Four Deep Brain Stimulation Targets for Obsessive-Compulsive Disorder: Are They Different?

Abstract

Deep brain stimulation (DBS) is a promising therapeutic approach for patients with treatmentresistant obsessive compulsive disorder (OCD), a condition linked to abnormalities in corticobasal ganglia networks. Effective targets are placed in one of four subcortical areas with the goal of capturing prefrontal, anterior cingulate, and basal ganglia connections linked to the limbic system. These include the anterior limb of the internal capsule, the ventral striatum, the subthalamic nucleus, and a midbrain target. The goal of this review is to examine these four targets with respect to the similarities and differences of their connections. Following a review of the connections for each target based on anatomic studies in nonhuman primates (NHPs), we examine the accuracy of diffusion magnetic resonance imaging (dMRI) tractography to replicate those connections in the NHP, before evaluating the connections in the human brain based on dMRI tractography. Results demonstrate that the four targets generally involve similar connections, all of which are part of the internal capsule. Nonetheless, some connections are unique to each site. Delineating the similarities and differences across targets is a critical step for evaluating and comparing the effectiveness of each and how circuits contribute to the therapeutic outcome. It also underscores the importance that the terminology used for each target accurately reflects its position and its anatomic connections, so as to enable comparisons across clinical studies and for basic scientists to probe mechanisms underlying DBS.

Connectomic Deep Brain Stimulation for Obsessive-Compulsive Disorder

“…In the following years, different nuclei adjacent to the ALIC, including the ventral striatum (VS) containing the nucleus accumbens (NAc) as well as the bed nucleus of the stria terminalis (BNST), have been proposed as key regions for successful DBS (18,19). Through empiric evidence from DBS in movement disorders, other brain targets such as the subthalamic nucleus (STN), the inferior thalamic peduncle and the superolateral branch of the medial forebrain bundle (MFB; later referred to as ventral tegmental area projection pathway (20) or midbrain target (21)) have been successfully targeted in OCD (3,22,23). Remarkably, modulation of these distinct subcortical targets (Figure 1) all show the potential to improve obsessions and compulsions, pointing towards a common network responsible for clinical efficacy.…”

“…The authors observed a significant positive correlation between clinical improvements and the proximity ratio in favor of the MFB compared to the ATR. We note the nomenclature and conceptualization of this fiber tract identified as MFB, has since evolved (21) and that the original authors now refer to this structure as ventral tegmental area projection pathway (vtaPP) (20) while others referred to it as a midbrain projection (21) (see below for a detailed discussion).…”

“…Namely, the study by J o u r n a l P r e -p r o o f Liebrand et al suggested that the MFB, connecting the PFC with the ventral tegmental area, would be associated with a beneficial response (26) whereas other studies highlighted streamlines within the ALIC as being critical for OCD-DBS (28,32,42). Conventionally, the MFB is a transhypothalamic structure that does not traverse the ALIC (20,21) -and seen in this light, the studies would imply a conflicting finding. Reviewing the respective literature more in depth, however, suggests that this apparent discrepancy is in fact a matter of nomenclature.…”

A taxonomy of the brain’s white matter: Twenty-one major tracts for the twenty-first century

“…There is substantial confusion in the dMRI literature regarding the position of the medial forebrain bundle (Haber et al, 2020). This bundle does not ascend into the internal capsule; instead, it remains ventrally positioned until reaching its targets in the frontal lobe.…”

“…However, because of the previously mentioned issues with tracking brainstem fibers, there is a widespread misunderstanding of the types of connections DBS in different locations can affect. DBS of the internal capsule is not capturing the medial forebrain bundle, and therefore not capturing dopaminergic axons (Coenen et al, 2009;Haber et al, 2020).…”