Effects of general anaesthesia in early childhood on local and global visual processing: a post hoc analysis of the APEX cohort study.

BACKGROUND: Preclinical studies suggest that early exposure to anaesthesia alters the visual system in mice and non-human primates. We investigated whether exposure to general anaesthesia leads to visual attention processing changes in children, which could potentially impact essential life skills, including learning. METHODS: This was a post hoc analysis of data from the APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort study. A total of 24 healthy 9-10-yr-old children who were or were not exposed to general anaesthesia (for surgery) by a mean age of 3.8 (2.6) yr performed a visual attention task to evaluate ability to process either local details or general global visual information. Whether children were distracted by visual interference during global and local information processing was also assessed. RESULTS: Participants included in the analyses (n=12 participants exposed to general anaesthesia and n=12 controls) successfully completed (>90% of correct answers) the trial tasks. Children from both groups were equally distracted by visual interference. However, children who had been exposed to general anaesthesia were more attracted to global visual information than were control children (P=0.03). CONCLUSIONS: These findings suggest lasting effects of early-life exposure to general anaesthesia on visuospatial abilities. Further investigations of the mechanisms by which general anaesthesia could have delayed effects on how children perceive their visual environment are needed.

Human intraparietal sulcal morphology relates to individual differences in language and memory performance.

The sulco-gyral pattern is a qualitative feature of the cortical anatomy that is determined in utero, stable throughout lifespan and linked to brain function. The intraparietal sulcus (IPS) is a nodal associative brain area, but the relation between its morphology and cognition is largely unknown. By labelling the left and right IPS of 390 healthy participants into two patterns, according to the presence or absence of a sulcus interruption, here we demonstrate a strong association between the morphology of the right IPS and performance on memory and language tasks. We interpret the results as a morphological advantage of a sulcus interruption, probably due to the underlying white matter organization. The right-hemisphere specificity of this effect emphasizes the neurodevelopmental and plastic role of sulcus morphology in cognition prior to lateralisation processes. The results highlight a promising area of investigation on the relationship between cognitive performance, sulco-gyral pattern and white matter bundles.

Latent Network Analysis of Executive Functions Across Development.

Executive functions (EFs) are crucial for academic achievement, physical health, and mental well-being. Previous studies using structural equation models revealed EFs' developmental organization, evolving from one factor in childhood to three factors in adults: inhibition, cognitive flexibility, and updating. Recent network model studies confirmed this differentiation from childhood to adulthood. Reanalyzing previously published data from 1019 children (aged 7.8 to 15.3; 50.4% female; 59.1% White, 15.0% Latinx, 14.3% Bi-racial, 6.7% African American, 4.2% Asian American, 0.6% Other), this study compared three analytical methods to explore EF development: structural equation model, network model, and the novel latent variable network model. All approaches supported fine-grained EF-specific trajectories and differentiation throughout development, with inhibition being central in childhood and updating in early adolescence.

Are numerical abilities determined at early age? A brain morphology study in children and adolescents with and without developmental dyscalculia.

The intraparietal sulcus (IPS) has been associated with numerical processing. A recent study reported that the IPS sulcal pattern was associated with arithmetic and symbolic number abilities in children and adults. In the present study, we evaluated the link between numerical abilities and the IPS sulcal pattern in children with Developmental Dyscalculia (DD) and typically developing children (TD), extending previous analyses considering other sulcal features and the postcentral sulcus (PoCS). First, we confirm the longitudinal sulcal pattern stability of the IPS and the PoCS. Second, we found a lower proportion of left sectioned IPS and a higher proportion of a double-horizontal IPS shape bilaterally in DD compared to TD. Third, our analyses revealed that arithmetic is the only aspect of numerical processing that is significantly related to the IPS sulcal pattern (sectioned vs not sectioned), and that this relationship is specific to the left hemisphere. And last, correlation analyses of age and arithmetic in children without a sectioned left IPS indicate that although they may have an inherent disadvantage in numerical abilities, these may improve with age. Thus, our results indicate that only the left IPS sulcal pattern is related to numerical abilities and that other factors co-determine numerical abilities.

