Previous research investigated the cerebral volumetric correlates of impulsivity largely in moderate‐sized samples and few have examined the distinct correlates of dimensions of impulsivity, sex differences, or heritability of the correlates. Here, we performed voxel‐based morphometry analysis of data (n = 11,474; 5,452 girls, 9–10 years) curated from the Adolescent Brain Cognition Development project. In a linear regression with all five UPPS‐P subscores as regressors and age in months, total intracranial volume, study site, and scanner model as covariates, higher levels of lack of premeditation, and sensation seeking were correlated with larger cortical and subcortical gray matter volumes (GMVs). In contrast, higher positive urgency was correlated with smaller GMVs in many of the same regions. The dimensional impulsivity traits also involved distinct volumetric correlates, with, for instance, sensation seeking and positive urgency specifically implicating bilateral caudate head/mid‐cingulate cortex and bilateral lateral orbitofrontal cortex/left precentral gyrus, respectively. Boys relative to girls scored higher in all impulsivity dimensions. Girls relative to boys showed significantly stronger positive and negative correlations between sensation seeking and insula, putamen, and inferior frontal gyrus (IFG) GMVs and between positive urgency and cingulate cortex, insula, and IFG GMVs, respectively. With a subsample of twins, the dimensional impulsivity traits were weakly to moderately heritable in both girls and boys, and the GMV correlates were highly heritable in girls and boys combined. These findings collectively suggest shared and nonshared as well as sex differences in the cerebral volumetric bases of dimensional impulsivity traits and may facilitate research of externalizing psychopathology in children.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hbm.25810

Gray matter volumetric correlates of dimensional impulsivity traits in children: Sex differences and heritability

Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations.We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer's disease case-control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset.We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06-0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition.Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development. 

/pdf/gut-microbiome-cognitive-function-and-brain-structure-a-19fwxl83.pdf

Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis

The striatum is implicated in externalizing traits and cognitive dysfunction. The ventral and dorsal striatal subregions may play differentiable roles in externalizing behaviors and executive functions. We employed voxel-based morphometry to estimate the striatal gray matter volumes (GMVs) of 968 young adults (510 women) of the Human Connectome Project. We examined sex differences in striatal GMVs, tested how striatal GMVs related to an externalizing trait (Extn), and 2-back memory efficiency (Eff2), and examined whether these relationships exhibited sex differences. Men showed significantly higher ventral striatum (VS) and lentiform nucleus (LN) GMVs as well as higher Extn and Eff2 than women. Across all subjects, greater caudate and LN GMVs were correlated significantly with lower Eff2 though with limited effect sizes (r = −0.140, p < .001 and r = −0.093, p = .004, respectively) and the latter correlation was carried primarily by women (z = −3.070, p = .002, slope test). VS GMV showed positive correlation with Extn (r = 0.085, p = .008). Together, striatal GMVs are significantly but only weakly associated with externalizing behaviors and cognitive dysfunction in young adults. As key hubs of the fronto-striatal circuits, the ventral and dorsal striatum may contribute differently to externalizing psychopathology.

Striatal gray matter volumes, externalizing traits, and N-back task performance: An exploratory study of sex differences using the human connectome project data

Loss and frontal striatal reactivities characterize alcohol use severity and rule-breaking behavior in young adult drinkers.

https://www.biorxiv.org/content/biorxiv/early/2022/02/25/2022.02.18.481066.full.pdf

Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism in APP/PS1 mice

Epidemiological surveys suggest that excessive drinking is associated with higher risk of Alzheimer's disease (AD). The present study utilized data from the National Alzheimer's Coordinating Center to examine cognition as well as gray/white matter and ventricular volumes among participants with AD and alcohol use disorder (AD/AUD, n = 52), AD only (n = 701), AUD only (n = 67), and controls (n = 1283). AUD diagnosis was associated with higher Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) in AD than in non-AD. AD performed worse on semantic fluency and Trail Making Test A + B (TMT A + B) and showed smaller total GMV, WMV, and larger ventricular volume than non-AD. AD had smaller regional GMV in the inferior/superior parietal cortex, hippocampal formation, occipital cortex, inferior frontal gyrus, posterior cingulate cortex, and isthmus cingulate cortex than non-AD. AUD had significantly smaller somatomotor cortical GMV and showed a trend towards smaller volume in the hippocampal formation, relative to non-AUD participants. Misuse of alcohol has an additive effect on dementia severity among AD participants. Smaller hippocampal volume is a common feature of both AD and AUD. Although AD is associated with more volumetric deficits overall, AD and AUD are associated with atrophy in largely distinct brain regions.

Cognitive dysfunction and cerebral volumetric deficits in individuals with Alzheimer's disease, alcohol use disorder, and dual diagnosis.

The salience network, including the insula and anterior cingulate cortex (ACC), has been implicated in nicotine addiction. Structural imaging studies have reported diminished insula and ACC gray matter volumes (GMVs) in smokers as compared to nonsmokers. However, it remains unclear how insula and ACC GMVs may relate to years of smoking and addiction severity, or behavioral traits known to dispose individuals to smoking. Here, with a dataset curated from the Human Connectome Project and voxel-based morphometry, we replicated the findings of smaller GMVs of the insula and medial prefrontal cortex, including the dorsal ACC and supplementary motor area (dACC/SMA) in (70 heavy

Gray matter volumes of the insula and anterior cingulate cortex and their dysfunctional roles in cigarette smoking

Perceived stress, self-efficacy, and the cerebral morphometric markers in binge-drinking young adults.

Individuals engage in alcohol consumption to seek reward and/or alleviate negative emotions. The neural processes subserving reward response and negative emotion thus likely play important roles in motivating alcohol use. Cognitive control, in contrast, is thought to regulate these motivational processes to keep drinking in check. As such, the balance between motivational and control processes may determine drinking behavior. Importantly, this balance is likely dictated by individual differences in drinking motives, including positive alcohol expectancy and perceived social isolation. Here, we characterized how the relative strength of the reward, negative emotion, and control circuit activities during alcohol cue exposure predicted alcohol use severity in 71 adult drinkers. Path models were employed to delineate the relationships between the neural, psychological, and drinking measures. We found that positive alcohol expectancy was associated heightened craving and greater activity of the reward relative to cognitive control circuit during cue exposure. The higher this circuit activity difference, the more severe subjects’ drinking. A similar relationship was found for social isolation, craving, activity difference of negative emotion vs. cognitive control circuits, and alcohol use severity. Thus, distinct neural pathways motivate alcohol use through reward seeking and negative emotion. By characterizing the neural circuits underlying cognitive control and motivational processes, the current study sheds light on how positive and negative reinforcement perpetuates problem drinking.

Shefali Chaudhary

Papers

Cognitive dysfunction and cerebral volumetric deficits in individuals with Alzheimer's disease, alcohol use disorder, and dual diagnosis.

Gray matter volumes of the insula and anterior cingulate cortex and their dysfunctional roles in cigarette smoking

Perceived stress, self-efficacy, and the cerebral morphometric markers in binge-drinking young adults.

Problem drinking and the interaction of reward, negative emotion, and cognitive control circuits during cue-elicited craving