in neuroimaging have led to a better understanding of OCD circuitry. Such studies have implicated decision-making and fear circuitry, as well as pure motor pathways in the basal ganglia (Greenberg et al. 2010b). For example, among the most consistently activated structures is OFC that is known to participate heavily in judgement, executive functioning, impulse control and emotion-guided decision-making (Kent et al. 2003). Both fMRI and PET studies have further shown significant amygdalar activation in response to provocative, disease-relevant stimuli, as well as a failure of cortical structures, and OFC in particular, to downregulate activity within the amygdale (Saxena et al. 1999, 2004; Swedo et al. 1992). The argument for overlap between anxiety and motor circuitry is strengthened by the large number of patients with Tourette’s syndrome who are diagnosed with comorbid OCD (Cummings and Frankel 1985). It is further not uncommon for patients with striatal and other basal-ganglia pathology to develop tic- and OCD-like behaviours (Cummings and Frankel 1985). Indeed, the complex regionalization of neuroanatomy, particularly within motor circuitry is now being recognized. The subthalamic nucleus, for example, a traditionally ‘motor’ structure is now known to have distinct associative and limbic components, with unique efferent and afferent projections. The existence of parallel, yet overlapping, circuits within the same 5-mm structure, highlights the intimate relationship between these pathways, and how dysfunction in one ‘critical node’ can have network wide influence, and lead to a broad constellation of symptoms.

OCD was the first psychiatric condition to be investigated with DBS, in a report published in 1999 that described the anterior limb of the internal capsule (ALIC) as the target (Nuttin et al. 1999). Since then, several structures have been investigated, including the subthalamic nucleus (STN), VC/VS and ITP. Below we review the targets that have accumulated the most experience to date (Table 13.2).