Diverging prefrontal cortex fiber connection routes to the subthalamic nucleus and the mesencephalic ventral tegmentum investigated with long range (normative) and short range (ex-vivo high resolution) 7T DTI

Abstract

Uncertainties concerning anatomy and function of cortico-subcortical projections have arisen during the recent years. A clear distinction between cortico-subthalamic (hyperdirect) and cortico-tegmental projections (superolateral medial forebrain bundle, slMFB) so far is elusive. Deep Brain Stimulation (DBS) of the slMFB (for major depression, MD and obsessive compulsive disorders, OCD) has on the one hand been interpreted as actually involving limbic (prefrontal) hyperdirect pathways. On the other hand slMFB’s stimulation region in the mesencephalic ventral tegmentum is said to impact on other structures too, going beyond the antidepressant (or anti OCD) efficacy of sole modulation of the cortico-tegmental reward-associated pathways. We have here used a normative diffusion MRT template (HCP, n = 80) for long-range tractography and augmented this dataset with ex-vivo high resolution data (n = 1) in a stochastic brain space. We compared this data with histological information and used the high resolution ex-vivo data set to scrutinize the mesencephalic tegmentum for small fiber pathways present. Our work resolves an existing ambiguity between slMFB and prefrontal hyperdirect pathways which—for the first time—are described as co-existent. DBS of the slMFB does not appear to modulate prefrontal hyperdirect cortico-subthalamic but rather cortico-tegmental projections. Smaller fiber structures in the target region—as far as they can be discerned—appear not to be involved in slMFB DBS. Our work enfeebles previous anatomical criticism and strengthens the position of the slMFB DBS target for its use in MD and OCD.

White Matter Tracts Associated With Deep Brain Stimulation Targets in Major Depressive Disorder: A Systematic Review

“…There is an ongoing debate about which WMT actually contributes to anti-depressive mechanism. The VTA dopaminergic axons do not travel within internal capsule, while superolateral MFB (slMFB), a branch undercuts the thalamus, moving laterally toward the internal capsule in its ventral portion, and then goes profoundly into Nacc and PFC, may contribute to the antidepressant effect ( 42 – 44 ).…”

A Neuroanatomy of Positive Affect Display – Subcortical Fiber Pathways Relevant for Initiation and Modulation of Smiling and Laughing

“…The MFB (human) is a complex system connecting brainstem and cerebellum with subcortical and cortical structures and funneled through a common pipeline, the VTA. The MFB is – more functionally than anatomically – related to the mfb [rodent ( Nieuwenhuys et al, 1982 ; Veening et al, 1982 ; Geeraedts et al, 1990a , b )] and its trans-hypothalamic route ( Coenen et al, 2009 , 2011 , 2021 ). The MFB – especially its superolateral branch, the slMFB – is confluent with major parts of the reward (SEEKING) system ( Coenen et al, 2011 , 2012 , 2018b , 2020b ).…”

“The Heart Asks Pleasure First”—Conceptualizing Psychiatric Diseases as MAINTENANCE Network Dysfunctions through Insights from slMFB DBS in Depression and Obsessive–Compulsive Disorder

“…Test stimulation, autonomic responses: At the optimal stimulation point, anesthesiologists typically perceive an increase in the heart rate and the blood pressure. This is a transient phenomenon which wears off under 2-3 min of constant stimulation [10,25] in all patients who are not under beta-receptor blocking medication.…”

“…Panksepp's SEEKING system (capitalization refers to an anatomical system responding to intracranial electrical stimulation) entails the idea that it is not only the consummatory phase of reward but the animal's euphoric drive which makes the organism explore (seek) for a reward, which in turn characterizes this system [7][8][9]. In our current understanding, the biological substrate of SEEKING is the medial forebrain bundle (MFB) and this network can be accessed in its midbrain terminal field-located just medial and outside the STN (the greater MFB system), a region called the lateral ventral tegmental area (VTA), subserved by feedback fibers from the prefrontal cortex (PFC) as the slMFB (superolateral medial forebrain bundle) [10]. DBS of this region (slMFB close to the VTA) was consequently introduced as a therapy under investigation for TRD [2].…”