Social cognition difficulties in individuals with alcohol use disorders (AUD), including emotion perception deficits and deficits in theory of mind (ToM) processing, are more severe with greater alcohol misuse and persist despite extended abstinence. ToM is a key aspect of social cognition that refers to the ability to understand the intentions (cognitive ToM) and emotions (affective ToM) of self and others. Research suggests that females generally outperform males on measures of social cognition. However research on the neural correlates of ToM processing in AUD is scant and there are no studies of sex differences in individuals with AUD. The prefrontal cortex (PFC) is a key region of the ?default mode network? (DMN) that is engaged during ToM processing and, notably it is especially vulnerable to the neurotoxic effects of alcohol. Thus the DMN may be implicated in social cognition difficulties in individuals with AUD. Given evidence of sexual dimorphism in brain structure, sex differences in resting and task functional magnetic resonance imaging (FMRI) brain activation, and of a ?telescoping? effect on brain damage in women (women have more damage with less alcohol misuse than men), there is a strong rationale for the presence of sex differences in the damage from alcohol misuse to PFC and in ToM processing. We propose to conduct secondary analyses of existing data collected from the Human Connectome Project (HCP), with behavioral, clinical, demographic, and drug use data and resting FMRI, social cognition and emotion processing task FMRI, and structural MRI data of interest for this project, to investigate sex differences in the structure and function of ToM-related brain circuits in individuals with AUD. The HCP is an NIH-funded initiative to comprehensively map human brain circuits and their relationships to behavior in 1200 adults. Data from 500 subjects have been released to date. From those, we have identified 35 females and 35 males with AUD and 70 carefully matched healthy subjects (35M/35F), whose data will be used for this study. In addition, we will include new subjects identified from the next two HCP releases, which may more than double our final sample size to ~300-350 subjects.
Our specific aims are: 1) Use resting FMRI data to investigate DMN function and the relationships between DMN function, social cognition measures, sex and AUD, 2) Use task FMRI to investigate the connections between DMN and other key ToM brain circuits, sex, and AUD, and 3) Apply data fusion analysis to all MRI measurements combined together to identify ?features? of combined structure/function that will be uniquely related to AUD and sex.
While neuroimaging techniques have clearly demonstrated that structural and functional brain damage is present in individuals with alcohol use disorder, differences in brain circuitry between males and females that might underlie reported sex differences in the sensitivity to alcohol's acute effects, withdrawal severity, risk of relapse, and rewarding effects, remains understudied. In this proposal, we propose secondary analyses of existing data collected for the Human Connectome Project, an NIH-funded initiative to comprehensively map human brain circuits and their relationships to behavior in a large population of healthy adults, to investigate sex differences in brain circuitry in individuals with alcohol abuse and dependence.
| Nickerson, Lisa D (2018) Replication of Resting State-Task Network Correspondence and Novel Findings on Brain Network Activation During Task fMRI in the Human Connectome Project Study. Sci Rep 8:17543 |
| Cohen-Gilbert, Julia E; Nickerson, Lisa D; Sneider, Jennifer T et al. (2017) College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control. Front Psychol 8:1650 |
