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

Abstract

More than a decade ago, deep brain stimulation (DBS) of the superolateral medial forebrain bundle (slMFB), as part of the greater MFB system, had been proposed as a putative yet experimental treatment strategy for therapy refractory depression (TRD) and later for obsessive–compulsive disorders (OCD). Antidepressant and anti-OCD efficacy have been shown in open case series and smaller trials and were independently replicated. The MFB is anato-physiologically confluent with the SEEKING system promoting euphoric drive, reward anticipation and reward; functions realized through the mesocorticolimbic dopaminergic system. Growing clinical experience concerning surgical and stimulation aspects from a larger number of patients shows an MFB functionality beyond SEEKING and now re-informs the scientific rationale concerning the MFB’s (patho-) physiology. In this white paper, we combine observations from more than 75 cases of slMFB DBS. We integrate these observations with a selected literature review to provide a new neuroethological view on the MFB. We here formulate a re-interpretation of the MFB as the main structure of an integrated SEEKING/MAINTENANCE circuitry, allowing for individual homeostasis and well-being through emotional arousal, basic and higher affect valence, bodily reactions, motor programing, vigor and flexible behavior, as the basis for the antidepressant and anti-OCD efficacy.

Obsessive-compulsive symptoms in two patients with strategic basal ganglia lesions

“…Tractographic analysis of Case 2 shows a pallidal lesion (*) involving the “motor-control network” (blue fibers). C: Interplay of three involved networks (“affect, control, and reward network”) within the whole “OCD framework” (existing of the “affect, control, reward, and default-mode network” [ 2 , 13 ]) at distinct network hubs (taken and altered from [ 13 ]). The locations of lesions in Cases 1 and 2 are shown as green/blue crosses.…”

“…The tractography in Patient 2 showed an involvement of the “motor-control network”. Therefore, the tractographic work-up of both patients showed lesions in two distinct parts of the “OCD framework” [ 2 , 13 ]. The unilateral lesion in the right caudate of Patient 1 might have disturbed the interconnection of the “reward and affect network,” with reduced dampening of the latter and consecutive exacerbation of OCS.…”

Deep brain stimulation of medial forebrain bundle modulates the noradrenergic activity and feedforward circuitry in rodent depression model

“…Early research also revealed the rewarding effects by self-stimulating the rodent mfb, which was subsequently applied in various learning tasks [3]. Open-label clinical trials have shown that deep brain stimulation (DBS) of the superolateral branch of the MFB rapidly and sustainably alleviate depressive symptoms in drugrefractory patients [4][5][6][7][8][9]. The safety and antidepressive effect by applied chronic continuous mfb DBS was subsequentially demonstrated in different rodents models [10][11][12].…”