Stefan Gazdzinski

Deformation-based morphometry of brain changes in alcohol dependence and abstinence

Brain atrophy associated with chronic alcohol consumption is partially reversible after cessation of drinking. Recovering alcoholics (RA, 45+/-8 years) were studied with MRI within 1 week of entering treatment, with follow-up at 8 months. Light drinkers (LD) were studied with MRI twice 1 year apart. For each participant, deformation maps of baseline structure and longitudinal size changes between baseline and follow-up scans were created using nonlinear registration techniques. ANCOVA assessed group differences and regression methods examined relationships between deformation maps and measures of drinking severity or baseline atrophy. At baseline, RA showed significant atrophy in the frontal and temporal lobes. Longitudinally, abstainers recovered tissue volumes significantly faster than LD in parietal and frontal lobes. When comparing abstainers to relapsers, additional regions with significantly greater recovery in abstainers were temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Gray matter volume at baseline predicted volume recovery during abstinence better than white matter. Drinking severity was not significantly related to brain structural changes assessed with this method. Longitudinally, deformation-based morphometry confirmed tissue recovery in RAs who maintain long-term sobriety. Abstinence-associated tissue volume gains are significant in focal parts of the fronto-ponto-cerebellar circuit that is adversely affected by heavy drinking.

Body mass index and magnetic resonance markers of brain integrity in adults.

Obesity and being overweight during adulthood have been consistently linked to increased risk for development of dementia later in life, especially Alzheimers disease. They have also been associated with cognitive dysfunction and brain structural alterations in otherwise healthy adults. Although proton magnetic resonance spectroscopy may distinguish between neuronal and glial components of the brain and may point to neurobiological mechanisms underlying brain atrophy and cognitive changes, no spectroscopic studies have yet assessed the relationships between adiposity and brain metabolites.

Cigarette Smoking Exacerbates Chronic Alcohol-Induced Brain Damage: A Preliminary Metabolite Imaging Study

BACKGROUND Cigarette smoking is common among alcohol-dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol-induced brain injury and neurocognition. METHODS Twenty-four 1-week-abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light-drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short-echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status. RESULTS Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N-acetylaspartate (NAA) and frontal choline-containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four-group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1-week-abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory. CONCLUSIONS These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol-induced neuronal injury and cell membrane damage in the frontal lobes of RAs and has independent adverse effects on neuronal viability and cell membranes in the midbrain and on cell membranes of the cerebellar vermis. Higher smoking levels are associated with metabolite concentrations in select subcortical structures. Greater consideration of the potential effects of comorbid cigarette smoking on alcohol-induced brain damage and other diseases affecting the central nervous system is warranted.

Tract-Based Spatial Statistics (TBSS) of diffusion tensor imaging data in alcohol dependence: abnormalities of the motivational neurocircuitry.

Previous diffusion tensor imaging (DTI) studies indicated microstructural disruption of white matter in alcohol dependence. To investigate the microstructure of primary neurocircuitry involved in alcohol use disorders, the present study used Tract-Based Spatial Statistics (TBSS) of DTI measures as well as probabilistic tractography. Eleven recovering alcoholics in their first week of abstinence from alcohol were compared with 10 light-drinking controls; diffusion measures were correlated with measures of neurocognition and drinking severity. Regions characterized by low fractional anisotropy and high mean diffusivity included cortico-striatal fibers and those in frontal white matter and limbic pathways. Greater diffusion abnormalities in sections of commissural fibers (inter-hemispheric connections) were associated with greater drinking severity, and lower fractional anisotropy measures in frontal and limbic fiber tracts correlated with lower visuospatial memory performance. These study findings provide direct evidence of compromised integrity of the motivational brain circuitry in alcohol use disorders. These abnormalities in fiber connections could be partially responsible for deficiencies in executive functions, behavioral regulation, and impulse control commonly described in alcohol dependence.

