The role of the orbitofrontal cortex and the nucleus accumbens for craving in alcohol use disorder

Abstract

This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD.

Link between structural connectivity of the medial forebrain bundle, functional connectivity of the ventral tegmental area, and anhedonia in unipolar depression

“…Thus, it is possible that geometric tract measures (e.g., tract volume, number of tracts, and tract length) and mean diffusion properties have the potential to identify distinct and independent alterations of tract structural connectivity ( Denier et al, 2020 , Kubicki et al, 2019 ). Therefore, future studies should incorporate both measures in their analyses ( Bracht et al, 2021 ). Furthermore, additional research is warranted to advance our understanding of alterations in the structural connectivity of the slMFB that are specific for depression subtypes, or dependent on chronicity or psychopathology (e.g., melancholia) ( Bracht et al, 2015b ).…”

“…The following termination criteria were used: fractional anisotropy (FA) < 0.2 and angle threshold > 45°. ROIs were delineated as described in our previous work ( Bracht et al, 2021 , Bracht et al, 2019 , Denier et al, 2020 ). For both pathways (imMFB and slMFB), the VTA was encircled on a DWI horizontal section (see Supplementary Fig.…”

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

“…On one hand, it represents a structure which is not described by classical anatomy (“[…] mismatch between the surgical target (slMFB) and anatomical literature (mfb) […]” (Li et al 2020 ); “[…] not utilizing accepted anatomic structures or nomenclature […]” (Middlebrooks et al 2020 )) but on the other hand—and according to our judgement—emerges in several dMRI DBS aggregation studies as a resulting and causative structure for DBS efficacy (Smith et al 2020 ; Vlis et al 2020 ; Li et al 2020 ) (see also discussion on pertinent DBS studies below). This latter circumstance obviously has the potential to leave some authors open to doubt and in troubled waters; while some neuroscientists have understood and adopted the concept and nomenclature (Bracht et al 2014 , 2015 , 2019 , 2021 ; Zacharopoulos et al 2016 ; Denier et al 2020 ; MacNiven et al 2020 ; Fenoy et al 2021 ) others feel the urge to find different names for a structure which in their eyes by no means can be akin to the mfb. This is insofar remarkable, since an anatomical similarity of the slMFB with the classical mfb has never been claimed (Coenen et al 2012 ).…”

Reduced structural connectivity of the amygdala is associated with childhood trauma in adult patients with alcohol use disorder

“…Those alterations were amongst other influenced by age and severity of traumatic experiences 14 . However, grey matter alterations in adults with CT and in adults with AUD extend to further limbic and prefrontal brain regions such as the orbitofrontal cortex, the hippocampus, the nucleus accumbens, and the insula 18,20,21 . This suggests a pathology on a network level rather than an isolated pathology of the amygdala.…”

“…[23][24][25] Those pathways partially overlap with pathways that have been shown to be impaired in AUD. 21,23 Besides consistent findings of reduced amygdala volume in both patients with AUD and in adults with CT, structural connectivity of the amygdala has not been investigated specifically in AUD patients with CT. Even though AUD and CT often co-occur and represent a subtype that differs regarding onset, progression and treatment outcome of AUD, 4,11,13 to date no study has investigated whether AUD patients with CT differ from AUD patients without CT regarding structural connectivity, nor on the behavioural level regarding affect processing.…”