Volumetric Reductions of Subcortical Structures and Their Localizations in Alcohol-Dependent Patients

Abstract

Changes in brain morphometry have been extensively reported in various studies examining the effects of chronic alcohol use in alcohol-dependent patients. Such studies were able to confirm the association between chronic alcohol use and volumetric reductions in subcortical structures using FSL (FMRIB software library). However, each study that utilized FSL had different sets of subcortical structures that showed significant volumetric reduction. First, we aimed to investigate the reproducibility of using FSL to assess volumetric differences of subcortical structures between alcohol-dependent patients and control subjects. Second, we aimed to use Vertex analysis, a less utilized program, to visually inspect 3D meshes of subcortical structures and observe significant shape abnormalities that occurred in each subcortical structure. Vertex analysis results from the hippocampus and thalamus were overlaid on top of their respective subregional atlases to further pinpoint the subregional locations where shape abnormalities occurred. We analyzed the volumes of 14 subcortical structures (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens) in 21 alcohol-dependent subjects and 21 healthy controls using images acquired with 3T MRI. The images were run through various programs found in FSL, such as SIENAX, FIRST, and Vertex analysis. We found that in alcohol-dependent patients, the bilateral thalamus (left: p < 0.01, right: p = 0.01), bilateral putamen (left: p = 0.02, right: p < 0.01), right globus pallidus (p < 0.01), bilateral hippocampus (left: p = 0.05, right: p = 0.03) and bilateral nucleus accumbens (left: p = 0.05, right: p = 0.03) were significantly reduced compared to the corresponding subcortical structures of healthy controls. With vertex analysis, we observed surface reductions of the following hippocampal subfields: Presubiculum, hippocampal tail, hippocampal molecular layer, hippocampal fissure, fimbria, and CA3. We reproduced the assessment made in previous studies that reductions in subcortical volume were negatively associated with alcohol dependence by using the FMRIB Software Library. In addition, we identified the subfields of the thalamus and hippocampus that showed volumetric reduction.

Abnormal functional connectivity and effective connectivity between the default mode network and attention networks in patients with alcohol-use disorder

“…A comprehensive neurobiological understanding of alcohol reactivity is critical for identifying the neuropathology of AUD and developing appropriate treatments to reduce relapse (3–6). AUD is marked by widespread gray and white matter damage in selected neural circuits (3–8). Morphometric magnetic resonance imaging (MRI) studies have reported reduced volume in cortical and subcortical cerebral structures in patients with AUD.…”

Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use

“…Smoking has been associated with smaller nucleus accumbens 6,7 , amygdala 7–9 , hippocampus 10 , pallidum 9 and thalamus 7,9,11 volumes, to smaller 8 and larger 12 caudate volume, and to larger putamen volume 6 . Alcohol (ab)use has been associated with smaller nucleus accumbens 13,14 , amygdala 15 , hippocampus 13,14,16 , pallidum 14,17 and with smaller 18 and larger 19 caudate, smaller 13,14,16 and larger 20 thalamus and smaller 14 and larger 20 putamen volumes. Recently, the ENIGMA addiction working group attempted to resolve these inconsistent findings with a mega-analysis of subcortical thickness and surface area (volume being its product), among 1,628 controls and 2,277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis 21 .…”

Gene expression profiling in the hippocampus of adolescent rats after chronic alcohol administration

“…The adult high-risk drinking rate is 14.2% in South Korea, and the onset of alcohol drinking is 13.3 years. 1 In addition, 16.9% of adolescents drink alcohol more than once within 30 days and half of them are high-risk alcohol drinkers. 1 Early onset of drinking in adolescents is relevant to alcohol-related problems in adulthood.…”

“…11,12 Previous studies have reported that chronic alcohol consumption causes negative changes in CA3 synapses in the hippocampus and a decrease in hippocampal volume in both human beings and animal models. [13][14][15][16] Binge alcohol use in adolescence also causes mitochondrial impairment in the hippocampus, and its damage continues into adulthood. 17 Recently, the effects of alcohol on the hippocampus at the cellular and molecular levels have been studied through large-scale transcriptome profiling.…”

“…Its impairment due to alcohol abuse leads to cognitive decline and memory loss . Previous studies have reported that chronic alcohol consumption causes negative changes in CA3 synapses in the hippocampus and a decrease in hippocampal volume in both human beings and animal models . Binge alcohol use in adolescence also causes mitochondrial impairment in the hippocampus, and its damage continues into adulthood …”