Orbitofrontal sulcal patterns in catatonia.

BACKGROUND: Catatonia is a psychomotor syndrome frequently observed in disorders with neurodevelopmental impairments, including psychiatric disorders such as schizophrenia. The orbitofrontal cortex (OFC) has been repeatedly associated with catatonia. It presents with an important interindividual morphological variability, with three distinct H-shaped sulcal patterns, types I, II, and III, based on the continuity of the medial and lateral orbital sulci. Types II and III have been identified as neurodevelopmental risk factors for schizophrenia. The sulcal pattern of the OFC has never been investigated in catatonia despite the role of the OFC in the pathophysiology and the neurodevelopmental component of catatonia. METHODS: In this context, we performed a retrospective analysis of the OFC sulcal pattern in carefully selected homogeneous and matched subgroups of schizophrenia patients with catatonia (N = 58) or without catatonia (N = 65), and healthy controls (N = 82). RESULTS: Logistic regression analyses revealed a group effect on OFC sulcal pattern in the left (χ2 = 18.1; p < .001) and right (χ2 = 28.3; p < .001) hemispheres. Catatonia patients were found to have more type III and less type I in both hemispheres compared to healthy controls and more type III on the left hemisphere compared to schizophrenia patients without catatonia. CONCLUSION: Because the sulcal patterns are indirect markers of early brain development, our findings support a neurodevelopmental origin of catatonia and may shed light on the pathophysiology of this syndrome.

Lateralization of the cerebral network of inhibition in children before and after cognitive training.

Inhibitory control (IC) plays a critical role in cognitive and socio-emotional development. IC relies on a lateralized cortico-subcortical brain network including the inferior frontal cortex, anterior parts of insula, anterior cingulate cortex, caudate nucleus and putamen. Brain asymmetries play a critical role for IC efficiency. In parallel to age-related changes, IC can be improved following training. The aim of this study was to (1) assess the lateralization of IC network in children (N = 60, 9-10 y.o.) and (2) examine possible changes in neural asymmetry of this network from anatomical (structural MRI) and functional (resting-state fMRI) levels after 5-week computerized IC vs. active control (AC) training. We observed that IC training, but not AC training, led to a leftward lateralization of the putamen anatomy, similarly to what is observed in adults, supporting that training could accelerate the maturation of this structure.

Differential effects of mindfulness meditation and cognitive training on cool and hot inhibitory control in children and adolescents.

Inhibitory control (IC) can occur either in a neutral context (cool) or in social contexts involving emotions (hot). Cool and hot IC have specific developmental trajectories; cool IC develops linearly from childhood to adulthood, whereas hot IC follows a quadratic trajectory. Some activities can improve the IC, such as cognitive training (CT) and mindfulness meditation (MM). The aim of our study was to compare the effects of 5 weeks of computerized MM versus CT on IC performance in 66 children (9-10 years old) and 63 adolescents (16-17 years old) by specifically analyzing cool and hot dimensions in the same participants and from a developmental perspective. We fit a linear mixed-effect model on the Stroop interference score with time (pretest vs. posttest) and type of conflict (cool vs. hot) as within-participant factors and intervention group (CT vs. MM) and age group (child vs. adolescent) as between-participant factors. The findings revealed that children but not adolescents benefitted from interventions. More specifically, CT improved cool IC but not hot IC, whereas MM practice improved hot IC but not cool IC. This study supports the benefits of MM at a young age. Theoretical issues linking MM programs to emotional competence grounded in hot IC skills are considered in academic settings.

Consequences of General Anesthesia in Infancy on Behavior and Brain Structure.

BACKGROUND: One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes. METHODS: A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy. RESULTS: The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4-80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5-14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33-9.10; P = .06) and a 6.1% (95% CI, 4.3-7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure. CONCLUSIONS: The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.

