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.
Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and ...fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies.
We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB's FIRST. This approach involves training Active Appearance Models (AAMs) using hand-delineated examples. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I–V, VI–VII, and VIII–X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting.
The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test–retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM approach offers superior reliability and validity. Extensions of CATK to cerebellar hemisphere parcels are envisioned.
•We apply an active appearance modeling framework to cerebellar segmentation.•Validation using manual delineations indicates high reliability and validity.•Comparison with FreeSurfer and SUIT shows better performance than atlas-based methods.•Detected teratogenic effects in adolescents with history of prenatal alcohol exposure
Abstract Most prior studies of the effects of excessive alcohol intake on the adolescent brain examined alcohol-use-dependent samples with comorbid psychiatric and substance use disorders. In the ...Cape Town region, we identified a sizeable cohort of adolescents with alcohol use disorders (AUD) without externalizing or other psychiatric disorders. We examined brain morphology in 64 such adolescents compared to age- and gender-matched healthy controls. Magnetic resonance imaging data were analyzed using FSL's FIRST software for subcortical volumes, and cortical gray matter (GM) was analyzed using voxel-based morphometry (VBM) and regions of interest (ROI) analysis. AUD boys had smaller thalamic and putamen volumes compared to non-drinking boys, while AUD girls had larger thalamic and putamen volumes compared to non-drinking girls. VBM revealed a large region of decreased GM density in AUDs compared to controls located in the left lateral frontal, temporal, and parietal lobes, extending medially deep into the parietal lobe. Smaller GM volume in this region was also present when examined using ROI analysis. Our lack of findings in other brain regions, particularly the hippocampus, suggests that reports of smaller brain volumes in adolescent AUDs in the literature are a consequence of psychiatric and substance abuse comorbidities.
In two studies of long-term abstinent alcoholics (LTAAs), we found that about 17% had a current major depressive disorder (MDD). We tested the hypothesis that LTAAs with a current MDD diagnosis do ...not exhibit the reduced P3b event-related potential amplitude endophenotype for alcoholism. This is consistent with the majority of LTAAs with a current MDD having developed alcohol dependence via self-medication of their MDD rather than their alcohol dependence arising from the alcoholism endophenotype.
We revisited the P3b data from the two LTAAs studies, comparing LTAAs with a current MDD vs. LTAAs without a current MDD to each other and to non-substance abusing controls (NSACs). In northern California, 48 LTAAs and 48 non-substance abusing controls were studied, while in Honolulu, 105 LTAAs and 77 NSACs were studied. A total of 26 LTAAs had a current MDD (10 in California and 16 in Honolulu). The difference in P3b amplitude and latency (measured in targets-standards) in a 3-condition visual oddball paradigm was compared to MDD diagnoses gathered using the computerized Diagnostic Interview Schedule. Across both study sites, LTAAs without a current MDD (either with no lifetime MDD or a lifetime, but not current MDD) had lower P3b amplitudes than NSACs. In contrast, P3b amplitudes in LTAAs with a current MDD did not differ from controls. We conclude that alcohol dependence in LTAAs with a current MDD did not derive from the alcoholism endophenotype. This group may not exhibit the externalizing diathesis characterized by impulsive, disinhibited behavior and may have developed alcohol dependence via excessive drinking in an attempt to self-medicate their MDD. These results have major implications for targeted treatments of alcoholism and comorbid MDD.
•LTAA with current MDD do not have the externalizing diathesis driving their alcoholism unlike LTAA w/o a current MDD.•In this paper we examine P3b amplitude in those data and in LTAA and control samples from Northern California.•The P3b result is consistent with our earlier paper examining rs-fMRI functional connectivity.•P300 is not reduced in LTAA with a current MDD Dx, suggesting no genetic predisposition to externalizing disorders.•Different brain activity pattern and treatment needs are suggested in alcoholics with vs. without a current MDD.
Borderline personality disorder (BPD) is often a complicating comorbid factor in alcohol use disorders and substance use disorders. Previous work showed that abstinent alcoholics endorsed lifetime ...and current symptoms of most of the BPD criteria at much higher rates than controls, with much higher symptom counts for short-term abstinent alcoholic (STAA) women than men, which is consistent with such symptoms negatively affecting female alcoholics' ability to maintain abstinence. Because prior work has also shown that treatment-naïve alcoholics (TNA) are not the same as treated alcoholics observed earlier in their alcohol dependence, but rather are a different population with potentially lower psychiatric comorbidity, in this study we compared BPD symptom criteria between TNA samples of comparable age to the control and STAA samples, including both men and women and individuals dependent on alcohol only or with lifetime dependence on both alcohol and drugs. BPD symptoms were obtained using the SCID-II, and endorsed symptoms were classified as current or lifetime. Logistic regression analyses were used to test for effects of group, sex, presence of a lifetime drug dependence diagnosis, and their interactions for lifetime and current symptom endorsement for each BPD criteria. Groups were compared pairwise (TNA vs. NSAC, and STAA vs. TNA). The effect of a lifetime drug dependence diagnosis was not significant for any BPD symptom variable, consistent with the alcohol groups’ BPD symptoms being unaffected by the presence of a comorbid drug dependence. The primary result presented here is that TNA women have borderline symptomatology more similar to that of treated STAA than to NSAC, while TNA men have borderline symptomatology more similar to NSAC than to STAA. A visual examination of co-occurring BPD symptoms showed that while more BPD symptoms are likely to be present in TNA and STAA vs. NSAC, there is no grouping of criteria (i.e., symptom cluster) that is characteristic of TNA or STAA.
