Search bioRxiv⌕ Search

Biology subjects

Sawyer, K. S.

Publications and source records attributed to Sawyer, K. S..

9 recordsLinked to original sources

Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with Alcohol Use Disorder

AimsAlcohol use disorder (AUD), has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, results of existing studies have been conflicting. Brain metabolite levels and cognitive functions were examined in a cross section of men with AUD (AUDm) and women with AUD (AUDw) to determine degree of abnormalities after extended periods of abstinence (mean, six years), and to evaluate gender differences in cognitive and metabolite measures. MethodsParticipants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetylaspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. ResultsMetabolite levels in the AUD group showed no significant differences from the NC group. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no Group-by-Gender interactions for the four metabolite ratios. ConclusionsThese findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide evidence of associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

neuroscience↗

Students Attitudes Surrounding STEM: A Social Cognitive Career Theory Instrument for High School

To broaden participation in science, technology, engineering, and math (STEM), we must understand the factors that shape perspectives and beliefs around career selection. Good measurement of these factors is crucial to quantify how effectively educational interventions impact student attitudes towards STEM. Adolescents are particularly suited for quantifying intervention efficacy because students build their identities during these formative years and make important career choices. To better quantify intervention efficacy at the high school level, we developed an instrument entitled Student Attitudes Surrounding STEM (SASS), which builds upon the social cognitive career theory (SCCT) framework for understanding career selection. Questionnaire responses were collected from 932 high school students and split into samples of 400 for exploratory factor analysis and 532 for confirmatory factor analysis. The 37 questions clustered into six factors: Self-Efficacy-Experience, Self-Efficacy-Academic, Outcome Expectations, Interests, Negative Perceptions of Scientists, and Career Awareness. Adequate construct validity for the factors indicated in the SASS model was suggested by the fit indices and theoretical considerations. Furthermore, the analyses supported criterion validity, internal consistency, and test-retest reliability. This tool represents a novel integration of three latent variables into SCCT: Negative Perceptions of Scientists, Career Awareness, and an experience factor for Self-Efficacy.

scientific communication and education↗

Alcohol cues elicit different abnormalities in brain networks of abstinent men and women with alcohol use disorders

We employed fMRI in 84 men and women with and without a history of alcohol use disorders (ALC and NC, respectively), to explore how gender interacts with alcoholism as reflected in brain activity elicited by alcohol cues. Brain activation was measured in a working memory task (delayed matching-to-sample) with emotional faces as the sample and match cues. During the delay period, intervening distractors were either reward-salient cues (alcoholic beverages) or neutral cues (nonalcoholic beverages or scrambled pictures). ALC women (ALCw) had higher accuracy than ALC men (ALCm). Analyses of scans during the viewing of distractor images revealed significant group-by-gender interactions. Compared to NC men, ALCm evidenced lower activation contrast between reward-salient cues and neutral cues in default mode network regions (including superior prefrontal and precuneus areas), while ALCw had more activation than NC women. Similar interactions were observed for task-regions (including superior parietal, lateral occipital, and prefrontal areas). Region of interest analyses showed that the ALC group had significantly higher levels of activation throughout reward-related circuitry during alcohol distractor interference than during scrambled picture interference. These results suggest that abstinent ALCm and ALCw differ in processing reward-salient cues, which can impact treatment and recovery. HighlightsBrain reward regions activate highly when individuals with a history of alcohol use disorders view alcoholic beverages. The brain regions identified subserve vision, memory, and judgement. Opposite abnormalities in activation patterns appeared for alcoholic men and women.

neuroscience↗

Hippocampal subfield volumes in abstinent men and women with a history of alcoholism

Alcohol use disorder (AUD) has been associated with abnormalities in hippocampal volumes, but these relationships have not been fully explored with respect to sub-regional volumes, nor in association with individual characteristics such as gender differences, age, and memory. The present study examined the impact of those variables in relation to hippocampal subfield volumes in abstinent men and women with a history of AUD. Using Magnetic Resonance Imaging at 3 Tesla, we obtained brain images from 67 participants (31 women) with AUD and 63 healthy control (NC) participants (30 women) without AUD. We used Freesurfer 6.0 to segment the hippocampus into 12 regions. These were imputed into mixed models to examine the relationships of brain volume with AUD group, gender, age, drinking history, and memory. The AUD group had approximately 5% smaller CA1, hippocampal tail, and molecular layer regions than the NC group. Age was negatively associated with volumes for the AUD group in the hippocampal tail, subiculum, and presubiculum. The relationships for delayed and immediate memory with hippocampal tail volume differed for AUD and NC groups: Higher scores were associated with smaller volumes in the AUD group, but larger volumes in the NC group. Length of sobriety was associated with decreasing CA1 volume in women (0.02% per year) and increasing volume size in men (0.03% per year). These findings confirm and extend evidence that AUD, gender, age, and abstinence differentially impact volumes of component parts of the hippocampus. The course of abstinence on CA1 volume differed for men and women, and the differential relationships of subregional volumes to age and memory could indicate a distinction in the impact of AUD on functions of the hippocampal tail.