The effect of early trauma on suicidal vulnerability depends on fronto-insular sulcation.

Improving our understanding of pathophysiology of suicidal behavior (SB) is an important step for prevention. Assessment of suicide risk is based on socio-demographic and clinical risk factors with a poor predictivity. Current understanding of SB is based on a stress-vulnerability model, whereby early-life adversities are predominant. SB may thus result from a cascade of developmental processes stemming from early-life abuse and/or neglect. Some cerebral abnormalities, particularly in fronto-limbic regions, might also provide vulnerability to develop maladaptive responses to stress, leading to SB. We hypothesized that SB is associated with interactions between early trauma and neurodevelopmental deviations of the frontal and insular cortices. We recruited 86 euthymic women, including 44 suicide attempters (history of depression and SB) and 42 affective controls (history of depression without SB). The early development of prefrontal cortex (PFC) and insula was inferred using 3D magnetic resonance imaging-derived regional sulcation indices, which are indirect markers of early neurodevelopment. The insula sulcation index was higher in emotional abused subjects; among those patients, PFC sulcation index was reduced in suicide attempters, but not in affective controls. Such findings provide evidence that SB likely traced back to early stages of brain development in interaction with later environmental factors experienced early in life.

A network analysis of executive functions before and after computerized cognitive training in children and adolescents.

Executive functions (EFs) play a key role in cognitive and socioemotional development. Factor analyses have revealed an age dependent structure of EFs spanning from a single common factor in early childhood to three factors in adults corresponding to inhibitory control (IC), switching and updating. IC performances change not only with age but also with cognitive training. Surprisingly, few studies have investigated training-related changes in EFs structure. We used the regularized partial correlation network model to analyze EFs structure in 137 typically developing children (9-10 years) and adolescents (15-17 years) before and after computerized cognitive training. Network models (NMs) -a graph theory-based approach allowing us to describe the structure of complex systems- can provide a priori free insight into EFs structures. We tested the hypothesis that training-related changes may mimic developmental-related changes. Quantitative and qualitative changes were detected in the EFs network structure with age and also with cognitive training. Of note, the EFs network structure in children after training was more similar to adolescents' networks than before training. This study provided the first evidence of structural changes in EFs that are age and training-dependent and supports the hypothesis that training could accelerate the development of some structural aspects of EFs. Due to the sample size, these findings should be considered preliminary before replication in independent larger samples.

Towards Deciphering the Fetal Foundation of Normal Cognition and Cognitive Symptoms From Sulcation of the Cortex.

Growing evidence supports that prenatal processes play an important role for cognitive ability in normal and clinical conditions. In this context, several neuroimaging studies searched for features in postnatal life that could serve as a proxy for earlier developmental events. A very interesting candidate is the sulcal, or sulco-gyral, patterns, macroscopic features of the cortex anatomy related to the fold topology-e.g., continuous vs. interrupted/broken fold, present vs. absent fold-or their spatial organization. Indeed, as opposed to quantitative features of the cortical sheet (e.g., thickness, surface area or curvature) taking decades to reach the levels measured in adult, the qualitative sulcal patterns are mainly determined before birth and stable across the lifespan. The sulcal patterns therefore offer a window on the fetal constraints on specific brain areas on cognitive abilities and clinical symptoms that manifest later in life. After a global review of the cerebral cortex sulcation, its mechanisms, its ontogenesis along with methodological issues on how to measure the sulcal patterns, we present a selection of studies illustrating that analysis of the sulcal patterns can provide information on prenatal dispositions to cognition (with a focus on cognitive control and academic abilities) and cognitive symptoms (with a focus on schizophrenia and bipolar disorders). Finally, perspectives of sulcal studies are discussed.

Automatic recognition of specific local cortical folding patterns.

