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.
Highlights
Direct connections of the human cortex with subcortical structures are of special interest for the regulation of behaviour
As a direct connection between the prefrontal cortex and subcortical structures like the nucleus accumbens (NAC) and mesencephalic ventral tegmentum (MVT) it appeared to be a promising candidate for Deep Brain Stimulation (DBS) antidepressant efficacy
We further investigated the cortical origin of medial (MVT) and lateral (STN) projections both on a normative group level (HCP, n = 80) and in our post-mortem specimen (n = 1) in MNI space
Summary
Direct connections of the human cortex with subcortical structures are of special interest for the regulation of behaviour. The original lHDP description is not fully in line with the strict definition of a hyperdirect pathway especially since part of the limbic connections to the STN are vastly unclear; Haynes and Haber defined a limbic STN cone to explain the part of their traced fibers which terminated in the lateral hypothalamus, medial and outside the STN. In doing so, they appear to ignore any direct access of the PFC to the MVT (Wu et al 2013), e.g., a PFC to MVT feedback pathway (Oades and Halliday 1987). There is a fundamental disagreement concerning a potential functional and anatomical disentanglement of these lateral and medial pathways which finds its expression in conflicting concepts (lHDP vs. slMFB)
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