Search

Summary: Background: Depressive symptoms are rising in the general population, but their associated factors are unclear. Although the link between sleep disturbances and depressive symptoms severity (DSS) is reported, the predictive role of sleep on DSS and the impact of anxiety and the brain on their relationship remained obscure. Methods: Using three population-based datasets (N = 1813), we trained the machine learning models in the primary dataset (N = 1101) to assess the predictive role of sleep quality, anxiety problems, and brain structural (and functional) measurements on DSS, then we tested our models’ performance in two independent datasets (N = 378, N = 334) to test the generalizability of our findings. Furthermore, we applied our model to a smaller longitudinal subsample (N = 66). In addition, we performed a mediation analysis to identify the role of anxiety and brain measurements on the sleep quality and DSS association. Findings: Sleep quality could predict individual DSS (r = 0.43, R2 = 0.18, rMSE = 2.73), and adding anxiety, contrary to brain measurements, strengthened its prediction performance (r = 0.67, R2 = 0.45, rMSE = 2.25). Importantly, out-of-cohort validations in other cross-sectional datasets and a longitudinal subsample provided robust similar results. Furthermore, anxiety scores, contrary to brain measurements, mediated the association between sleep quality and DSS. Interpretation: Poor sleep quality could predict DSS at the individual subject level across three datasets. Anxiety scores not only increased the predictive model's performance but also mediated the link between sleep quality and DSS. Funding: The study is supported by Helmholtz Imaging Platform grant (NimRLS, ZTI-PF-4-010), the Deutsche Forschungsgemeinschaft (DFG, GE 2835/2–1, GE 2835/4-1), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 431549029—SFB 1451, the programme “Profilbildung 2020” (grant no. PROFILNRW-2020-107-A), an initiative of the Ministry of Culture and Science of the State of Northrhine Westphalia.

Abstract Sleep health is both conceptually and operationally a composite concept containing multiple domains of sleep. In line with this, high dependence and interaction across different domains of sleep health encourage a transition in sleep health research from categorical to dimensional approaches that integrate neuroscience and sleep health. Here, we seek to identify the covariance patterns between multiple sleep health domains and distributed intrinsic functional connectivity by applying a multivariate approach (partial least squares). This multivariate analysis reveals a composite sleep health dimension co-varying with connectivity patterns involving the attentional and thalamic networks and which appear relevant at the neuromolecular level. These findings are further replicated and generalized to several unseen independent datasets. Critically, the identified sleep-health related connectome shows diagnostic potential for insomnia disorder. These results together delineate a potential brain connectome biomarker for sleep health with high potential for clinical translation.

Multivariate brain-behaviour associations are studied with regularized canonical correlation analysis and a machine learning framework, showing that behavioural inter-individual variability is linked to inter-individual variability in brain structure.

Abstract The study of associations between inter-individual differences in brain structure and behaviour has a long history in psychology and neuroscience. Many associations between psychometric data, particularly intelligence and personality measures and local variations of brain structure have been reported. While the impact of such reported associations often goes beyond scientific communities, resonating in the public mind, their replicability is rarely evidenced. Previously, we have shown that associations between psychometric measures and estimates of grey matter volume (GMV) result in rarely replicated findings across large samples of healthy adults. However, the question remains if these observations are at least partly linked to the multidetermined nature of the variations in GMV, particularly within samples with wide age-range. Therefore, here we extended those evaluations and empirically investigated the replicability of associations of a broad range of psychometric variables and cortical thickness in a large cohort of healthy young adults. In line with our observations with GMV, our current analyses revealed low likelihood of significant associations and their rare replication across independent samples. We here discuss the implications of these findings within the context of accumulating evidence of the general poor replicability of structural-brain-behaviour associations, and more broadly of the replication crisis.

An increasing number of studies have investigated the relationships between inter-individual variability in brain regions’ connectivity and behavioral phenotypes, making use of large population neuroimaging datasets. However, the replicability of brain-behavior associations identified by these approaches remains an open question. In this study, we examined the cross-dataset replicability of brain-behavior association patterns for fluid cognition and openness predictions using a previously developed region-wise approach, as well as using a standard whole-brain approach. Overall, we found moderate similarity in patterns for fluid cognition predictions across cohorts, especially in the Human Connectome Project Young Adult, Human Connectome Project Aging, and Enhanced Nathan Kline Institute Rockland Sample cohorts, but low similarity in patterns for openness predictions. In addition, we assessed the generalizability of prediction models in cross-dataset predictions, by training the model in one dataset and testing in another. Making use of the region-wise prediction approach, we showed that first, a moderate extent of generalizability could be achieved with fluid cognition prediction, and that, second, a set of common brain regions related to fluid cognition across cohorts could be identified. Nevertheless, the moderate replicability and generalizability could only be achieved in specific contexts. Thus, we argue that replicability and generalizability in connectivity-based prediction remain limited and deserve greater attention in future studies.

High co-morbidity and substantial overlap across psychiatric disorders encourage a transition in psychiatry research from categorical to dimensional approaches that integrate neuroscience and psychopathology. Converging evidence suggests that the cerebellum is involved in a wide range of cognitive functions and mental disorders. An important question thus centers on the extent to which cerebellar function can be linked to transdiagnostic dimensions of psychopathology. To address this question, we used a multivariate data-driven statistical technique (partial least squares) to identify latent dimensions linking human cerebellar connectome as assessed by functional MRI to a large set of clinical, cognitive, and trait measures across 198 participants, including healthy controls (n = 92) as well as patients diagnosed with attention-deficit/hyperactivity disorder (n = 35), bipolar disorder (n = 36), and schizophrenia (n = 35). Macroscale spatial gradients of connectivity at voxel level were used to characterize cerebellar connectome properties, which provide a low-dimensional representation of cerebellar connectivity, i.e., a sensorimotor-supramodal hierarchical organization. This multivariate analysis revealed significant correlated patterns of cerebellar connectivity gradients and behavioral measures that could be represented into four latent dimensions: general psychopathology, impulsivity and mood, internalizing symptoms and executive dysfunction. Each dimension was associated with a unique spatial pattern of cerebellar connectivity gradients across all participants. Multiple control analyses and 10-fold cross-validation confirmed the robustness and generalizability of the yielded four dimensions. These findings highlight the relevance of cerebellar connectivity as a necessity for the study and classification of transdiagnostic dimensions of psychopathology and call on researcher to pay more attention to the role of cerebellum in the dimensions of psychopathology, not just within the cerebral cortex.