Joint Independent Component Analysis Research Articles

Abnormality in Peripheral and Brain Iron Contents and the Relationship with Grey Matter Volumes in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of "MCCA+jICA" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the "MCCA+jICA" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from "MCCA+jICA" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.

Parallel Multilink Group Joint ICA: Fusion of 3D Structural and 4D Functional Data Across Multiple Resting fMRI Networks.

Multimodal neuroimaging research plays a pivotal role in understanding the complexities of the human brain and its disorders. Independent component analysis (ICA) has emerged as a widely used and powerful tool for disentangling mixed independent sources, particularly in the analysis of functional magnetic resonance imaging (fMRI) data. This paper extends the use of ICA as a unifying framework for multimodal fusion, introducing a novel approach termed parallel multilink group joint ICA (pmg-jICA). The method allows for the fusion of gray matter maps from structural MRI (sMRI) data to multiple fMRI intrinsic networks, addressing the limitations of previous models. The effectiveness of pmg-jICA is demonstrated through its application to an Alzheimer's dataset, yielding linked structure-function outputs for 53 brain networks. Our approach leverages the complementary information from various imaging modalities, providing a unique perspective on brain alterations in Alzheimer's disease. The pmg-jICA identifies several components with significant differences between HC and AD groups including thalamus, caudate, putamen with in the subcortical (SC) domain, insula, parahippocampal gyrus within the cognitive control (CC) domain, and the lingual gyrus within the visual (VS) domain, providing localized insights into the links between AD and specific brain regions. In addition, because we link across multiple brain networks, we can also compute functional network connectivity (FNC) from spatial maps and subject loadings, providing a detailed exploration of the relationships between different brain regions and allowing us to visualize spatial patterns and loading parameters in sMRI along with intrinsic networks and FNC from the fMRI data. In essence, developed approach combines concepts from joint ICA and group ICA to provide a rich set of output characterizing data-driven links between covarying gray matter networks, and a (potentially large number of) resting fMRI networks allowing further study in the context of structure/function links. We demonstrate the utility of the approach by highlighting key structure/function disruptions in Alzheimer's individuals.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

The covariant structural and functional neuro-correlates of cognitive impairments in patients with end-stage renal diseases.

Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear. In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins. Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all p < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all p < 0.05). The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.

Characterizing Typhoon-related Posttraumatic Stress Disorder Based on Multimodal Fusion of Structural, Diffusion, and Functional Magnetic Resonance Imaging

Diagnosing posttraumatic stress disorder (PTSD) using only single-modality images is controversial. We aimed to use multimodal magnetic resonance imaging (MRI) combining structural, diffusion, and functional MRI to possibly provide a more comprehensive viewpoint on the decisive characteristics of PTSD patients. Typhoon-exposed individuals with (n = 26) and without PTSD (n = 32) and healthy volunteers (n = 30) were enrolled. Five MRI features from three modalities, including two resting-state functional MRI (rs-fMRI) features (amplitude of low-frequency fluctuation, ALFF; and regional homogeneity, ReHo), one structural MRI feature (gray matter density, GM), and two diffusion tensor imaging (DTI) features (fractional anisotropy, FA; and mean diffusivity, MD) were investigated simultaneously with a multimodal canonical correlation analysis + joint independent component analysis model to identify abnormalities in the PTSD brain. We identified statistical differences between PTSD patients and healthy controls in terms of 1 rs-fMRI (ALFF, ReHo) alterations in the superior frontal gyrus, precuneus, inferior parietal lobule (IPL), anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC), 2 DTI (FA, MD) changes in the pons, genu, and splenium of the corpus callosum, and 3 Structural MRI abnormalities in the precuneus, IPL, ACC, and PCC. A novel ReHo component was found to distinguish PTSD and trauma-exposed controls, including the precuneus, IPL, middle frontal gyrus, middle occipital gyrus, and cerebellum. This study reveals that PTSD individuals exhibit intertwined functional and structural anomalies within the default mode network. Some alterations within this network may serve as a potential marker to distinguish between PTSD patients and trauma-exposed controls.

