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ABSTRACT Schizophrenia (SZ) patients exhibit abnormal static and dynamic functional connectivity across various brain domains. We present a novel approach based on static and dynamic inter‐network connectivity entropy (ICE), which represents the entropy of a given network's connectivity to all the other brain networks. This novel approach enables the investigation of how connectivity strength is heterogeneously distributed across available targets in both SZ patients and healthy controls. We analyzed fMRI data from 151 SZ patients and 160 demographically matched healthy controls (HC). Our assessment encompassed both static and dynamic ICE, revealing significant differences in the heterogeneity of connectivity levels across available functional brain networks between SZ patients and HC. These networks are associated with subcortical (SC), auditory (AUD), sensorimotor (SM), visual (VIS), cognitive control (CC), default mode network (DMN), and cerebellar (CB) functional brain domains. Elevated ICE observed in individuals with SZ suggests that patients exhibit significantly higher randomness in the distribution of time‐varying connectivity strength across functional regions from each source network, compared to HC. C‐means fuzzy clustering analysis of functional ICE correlation matrices revealed that SZ patients exhibit significantly higher occupancy weights in clusters with weak, low‐scale functional entropy correlation, while the control group shows greater occupancy weights in clusters with strong, large‐scale functional entropy correlation. K‐means clustering analysis on time‐indexed ICE vectors revealed that cluster with highest ICE have higher occupancy rates in SZ patients whereas clusters characterized by lowest ICE have larger occupancy rates for control group. Furthermore, our dynamic ICE approach revealed that in HC, the brain primarily communicates through complex, less structured connectivity patterns, with occasional transitions into more focused patterns. Individuals with SZ are significantly less likely to attain these more focused and structured transient connectivity patterns. The proposed ICE measure presents a novel framework for gaining deeper insight into mechanisms of healthy and diseased brain states and represents a useful step forward in developing advanced methods to help diagnose mental health conditions. 

ABSTRACT With the increasing availability of large‐scale multimodal neuroimaging datasets, it is necessary to develop data fusion methods which can extract cross‐modal features. A general framework, multidataset independent subspace analysis (MISA), has been developed to encompass multiple blind source separation approaches and identify linked cross‐modal sources in multiple datasets. In this work, we utilized the multimodal independent vector analysis (MMIVA) model in MISA to directly identify meaningful linked features across three neuroimaging modalities—structural magnetic resonance imaging (MRI), resting state functional MRI and diffusion MRI—in two large independent datasets, one comprising of control subjects and the other including patients with schizophrenia. Results show several linked subject profiles (sources) that capture age‐associated decline, schizophrenia‐related biomarkers, sex effects, and cognitive performance. For sources associated with age, both shared and modality‐specific brain‐age deltas were evaluated for association with non‐imaging variables. In addition, each set of linked sources reveals a corresponding set of cross‐modal spatial patterns that can be studied jointly. We demonstrate that the MMIVA fusion model can identify linked sources across multiple modalities, and that at least one set of linked, age‐related sources replicates across two independent and separately analyzed datasets. The same set also presented age‐adjusted group differences, with schizophrenia patients indicating lower multimodal source levels. Linked sets associated with sex and cognition are also reported for the UK Biobank dataset.