The Neural Mechanisms Underlying Alcohol Relapse

Alcohol addiction,a major public health problem,is a chronic and relapsing mental disorder.It is one of the world’s leading health risks and up to 4% of all deaths worldwide are related to alcohol use.Alcohol dependency consists of a cluster of physiological,behavioral and cognitive phenomena,and can be characterized by a strong desire to consume alcohol,the loss of control in consumption,physiological withdrawal states,tolerance,persistent alcohol use,despite the clear negative consequences and progressive neglect of alternative interests.Biological,genetic and environmental factors play a crucial role in the development and the persistence of alcohol addiction.Misuse of alcohol contributes significantly to the risk of developing a medical illness,gastrointestinal and cardiovascular diseases,cancer,diabetes mellitus,physical injuries,foetal alcohol syndrome,and pre-term birth complications.Because heavy alcohol intake weakens the immune system and may effectuate risky sexual behaviour in some persons,alcohol-abusing persons are at increased risk to get an infectious disease.Furthermore alcohol addiction is associated with different neuropsychiatric disorders.In the past two decades,research has increasingly supported the view that addiction is a disease of the brain.Although the brain disease model of addiction has yielded effective preventive measures,treatment interventions,and public health policies to address substance-use disorders,the underlying concept of substance abuse as a brain disease continues to be questioned,perhaps because the aberrant,impulsive,and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology.Alcohol addiction is characterized by a high relapse risk,even when patients arecompletely detoxified.Relapse is defined as a dynamic process that ultimately results in a return of previous behavior patterns.Different outcome measures are available to assess relapse: i.e.time to the first drink,time to the first heavy drinking day,and frequency of drinking days.Reducing the relapse rates is the key to the success of the treatment.Alcohol affects the physical and mental function by changing the level of neurotransmitters in the related brain regions.The alcohol-induced release of dopamine triggers neuroplasticity(systematic changes in the synaptic signaling,or communication,between neurons in various reward regions of the brain).Recently,magnetic resonance imaging technology has been widely applied to the research of alcohol addiction,and many damages of alcohol to the brain structure and function has been found.The aim of this study is to explore the neural mechanism of alcohol relapse.Four weeks after the HF-rTMS stimulation,we ask patients whether they had already consumed any amount of alcohol by phone.First,we compare the differences in brain structure between relapse and abstainer;then,we compare the differences in the brain activation between relapse and abstainer during the acute craving state by cue-induced;finally,we compare the differences in resting state functional connectivity between relapse and abstainer.Alcohol relapse has a structural basis of brain.In this study,a voxel-based morphological analysis method was applied to compare the gray matter volume difference in brain structures between relapse and abstainer.The results showed that,compared with the abstainer,the volume of gray matter in the right frontal lobe,right dorsal anterior cingulate gyrus,cerebellum,right hippocampus,left amygdala,bilateral precuneus,right insular and bilateral temporal area was significantly reduced in the relapse.The results suggest that the relapsers’ brain structures injury is more serious than the abstainers in the executive control system and memory system.These brain regions may be the key brain areas of alcohol relapse,which can provide theoretical support and guidance for predicting and intervening the alcohol relapse.Then,we compare the differences in the brain activation between relapse and abstainer during the acute craving state by cue-induced.Before and after stimulation,during fMRI patients were confronted with a block cue-exposure paradigm with alcohol-related cues.Relapse was defined as the consumption of any amount of alcoholwithin four weeks after the stimulation.A region of interest(ROI)analysis was performed to evaluate how HF-rTMS exerts its effect on the relapse neurocircuit.The results showed that,after four weeks,thirteen out of nineteen patients already consumed alcohol.When abstainers were compared to patients who had relapsed,we found higher dorsal anterior cingulate cortex(dACC)activation at baseline.Finally,according to the results in research one and literature,we selected region of interest to compare the differences in resting-state functional connectivity between relapse and abstainer.Resting-state functional connectivity network can reveal the differences of relapse and abstainer’s brain activation in the baseline levels.Summary of the connectivity in network-related brain regions,compared to abstainer,the relapse show reduced connectivity in DMN and SN;the relapse show reduced DMN connectivity in posterior cingulate and frontal connections,temporal lobe,parietal lobe;enhanced DMN connectivity in hippocampus and precuneus;the relapse show reduced SN connectivity in the anterior cingulate and insula;the relapse also show enhanced connectivity in the cerebellum and precuneus,superior frontal gyrus,superior temporal gyrus,the insular.To sum up,this study combines voxel-based morphological analysis,task fMRI analysis and resting-state functional connectivity analysis to explore the neural mechanisms underlying alcohol relapse.Our findings provide new evidence for the viewpoint that alcohol addiction is a brain disease,and provide guidance for prevention and treatment of alcoholism.In addition,HF-rTMS can save more time than rTMS,but there is little research on its therapeutic effect.This study explored the therapeutic effect of HF-rTMS on alcohol addicted individuals,so as to develop alcoholic products.