Structural and functional pathology in cocaine use disorder with polysubstance use: A multimodal fusion approach structural-functional pathology in cocaine use disorder

Cocaine use disorder (CUD) is described as a compulsive urge to seek and consume cocaine despite the inimical consequences. MRI studies from different modalities have shown that CUD patients exhibit structural and/or functional connectivity pathology among several brain regions. Nevertheless, both connectivities are commonly studied and analyzed separately, which may potentially obscure its relationship between them, and with the clinical pathology. Here, we compare structural and functional brain networks in CUD patients and healthy controls (HC) using multimodal fusion. The sample consisted of 63 (8 females) CUD patients and 42 (9 females) healthy controls (HC), recruited as part of the SUDMEX CONN database. For this, we computed a battery of graph-based measures from multi-shell diffusion-weighted imaging and resting state fc-fMRI to quantify local and global connectivity. Then we used multimodal canonical component analysis plus joint independent component analysis (mCCA+jICA) to compare between techniques and evaluate group differences and its association with clinical alteration. Unimodal results showed a striatal decrease in the participation coefficient but applied supervised data fusion revealed other regions with cocaine-related alterations in joint functional communication. When performing multimodal fusion analysis, we observed a higher centrality of the interrelationship and a lower participation coefficient in patients with CUD. In contrast to the unimodal approach, the multimodal fusion method was able to reveal latent information about brain regions involved in impairment due to cocaine abuse. The present results could help in understanding the pathology of CUD to develop better pre-treatment/post-treatment intervention designs.

Structure of brain grey and white matter in infants with spastic cerebral palsy and periventricular white matter injury.

To investigate the possible covariation of grey matter volume (GMV) and white matter fractional anisotropy in infants with spastic cerebral palsy (CP) and periventricular white matter injury. Thirty-nine infants with spastic CP and 25 typically developing controls underwent structural magnetic resonance imaging and diffusion tensor imaging. Multimodal canonical correlation analysis with joint independent component analysis were used to capture differences in GMV and fractional anisotropy between groups. Correlation analysis was performed between imaging findings and clinical features. Infants with spastic CP showed one joint group-discriminating component (i.e. GMV-fractional anisotropy) associated with regions in the cortico-basal ganglia-thalamo-cortical loop and in the corpus callosum compared to typically developing controls and one modality-specific group-discriminating component (i.e. GMV). Significant negative correlations were found between loadings in certain regions and the motor function score in spastic CP. In infants with spastic CP, covarying GMV-fractional anisotropy and altered GMV in specific regions were implicated in motor dysfunction, which confirmed that simultaneous GMV and fractional anisotropy changes underly motor deficits, but might also extend to sensory, cognitive, or visual dysfunction. These findings also suggest that multimodal fusion analysis allows for a more comprehensive understanding of the relevance between grey and white matter structures and its crucial role in the neuropathological mechanisms of spastic CP.

Multimodal fusion of multiple rest fMRI networks and MRI gray matter via parallel multilink joint ICA reveals highly significant function/structure coupling in Alzheimer's disease.

In this article, we focus on estimating the joint relationship between structural magnetic resonance imaging (sMRI) gray matter (GM), and multiple functional MRI (fMRI) intrinsic connectivity networks (ICNs). To achieve this, we propose a multilink joint independent component analysis (ml-jICA) method using the same core algorithm as jICA. To relax the jICA assumption, we propose another extension called parallel multilink jICA (pml-jICA) that allows for a more balanced weight distribution over ml-jICA/jICA. We assume a shared mixing matrix for both the sMRI and fMRI modalities, while allowing for different mixing matrices linking the sMRI data to the different ICNs. We introduce the model and then apply this approach to study the differences in resting fMRI and sMRI data from patients with Alzheimer's disease (AD) versus controls. The results of the pml-jICA yield significant differences with large effect sizes that include regions in overlapping portions of default mode network, and also hippocampus and thalamus. Importantly, we identify two joint components with partially overlapping regions which show opposite effects for AD versus controls, but were able to be separated due to being linked to distinct functional and structural patterns. This highlights the unique strength of our approach and multimodal fusion approaches generally in revealing potentially biomarkers of brain disorders that would likely be missed by a unimodal approach. These results represent the first work linking multiple fMRI ICNs to GM components within a multimodal data fusion model and challenges the typical view that brain structure is more sensitive to AD than fMRI.

