Cigarette smoking history is associated with poorer recovery in multiple neurocognitive domains following treatment for an alcohol use disorder.

Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n = 132) and reassessed after 8 months of sobriety (AP2; n = 54). Never-smoking controls (CON; n = 33) completed a baseline and follow-up (n = 19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD

Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome.

We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions

Magnetic Resonance Spectroscopy of the Brain in Alcohol Abuse.

Magnetic resonance (MR) technology produces data on brain structure and activity without relying on radiation or invasive surgery. Magnetic resonance imaging (MRI) creates images, and magnetic resonance spectroscopy (MRS) produces spectra based on the ability of atomic nuclei in tissues to absorb and release pulses of energy. MRS studies of alcohol in the brain reveal that only a portion of the alcohol in the brain can be detected by MR technology, suggesting that alcohol there exists in multiple pools. The pools not visible using MRS is hypothesized to be bound to cell membranes. Indirect evidence from MR studies of chronic alcohol abusers suggests that tolerance to alcohol's effects results in an increased rigidity of cell membranes that forces more alcohol to remain in the MR-visible pool (i.e., the pool not bound to membranes) compared with alcohol in the brains of nontolerant people

Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions

BACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. METHODS: Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. RESULTS: Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. CONCLUSIONS: Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions

The gray matter structural connectome and its relationship to alcohol relapse: Reconnecting for recovery.

Gray matter (GM) atrophy associated with alcohol use disorders (AUD) affects predominantly the frontal lobes. Less is known how frontal lobe GM loss affects GM loss in other regions and how it influences drinking behavior or relapse after treatment. The profile similarity index (PSI) combined with graph analysis allows to assess how GM loss in one region affects GM loss in regions connected to it, ie, GM connectivity. The PSI was used to describe the pattern of GM connectivity in 21 light drinkers (LDs) and in 54 individuals with AUD (ALC) early in abstinence. Effects of abstinence and relapse were determined in a subgroup of 36 participants after 3 months. Compared with LD, GM losses within the extended brain reward system (eBRS) at 1-month abstinence were similar between abstainers (ABST) and relapsers (REL), but REL had also GM losses outside the eBRS. Lower GM connectivities in ventro-striatal/hypothalamic and dorsolateral prefrontal regions and thalami were present in both ABST and REL. Between-networks connectivity loss of the eBRS in ABST was confined to prefrontal regions. About 3 months later, the GM volume and connectivity losses had resolved in ABST, and insula connectivity was increased compared with LD. GM losses and GM connectivity losses in REL were unchanged. Overall, prolonged abstinence was associated with a normalization of within-eBRS connectivity and a reconnection of eBRS structures with other networks. The re-formation of structural connectivities within and across networks appears critical for cognitive-behavioral functioning related to the capacity to maintain abstinence after outpatient treatment

Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol.

Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+) and 25 matched alcohol-dependent individuals who had not received GBP (GBP-). Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP- and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP- and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM) than GBP-, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA

Cigarette smoking is associated with cortical thinning in anterior frontal regions, insula and regions showing atrophy in early Alzheimer’s Disease

Background Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure primarily focused on cortical volumes. Much less is known about the effects of smoking on cortical thickness. Smokers and Non-smokers were compared on regional cortical thickness. We predicted smokers would demonstrate greater age-related thinning localized to anterior frontal regions that serve as nodes for the executive, salience, and emotional regulation networks (ESER regions) and those demonstrating significant atrophy in early Alzheimer’s Disease (AD regions). Methods Non-smokers (n = 41) and smokers (n = 41), 22–70 years of age, completed a 4 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. In smokers, associations between smoking severity, decision-making, impulsivity, and regional cortical thickness were examined. Results Smokers demonstrated cortical thinning in the medial and lateral OFC, insula, entorhinal, fusiform, middle temporal, and Composite AD regions. In Smokers, greater pack-years were associated with thinner lateral OFC, middle temporal, inferior parietal, fusiform, precuneus, and Composite AD regions. In Smokers, poorer decision-making/greater risk taking was related to thinner cortices in caudal ACC, rostral middle frontal and superior frontal gyri, and Composite ESER. Higher self-reported impulsivity was associated with thinner rostral and caudal ACC. Conclusions This study provides additional evidence that cigarette smoking is associated with thinner cortices in regions implicated in the development and maintenance of substance use disorders and in regions demonstrating significant atrophy in early AD. The novel structure-function relationships in Smokers further our understanding of the neurobiological substrates potentially underlying the neuropsychological abnormalities documented in smokers