neuroscience↗

White Matter Connectometry Among Individuals with Self-Reported Family History of Drug and Alcohol Use Disorders

Heredity is an important risk factor for alcoholism. Several studies have been conducted on small groups of alcohol naive adolescents which show lowered fractional anisotropy of frontal white matter in FH+ groups. We sought to compare large FH+ and FH-groups using white matter connectometry, as opposed to the previously used global tractography method, as it is more sensitive to regional variability. Imaging and behavioral data from the Human Connectome Project (WU-MINN HCP 1200) was used. Groups of participants were positive (n=109) and negative (n=109) for self-reported drug and alcohol use disorders in at least one parent. Groups were matched on gender, age, education, current alcohol usage, and alcohol use disorders (AUD). Connectometry was performed on diffusion MRI in DSI-Studio using q-space diffeomorphic reconstruction, and multiple regression was completed with 5000 permutations. Analyses showed decreased major tract (>40 mm) connectivity in the FH+ group in left inferior longitudinal fasciculus, bilateral cortico-striatal pathway, left cortico-thalamic pathway, and corpus callosum, compared to the FH- group. For cognitive tasks related to reward processing, inhibition, and monitoring, there were a number of interactions, such that the relationship between identified networks and behavior differed significantly between groups. Positive self-report of family history of alcoholism was associated with decreased connectivity in reward signaling pathways, controlling for alcohol consumption and AUD. This is the first connectometry study of FH+, and extends the neural basis of the hereditary diathesis of alcoholism beyond that demonstrated with global tractography. Regions associated with FH+ are similar to those associated with AUD.

neuroscience↗

Brain Responsivity to Emotional Faces Differs in Alcoholic Men and Women

Inclusion of women in alcoholism research has shown that gender differences contribute to unique profiles of cognitive, emotional, and neuropsychological dysfunction. We employed functional magnetic resonance imaging (fMRI) of abstinent long-term alcoholics (21 women [ALCw] and 21 men [ALCm]) and demographically-similar nonalcoholic controls (21 women [NCw] and 21 men [NCm]) to explore how gender and alcoholism interact to influence emotional processing and memory. Participants completed a delayed match-to-sample emotional face memory fMRI task. While the results corroborated reports implicating amygdalar, superior temporal, and cerebellar involvement in emotional processing overall, the alcoholic participants showed hypoactivation of the left intraparietal sulcus to encoding the identity of the emotional face stimuli. The nonalcoholic participants demonstrated more reliable gender differences in neural responses to encoding the identity of the emotional faces than did the alcoholic group, and widespread neural responses to these stimuli were more pronounced in the NCw than in the NCm. By comparison, gender differences among ALC participants were either smaller or in the opposite direction (higher brain activation in ALCm than ALCw). Specifically, Group by Gender interaction effects indicated stronger responses to emotional faces by ALCm than ALCw in the left superior frontal gyrus and the right inferior frontal sulcus, while NCw had stronger responses than NCm. However, this pattern was inconsistent throughout the brain, with results suggesting the reverse direction of gender effects in the hippocampus and anterior cingulate cortex. Together, these findings demonstrated that gender plays a significant role in the profile of functional brain abnormalities observed in alcoholism.

