Tractographic Analysis of Historical Lesion Surgery for Depression

Abstract

Various surgical brain ablation procedures for the treatment of refractory depression were developed in the twentieth century. Most notably, key target sites were (i) the anterior cingulum, (ii) the anterior limb of the internal capsule, and (iii) the subcaudate white matter, which were regarded as effective targets. Long-term symptom remissions were better following lesions of the anterior internal capsule and subcaudate white matter than of the cingulum. It is possible that the observed clinical improvements of these various surgical procedures may reflect shared influences on presently unspecified brain affect-regulating networks. Such possibilities can now be analyzed using modern brain connectivity procedures such as diffusion tensor imaging (DTI) tractography. We determined whether the shared connectivities of the above lesion sites in healthy volunteers might explain the therapeutic effects of the various surgical approaches. Accordingly, modestly sized historical lesions, especially of the anatomical overlap areas, were 'implanted' in brain-MRI scans of 53 healthy subjects. These were entered as seed regions for probabilistic DTI connectivity reconstructions. We analyzed for the shared connectivities of bilateral anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and stereotactic limbic leucotomy (a combination of the last two lesion sites). Shared connectivities between the four surgical approaches mapped onto the most mediobasal aspects of bilateral frontal lobe fibers, including the forceps minor and the anterior thalamic radiations that contacted subgenual cingulate regions. Anatomically, convergence of these shared connectivities may derive from the superolateral branch of the medial forebrain bundle (MFB), a structure that connects these frontal areas to the origin of the mesolimbic dopaminergic 'reward' system in the midbrain ventral tegmental area. Thus, all four surgical anti-depressant approaches may be promoting positive affect by converging influences onto the MFB.

Multi-tensor investigation of orbitofrontal cortex tracts affected in subcaudate tractotomy

“…In addition, our correlation with anatomical primate data further strengthens the elucidated fiber connections. Importantly, our approach, which uses clinical data rather than simulation (Schoene-Bake et al 2010), shows the clinical relevance of the anatomical organization of these fiber tracts involved in OCD.…”

Target-specific deep brain stimulation of the ventral capsule/ventral striatum for the treatment of neuropsychiatric disease

“…DBS stimulation of the NAc therefore has the potential to affect reward-seeking behavior, emotional behavior, and motivational behavior, which could have a major effect on disorders such as depression and drug addiction. Some research suggests that combining cingulotomy with accumbens stimulation does not yield better results than cingulotomy alone (31), as both targets ultimately influence the same common pathway where all four classical psychosurgical approaches (i.e., bilateral anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and limbic leucotomy) converge in their effects (32). However, this idea is based on observations in a small number of patients, and dismisses the possibility of a theoretically effective target that should be defined by its relative prominence, its functional, effective, and structural connectivity, and its role within a circuit driving the target behavior or symptoms.…”

Identification of the stria medullaris thalami using diffusion tensor imaging

“…Several targets have been implicated in treatment resistant depression (TRD) including subgenual cingulate cortex (SCC), nucleus accumbens (NAcc), ventral capsule/ventral striatum (VA/VS), lateral habenula (LHb), inferior thalamic peduncle (ITP), and the medial forebrain bundle (MFB) (Bewernick and Schlaepfer, 2013, Malone et al, 2009, Holtzheimer et al, 2012, Lozano et al, 2008, Sartorius and Henn, 2007, Coenen et al, 2011). More recently, the use of diffusion tensor imaging (DTI) based fiber tracking has heightened interest in anatomical targeting of white matter tracts that have been implicated in disease states like TRD (Schoene-Bake et al, 2010, Anthofer et al, 2015). Stimulation of the supero-lateral branch of the medial forebrain bundle (slMFB), a white matter tract that interconnects various centers of the reward pathway including the NAcc, ventral tegmental area (VTA), hypothalamus, and amygdala has shown promising results in the treatment of TRD and has spurred interest in the identification and stimulation of other white matter tracts involved in the pathophysiology of TRD (Coenen et al, 2009, Coenen et al, 2011, Coenen et al, 2012).…”