Functional and structural brain reorganization in patients with ischemic stroke: a multimodality MRI fusion study.

Understanding how structural and functional reorganization occurs is crucial for stroke diagnosis and prognosis. Previous magnetic resonance imaging (MRI) studies focused on the analyses of a single modality and demonstrated abnormalities in both lesion regions and their associated distal regions. However, the relationships of multimodality alterations and their associations with poststroke motor deficits are still unclear. In this study, 71 hemiplegia patients and 41 matched healthy controls (HCs) were recruited and underwent MRI examination at baseline and at 2-week follow-up sessions. A multimodal fusion approach (multimodal canonical correlation analysis + joint independent component analysis), with amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) as features, was used to extract the co-altered patterns of brain structure and function. Then compared the changes in patients' brain structure and function between baseline and follow-up sessions. Compared with HCs, the brain structure and function of stroke patients decreased synchronously in the local lesions and their associated distal regions. Damage to structure and function in the local lesion regions was associated with motor function. After 2 weeks, ALFF in the local lesion regions was increased, while GMV did not improve. Taken together, the brain structure and function in the local lesions and their associated distal regions were damaged synchronously after ischemic stroke, while during motor recovery, the 2 modalities were changed separately.

Symmetric data-driven fusion of diffusion tensor MRI: Age differences in white matter.

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of symmetric fusion to study healthy aging WM. This data-driven approach allows simultaneous examination of age differences in all four DTI parameters. We used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) in cognitively healthy adults (age 20-33, n = 51 and age 60-79, n = 170). Four-way mCCA + jICA yielded one high-stability modality-shared component with co-variant patterns of age differences in RD and AD in the corpus callosum, internal capsule, and prefrontal WM. The mixing coefficients (or loading parameters) showed correlations with processing speed and fluid abilities that were not detected by unimodal analyses. In sum, mCCA + jICA allows data-driven identification of cognitively relevant multimodal components within the WM. The presented method should be further extended to clinical samples and other MR techniques (e.g., myelin water imaging) to test the potential of mCCA+jICA to discriminate between different WM disease etiologies and improve the diagnostic classification of WM diseases.

Concordance between focal brain temperature elevations and focal edema in temporal lobe epilepsy.

Neuroinflammation (NI) is a pathophysiological factor in many neurological disorders, including epilepsy. Because NI causes microstructural tissue damage that worsens with increasing brain temperature, abnormally elevated brain temperatures may be a surrogate measure of the biochemical consequences of NI. This study investigated whether patients with temporal lobe epilepsy (TLE) have abnormal brain temperature elevations (TCRE ) in seizure-producing regions that show evidence of edema and/or microstructural damage. Twenty adults with TLE and 20 healthy controls (HCs) were scanned at 3-Tesla. TCRE in each voxel was calculated (TCRE =-102.61(ΔH20-CRE) + 206.1°C) by non-invasive volumetric magnetic resonance spectroscopic imaging and thermometry (MRSI-t). Multi-shell diffusion images were processed by neurite orientation and density imaging (NODDI). Voxel wise two-sample t tests computed group differences in imaging data. Multimodal data fusion (joint independent component analysis [ICA]) determined the spatial coupling of TCRE with NODDI. TCRE analyses showed that, compared to HCs, TLEs had higher TCRE (p < .001). NODDI analyses showed increased extracellular free water (pFWE < 0.05) in the medial temporal lobes, with the most pronounced increases ipsilateral to seizure onset. TLEs also had increased angular dispersion of neurites (p < .001) and decreased neurite density (pFWE <0.05) in the ictal-onset medial temporal lobe, as well as more widespread, bilateral patterns of abnormalities. Focal increases in TCRE were spatially concordant with increased free water in the left inferior and middle temporal gyri and the associated cortex. In TLE, ICA loadings extracted from this region of overlap were associated with greater mood disturbance (r=.34, p=.02) and higher depression scores (r=.37, p=.009). The spatial concordance between focal TCRE elevations and edema in TLE supports the notion that brain thermometry visualizes the correlates of focal NI. MRSI-t-based TCRE elevations may, therefore, be a useful biomarker for identifying seizure-producing tissue in patients with focal epilepsy caused by brain damage.

