Reversibility of Impaired Large-Scale Functional Brain Networks in Cushing's Disease after Surgery Treatment: A Longitudinal Study.

INTRODUCTION: Chronic exposure to excessive endogenous cortisol leads to brain changes in Cushing's disease (CD). However, it remains unclear how CD affects large-scale functional networks (FNs) and whether these effects are reversible after treatment. This study aimed to investigate functional network changes of CD patients and their reversibility in a longitudinal cohort. METHODS: Active CD patients (N = 37) were treated by transsphenoidal pituitary surgery and reexamined 3 months later. FNs were computed from resting-state fMRI data of the CD patients and matched normal controls (NCs, N = 37). A pattern classifier was built on the FNs to distinguish active CD patients from controls and applied to FNs of the CD patients at the 3-month follow-up. Two subgroups of endocrine-remitted CD patients were identified according to their classification scores, referred to as image-based phenotypically (IBP) recovered and unrecovered CD patients, respectively. The informative FNs identified by the classification model were compared between NCs, active CD patients, and endocrine-remitted patients as well as between IBP recovered and unrecovered CD patients to explore their functional network reversibility. RESULTS: All 37 CD patients reached endocrine remission after treatment. The classification model identified three informative FNs, including cerebellar network (CerebN), fronto-parietal network (FPN), and default mode network. Among them, CerebN and FPN partially recovered toward normal at 3 months after treatment. Moreover, the informative FNs were correlated with 24-h urinary-free cortisol and emotion scales in CD patients. CONCLUSION: These findings suggest that CD patients have aberrant FNs that are partially reversible toward normal after treatment.

GABRA2 rs279858-linked variants are associated with disrupted structural connectome of reward circuits in heroin abusers.

The reward system plays a vital role in drug addiction. The purpose of this study is to investigate the structural connectivity characteristics and driving-control subnetwork patterns of reward circuits in heroin abusers and assess the genetic modulation on the reward network. We first defined the reward network based on systematic literature review, and built the reward network based on diffusion tensor imaging data of 78 heroin abusers (HAs) and 79 healthy controls (HCs) using structural connectomics. Then we assessed genetic factors that might modulate changes in the reward network by performing imaging-genetic screening for 22 addiction-related polymorphisms. The genetic association was validated by performing genetic associations (1032 HAs and 2863 HCs) and expanded-variant analysis. Finally, we estimated the association between these genetic variations, reward network, and clinical performance. We found that HAs had widespread deficiencies in the structural connectivity of the reward circuit (center in VTA-linked connections), which correlated with cognition deficiency. The disruptions synchronously were shown on the reward driving system and reward control system. GABRA2 rs279858-linked variants might be a key genetic modulator for heroin vulnerability by affecting the connections of reward network and cognition. The role of the reward network connections that mediates the effects of rs279858 on cognition would be disrupted by heroin addiction. These findings provide new insights into the neurocircuitry and genetic mechanisms of addiction.