The "central" importance of loneliness in mental health: A network psychometric study.

Loneliness is linked to negative mental health outcomes like depression and social anxiety. However, it is unclear how loneliness and these conditions are connected. This study aims to address two questions: (a) Are there pathways connecting loneliness to these conditions? (b) What symptoms play a role in these pathways? Using network analyses, the study examined a representative sample of 962 adults from the UK (mean age = 46, females = 492). The network analysis revealed four dimensions: depression, social anxiety and two dimensions for loneliness (isolation and social connectedness). Two distinct pathways were identified for the transmission of symptoms between loneliness, social anxiety and depression. The depression-isolation pathway involved a node representing the perceived loss of social connections. The social anxiety-social connectedness pathway was characterised by intimate interaction contexts. These findings suggest that loneliness is associated with different symptom pathways, potentially contributing to comorbidity between loneliness, social anxiety and depression.

Robust BOLD Responses to Faces But Not to Conditioned Threat: Challenging the Amygdala's Reputation in Human Fear and Extinction Learning.

Most of our knowledge about human emotional memory comes from animal research. Based on this work, the amygdala is often labeled the brain's "fear center", but it is unclear to what degree neural circuitries underlying fear and extinction learning are conserved across species. Neuroimaging studies in humans yield conflicting findings, with many studies failing to show amygdala activation in response to learned threat. Such null findings are often treated as resulting from MRI-specific problems related to measuring deep brain structures. Here we test this assumption in a mega-analysis of three studies on fear acquisition (n = 98; 68 female) and extinction learning (n = 79; 53 female). The conditioning procedure involved the presentation of two pictures of faces and two pictures of houses: one of each pair was followed by an electric shock [a conditioned stimulus (CS+)], the other one was never followed by a shock (CS-), and participants were instructed to learn these contingencies. Results revealed widespread responses to the CS+ compared with the CS- in the fear network, including anterior insula, midcingulate cortex, thalamus, and bed nucleus of the stria terminalis, but not the amygdala, which actually responded stronger to the CS- Results were independent of spatial smoothing, and of individual differences in trait anxiety and conditioned pupil responses. In contrast, robust amygdala activation distinguished faces from houses, refuting the idea that a poor signal could account for the absence of effects. Moving forward, we suggest that, apart from imaging larger samples at higher resolution, alternative statistical approaches may be used to identify cross-species similarities in fear and extinction learning.SIGNIFICANCE STATEMENT The science of emotional memory provides the foundation of numerous theories on psychopathology, including stress and anxiety disorders. This field relies heavily on animal research, which suggests a central role of the amygdala in fear learning and memory. However, this finding is not strongly corroborated by neuroimaging evidence in humans, and null findings are too easily explained away by methodological limitations inherent to imaging deep brain structures. In a large nonclinical sample, we find widespread BOLD activation in response to learned fear, but not in the amygdala. A poor signal could not account for the absence of effects. While these findings do not disprove the involvement of the amygdala in human fear learning, they challenge its typical portrayals and illustrate the complexities of translational science.

Temperament and psychopathology: The "community" to which you belong matters.

We utilized a community detection approach to longitudinally (a) identify distinct groups of children with common temperament profiles in infancy and at 2 and 3 years of age and (b) determine whether co-occurrence of certain temperament traits may be early predictors of internalizing problems at 5 years of age. Seven hundred and seventy-four infants (360 girls; 88.6% White, 9.8% Hispanic, and 1.6% other races) were recruited from the Boston area. Data collection spanned from 2012 to 2021. The analysis yielded three distinct groups of children with different temperament traits and was associated with significant variation in levels of internalizing symptoms and anxiety diagnosis rate. Our findings suggest that stable temperament "communities" can be detected in early childhood and may predict risk for psychopathology later in life.

A Hierarchical Watershed Model of Fluid Intelligence in Childhood and Adolescence.

