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Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and works by applying an electric current through the brain. The applied current generates an electric field (E-field) and seizure activity, changing the brain’s functional organization. The E-field, which is determined by electrode placement (right unilateral or bitemporal) and pulse amplitude (600, 700, or 800 milliamperes), is associated with the ECT response. However, the neural mechanisms underlying the relationship between E-field, functional brain changes, and clinical outcomes of ECT are not well understood. Here, we investigated the relationships between whole-brain E-field (E_brain, the 90^thpercentile of E-field magnitude in the brain), cerebro-cerebellar functional network connectivity (FNC), and clinical outcomes (cognitive performance and depression severity). A fully automated independent component analysis framework determined the FNC between the cerebro-cerebellar networks. We found a linear relationship between E_brainand cognitive outcomes. The mediation analysis showed that the cerebellum to middle occipital gyrus (MOG)/posterior cingulate cortex (PCC) FNC mediated the effects of E_brainon cognitive performance. In addition, there is a mediation effect through the cerebellum to parietal lobule FNC between E_brainand antidepressant outcomes. The pair-wise t-tests further demonstrated that a larger E_brainwas associated with increased FNC between cerebellum and MOG and decreased FNC between cerebellum and PCC, which were linked with decreased cognitive performance. This study implies that an optimal E-field balancing the antidepressant and cognitive outcomes should be considered in relation to cerebro-cerebellar functional neuroplasticity.

 

Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP.

Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability in discriminating among SZ, SAD, and BP. We observed shared links to functional and structural covariation in prefrontal, medial temporal, anterior cingulate, and insular cortices among SZ, SAD, and BP, although they were linked with different clinical domains. The salience (SAN), default mode (DMN), and fronto-limbic (FLN) networks were the three identified multimodal MRI features within the psychosis spectrum disorders from psychotic symptom, mood, and cognition associations. In addition, using these networks, we can classify patients and controls and distinguish among SZ, SAD, and BP, including their first-degree relatives. The identified multimodal SAN may be informative regarding neural mechanisms of comorbidity for psychosis spectrum disorders, along with DMN and FLN may serve as potential biomarkers in discriminating among SZ, SAD, and BP, which may help investigators better understand the underlying mechanisms of psychotic comorbidity from three different disorders via a multimodal neuroimaging perspective.

 

Functional network connectivity (FNC) is a useful measure for evaluating the temporal dependency among brain networks. Longitudinal changes of intrinsic function are of great interest, but to date there has been little focus on multivariate patterns of FNC changes with development. In this paper, we proposed a novel approach that uses FNC matrices to estimate multiple overlapping brain functional change patterns (FCPs). We applied this approach to the large-scale Adolescent Brain and Cognitive Development (ABCD) data. Results reveal several highly structured FCPs showing a significant change over a two-year period including brain functional connectivity between visual (VS) and sensorimotor (SM) domains. This pattern of FNC expression becomes stronger with age. We also found a differential pattern of changes between male and female individuals. Our approach provides a powerful way to evaluate whole brain functional changes in longitudinal data. 

Graph-theoretical methods have been widely used to study human brain networks in psychiatric disorders. However, the focus has primarily been on global graphic metrics with little attention to the information contained in paths connecting brain regions. Details of disruption of these paths may be highly informative for understanding disease mechanisms. To detect the absence or addition of multistep paths in the patient group, we provide an algorithm estimating edges that contribute to these paths with reference to the control group. We next examine where pairs of nodes were connected through paths in both groups by using a covariance decomposition method. We apply our method to study resting-state fMRI data in schizophrenia versus controls. Results show several disconnectors in schizophrenia within and between functional domains, particularly within the default mode and cognitive control networks. Additionally, we identify new edges generating additional paths. Moreover, although paths exist in both groups, these paths take unique trajectories and have a significant contribution to the decomposition. The proposed path analysis provides a way to characterize individuals by evaluating changes in paths, rather than just focusing on the pairwise relationships. Our results show promise for identifying path-based metrics in neuroimaging data.

