Depression is closely associated with abnormalities in brain function. Traditional static functional connectivity analyses offer limited insight into the temporal variability of brain activity. Recent advances in dynamic analyses enable a deeper understanding of how depression relates to temporal fluctuations in brain activity.

This study utilized a large resting-state functional magnetic resonance imaging dataset (N = 696) to examine the association between brain dynamics and depression. Two complementary approaches were employed. Hidden Markov modeling (HMM) was used to identify discrete brain states and quantify their temporal switching patterns; temporal variability was computed within and between large-scale functional networks to capture time-varying fluctuations in functional connectivity.

Depression scores were positively associated with switching rate and negatively associated with maximum fractional occupancy. Furthermore, depression scores were significantly associated with greater temporal variability both within and between networks, with particularly strong effects observed in the default mode network, ventral attention network, and frontoparietal network. Together, these findings suggest that individuals with higher depression scores exhibit more unstable brain dynamics.

Our findings reveal that individuals with higher depression levels exhibit greater instability in brain state transitions and increased temporal variability in functional connectivity across large-scale networks. This instability in brain dynamics may contribute to difficulties in emotion regulation and cognitive control. By capturing whole-brain temporal patterns, this study offers a novel perspective on the neural basis of depression.

Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES).

Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation. Connectome features of each CAP were derived using an edge-centric method. The occurrence for each CAP and the balance ratio for antagonistic CAPs were calculated and compared between two groups, and correlations between temporal dynamic metrics and symptom burdens were explored.

Functional reconfigurations in CAPs exhibited significant differences between the activation and deactivation states of SN. During SN activation, FES more frequently recruited a CAP characterized by activated default network, language network, control network, and the caudate, compared to HCs (F = 8.54, FDR-p = 0.030). Moreover, FES displayed a tilted balance towards a CAP featuring SN-coactivation with the control network, caudate, and thalamus, as opposed to its antagonistic CAP (F = 7.48, FDR-p = 0.030). During SN deactivation, FES exhibited increased recruitment of a CAP with activated visual and dorsal attention networks but decreased recruitment of its opposing CAP (F = 6.58, FDR-p = 0.034).

Our results suggest that neuroregulatory dysfunction in dopaminergic pathways involving SN potentially mediates aberrant time-varying functional reorganizations in schizophrenia. This finding enriches the dopamine hypothesis of schizophrenia from the perspective of brain dynamics.

Autism spectrum disorder (ASD) is among the most common and pervasive neurodevelopmental disorders. Yet, despite decades of research, the neurobiology of ASD is still poorly understood, as inconsistent findings preclude the identification of robust and interpretable neurobiological markers and predictors of clinical symptoms.

Identify robust and interpretable dynamic brain markers that distinguish children with ASD from typically-developing (TD) children and predict clinical symptom severity.

We leverage multiple functional brain imaging cohorts (ABIDE, Stanford; N = 1004) and exciting recent advances in explainable artificial intelligence (xAI), to develop a novel multivariate time series deep neural network model that extracts informative brain dynamics features that accurately distinguish between ASD and TD children, and predict clinical symptom severity.

Our model achieved consistently high classification accuracies in cross-validation analysis of data from the ABIDE cohort. Crucially, despite the differences in symptom profiles, age, and data acquisition protocols, our model also accurately classified data from an independent Stanford cohort without additional training. xAI analyses revealed that brain features associated with the default mode network, and the human voice/face processing and communication systems, most clearly distinguished ASD from TD children in both cohorts. Furthermore, the posterior cingulate cortex emerged as robust predictor of the severity of social and communication deficits in ASD in both cohorts.

Our findings, replicated across two independent cohorts, reveal robust and neurobiologically interpretable brain features that detect ASD and predict core phenotypic features of ASD, and have the potential to transform our understanding of the etiology and treatment of the disorder.

No significant relationships.