Fluid intelligence is the capacity to solve novel problems in the absence of task-specific knowledge and is highly predictive of outcomes like educational attainment and psychopathology. Here, we modeled the neurocognitive architecture of fluid intelligence in two cohorts: the Centre for Attention, Leaning and Memory sample (CALM) (N = 551, aged 5-17 years) and the Enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) (N = 335, aged 6-17 years). We used multivariate structural equation modeling to test a preregistered watershed model of fluid intelligence. This model predicts that white matter contributes to intermediate cognitive phenotypes, like working memory and processing speed, which, in turn, contribute to fluid intelligence. We found that this model performed well for both samples and explained large amounts of variance in fluid intelligence (R2CALM = 51.2%, R2NKI-RS = 78.3%). The relationship between cognitive abilities and white matter differed with age, showing a dip in strength around ages 7-12 years. This age effect may reflect a reorganization of the neurocognitive architecture around pre- and early puberty. Overall, these findings highlight that intelligence is part of a complex hierarchical system of partially independent effects.

Just a phase? Mapping the transition of behavioural problems from childhood to adolescence.

PURPOSE: Young people change substantially between childhood and adolescence. Yet, the current description of behavioural problems does not incorporate any reference to the developmental context. In the current analysis, we aimed to identify common transitions of behavioural problems between childhood and adolescence. METHOD: We followed 6744 individuals over 6 years as they transitioned from childhood (age 10) into adolescence (age 16). At each stage, we used a data-driven hierarchical clustering method to identify common profiles of behavioural problems, map transitions between profiles and identify factors that predict specific transitions. RESULTS: Common profiles of behavioural problems matched known comorbidity patterns but crucially showed that the presentation of behavioural problems changes markedly between childhood and adolescence. While problems with hyperactivity/impulsivity, motor control and conduct were prominent in childhood, adolescents showed profiles of problems related to emotional control, anxiety and inattention. Transitions were associated with socio-economic status and cognitive performance in childhood CONCLUSION: We show that understanding behavioural difficulties and mental ill-health must take into account the developmental context in which the problems occur, and we establish key risk factors for specific negative transitions as children become adolescents.

Mapping differential responses to cognitive training using machine learning.

We used two simple unsupervised machine learning techniques to identify differential trajectories of change in children who undergo intensive working memory (WM) training. We used self-organizing maps (SOMs)-a type of simple artificial neural network-to represent multivariate cognitive training data, and then tested whether the way tasks are represented changed as a result of training. The patterns of change we observed in the SOM weight matrices implied that the processes drawn upon to perform WM tasks changed following training. This was then combined with K-means clustering to identify distinct groups of children who respond to the training in different ways. Firstly, the K-means clustering was applied to an independent large sample (N = 616, Mage  = 9.16 years, range = 5.16-17.91 years) to identify subgroups. We then allocated children who had been through cognitive training (N = 179, Mage  = 9.00 years, range = 7.08-11.50 years) to these same four subgroups, both before and after their training. In doing so, we were able to map their improvement trajectories. Scores on a separate measure of fluid intelligence were predictive of a child's improvement trajectory. This paper provides an alternative approach to analysing cognitive training data that go beyond considering changes in individual tasks. This proof-of-principle demonstrates a potentially powerful way of distinguishing task-specific from domain-general changes following training and of establishing different profiles of response to training.

Brain structure in children with congenital visual disorders and visual impairment.

AIM: To examine if congenital visual impairment is associated with differences in brain anatomy in children. METHOD: Ten children (8-12y) with congenital disorders of the peripheral visual system with severe visual impairment (SVI; >0.8 logMAR) or mild-to-moderate visual impairment (MVI; 0.6-0.8 logMAR) were compared to 21 typically sighted comparison (TSC) children. Thalamus volume, grey matter density, white matter microstructure, and integrity of visual tracts were investigated in SVI, MVI, and TSC groups with anatomical and diffusion-weighted magnetic resonance imaging. RESULTS: Compared to the TSC group, the SVI group had lower white matter integrity in tracts of the visual system (optic radiations: SVI 0.35±0.015, TSC 0.39±0.007 [p=0.022]; posterior corpus callosum: SVI 0.37±0.019; TSC 0.42±0.009 [p=0.033]) and lower left thalamus volume (SVI 4.37±0.087; TSC 4.99±0.339 [p=0.015]). Neuroanatomical differences were greater in the SVI group, while no consistent differences between the MVI and TSC group were observed. INTERPRETATION: Posterior tracts of the visual system are compromised in children with congenital visual impairment versus those who are typically sighted. The severity of visual input appears to have affected neuroanatomical development as significant reductions were only found in the SVI group. WHAT THIS PAPER ADDS: Severe visual impairment in mid-childhood is associated with reduced integrity of visual pathways and reduced thalamus volume.

