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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.

 

Background Schizophrenia is a brain disorder characterized by diffuse, diverse, and wide-spread changes in gray matter volume (GM) and white matter structure (fractional anisotropy, FA), as well as cognitive impairments that greatly impact an individual’s quality of life. While the relationship of each of these image modalities and their links to schizophrenia status and cognitive impairment has been investigated separately, a multimodal fusion via parallel independent component analysis (pICA) affords the opportunity to explore the relationships between the changes in GM and FA, and the implications these network changes have on cognitive performance. Methods Images from 73 subjects with schizophrenia (SZ) and 82 healthy controls (HC) were drawn from an existing dataset. We investigated 12 components from each feature (FA and GM). Loading coefficients from the images were used to identify pairs of features that were significantly correlated and showed significant group differences between HC and SZ. MANCOVA analysis uncovered the relationships the identified spatial maps had with age, gender, and a global cognitive performance score. Results Three component pairs showed significant group differences (HC > SZ) in both gray and white matter measurements. Two of the component pairs identified networks of gray matter that drove significant relationships with cognition (HC > SZ) after accounting for age and gender. The gray and white matter structural networks identified in these three component pairs pull broadly from many regions, including the right and left thalamus, lateral occipital cortex, multiple regions of the middle temporal gyrus, precuneus cortex, postcentral gyrus, cingulate gyrus/cingulum, lingual gyrus, and brain stem. Conclusion The results of this multimodal analysis adds to our understanding of how the relationship between GM, FA, and cognition differs between HC and SZ by highlighting the correlated intermodal covariance of these structural networks and their differential relationships with cognitive performance. Previous unimodal research has found similar areas of GM and FA differences between these groups, and the cognitive deficits associated with SZ have been well documented. This study allowed us to evaluate the intercorrelated covariance of these structural networks and how these networks are involved the differences in cognitive performance between HC and SZ. 

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 present study examined the relationship between subthreshold depressive symptoms and gray matter volume in subregions of the posterior cerebellum. Structural magnetic resonance imaging data from 38 adults aged 51 to 80 years were analyzed along with participants’ responses to the Center for Epidemiologic Studies Depression Scale. Subscale scores for depressed mood, somatic symptoms, and lack of positive affect were calculated, and multiple regression analyses were used to examine the relationship between symptom dimensions and cerebellar volumes. Greater total depressive symptoms and greater somatic symptoms of depression were significantly related to larger volumes of vermis VI, a region within the salience network, which is altered in depression. Exploratory analyses revealed that higher scores on the lack of positive affect subscale were related to larger vermis VIII volumes. These results support that depressive symptom profiles have unique relationships within the cerebellum that may be important as the field move towards targeted treatment approaches for depression.

 

Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting‐state fMRI (rs‐fMRI) sample from the PREDICT‐HD study (N = 183 Huntington disease gene mutation carriers [HDgmc] andN = 78 healthy control [HC] participants) to examine whole‐brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs‐fMRI data to obtain whole‐brain resting state networks. FNC was defined as the correlation between RSN time‐courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k‐means clustering algorithm. HDgmc individuals spent significantly more time in State‐1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State‐4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State‐1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex.