The Role of Visual Association Cortex in Associative Memory Formation across Development

Associative learning underlies the formation of new episodic memories. Associative memory improves across development, and this age-related improvement is supported by the development of the hippocampus and pFC. Recent work, however, additionally suggests a role for visual association cortex in the formation of associative memories. This study investigated the role of category-preferential visual processing regions in associative memory across development using a paired associate learning task in a sample of 56 youths (age 6–19 years). Participants were asked to bind an emotional face with an object while undergoing fMRI scanning. Outside the scanner, participants completed a memory test. We first investigated age-related changes in neural recruitment and found linear age-related increases in activation in lateral occipital cortex and fusiform gyrus, which are involved in visual processing of objects and faces, respectively. Furthermore, greater activation in these visual processing regions was associated with better subsequent memory for pairs over and above the effect of age and of hippocampal and pFC activation on performance. Recruitment of these visual processing regions mediated the association between age and memory performance, over and above the effects of hippocampal activation. Taken together, these findings extend the existing literature to suggest that greater recruitment of category-preferential visual processing regions during encoding of associative memories is a neural mechanism explaining improved memory across development

Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing

Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared to non-abused adolescents, although most prior research is based on adults and volume-based measures. The current study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence

Maltreatment Exposure, Brain Structure and Fear Conditioning in Children and Adolescents

Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6–18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS−) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS−, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS− during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat–safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children

A Comparison of Methods to Harmonize Cortical Thickness Measurements Across Scanners and Sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ 2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ 2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ 2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder:Results from the ENIGMA-PGC PTSD Consortium

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1,300 PTSD cases and >2,000 trauma-exposed controls (age 6.2-85.2 years) by the ENIGMA-PGC PTSD working group. Cortical regions in the network were rank-ordered by effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2 to 148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared to the mean SC of 5,000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD controls, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The structural covariance networks that are perturbed in PTSD comport with converging evidence from resting state functional connectivity networks and networks impacted by inflammatory processes, and stress hormones in PTSD

Subjective social status, symbolic capital, and psychopathology in adolescence.

Thesis (Ph.D.)--University of Washington, 2021Adolescents’ ratings of subjective social status within their peer community may represent a useful index of socioeconomic status (SES) which is strongly associated with adolescent psychopathology. However, adolescent subjective social status does not correlate to traditional indicators of SES such as family income. Instead, subjective social status may reflect access to other forms of resources more salient to adolescents such as symbolic capital (behaviors and consumer goods symbolic of social position). I conducted a cultural consensus analysis based on interviews and questionnaire data from 66 students in two high schools in the Pacific Northwest to produce a consensually agreed upon set of symbolic capital markers in those schools. In a separately recruited sample of 80 adolescents, I tested associations between subjective social status, symbolic capital ownership, and psychopathology. Contrary to my hypotheses, subjective social status and symbolic capital were not correlated, although both were associated with parent rated social competence. Subjective social status was associated with psychopathology, but symbolic capital was not. My findings suggest that symbolic capital and subjective social status may convey different information about adolescents’ social competence, and that performing a high-status identity may be less important to socio-emotional functioning than perceiving oneself as well-liked and respected