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Background: Schizophrenia (SZ) is a psychiatric condition that adversely affects an individual's cognitive, emotional, and behavioral aspects. The etiology of SZ, although extensively studied, remains unclear, as multiple factors come together to contribute toward its development. There is a consistent body of evidence documenting the presence of structural and functional deviations in the brains of individuals with SZ. Moreover, the hereditary aspect of SZ is supported by the significant involvement of genomics markers. Therefore, the need to investigate SZ from a multi-modal perspective and develop approaches for improved detection arises. Methods: Our proposed method employed a deep learning framework combining features from structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and genetic markers such as single nucleotide polymorphism (SNP). For sMRI, we used a pre-trained DenseNet to extract the morphological features. To identify the most relevant functional connections in fMRI and SNPs linked to SZ, we applied a 1-dimensional convolutional neural network (CNN) followed by layerwise relevance propagation (LRP). Finally, we concatenated these obtained features across modalities and fed them to the extreme gradient boosting (XGBoost) treebased classifier to classify SZ from healthy control (HC). Results: Experimental evaluation on clinical dataset demonstrated that, compared to the outcomes obtained from each modality individually, our proposed multi-modal approach performed classification of SZ individuals from HC with an improved accuracy of 79.01%. Conclusion: We proposed a deep learning based framework that selects multimodal (sMRI, fMRI and genetic) features efficiently and fuse them to obtain improved classification scores. Additionally, by using Explainable AI (XAI), we were able to pinpoint and validate significant functional network connections and SNPs that contributed the most toward SZ classification, providing necessary interpretation behind our findings. [ABSTRACT FROM AUTHOR]

Resting‐state functional network connectivity (rsFNC) has shown utility for identifying characteristic functional brain patterns in individuals with psychiatric and mood disorders, providing a promising avenue for biomarker development. However, several factors have precluded widespread clinical adoption of rsFNC diagnostics, namely a lack of standardized approaches for capturing comparable and reproducible imaging markers across individuals, as well as the disagreement on the amount of data required to robustly detect intrinsic connectivity networks (ICNs) and diagnostically relevant patterns of rsFNC at the individual subject level. Recently, spatially constrained independent component analysis (scICA) has been proposed as an automated method for extracting ICNs standardized to a chosen network template while still preserving individual variation. Leveraging the scICA methodology, which solves the former challenge of standardized neuroimaging markers, we investigate the latter challenge of identifying a minimally sufficient data length for clinical applications of resting‐state fMRI (rsfMRI). Using a dataset containing rsfMRI scans of individuals with schizophrenia and controls (M = 310) as well as simulated rsfMRI, we evaluated the robustness of ICN and rsFNC estimates at both the subject‐ and group‐level, as well as the performance of diagnostic classification, with respect to the length of the rsfMRI time course. We found individual estimates of ICNs and rsFNC from the full‐length (5 min) reference time course were sufficiently approximated with just 3–3.5 min of data (r = 0.85, 0.88, respectively), and significant differences in group‐average rsFNC could be sufficiently approximated with even less data, just 2 min (r = 0.86). These results from the shorter clinical data were largely consistent with the results from validation experiments using longer time series from both simulated (30 min) and real‐world (14 min) datasets, in which estimates of subject‐level FNC were reliably estimated with 3–5 min of data. Moreover, in the real‐world data we found rsFNC and ICN estimates generated across the full range of data lengths (0.5–14 min) more reliably matched those generated from the first 5 min of scan time than those generated from the last 5 min, suggesting increased influence of "late scan" noise factors such as fatigue or drowsiness may limit the reliability of FNC from data collected after 10+ min of scan time, further supporting the notion of shorter scans. Lastly, a diagnostic classification model trained on just 2 min of data retained 97%–98% classification accuracy relative to that of the full‐length reference model. Our results suggest that, when decomposed with scICA, rsfMRI scans of just 2–5 min show good clinical utility without significant loss of individual FNC information of longer scan lengths. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a burden to society creating social and health problems. Detection of AUD and its effects on the brain are difficult to assess. This problem is enhanced by the comorbid use of other substances such as nicotine that has been present in previous studies. Recent machine learning algorithms have raised the attention of researchers as a useful tool in studying and detecting AUD. This work uses AUD and controls samples free of any other substance use to assess the performance of a set of commonly used machine learning classifiers detecting AUD from resting state functional network connectivity (rsFNC) derived from independent component analysis. The cohort used included 51 alcohol dependent subjects and 51 control subjects. Despite alcohol, none of the 102 subjects reported use of nicotine, cannabis or any other dependence or habit formation substance. Classification features consisted of whole brain rsFNC estimates undergoing a feature selection process using a random forest approach. Features were then fed to 10 different machine learning classifiers to be evaluated based on their classification performance. A neural network classifier showed the highest performance with an area under the curve (AUC) of 0.79. Other good performers with similar AUC scores were logistic regression, nearest neighbor, and support vector machine classifiers. The worst results were obtained with Gaussian process and quadratic discriminant analysis. The feature selection outcome pointed to functional connections between visual, sensorimotor, executive control, reward, and salience networks as the most relevant for classification. We conclude that AUD can be identified using machine learning classifiers in the absence of nicotine comorbidity. [ABSTRACT FROM AUTHOR]