Association of Superoxide Dismutase 2 (SOD2) Genotype with Gray Matter Volume Shrinkage in Chronic Alcohol Users: Replication and Further Evaluation of an Addiction Gene Panel.

BackgroundReduction in brain volume, especially gray matter volume, has been shown to be one of the many deleterious effects of prolonged alcohol consumption. High variance in the degree of gray matter tissue shrinkage among alcohol-dependent individuals and a previous neuroimaging genetics report suggest the involvement of environmental and/or genetic factors, such as superoxide dismutase 2 (SOD2). Identification of such underlying factors will help in the clinical management of alcohol dependence.MethodsWe analyzed quantitative magnetic resonance imaging and genotype data from 103 alcohol users, including both light drinkers and treatment-seeking alcohol-dependent individuals. Genotyping was performed using a custom gene array that included genes selected from 8 pathways relevant to chronic alcohol-related brain volume loss.ResultsWe replicated a significant association of a functional SOD2 single nucleotide polymorphism with normalized gray matter volume, which had been reported previously in an independent smaller sample of alcohol-dependent individuals. The SOD2-related genetic protection was observed only at the cohort's lower drinking range. Additional associations between normalized gray matter volume and other candidate genes such as alcohol dehydrogenase gene cluster (ADH), GCLC, NOS3, and SYT1 were observed across the entire sample but did not survive corrections for multiple comparisons.ConclusionConverging independent evidence for a SOD2 gene association with gray matter volume shrinkage in chronic alcohol users suggests that SOD2 genetic variants predict differential brain volume loss mediated by free radicals. This study also provides the first catalog of genetic variations relevant to gray matter loss in chronic alcohol users. The identified gene-brain structure relationships are functionally pertinent and merit replication

Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation.

ObjectiveProton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.MethodsSingle-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.ResultsCompared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.ConclusionThe anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment

DTI studies in patients with Alzheimer's disease, mild cognitive impairment, or normal cognition with evaluation of the intrinsic background gradients

IntroductionThe objective of the study was to explore the impact of the background gradients on diffusion tensor (DT) magnetic resonance imaging (DT-MRI) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), or cognitively normal (CN) aging.MethodsTwo DT-MRI sets with positive and negative polarities of the diffusion-sensitizing gradients were obtained in 15 AD patients, 18 MCI patients, and 16 CN control subjects. The maps of mean diffusivity (MD) and fractional anisotropy (FA) were computed separately for positive (p: pMD and pFA) and negative (n: nMD and nFA) polarities, and we computed the geometric mean (gm) of the DT-MRI to obtain the gmFA and gmMD with reducing the background gradient effects. Regional variations were assessed across the groups using one-way analysis of variance.ResultsIncreased regional gmMD values in the AD subjects, as compared to the regional gmMD values in the MCI and CN subjects, were found primarily in the frontal, limbic, and temporal lobe regions. We also found increased nMD and pMD values in the AD subjects compared to those values in the MCI and CN subjects, including in the temporal lobe and the left limbic parahippocampal gyrus white matter. Results of comparisons among the three methods showed that the left limbic parahippocampal gyrus and right temporal gyrus were the increased MD in the AD patients for all three methods.ConclusionBackground gradients affect the DT-MRI measurements in AD patients. Geometric average diffusion measures can be useful to minimize the intrinsic local magnetic susceptibility variations in brain tissue