Development of the neural correlates of recollection.

Recollection of past events has been associated with the core recollection network comprising the posterior medial temporal lobe and parietal regions, as well as the medial prefrontal cortex (mPFC). The development of the brain basis for recollection is understudied. In a sample of adults (n = 22; 18-25 years) and children (n = 23; 9-13 years), the present study aimed to address this knowledge gap using a cued recall paradigm, known to elicit recollection experience. Successful recall was associated with activations in regions of the core recollection network and frontoparietal network. Adults exhibited greater successful recall activations compared with children in the precuneus and right angular gyrus. In contrast, similar levels of successful recall activations were observed in both age groups in the mPFC. Group differences were also seen in the hippocampus and lateral frontal regions. These findings suggest that the engagement of the mPFC in episodic retrieval may be relatively early maturing, whereas the contribution to episodic retrieval of more posterior regions such as the precuneus and angular gyrus undergoes more protracted maturation.

Development of self-referential effect on memory recollection.

Information learned in relation to oneself is typically better remembered, termed the self-reference effect (SRE). This study aimed to elucidate the developmental trajectory of the SRE in recollection and source memory from mid-childhood to young adulthood. In 2018-2019 in Baltimore, Maryland, 136 seven- to thirty-year-olds (77 female; approximately 80% White, 15% Asian American, 5% Black) viewed objects on one of two backgrounds and answered a self-referential or semantic question for each. A recognition test probed memory for objects and source details (inherent: question type; peripheral: background image). SRE increased with age for detailed recollection (r = .189), but not familiarity, and extended to inherent source memory. This suggests that self-referencing promotes richer memory in children and develops into young adulthood.

Brain functional organization and structure in patients with arteriovenous malformations.

PURPOSE: Developmental in nature, brain arteriovenous malformations (AVM) have the potential to affect whole brain organization. Here we investigated the impact of AVM on functional and structural brain organization using resting-state functional MRI (rsfMRI) and cortical thickness measures. METHODS: We investigated brain functional organization and structure using rsfMRI in conjunction with cortical thickness analyses in 23 patients with cerebral arteriovenous malformations (AVMs) and 20 healthy control subjects. RESULTS: Healthy controls showed the expected anti-correlation between activity in the default mode network (DMN) and frontal areas that are part of the attentional control network. By contrast, patients demonstrated a disruption of this anti-correlation. Disruptions to this anti-correlation were even observed in a subgroup of patients with lesions remote from the main nodes of the DMN and were unrelated to differences in perfusion. Functional connectivity differences were accompanied by reduced cortical thickness in frontal attentional areas in patients compared to the controls. CONCLUSIONS: These results contribute to the discussion that AVMs affect whole brain networks and not simply the area surrounding the lesion.

Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.

Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbic WM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturational WM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches.

Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human capacity to learn a second language can be predicted by an individual's intrinsic functional connectivity within the language network.

Simultaneous learning of two languages from birth positively impacts intrinsic functional connectivity and cognitive control.

This study explores the effect of individual differences in the age of acquisition of a second language using resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional connectivity and its relation with cognitive control within bilinguals. We compared simultaneous bilinguals, who learned two languages from birth, to sequential bilinguals, who learned a second language following mastery of their first language. Results show an effect of language experience on the strength of anticorrelation between the default mode network and the task-positive attention network and on cognitive control, with simultaneous bilinguals demonstrating stronger anticorrelations between the two networks, as well as superior cognitive control compared to sequential bilinguals. These findings demonstrate that the timing of language learning may have an impact on cognitive control, with the simultaneous learning of two languages being associated with more optimal brain connectivity for cognitive control compared to sequential language learning.

Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers.