BRAIN MORPHOLOGY AT ENTRY INTO TREATMENT FOR ALCOHOL DEPENDENCE IS RELATED TO RELAPSE PROPENSITY

BACKGROUND We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers. METHODS Individuals in alcohol dependence treatment (n = 75) underwent magnetic resonance imaging approximately 6 ± 4 days after their last alcoholic drink, and 40 age-matched nonsmoking light drinkers (LD) were studied as control subjects. At follow-up 7.8 ± 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and LD. RESULTS Compared with LD, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex and bilaterally in the thalamus and adjacent subcortical white matter (WM) and had larger volume in the left lateral orbitofrontal region. Compared with LD, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared with future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities. CONCLUSIONS At entry into alcohol dependence treatment, the brain structure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry might confer greater risk for resumption of hazardous drinking after treatment and might contribute to the definition of a neurobiological relapse risk profile in alcohol dependence.

BMI and Neuronal Integrity in Healthy, Cognitively Normal Elderly: A Proton Magnetic Resonance Spectroscopy Study

Recent studies associated excess body weight with brain structural alterations, poorer cognitive function, and lower prefrontal glucose metabolism. We found that higher BMI was related to lower concentrations of N‐acetyl‐aspartate (NAA, a marker of neuronal integrity) in a healthy middle‐aged cohort, especially in frontal lobe. Here, we evaluated whether NAA was also associated with BMI in a healthy elderly cohort. We used 4 Tesla proton magnetic resonance spectroscopy (1H MRS) data from 23 healthy, cognitively normal elderly participants (69.4 ± 6.9 years; 12 females) and measured concentrations of NAA, glutamate (Glu, involved in cellular metabolism), choline‐containing compounds (Cho, involved in membrane metabolism), and creatine (Cr, involved in high‐energy metabolism) in anterior (ACC) and posterior cingulate cortices (PCC). After adjustment for age, greater BMI was related to lower NAA/Cr and NAA/Cho ratios (β < −0.56, P < 0.008) and lower Glu/Cr and Glu/Cho ratios (β < −0.46, P < 0.02) in ACC. These associations were not significant in PCC (β > −0.36, P > 0.09). The existence of an association between NAA and BMI in ACC but not in PCC is consistent with our previous study in healthy middle‐aged individuals and with reports of lower frontal glucose metabolism in young healthy individuals with elevated BMI. Taken together, these results provide evidence that elevated BMI is associated with neuronal abnormalities mostly in frontal brain regions that subserve higher cognitive functions and impulse control. Future studies need to evaluate whether these metabolite abnormalities are involved in the development and maintenance of weight problems.

Cerebral white matter recovery in abstinent alcoholics—a multimodality magnetic resonance study

Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P<0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P=0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P=0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P=0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non-smoking alcohol-dependent individuals, the increase in fractional anisotropy of temporal white matter (P=0.003) was accompanied by a pattern of decreases mean diffusivity in all regions over 1 month of abstinence; no corresponding changes were observed in smoking alcohol-dependent individuals. In contrast, a pattern of white matter volume increase in frontal and temporal lobes was apparent in smoking alcohol-dependent individuals but not in non-smoking alcohol-dependent individuals. These results were not accompanied by significant changes in metabolite concentrations. Finally, there were no consistent patterns of association between measures obtained with different imaging modalities, either cross-sectionally or longitudinally. These data demonstrate significant white matter improvements with abstinence from alcohol, reflected either as microstructural recovery or volumetric increases that depend on the smoking status of the participants. We believe our results to be important, as they demonstrate that use of a single imaging modality provides an incomplete picture of neurobiological processes associated with alcohol-induced brain injury and recovery thereof that may even lead to improper interpretation of results.

Chronic cigarette smoking modulates injury and short-term recovery of the medial temporal lobe in alcoholics

Memory function is largely mediated by the medial temporal lobe (MTL), and its compromise has been observed in alcohol dependence and chronic cigarette smoking. The effects of heavy alcohol consumption and chronic smoking on hippocampal volumes and MTL metabolites and their recovery during abstinence from alcohol have not been assessed. Male alcoholics in treatment (ALC) [13 smokers (sALC) and 11 non-smokers (nsALC)] underwent quantitative magnetic resonance imaging and short-echo proton magnetic resonance spectroscopic imaging at 1 week and 1 month of sobriety. Outcome measures were compared with 14 age-matched, non-smoking light-drinkers and were related to visuospatial learning and memory. Over 1 month of abstinence, N-acetyl-aspartate, a neuronal marker, and membrane-associated choline-containing metabolites normalized in the MTL of nsALC subjects, but remained low in the MTL of sALC subjects. Metabolite concentration changes in both groups were associated with improvements in visuospatial memory. Hippocampal volumes increased in both groups during abstinence, but increasing volumes correlated with visuospatial memory improvements only in nsALC subjects. In summary, chronic cigarette smoking in alcohol-dependent men appears to have adverse effects on MTL metabolite recovery during short-term sobriety. These data may also have implications for other conditions with established MTL involvement and significant smoking co-morbidity, such as schizophrenia-spectrum and mood disorders.