The study of brain network connectivity as a time-varying property began relatively recently and, to date, has remained primarily concerned with capturing a handful of discrete static states that characterize connectivity as measured on a timescale shorter than that of the full scan. Capturing group-level representations of temporally evolving patterns of connectivity is a challenging and important next step in fully leveraging the information available in large resting state functional magnetic resonance imaging (rs-fMRI) studies. We introduce a flexible, extensible data-driven framework for the stable identification of group-level multiframe (movie-style) dynamic functional network connectivity (dFNC) states. Our approach employs uniform manifold approximation and embedding (UMAP) to produce a continuity-preserving planar embedding of high-dimensional time-varying measurements of whole-brain functional network connectivity. Planar linear exemplars summarizing dominant dynamic trends across the population are computed from local linear approximations to the two-dimensional 2D embedded trajectories. A high-dimensional representation of each 2D exemplar segment is obtained by averaging the dFNC observations corresponding to the n planar nearest neighbors of τ evenly spaced points along the 2D line segment representation (where n is the UMAP number-of-neighbors parameter and τ is the temporal duration of trajectory segments being approximated). Each of the 2D exemplars thus "lifts" to a multiframe high-dimensional dFNC trajectory of length τ. The collection of high-dimensional temporally evolving dFNC representations (EVOdFNCs) derived in this manner are employed as dynamic basis objects with which to characterize observed high-dimensional dFNC trajectories, which are then expressed as weighted combination of these basis objects. Our approach yields new insights into anomalous patterns of fluidly varying whole-brain connectivity that are significantly associated with schizophrenia as a broad diagnosis as well as with certain symptoms of this serious disorder. Importantly, we show that relative to conventional hidden Markov modeling with single-frame unvarying dFNC summary states, EVOdFNCs are more sensitive to positive symptoms of schizophrenia including hallucinations and delusions, suggesting that a more dynamic characterization is needed to help illuminate such a complex brain disorder. [ABSTRACT FROM AUTHOR]

Psychosis disorders share overlapping symptoms and are characterized by a wide-spread breakdown in functional brain integration. Although neuroimaging studies have identified numerous connectivity abnormalities in affective and non-affective psychoses, whether they have specific or unique connectivity abnormalities, especially within the early stage is still poorly understood. The early phase of psychosis is a critical period with fewer chronic confounds and when treatment intervention may be most effective. In this work, we examined whole-brain functional network connectivity (FNC) from both static and dynamic perspectives in patients with affective psychosis (PAP) or with non-affective psychosis (PnAP) and healthy controls (HCs). A fully automated independent component analysis (ICA) pipeline called "Neuromark" was applied to high-quality functional magnetic resonance imaging (fMRI) data with 113 early-phase psychosis patients (32 PAP and 81 PnAP) and 52 HCs. Relative to the HCs, both psychosis groups showed common abnormalities in static FNC (sFNC) between the thalamus and sensorimotor domain, and between subcortical regions and the cerebellum. PAP had specifically decreased sFNC between the superior temporal gyrus and the paracentral lobule, and between the cerebellum and the middle temporal gyrus/inferior parietal lobule. On the other hand, PnAP showed increased sFNC between the fusiform gyrus and the superior medial frontal gyrus. Dynamic FNC (dFNC) was investigated using a combination of a sliding window approach, clustering analysis, and graph analysis. Three reoccurring brain states were identified, among which both psychosis groups had fewer occurrences in one antagonism state (state 2) and showed decreased network efficiency within an intermediate state (state 1). Compared with HCs and PnAP, PAP also showed a significantly increased number of state transitions, indicating more unstable brain connections in affective psychosis. We further found that the identified connectivity features were associated with the overall positive and negative syndrome scale, an assessment instrument for general psychopathology and positive symptoms. Our findings support the view that subcortical-cortical information processing is disrupted within five years of the initial onset of psychosis and provide new evidence that abnormalities in both static and dynamic connectivity consist of shared and unique features for the early affective and non-affective psychoses. [ABSTRACT FROM AUTHOR]