neuroscience↗

Components of Executive Function Predict Regional Prefrontal Volumes

Objective: Designed to measure a diversity of executive functioning (EF) through classical neuropsychological tests, the Delis-Kaplan Executive Function Scale (D-KEFS) allows for the investigation of the neural architecture of EF. We examined how the D-KEFS Tower, Verbal Fluency, Design Fluency, Color-Word Interference, and Trail Making Test tasks related to regional frontal lobe volumes, quantifying how components of EF were represented in disparate neural networks. Method: Adults from the Nathan Kline Institute - Rockland Sample (NKI-RS), an open-access community study of brain development, with complete MRI (3T scanner) and D-KEFS data were selected for analysis (N = 478; ages 20-85). In a mixed-effects model predicting volume, D-KEFS task, D-KEFS score, region of interest (ROI; 13 frontal, 1 occipital control), were entered as fixed effects with intercepts for participants as random effects. Results: Unitary EF (average of D-KEFS scores) was positively associated with superior frontal, rostral middle frontal, and lateral orbitofrontal volumes; a negative association was observed with frontal pole volume (| z-score slope | range = 0.040 to 0.051). Diverse EF skills (individual D-KEFS task scores) were differentially associated with two or three ROIs, respectively, but to a stronger extent (| z-score slope | range = 0.053 to 0.103). Conclusions: The neural correlates found for the D-KEFS support the prefrontal modularity of EF at both the unitary (aspects of EF ability common to all tasks) and task (diverse EF skills) levels. The separation of task-general variance in neurocognition from task-specific variance can further evaluate neuropsychological tests as indices of brain integrity.

neuroscience↗

Cerebral White Matter Sex Dimorphism in Alcoholism: A Diffusion Tensor Imaging Study

Background: Excessive alcohol consumption is associated with widespread brain damage, including abnormalities in frontal and limbic brain regions. In a prior study of neuronal circuitry connecting the frontal lobes and limbic system structures in abstinent alcoholic men, we demonstrated decreases in white matter fractional anisotropy (FA) on diffusion tensor magnetic resonance imaging (dMRI). In the present study, we examined sex differences in alcoholism-related abnormalities of white matter connectivity. Methods: dMRI scans were acquired from 49 abstinent alcoholic individuals (26 women) and 41 nonalcoholic controls (22 women). Tract-based spatial statistical tools were used to estimate regional FA of white matter tracts and to determine sex differences and their relation to measures of alcoholism history. Results: Sex-related differences in white matter connectivity were observed in association with alcoholism: Compared to nonalcoholic men, alcoholic men had diminished FA in portions of the corpus callosum, the superior longitudinal fasciculi II and III, and the arcuate fasciculus and extreme capsule. In contrast, alcoholic women had higher FA in these regions. Sex differences also were observed for correlations between corpus callosum FA and length of sobriety. Conclusions: Sexual dimorphism in white matter microstructure in abstinent alcoholics may implicate underlying differences in the neurobehavioral liabilities for developing alcohol abuse disorders, or for sequelae following abuse.

neuroscience↗

On the Impact of Interhemispheric White Matter: Age, Executive Functioning, and Dedifferentiation in the Frontal Lobes

IntroductionIn middle age, declines in executive functioning (EF) are associated with decrements in the quality and/or quantity of white and grey matter. Recruitment of homologous regions has been identified as a compensatory mechanism for cognitive decline in later middle age, however research into neural substrates of EF has yet to be guided by dedifferentiation models. We hypothesized that frontal-parietal grey matter volume, interhemispheric white matter and intrahemispheric white matter fractional anisotropy (FA) will be predictive of EF. Further, we hypothesized that the comparative association between interhemispheric white matter and EF will increase with age, because of compensatory recruitment.\n\nMethodsNeurocognitive test data, DTI, and T1 MPRAGE scans (n = 444) were obtained from the NKI-Rockland Sample. Structural equation modeling was used to examine the relationship between age, EF, interhemispheric white matter (forceps minor; FM), intrahemispheric white matter (superior longitudinal fasciculus; SLF), and a frontal-parietal grey matter network. EF and grey matter were modelled as latent variables, with EF examined as the criterion. Additionally, a subsample of participants aged 55-85 (n = 168) was analyzed to examine the influence of age related compensatory mechanisms.\n\nResultsThere was a significant relationship between FM, grey matter, and EF, which was fully mediated by age. There was a significant relationship between SLF and EF, which was not mediated by age. For older adults, only the age-mediated pathway from FM to EF was significant.\n\nDiscussionUsing structural imaging data, support was found for age-related interhemispheric mechanisms of compensation, but not intrahemispheric mechanisms.\n\nKey points(1) Neural substrates of executive functioning are not static across the lifespan. (2) In older adults, white matter becomes more salient as a structural correlate of executive functioning, as recruitment needs increase. (3) While the importance of interhemispheric white matter is mediated by age, intrahemispheric recruitment remains consistent across the lifespan, and is not the primary mechanism of age-based compensation in community dwelling older adults.

neuroscience↗