•Abstinent alcoholics (AA) endorse borderline personality disorder (BPD) symptoms.•Treatment-naïve alcoholics have potentially lower psychiatric comorbidity.•BPD symptom criteria are compared between treatment-naïve and AA men and women.•Treatment-naïve women have BPD symptoms more similar to treated AA than controls.•Treatment-naïve men have BPD symptoms more similar to controls than AA.
Background
Cerebellar atrophy (especially involving the superior–anterior cerebellar vermis) is among the most salient and clinically significant effects of chronic hazardous alcohol consumption on ...brain structure. Smaller cerebellar volumes are also associated with chronic cigarette smoking. The present study investigated effects of both chronic alcohol consumption and cigarette smoking on cerebellar structure and its relation to performance on select cognitive/behavioral tasks.
Methods
Using T1‐weighted Magnetic Resonance Images (MRIs), the Cerebellar Analysis Tool Kit segmented the cerebellum into bilateral hemispheres and 3 vermis parcels from 4 participant groups: smoking (s) and nonsmoking (ns) abstinent alcohol‐dependent treatment seekers (ALC) and controls (CON) (i.e., sALC, nsALC, sCON, and nsCON). Cognitive and behavioral data were also obtained.
Results
We found detrimental effects of chronic drinking on all cerebellar structural measures in ALC participants, with largest reductions seen in vermis areas. Furthermore, both smoking groups had smaller volumes of cerebellar hemispheres but not vermis areas compared to their nonsmoking counterparts. In exploratory analyses, smaller cerebellar volumes were related to lower measures of intelligence. In sCON, but not sALC, greater smoking severity was related to smaller cerebellar volume and smaller superior–anterior vermis area. In sALC, greater abstinence duration was associated with larger cerebellar and superior–anterior vermis areas, suggesting some recovery with abstinence.
Conclusions
Our results show that both smoking and alcohol status are associated with smaller cerebellar structural measurements, with vermal areas more vulnerable to chronic alcohol consumption and less affected by chronic smoking. These morphometric cerebellar deficits were also associated with lower intelligence and related to duration of abstinence in sALC only.
Recent work suggests that faulty co-activation or synchrony of multiple brain regions comprising “networks,” or an imbalance between opposing brain networks, is important in alcoholism. Previous ...studies showed higher fMRI resting state synchrony (RSS) within the executive control (inhibitory control and emotion regulation) networks and lower RSS within the appetitive drive network in long-term (multi-year) abstinent alcoholics (LTAA) vs. non substance abusing controls (NSAC). Our goal was to identify EEG networks that are correlated with the appetitive drive and executive function networks identified with fMRI in our previous alcohol studies. We used parallel ICA for multimodal data fusion for the 20 LTAA and 21 NSAC that had both usable fMRI and 64-channel EEG data. Our major result was that parallel ICA identified a pair of components that significantly separated NSAC from LTAA and were correlated with each other. Examination of the resting-state fMRI seed-correlation map component showed higher bilateral nucleus accumbens seed-correlation in the dorsolateral prefrontal cortex bilaterally and lower seed-correlation in the thalamus. This single component thus encompassed both the executive control and appetitive drive networks, consistent with our previous work. The correlated EEG coherence component showed mostly higher theta and alpha coherence in LTAA compared to NSAC, and lower gamma coherence in LTAA compared to NSAC. The EEG theta and alpha coherence results suggest enhanced top-down control in LTAA and the gamma coherence results suggest impaired appetitive drive in LTAA. Our results support the notion that fMRI RSS is reflected in spontaneous EEG, even when the EEG and fMRI are not obtained simultaneously.
•fMRI and EEG were obtained for 20 long-term abstinent alcoholics and 21 controls.•Parallel ICA was used to identify analogous networks in each modality.•One pair of components separated groups and were correlated across modalities.•fMRI component encompassed executive control and appetitive drive networks.•EEG coherence component involves top-down control and appetitive drive.
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.
Abstract Alcoholism is characterized by a lack of control over an impulsive and compulsive drive toward excessive alcohol consumption despite significant negative consequences; our previous work ...demonstrated that successful abstinence is characterized by decreased resting-state synchrony (RSS) as measured with functional magnetic resonance imaging (fMRI), within appetitive drive networks and increased RSS in emotion regulation and inhibitory executive control networks. Our hypothesis is that LTAA (Long-Term Abstinent Alcoholics) with a current major depressive disorder (MDD) drank primarily to deal with the negative affect associated with their MDD and not because of a heightened externalizing diathesis (including heightened appetitive drive), and consequently, in achieving and maintaining abstinence, such individuals would not exhibit the RSS adaptations characteristic of pure alcoholics. We studied 69 NSAC (Non Substance Abusing Controls) and 40 LTAA (8 with current MDD, 32 without a current MDD) using resting-state fMRI and seed based connectivity analyses. In the inhibitory executive control network (nucleus accumbens vs. left dorsolateral prefrontal cortex), LTAA with a current MDD showed increased synchrony compared to NSAC. In the emotion regulation executive control network (subgenual anterior cingulate cortex vs. right dorsolateral prefrontal cortex), LTAA with current MDD did not show increased RSS. In the appetitive drive networks (nucleus accumbens vs, aspects of the caudate nucleus and thalamus), LTAA with a current MDD did not show a reduction of RSS compared to NSAC, but LTAA without a current MDD did. These results suggest different pathways to their alcohol dependence in LTAA with vs. without a current MDD, and different patterns of brain activity in long-term abstinence, suggesting different treatment needs.
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