 

Background: Schizophrenia affects around 1% of the global population. Functional connectivity extracted from resting-state functional magnetic resonance imaging (rs-fMRI) has previously been used to study schizophrenia and has great potential to provide novel insights into the disorder. Some studies have shown abnormal functional connectivity in the default mode network (DMN) of individuals with schizophrenia, and more recent studies have shown abnormal dynamic functional connectivity (dFC) in individuals with schizophrenia. However, DMN dFC and the link between abnormal DMN dFC and symptom severity have not been well-characterized. Method: Resting-state fMRI data from subjects with schizophrenia (SZ) and healthy controls (HC) across two datasets were analyzed independently. We captured seven maximally independent subnodes in the DMN by applying group independent component analysis and estimated dFC between subnode time courses using a sliding window approach. A clustering method separated the dFCs into five reoccurring brain states. A feature selection method modeled the difference between SZs and HCs using the state-specific FC features. Finally, we used the transition probability of a hidden Markov model to characterize the link between symptom severity and dFC in SZ subjects. Results: We found decreases in the connectivity of the anterior cingulate cortex (ACC) and increases in the connectivity between the precuneus (PCu) and the posterior cingulate cortex (PCC) (i.e., PCu/PCC) of SZ subjects. In SZ, the transition probability from a state with weaker PCu/PCC and stronger ACC connectivity to a state with stronger PCu/PCC and weaker ACC connectivity increased with symptom severity. Conclusions: To our knowledge, this was the first study to investigate DMN dFC and its link to schizophrenia symptom severity. We identified reproducible neural states in a data-driven manner and demonstrated that the strength of connectivity within those states differed between SZs and HCs. Additionally, we identified a relationship between SZ symptom severity and the dynamics of DMN functional connectivity. We validated our results across two datasets. These results support the potential of dFC for use as a biomarker of schizophrenia and shed new light upon the relationship between schizophrenia and DMN dynamics. 

The brain's functional architecture and organization undergo continual development and modification throughout adolescence. While it is well known that multiple factors govern brain maturation, the constantly evolving patterns of time‐resolved functional connectivity are still unclear and understudied. We systematically evaluated over 47,000 youth and adult brains to bridge this gap, highlighting replicable time‐resolved developmental and aging functional brain patterns. The largest difference between the two life stages was captured in a brain state that indicated coherent strengthening and modularization of functional coupling within the auditory, visual, and motor subdomains, supplemented by anticorrelation with other subdomains in adults. This distinctive pattern, which we replicated in independent data, was consistently less modular or absent in children and presented a negative association with age in adults, thus indicating an overall inverted U‐shaped trajectory. This indicates greater synchrony, strengthening, modularization, and integration of the brain's functional connections beyond adolescence, and gradual decline of this pattern during the healthy aging process. We also found evidence that the developmental changes may also bring along a departure from the canonical static functional connectivity pattern in favor of more efficient and modularized utilization of the vast brain interconnections. State‐based statistical summary measures presented robust and significant group differences that also showed significant age‐related associations. The findings reported in this article support the idea of gradual developmental and aging brain state adaptation processes in different phases of life and warrant future research via lifespan studies to further authenticate the projected time‐resolved brain state trajectories.

 

The validity and reliability of diagnoses in psychiatry is a challenging topic in mental health. The current mental health categorization is based primarily on symptoms and clinical course and is not biologically validated. Among multiple ongoing efforts, neurological observations alongside clinical evaluations are considered to be potential solutions to address diagnostic problems. The Bipolar‐Schizophrenia Network on Intermediate Phenotypes (B‐SNIP) has published multiple papers attempting to reclassify psychotic illnesses based on biological rather than symptomatic measures. However, the effort to investigate the relationship between this new categorization approach and other neuroimaging techniques, including resting‐state fMRI data, is still limited. This study focused on investigating the relationship between different psychotic disorders categorization methods and resting‐state fMRI‐based measures called dynamic functional network connectivity (dFNC) using state‐of‐the‐art artificial intelligence (AI) approaches. We applied our method to 613 subjects, including individuals with psychosis and healthy controls, which were classified using both the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) and the B‐SNIP biomarker‐based (Biotype) approach. Statistical group differences and cross‐validated classifiers were performed within each framework to assess how different categories. Results highlight interesting differences in occupancy in both DSM‐IV and Biotype categorizations compared to healthy individuals, which are distributed across specific transient connectivity states. Biotypes tended to show less distinctiveness in occupancy level and included fewer cellwise differences. Classification accuracy obtained by DSM‐IV and Biotype categories were both well above chance. Results provided new insights and highlighted the benefits of both DSM‐IV and biology‐based categories while also emphasizing the importance of future work in this direction, including employing further data types.