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Deleterious effects of adverse childhood experiences (ACE) on human brain volume are widely reported. First evidence points to differential effects of ACE on brain volume in terms of timing of ACE. Upcoming studies additionally point towards the impact of different types (i.e., neglect and abuse) of ACE in terms of timing. The current study aimed to investigate the correlation between retrospectively reported severity of type (i.e., the extent to which subjects were exposed to abuse and/or neglect, respectively) and timing of ACE on female brain volume in a sample of prolonged traumatized subjects. A female sample with ACE (N = 68) underwent structural magnetic resonance imaging and a structured interview exploring the severity of ACE from age 3 up to 17 using the "Maltreatment and Abuse Chronology of Exposure" (MACE). Random forest regression with conditional interference trees was applied to assess the impact of ACE severity as well as the severity of ACE type, (i.e. to what extent individuals were exposed to neglect and/or abuse) at certain ages on pre-defined regions of interest such as the amygdala, hippocampus, and anterior cingulate (ACC) volume. Analyses revealed differential type and timing-specific effects of ACE on stress sensitive brain structures: Amygdala and hippocampal volume were affected by ACE severity during a period covering preadolescence and early adolescence. Crucially, this effect was driven by the severity of neglect. [ABSTRACT FROM AUTHOR]

Within cognitive neuroscience, in nearly every experimental setting, subjects are presented with stimuli that appear at either constant or variable points in time, referred to as interstimulus intervals (ISIs). These temporal patterns differ in the degree to which an exact stimulus onset may be predicted. We investigated whether this experimental feature affects brain and behavior, and whether the impact is modulated by the cognitive demands of a task. Subjects (N = 26) were assessed via fMRI while solving three different tasks under either temporally predictable (constant ISI) or unpredictable (variable ISI) conditions. The tasks differed with regard to demands on working memory and response uncertainty. Compared to constant ISIs, variable (i.e., less predictable) ISIs led to a general increase in reaction time and in right amygdala activation. Depending on the cognitive demands required by the specific task, the left amygdala, the parietal cortex, the supplementary motor area, and the dorsolateral prefrontal cortex were engaged as well. The results indicate that the temporal structure in a stimulus sequence affects both overt and covert behaviors. Implicit temporal uncertainty increases activation in several brain regions depending on cognitive demands. Thus, an often-overlooked basic design feature, the application of constant or variable ISIs, may contribute to heterogeneity in cognitive neuroscience findings. [ABSTRACT FROM AUTHOR]

Background: Gene by environment (G×E) interaction between genetic variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) and stressful life events (SLEs) has been extensively studied in the context of depression. Recent findings suggest increased neural and endocrine stress sensitivity as a possible mechanism conveying elevated vulnerability to psychopathology. Furthermore, these G×E mediated alterations very likely reflect interrelated biological processes. Methods: In the present functional magnetic resonance imaging study, amygdala reactivity to fearful stimuli was assessed in healthy male adults (n = 44), who were previously found to differ with regard to endocrine stress reactivity as a function of 5-HTTLPR × SLEs. Furthermore, functional connectivity between the amygdala and the hypothalamus was measured as a potential mechanism linking elevated neural and endocrine responses during stressful/threatening situations. The study sample was carefully preselected regarding 5-HTTLPR genotype and SLEs. Results: We report significant G×E interaction on neural response patterns and functional amygdala-hypothalamus connectivity. Specifically, homozygous carriers of the 5-HTTLPR S'' allele with a history of SLEs (S''S''/high SLEs group) displayed elevated bilateral amygdala activation in response to fearful faces. Within the same sample, a comparable G×E interaction effect has previously been demonstrated regarding increased cortisol reactivity, indicating a cross-validation of heightened biological stress sensitivity. Furthermore, S''S''/high SLEs subjects were characterized by an increased functional coupling between the right amygdala and the hypothalamus, thus indicating a potential link between neural and endocrine hyperreactivity. Conclusions: The present findings contribute to the ongoing debate on 5-HTTLPR × SLEs interaction and are discussed with respect to clinical implications. [Copyright &y& Elsevier]