The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant "CBCL Anxious/Depressed by Age" interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (<9 years), but positively associated with thickness at older ages (15-22 years), with the shift in polarity occurring around age 12. This was secondary to a slower rate of vmPFC cortical thinning in subjects with higher scores. In young adults (18-22 years), Anxious/Depressed scores were also positively associated with precuneus/posterior cingulate cortical thickness. Potential neurobiological mechanisms underlying this maturation pattern are proposed. These results demonstrate the dynamic impact of age on relations between vmPFC and negative affect in the developing brain.

Early-life stress (ELS) exposure is associated with adverse outcomes across the lifespan. We examined the relation of ELS exposure to resting-state fMRI in children ages 4 to 7 years. ELS in the first years of life, but not concurrent, was associated with higher regional homogeneity of resting-state fMRI in the left lateral frontal cortex. Resting-state fMRI functional connectivity analyses showed that the region of left lateral frontal cortex demonstrating heightened regional homogeneity associated with ELS was negatively correlated with right temporal/parahippocampal areas. Moreover, higher regional homogeneity in the left lateral frontal cortex and its negative coupling with the right middle temporal/parahippocampal areas were associated with poorer performance on a reversal-learning task performed outside the scanner. Association of ELS exposure with regional homogeneity was independent of other early adversities. These findings suggest that ELS may influence the development of cognitive control in the lateral prefrontal cortex and its interactions with temporal cortex.

Autobiographical memory retrieval is associated with activity of a distributed network that is similar to the default-mode network (DMN) identified via activity correlations measured during rest. We tested whether activity correlations could be used to identify the autobiographical network during extended bouts of retrieval. Global-correlativity analysis identified regions with activity correlation differences between autobiographical-retrieval and resting states. Increased correlations were identified for retrieval versus resting states within a distributed network that included regions prototypical for autobiographical memory. This network segregated into two subnetworks comprised of regions related to memory versus cognitive control, suggesting greater functional segregation during autobiographical retrieval than rest. DMN regions were important drivers of these effects, with increased correlations between DMN and non-DMN regions and segregation of the DMN into distinct subnetworks during retrieval. Thus, the autobiographical network can be robustly identified via activity correlations and retrieval is associated with network functional organization distinct from rest.

Successful memory is normally accompanied by explicit awareness of retrieval and confidence in the accuracy of the retrieval product. Prior findings suggest that these features of metamemory can be dissociated from retrieval accuracy in Amnestic Mild Cognitive Impairment (aMCI). However, the literature on this question contains variable and conflicting results, likely because of differences in experimental conditions. We sought to systematically evaluate memory awareness disruptions in aMCI using multiple measures and stimulus formats within the same individuals. Memory awareness was tested with global predictions and postdictions, judgments of learning, confidence level ratings, and modified feeling-of-knowing ratings in tasks of visuospatial and verbal memory. These tests were administered to 14 individuals with aMCI and 15 healthy, age-matched controls. Memory awareness accuracy was calculated as the correspondence between subjective judgments and memory performance.Individuals with aMCI demonstrated impaired global and trial-level retrospective task awareness for visuospatial and verbal stimuli. Additionally, modified feeling-of-knowing awareness was impaired selectively for verbal stimuli. Statistical effect sizes for global awareness impairments were comparable to impairments in several objective neuropsychological memory assessments.Memory awareness (metamemory) disruptions in aMCI were most evident for a subset of subjective judgment types and task input modalities. These findings advance understanding of the nature of memory impairments in aMCI and support the utility of incorporating memory awareness testing to better characterize memory integrity in older adults.

Background The prefrontal cortex has been implicated in episodic memory and the awareness of memory. Few studies have probed the nature and necessity of its role via brain stimulation. There are uncertainties regarding whether the hemisphere of stimulation predicts effects on memory and whether effects of stimulation are format‐specific, with most previous studies utilizing verbal/semantic stimuli. Objective Our primary objective was to determine if theta‐burst transcranial magnetic stimulation (TBS) to prefrontal cortex modulates visual memory accuracy, visual memory awareness, or both, and whether these effects depend on brain hemisphere. Methods We administered TBS to 12 individuals in either left prefrontal, right prefrontal, or a sham location on three separate days. We then administered a visual associative‐memory task incorporating global‐level awareness judgments and feeling‐of‐knowing (FOK) judgments on test trials for which retrieval failed. Results Overall memory accuracy significantly improved after right hemisphere TBS compared to sham. Simultaneously, subjects were relatively underconfident after right TBS, suggesting minimal awareness of memory accuracy improvements. The correspondence between FOKs and later recognition accuracy suggested a pattern of disruption in prospective memory monitoring accuracy after left TBS. Conclusions Our findings provide unique evidence for improved visual memory accuracy after right prefrontal TBS. These results also suggest right prefrontal lateralization for visual memory and left‐hemisphere specialization for item‐level prospective memory awareness judgments. Taken together, these results provided continued support for noninvasive stimulation to prefrontal cortex as a means of potentially improving memory and causally influencing prospective memory awareness.