Although nicotine addiction is characterized by both structural and functional abnormalities in brain networks involved in salience and cognitive control, few studies have integrated these data to understand how these abnormalities may support addiction. This study aimed to (1) evaluate gray matter density and functional connectivity of the anterior insula in cigarette smokers and never smokers and (2) characterize how differences in these measures were related to smoking behavior. We compared structural magnetic resonance imaging (MRI) (gray matter density via voxel-based morphometry) and seed-based functional connectivity MRI data in 16 minimally deprived smokers and 16 matched never smokers. Compared with controls, smokers had lower gray matter density in left anterior insula extending into inferior frontal and temporal cortex. Gray matter density in this region was inversely correlated with cigarettes smoked per day. Smokers exhibited negative functional connectivity (anti-correlation) between the anterior insula and regions involved in cognitive control (left lPFC) and semantic processing/emotion regulation (lateral temporal cortex), whereas controls exhibited positive connectivity between these regions. There were differences in the anterior insula, a central region in the brain's salience network, when comparing both volumetric and functional connectivity data between cigarette smokers and never smokers. Volumetric data, but not the functional connectivity data, were also associated with an aspect of smoking behavior (daily cigarettes smoked).

Selective development of anticorrelated networks in the intrinsic functional organization of the human brain.

We examined the normal development of intrinsic functional connectivity of the default network (brain regions typically deactivated for attention-demanding tasks) as measured by resting-state fMRI in children, adolescents, and young adults ages 8-24 years. We investigated both positive and negative correlations and employed analysis methods that allowed for valid interpretation of negative correlations and that also minimized the influence of motion artifacts that are often confounds in developmental neuroimaging. As age increased, there were robust developmental increases in negative correlations, including those between medial pFC (MPFC) and dorsolateral pFC (DLPFC) and between lateral parietal cortices and brain regions associated with the dorsal attention network. Between multiple regions, these correlations reversed from being positive in children to negative in adults. Age-related changes in positive correlations within the default network were below statistical threshold after controlling for motion. Given evidence in adults that greater negative correlation between MPFC and DLPFC is associated with superior cognitive performance, the development of an intrinsic anticorrelation between MPFC and DLPFC may be a marker of the large growth of working memory and executive functions that occurs from childhood to young adulthood.

Development of deactivation of the default-mode network during episodic memory formation.

Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8-24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning.

From vision to memory: How scene-sensitive regions support episodic memory formation during child development.

Previous brain imaging studies have identified three brain regions that selectively respond to visual scenes, the parahippocampal place area (PPA), the occipital place area (OPA), and the retrosplenial cortex (RSC). There is growing evidence that these visual scene-sensitive regions process different types of scene information and may have different developmental timelines in supporting scene perception. How these scene-sensitive regions support memory functions during child development is largely unknown. We investigated PPA, OPA and RSC activations associated with episodic memory formation in childhood (5-7 years of age) and young adulthood, using a subsequent scene memory paradigm and a functional localizer for scenes. PPA, OPA, and RSC subsequent memory activation and functional connectivity differed between children and adults. Subsequent memory effects were found in activations of all three scene regions in adults. In children, however, robust subsequent memory effects were only found in the PPA. Functional connectivity during successful encoding was significant among the three regions in adults, but not in children. PPA subsequently memory activations and PPA-RSC subsequent memory functional connectivity correlated with accuracy in adults, but not children. These age-related differences add new evidence linking protracted development of the scene-sensitive regions to the protracted development of episodic memory.

High-effect gene-coding variants impact cognition, mental well-being, and neighborhood safety substrates in brain morphology.

Our genetic makeup, together with environmental and social influences, shape our brain's development. Yet, the imaging genetics field has struggled to integrate all these modalities to investigate the interplay between genetic blueprint, environment, human health, daily living skills and outcomes. Hence, we interrogated the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and corresponding implications on cognitive, behavioral, psychosocial, and socioeconomic traits. Specifically, we designed a holistic pattern-learning algorithm that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 962 behavioral variables spanning 20 categories in 7,657 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks, and specific parameters of the family well-being (increased parental and child stress, anxiety and depression) or neighborhood dynamics (decreased safety); effects extending beyond the impairment of cognitive ability or language capacity, dominantly reported in the CNV literature. Our investigation thus spotlights a far-reaching interplay between genetic variation and subjective life quality in adolescents and their families.