Combined Neuroimaging, Neurocognitive and Psychiatric Factors to Predict Alcohol Consumption Following Treatment for Alcohol Dependence

AIMS Resumption of hazardous drinking after treatment is common in alcohol use disorders (AUD). This study examined the ability of multimodality magnetic resonance, neurocognitive, psychiatric and demographic, to predict alcohol consumption after treatment for AUD. METHODS Seventy treatment-seeking participants completed 1.5T magnetic resonance studies, yielding regional gray matter (GM) and white matter (WM) surrogate markers of neuronal integrity (N-acetylaspartate: NAA) and cell membrane turnover/synthesis (choline: Cho), assessment of major psychiatric disorders and comprehensive neurocognitive assessment after approximately 1 month of abstinence. Participants were followed up 6-12 months after treatment and classified as Abstainers (no alcohol consumption; n=26) and Resumers (any alcohol consumption; n=44). Abstainers and Resumers were contrasted on various outcome measures, and those that significantly differed between groups were entered as factors in a logistical regression model to predict drinking status at follow-up. RESULTS The following variables were independent predictors of resumption of drinking: temporal GM NAA, frontal WM NAA, frontal GM Cho, processing speed and comorbid unipolar mood disorder. With each standard deviation unit decrease in temporal GM NAA, frontal WM NAA, frontal GM Cho and processing speed, the odds of resumption of drinking were increased 3.1, 3.3, 6.4 and 14.2 times, respectively. Diagnosis of a unipolar mood disorder was associated with 14.5-fold increased odds of resumed drinking. CONCLUSIONS The findings suggest that Resumers, relative to Abstainers, demonstrated greater abnormalities in anterior frontal-subcortical circuits involved in mood and behavioral regulation, and development and maintenance of alcohol use disorders, The magnetic resonance-derived variables used in this study may provide additional information regarding the prediction and neurobiological correlates of resumption of hazardous drinking.

MRSI and DTI: a multimodal approach for improved detection of white matter abnormalities in alcohol and nicotine dependence

Our previous proton magnetic resonance spectroscopic imaging (1H MRSI) studies showed that the frontal lobe white matter (WM) in smoking recovering alcoholics (sRA) had lower concentrations of N‐acetylaspartate (NAA), a marker for neuron viability, compared to both nonsmoking recovering alcoholics (nsRA) and a control group of nonsmoking light drinkers (nsLD). Using diffusion tensor imaging (DTI) in a similar population, we found lower fractional anistropy (FA), a microstructural measure of WM fiber integrity, in regions of specific fiber bundles within frontal WM of recovering alcoholics compared to light drinkers. In this study, we hypothesized that in these regions of lower FA, NAA concentrations in the alcoholic groups are lower than in non‐alcoholic controls. We hypothesized further that sRA have lower regional NAA concentrations than nsRA. We retrospectively analyzed existing 1H MRSI data by quantitating metabolite concentrations from voxels that corresponded to previously identified WM regions of lower FA, and from a control region of normal FA in alcoholics. We found significant NAA concentration differences between groups in regions of abnormal FA. In particular, sRA had significantly lower NAA concentration than nsLD, but in no region was NAA significantly lower in nsRA than nsLD. Furthermore, no NAA group differences were detected in a frontal WM region of normal FA. These results indicate regionally localized NAA loss within the frontal WM, and specifically NAA loss in regions of low FA. Compared to our previous lobar analyses, DTI‐guided MRSI analysis allows the selective evaluation of small WM regions with microstructural injury, thereby increasing statistical power to detect relevant pathology and group differences. DTI‐guided MRSI analyses promise to contribute to a better understanding of brain injury in alcohol and nicotine dependence and, by extension, perhaps in other neurodegenerative diseases as well. Copyright