Human Medial Forebrain Bundle (MFB) and Anterior Thalamic Radiation (ATR): Imaging of Two Major Subcortical Pathways and the Dynamic Balance of Opposite Affects in Understanding Depression

Abstract

The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.

The Structural Connectome of the Human Central Homeostatic Network

“…The two branches of the MFB were the inferomedial medial forebrain bundle (imMFB) and superolateral medial forebrain bundle (slMFB), consistent with nomenclature recently proposed (Coenen et al, 2012). The main site of imMFB connectivity was the orbitofrontal cortex, a region that was not a prespecified target in this study, but that was readily identified as a site that connected with all of the brainstem nuclei analyzed (Fig.…”

“…3), as previously described in human adults (Coenen et al, 2012). From there, slMFB streamlines connected with the prefrontal lobe.…”

“…We observed that brainstem pathways in the tegmentum of the medulla and pons sampled in this study converge into newly described caudal and rostral divisions of an MHB in the midbrain, and in turn, into the MFB on either side of the third ventricle. Recently, the MFB was visualized for the first time in the human brain with diffusion tractography (Coenen et al, 2009(Coenen et al, , 2012 and was shown to traverse the anterior limb of the internal capsule on its way to the prefrontal cortex. We confirmed the capsular trajectory of the slMFB and its prefrontal connections, but we also visualized connections with the insula and superior temporal gyrus, two forebrain targets that are known to contribute to homeostatic regulation.…”

“…Therefore, the size of the target ROI remains a potential confound in these SP measurements. To ensure that the target ROI size was not the only factor contributing to the SP, we verified that the SP measurements were derived from anatomically plausible pathways for which information was available from animal models (Azmitia and Gannon, 1986;Vertes, 1984a,b) or other diffusion tractography studies of subcortical pathways in the human brain (Coenen et al, 2012;Edlow et al, 2012).…”

Neuroradiology, Anesthesia, Bioengineering, and Hardware Programming in the Clinical Applications of Deep Brain Stimulation

“…This has often been attributed to the diffusion of current into the inferior and medial STN, although recent work with DTI has suggested that the medial forebrain bundle (MFB) may be responsible, and as such, it may serve as a potential target for DBS in the treatment of refractory major depression [102]. The MFB is an important structure of reward-seeking circuitry.…”