The study of local cortical folding patterns showed links with psychiatric illnesses as well as cognitive functions. Despite the tools now available to visualize cortical folds in 3D, manually classifying local sulcal patterns is a time-consuming and tedious task. In fact, 3D visualization of folds helps experts to identify different sulcal patterns but fold variability is so high that the distinction between these patterns sometimes requires the definition of complex criteria, making manual classification difficult and not reliable. However, the assessment of the impact of these patterns on the functional organization of the cortex could benefit from the study of large databases, especially when studying rare patterns. In this paper, several algorithms for the automatic classification of fold patterns are proposed to allow morphological studies to be extended and confirmed on such large databases. Three methods are proposed, the first based on a Support Vector Machine (SVM) classifier, the second on the Scoring by Non-local Image Patch Estimator (SNIPE) approach and the third based on a 3D Convolution Neural Network (CNN). These methods are generic enough to be applicable to a wide range of folding patterns. They are tested on two types of patterns for which there is currently no method to automatically identify them: the Anterior Cingulate Cortex (ACC) patterns and the Power Button Sign (PBS). The two ACC patterns are almost equally present whereas PBS is a particularly rare pattern in the general population. The three models proposed achieve balanced accuracies of approximately 80% for ACC patterns classification and 60% for PBS classification. The CNN-based model is more interesting for the classification of ACC patterns thanks to its rapid execution. However, SVM and SNIPE-based models are more effective in managing unbalanced problems such as PBS recognition.

Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine.

INTRODUCTION: Urgent action is needed to fight the ongoing coronavirus disease 2019 (COVID-19) pandemic by reducing the number of infected cases, contagiousness and severity. Chlorpromazine (CPZ), an antipsychotic from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and has antiviral activity against severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus. The aim of this in-vitro study was to test CPZ against SARS-CoV-2 in monkey and human cells. MATERIALS AND METHODS: Monkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in the presence of various concentrations of CPZ. Supernatants were harvested at day 2 and analysed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for the presence of SARS-CoV-2 RNA. Cell viability was assessed in non-infected cells. RESULTS: CPZ was found to have antiviral activity against SARS-CoV-2 in monkey VeroE6 cells, with a half maximal inhibitory concentration (IC50) of 8.2 µM, half maximal cytotoxic concentration (CC50) of 13.5 µM, and selectivity index (SI) of 1.65. In human A549-ACE2 cells, CPZ was also found to have anti-SARS-CoV-2 activity, with IC50 of 11.3 µM, CC50 of 23.1 µM and SI of 2.04. DISCUSSION: Although the measured SI values are low, the IC50 values measured in vitro may translate to CPZ dosages used in routine clinical practice because of the high biodistribution of CPZ in lungs and saliva. Also, the distribution of CPZ in brain could be of interest for treating or preventing neurological and psychiatric forms of COVID-19. CONCLUSIONS: These preclinical findings support clinical investigation of the repurposing of CPZ, a drug with mild side effects, in the treatment of patients with COVID-19.

The forest, the trees, and the leaves in preterm children: the impact of prematurity on a visual search task containing three-level hierarchical stimuli.

Very preterm (VPT; < 33 gestational weeks) children are at risk of developing visuospatial deficits, including local/global attention deficits. They are also more likely to develop poorer inhibitory control. Here, we investigated, using the same stimuli, the potential local/global attention and inhibitory control deficits of VPT children using three levels compound stimuli (global, intermediate, and local levels), more ecological than the ones used in a classic global/local task (Navon task). We compared the results from 22 VPT children to those of a control group of 21 children to investigate (1) how VPT children processed compound stimuli with three-level information and (2) how inhibitory control in a visual task differs between VPT and control children. The results revealed that VPT children had no difficulty processing information presented at the local level. By contrast, VPT children were impaired when considering the intermediate and global levels of processing in comparison to control children. Finally, a reduced efficiency in VPT children in inhibiting visual distractors was evidenced for the conditions with a larger number of distractors. These results are discussed in terms of neurodevelopmental disorders of both dorsal stream (global visual processing) and prefrontal regions (inhibitory control) in VPT children. Given the central role of visuospatial and inhibitory control in day-to-day situations, the present results provide important clues for pedagogical implications regarding the organization of visual information presented to VPT children.

Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia.

All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.

Deviations in early hippocampus development contribute to visual hallucinations in schizophrenia.

Auditory hallucinations (AHs) are certainly the most emblematic experiences in schizophrenia, but visual hallucinations (VHs) are also commonly observed in this developmental psychiatric disorder. Notably, several studies have suggested a possible relationship between the clinical variability in hallucinations' phenomenology and differences in brain development/maturation. In schizophrenia, impairments of the hippocampus, a medial temporal structure involved in mnesic and neuroplastic processes, have been repeatedly associated with hallucinations, particularly in the visual modality. However, the possible neurodevelopmental origin of hippocampal impairments in VHs has never been directly investigated. A classic marker of early atypical hippocampal development is incomplete hippocampal inversion (IHI). In this study, we compared IHI patterns in healthy volunteers, and two subgroups of carefully selected schizophrenia patients experiencing frequent hallucinations: (a) those with pure AHs and (b) those with audio-visual hallucinations (A+VH). We found that VHs were associated with a specific IHI pattern. Schizophrenia patients with A+VH exhibited flatter left hippocampi than patients with pure AHs or healthy controls. This result first confirms that the greater clinical impairment observed in A+VH patients may relate to an increased neurodevelopmental weight in this subpopulation. More importantly, these findings bring crucial hints to better specify the sensitivity period of A+VH-related IHI during early brain development.

Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence.

A number of training interventions have been designed to improve executive functions and inhibitory control (IC) across the lifespan. Surprisingly, no study has investigated the structural neuroplasticity induced by IC training from childhood to late adolescence, a developmental period characterized by IC efficiency improvement and protracted maturation of prefrontal cortex (PFC) subregions involved in IC. The aim of the present study was to investigate the behavioral and structural changes induced by a 5-week computerized and adaptive IC training in school-aged children (10-year-olds) and in adolescents (16-year-olds). Sixty-four children and 59 adolescents were randomly assigned to an IC (i.e. Color-Word Stroop and Stop-Signal tasks) or an active control (AC) (knowledge- and vocabulary-based tasks) training group. In the pre- and posttraining sessions, participants performed the Color-Word Stroop and Stop-signal tasks, and an anatomical resonance imaging (MRI) was acquired for each of them. Children's IC efficiency improved from the pre- to the posttraining session in boys but not in girls. In adolescents, IC efficiency did not improve after IC training. Similar to the neuroplastic mechanisms observed during brain maturation, we observed IC training-related changes in cortical thickness and cortical surface area in several PFC subregions (e.g. the pars opercularis, triangularis, and orbitalis of the inferior frontal gyri) that were age- and gender-specific. Because no correction for multiple comparisons was applied, the results of our study provide only preliminary evidence of the complex structural neuroplastic mechanisms at the root of behavioral changes in IC efficiency from pre- to posttraining in school-aged children and adolescents.

The local properties of bold signal fluctuations at rest monitor inhibitory control training in adolescents.

Inhibitory control (IC) plays a critical role in cognitive and socio-emotional development. Short-term IC training improves IC abilities in children and adults. Surprisingly, few studies have investigated the IC training effect during adolescence, a developmental period characterized by high neuroplasticity and the protracted development of IC abilities. We investigated behavioural and functional brain changes induced by a 5-week computerized and adaptive IC training in adolescents. We focused on the IC training effects on the local properties of functional Magnetic Resonance Imaging (fMRI) signal fluctuations at rest (i.e., Regional Homogeneity [ReHo] and fractional Amplitude of Low Frequency Fluctuations [fALFF]). Sixty adolescents were randomly assigned to either an IC or an active control training group. In the pre- and post-training sessions, cognitive ('Cool') and emotional ('Hot') IC abilities were assessed using the Colour-Word and Emotional Stroop tasks. We found that ReHo and fALFF signals in IC areas (IFG, ACC, Striatum) were associated with IC efficiency at baseline. This association was different for Cool and Hot IC. Analyses also revealed that ReHo and fALFF signals were sensitive markers to detect and monitor changes after IC training, while behavioural data did not, suggesting that brain functional changes at rest precede behavioural changes following training.

A Resting-State Functional MR Imaging and Spectroscopy Study of the Dorsal Hippocampus in the Chronic Unpredictable Stress Rat Model.

Exposure to chronic stress leads to an array of anatomical, functional, and metabolic changes in the brain that play a key role in triggering psychiatric disorders such as depression. The hippocampus is particularly well known as a target of maladaptive responses to stress. To capture stress-induced changes in metabolic and functional connectivity in the hippocampus, stress-resistant (low-responders) or -susceptible (high-responders) rats exposed to a chronic unpredictable stress paradigm (categorized according to their hormonal and behavioral responses) were assessed by multimodal neuroimaging; the latter was achieved by using localized 1H MR spectroscopy and resting-state functional MRI (fMRI) at 11,7T data from stressed (n = 25) but also control (n = 15) male Wistar rats.Susceptible animals displayed increased GABA-glutamine (+19%) and glutamate-glutamine (+17%) ratios and decreased levels of macromolecules (-11%); these changes were positively correlated with plasma corticosterone levels. In addition, the neurotransmitter levels showed differential associations with functional connectivity between the hippocampus and the amygdala, the piriform cortex and thalamus between stress-resistant and -susceptible animals. Our observations are consistent with previously reported stress-induced metabolomic changes that suggest overall neurotransmitter dysfunction in the hippocampus. Their association with the fMRI data in this study reveals how local adjustments in neurochemistry relate to changes in the neurocircuitry of the hippocampus, with implications for its stress-associated dysfunctions.SIGNIFICANCE STATEMENT Chronic stress disrupts brain homeostasis, which may increase the vulnerability of susceptible individuals to neuropsychiatric disorders such as depression. Characterization of the differences between stress-resistant and -susceptible individuals on the basis of noninvasive imaging tools, such as magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI), contributes to improved understanding of the mechanisms underpinning individual differences in vulnerability and can facilitate the design of new diagnostic and intervention strategies. Using a combined functional MRI/MRS approach, our results demonstrate that susceptible- and non-susceptible subjects show differential alterations in hippocampal GABA and glutamate metabolism that, in turn, associate with changes in functional connectivity.

ACC Sulcal Patterns and Their Modulation on Cognitive Control Efficiency Across Lifespan: A Neuroanatomical Study on Bilinguals and Monolinguals.

The anterior cingulate cortex (ACC) is a key structure implicated in the regulation of cognitive control (CC). Previous studies suggest that variability in the ACC sulcal pattern-a neurodevelopmental marker unaffected by maturation or plasticity after birth-is associated with intersubject differences in CC performance. Here, we investigated whether bilingual experience modulates the effects of ACC sulcal variability on CC performance across the lifespan. Using structural MRI, we first established the distribution of the ACC sulcal patterns in a large sample of healthy individuals (N = 270) differing on gender and ethnicity. Second, a participants' subsample (N = 157) was selected to test whether CC performance was differentially affected by ACC sulcation in bilinguals and monolinguals across age. A prevalent leftward asymmetry unaffected by gender or ethnicity was reported. Sulcal variability in the ACC predicted CC performance differently in bilinguals and monolinguals, with a reversed pattern of structure-function relationship: asymmetrical versus symmetrical ACC sulcal patterns were associated with a performance advantage in monolinguals and a performance detriment to bilinguals and vice versa. Altogether, these findings provide novel insights on the dynamic interplay between early neurodevelopment, environmental background and cognitive efficiency across age.