The development of brain systems associated with successful memory retrieval of scenes.

Neuroanatomical and psychological evidence suggests prolonged maturation of declarative memory systems in the human brain from childhood into young adulthood. Here, we examine functional brain development during successful memory retrieval of scenes in children, adolescents, and young adults ages 8-21 via functional magnetic resonance imaging. Recognition memory improved with age, specifically for accurate identification of studied scenes (hits). Successful retrieval (correct old-new decisions for studied vs unstudied scenes) was associated with activations in frontal, parietal, and medial temporal lobe (MTL) regions. Activations associated with successful retrieval increased with age in left parietal cortex (BA7), bilateral prefrontal, and bilateral caudate regions. In contrast, activations associated with successful retrieval did not change with age in the MTL. Psychophysiological interaction analysis revealed that there were, however, age-relate changes in differential connectivity for successful retrieval between MTL and prefrontal regions. These results suggest that neocortical regions related to attentional or strategic control show the greatest developmental changes for memory retrieval of scenes. Furthermore, these results suggest that functional interactions between MTL and prefrontal regions during memory retrieval also develop into young adulthood. The developmental increase of memory-related activations in frontal and parietal regions for retrieval of scenes and the absence of such an increase in MTL regions parallels what has been observed for memory encoding of scenes.

Anticorrelations in resting state networks without global signal regression.

Anticorrelated relationships in spontaneous signal fluctuation have been previously observed in resting-state functional magnetic resonance imaging (fMRI). In particular, it was proposed that there exists two systems in the brain that are intrinsically organized into anticorrelated networks, the default mode network, which usually exhibits task-related deactivations, and the task-positive network, which usually exhibits task-related activations during tasks that demands external attention. However, it is currently under debate whether the anticorrelations observed in resting state fMRI were valid or were instead artificially introduced by global signal regression, a common preprocessing technique to remove physiological and other noise in resting-state fMRI signal. We examined positive and negative correlations in resting-state connectivity using two different preprocessing methods: a component base noise reduction method (CompCor, Behzadi et al., 2007), in which principal components from noise regions-of-interest were removed, and the global signal regression method. Robust anticorrelations between a default mode network seed region in the medial prefrontal cortex and regions of the task-positive network were observed under both methods. Specificity of the anticorrelations was similar between the two methods. Specificity and sensitivity for positive correlations were higher under CompCor compared to the global regression method. Our results suggest that anticorrelations observed in resting-state connectivity are not an artifact introduced by global signal regression and might have biological origins, and that the CompCor method can be used to examine valid anticorrelations during rest.

Correction: Self-referential encoding of source information in recollection memory.

[This corrects the article DOI: 10.1371/journal.pone.0248044.].

Self-referential encoding of source information in recollection memory.

Information that is encoded in relation to the self has been shown to be better remembered, yet reports have disagreed on whether the memory benefit from self-referential encoding extends to source memory (the context in which information was learned). In this study, we investigated the self-referential effect on source memory in recollection and familiarity-based memory. Using a Remember/Know paradigm, we compared source memory accuracy under self-referential encoding and semantic encoding. Two types of source information were included, a "peripheral" source which was not inherent to the encoding activity, and a source information about the encoding context. We observed the facilitation in item memory from self-referential encoding compared to semantic encoding in recollection but not in familiarity-based memory. The self-referential benefit to source accuracy was observed in recollection memory, with source memory for the encoding context being stronger in the self-referential condition. No significant self-referential effect was observed with regards to peripheral source information (information not required for the participant to focus on), suggesting not all source information benefit from self-referential encoding. Self-referential encoding also resulted in a higher ratio of "Remember/Know" responses rate than semantically encoded items, denoting stronger recollection. These results suggest self-referential encoding creates a richer, more detailed memory trace which can be recollected later on.

Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.

Sex differences in directional cue use in a virtual landscape.