Conventionally, brain function is inferred from the magnitude data of the complex-valued fMRI output. Since the fMRI phase image (unwrapped) provides a representation of brain internal magnetic fieldmap (by a constant scale difference), it can also be used to study brain function while providing a more direct representation of the brain's magnetic state. In this study, we collected a cohort of resting-state fMRI magnitude and phase data pairs from 600 subjects (age from 10 to 76, 346 males), decomposed the phase data by group independent component analysis (pICA), calculated the functional network connectivity (pFNC). In comparison with the magnitude-based brain function analysis (mICA and mFNC), we find that the pFNC matrix contains fewer significant functional connections (with p -value thresholding) than the mFNC matrix, which are sparsely distributed across the whole brain with near/far interconnections and positive/negative correlations in rough balance. We also find a few of brain rest sub-networks within the phase data, primarily in subcortical, cerebellar, and visual regions. Overall, our findings offer new insights into brain function connectivity in the context of a focus on the brain's internal magnetic state. [ABSTRACT FROM AUTHOR]

Background: Differentiating bipolar disorder (BD) from major depressive disorder (MDD) often poses a major clinical challenge, and optimal clinical care can be hindered by misdiagnoses. This study investigated the differences between BD and MDD in resting-state functional network connectivity (FNC) using a data-driven image analysis method.Methods: In this study, fMRI data were collected from unmedicated subjects including 13 BD, 40 MDD and 33 healthy controls (HC). The FNC was calculated between functional brain networks derived from fMRI using group independent component analysis (ICA). Group comparisons were performed on connectivity strengths and other graph measures of FNC matrices.Results: Statistical tests showed that, compared to MDD, the FNC in BD was characterized by more closely connected and more efficient topological structures as assessed by graph theory. The differences were found at both the whole-brain-level and the functional-network-level in prefrontal networks located in the dorsolateral/ventrolateral prefrontal cortex (DLPFC, VLPFC) and anterior cingulate cortex (ACC). Furthermore, interconnected structures in these networks in both patient groups were negatively associated with symptom severity on depression rating scales.Limitations: As patients were unmedicated, the sample sizes were relatively small, although they were comparable to those in previous fMRI studies comparing BD and MDD.Conclusions: Our results suggest that the differences in FNC of the PFC reflect distinct pathophysiological mechanisms in BD and MDD. Such findings ultimately may elucidate the neural pathways in which distinct functional changes can give rise to the clinical differences observed between these syndromes. [ABSTRACT FROM AUTHOR]

Functional connectivity analysis of the human brain is an active area in fMRI research. It focuses on identifying meaningful brain networks that have coherent activity either during a task or in the resting state. These networks are generally identified either as collections of voxels whose time series correlate strongly with a pre-selected region or voxel, or using data-driven methodologies such as independent component analysis (ICA) that compute sets of maximally spatially independent voxel weightings (component spatial maps (SMs)), each associated with a single time course (TC). Studies have shown that regardless of the way these networks are defined, the activity coherence among them has a dynamic nature which is hard to estimate with global coherence analysis such as correlation or mutual information. Sliding window analyses in which functional network connectivity (FNC) is estimated separately at each time window is one of the more widely employed approaches to studying the dynamic nature of functional network connectivity (dFNC). Observed FNC patterns are summarized and replaced with a smaller set of prototype connectivity patterns (“states” or “components”), and then a dynamical analysis is applied to the resulting sequences of prototype states. In this work we are looking for a small set of connectivity patterns whose weighted contributions to the dynamically changing dFNCs are independent of each other in time. We discuss our motivation for this work and how it differs from existing approaches. Also, in a group analysis based on gender we show that males significantly differ from females by occupying significantly more combinations of these connectivity patterns over the course of the scan. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain׳s neural architecture, from the micro to macro scales, have yet to be investigated. Using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ( 1 H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-state networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. 1 H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t -tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal–parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia ( p <0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. The observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders. [ABSTRACT FROM AUTHOR]