Remapping the cognitive and neural profiles of children who struggle at school.

Our understanding of learning difficulties largely comes from children with specific diagnoses or individuals selected from community/clinical samples according to strict inclusion criteria. Applying strict exclusionary criteria overemphasizes within group homogeneity and between group differences, and fails to capture comorbidity. Here, we identify cognitive profiles in a large heterogeneous sample of struggling learners, using unsupervised machine learning in the form of an artificial neural network. Children were referred to the Centre for Attention Learning and Memory (CALM) by health and education professionals, irrespective of diagnosis or comorbidity, for problems in attention, memory, language, or poor school progress (n = 530). Children completed a battery of cognitive and learning assessments, underwent a structural MRI scan, and their parents completed behavior questionnaires. Within the network we could identify four groups of children: (a) children with broad cognitive difficulties, and severe reading, spelling and maths problems; (b) children with age-typical cognitive abilities and learning profiles; (c) children with working memory problems; and (d) children with phonological difficulties. Despite their contrasting cognitive profiles, the learning profiles for the latter two groups did not differ: both were around 1 SD below age-expected levels on all learning measures. Importantly a child's cognitive profile was not predicted by diagnosis or referral reason. We also constructed whole-brain structural connectomes for children from these four groupings (n = 184), alongside an additional group of typically developing children (n = 36), and identified distinct patterns of brain organization for each group. This study represents a novel move toward identifying data-driven neurocognitive dimensions underlying learning-related difficulties in a representative sample of poor learners.

Children's academic attainment is linked to the global organization of the white matter connectome.

Literacy and numeracy are important skills that are typically learned during childhood, a time that coincides with considerable shifts in large-scale brain organization. However, most studies emphasize focal brain contributions to literacy and numeracy development by employing case-control designs and voxel-by-voxel statistical comparisons. This approach has been valuable, but may underestimate the contribution of overall brain network organization. The current study includes children (N = 133 children; 86 male; mean age = 9.42, SD = 1.715; age range = 5.92-13.75y) with a broad range of abilities, and uses whole-brain structural connectomics based on diffusion-weighted MRI data. The results indicate that academic attainment is associated with differences in structural brain organization, something not seen when focusing on the integrity of specific regions. Furthermore, simulated disruption of highly-connected brain regions known as hubs suggests that the role of these regions for maintaining the architecture of the network may be more important than specific aspects of processing. Our findings indicate that distributed brain systems contribute to the etiology of difficulties with academic learning, which cannot be captured using a more traditional voxel-wise statistical approach.

Differences in brain morphology and working memory capacity across childhood.

Working memory (WM) skills are closely associated with learning progress in key areas such as reading and mathematics across childhood. As yet, however, little is known about how the brain systems underpinning WM develop over this critical developmental period. The current study investigated whether and how structural brain correlates of components of the working memory system change over development. Verbal and visuospatial short-term and working memory were assessed in 153 children between 5.58 and 15.92 years, and latent components of the working memory system were derived. Fractional anisotropy and cortical thickness maps were derived from T1-weighted and diffusion-weighted MRI and processed using eigenanatomy decomposition. There was a greater involvement of the corpus callosum and posterior temporal white matter in younger children for performance associated with the executive part of the working memory system. For older children, this was more closely linked with the thickness of the occipitotemporal cortex. These findings suggest that increasing specialization leads to shifts in the contribution of neural substrates over childhood, moving from an early dependence on a distributed system supported by long-range connections to later reliance on specialized local circuitry. Our findings demonstrate that despite the component factor structure being stable across childhood, the underlying brain systems supporting working memory change. Taking the age of the child into account, and not just their overall score, is likely to be critical for understanding the nature of the limitations on their working memory capacity.