How males and females differ in their use of cues for spatial navigation is an important question. Although women and men appear to respond differently to close and distant objects, object features and the geometry of spaces, the common denominator of these sex-specific cue preferences is unknown. By constructing virtual landscapes from either directional (graded, gradient) or positional (pinpoint) cues, the authors tested the hypothesis that sex differences arise from preferences for cues that provide primarily direction or position, as predicted by the parallel map model of the cognitive map. Women and men learned a target location in the presence of either one or the other class of cues. Men were more accurate in estimating the target location overall, but the navigation accuracy difference between men and women was greater in the presence of directional cues. Our findings provide support for the parallel map model and suggest that the previously reported male advantage in the presence of distant objects and geometric cues derives from their function as directional cues.

Intrinsic Functional Brain Connectivity Predicts Onset of Major Depression Disorder in Adolescence: A Pilot Study.

Children with familial risk for major depressive disorder (MDD) have elevated risk for developing depression as adolescents. Here, we investigated longitudinally whether resting-state functional connectivity (RSFC) could predict the onset of MDD. In this pilot study, we followed a group of never-depressed children with familial risk for MDD and a group of age-matched controls without familial risk who had undergone an MRI study at 8-14 years of age. Participants were reassessed 3-4 years later with diagnostic interviews. We first investigated group differences in RSFC from regions in the emotion regulation, cognitive control, and default mode networks in the children who later developed MDD (converted), the children who did not develop MDD (nonconverted), and the control group. We then built a prediction model based on baseline RSFC that was independent of the group differences to classify the individuals who later developed MDD. Compared with the nonconverted group, the converted group exhibited hypoconnectivity between subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices. The nonconverted group exhibited higher sgACC-IPL connectivity than did both the converted and control groups, suggesting a possible resilience factor to MDD. Classification between converted and nonconverted individuals based on baseline RSFC yielded high predictive accuracy with high sensitivity and specificity that was superior to classification based on baseline clinical rating scales. Intrinsic brain connectivity measured in healthy children with familial risk for depression has the potential to predict MDD onset, and it can be a useful neuromarker in early identification of children for preventive treatment.

Language learning experience and mastering the challenges of perceiving speech in noise.

Given the ubiquity of noisy environments and increasing globalization, the necessity to perceive speech in noise in a non-native language is common and necessary for successful communication. In the current investigation, bilingual individuals who learned their non-native language at different ages underwent magnetic resonance imaging while listening to sentences in both of their languages, in quiet and in noise. Sentence context was varied such that the final word could be of high or low predictability. Results show that early non-native language learning is associated with superior ability to benefit from contextual information behaviourally, and a pattern of neural recruitment in the left inferior frontal gyrus that suggests easier processing when perceiving non-native speech in noise. These findings have implications for our understanding of speech processing in non-optimal listening conditions and shed light on how individuals navigate every day complex communicative environments, in a native and non-native language.

Neural markers of depression risk predict the onset of depression.

Although research highlights neural correlates of Major Depressive Disorder (MDD), it is unclear whether these correlates reflect the state of depression or a pre-existing risk factor. The current study examined whether baseline differences in brain activations, resting-state connectivity, and brain structural differences between non-symptomatic children at high- and low-risk for MDD based on familial depression prospectively predict the onset of a depressive episode or increases in depressive symptomatology. We re-assessed 44 participants (28 high-risk; 16 low-risk) who had undergone neuroimaging in a previous study 3-4 years earlier (Mean age at follow-up = 14.3 years, SD = 1.9 years; 45% females; 70% Caucasian). We investigated whether baseline brain imaging data (including an emotional face match task fMRI, resting-state fMRI and structural MRI) that differentiated the risk groups also predicted the onset of depression. Resting-state functional connectivity abnormalities in the default mode and cognitive control network that differentiated high-risk from low-risk youth at baseline predicted the onset of MDD during adolescence, after taking risk status into account. Increased functional activation to both happy and fearful faces was associated with greater decreases in self-reported depression symptoms at follow-up. This preliminary evidence could be used to identify youth at-risk for depression and inform early intervention strategies.