Abnormal Brain Circuits Characterize Borderline Personality and Mediate the Relationship between Childhood Traumas and Symptoms: A mCCA+jICA and Random Forest Approach.

Borderline personality disorder (BPD) is a severe personality disorder whose neural bases are still unclear. Indeed, previous studies reported inconsistent findings concerning alterations in cortical and subcortical areas. In the present study, we applied for the first time a combination of an unsupervised machine learning approach known as multimodal canonical correlation analysis plus joint independent component analysis (mCCA+jICA), in combination with a supervised machine learning approach known as random forest, to possibly find covarying gray matter and white matter (GM-WM) circuits that separate BPD from controls and that are also predictive of this diagnosis. The first analysis was used to decompose the brain into independent circuits of covarying grey and white matter concentrations. The second method was used to develop a predictive model able to correctly classify new unobserved BPD cases based on one or more circuits derived from the first analysis. To this aim, we analyzed the structural images of patients with BPD and matched healthy controls (HCs). The results showed that two GM-WM covarying circuits, including basal ganglia, amygdala, and portions of the temporal lobes and of the orbitofrontal cortex, correctly classified BPD against HC. Notably, these circuits are affected by specific child traumatic experiences (emotional and physical neglect, and physical abuse) and predict symptoms severity in the interpersonal and impulsivity domains. These results support that BPD is characterized by anomalies in both GM and WM circuits related to early traumatic experiences and specific symptoms.

Cognitive domain-independent aberrant frontoparietal network strength in individuals with excessive smartphone use

Excessive smartphone use (ESU) may fulfill criteria for addictive behavior. In contrast to other related behavioral addictions, particularly Internet Gaming Disorder, little is known about the neural correlates underlying ESU. In this study, we used functional magnetic resonance imaging (fMRI) to acquire task data from three distinct behavioral paradigms, i.e. cue-reactivity, inhibition, and working memory, in individuals with psychometrically defined ESU (n = 19) compared to controls (n-ESU; n = 20). The Smartphone Addiction Inventory (SPAI) was used to quantify ESU-severity according to a novel five-factor model (SPAI-I). A multivariate data fusion approach, i.e. joint Independent Component Analysis (jICA) was employed to analyze fMRI-data derived from three separate experimental conditions, but analyzed jointly to detect converging and domain-independent neural signatures that differ between persons with vs. those without ESU. Across the three functional tasks, jICA identified a predominantly frontoparietal system that showed lower network strength in individuals with ESU compared to n-ESU (p < 0.05 FDR-corrected). Furthermore, significant associations between frontoparietal network strength and SPAI-I's dimensions “time spent” and “craving” were found. The data suggest a frontoparietal cognitive control network as cognitive domain-independent neural signature of excessive and potentially addictive smartphone use.

Chinese adult brain atlas with functional and white matter parcellation

Brain atlases play important roles in studying anatomy and function of the brain. As increasing interests in multi-modal magnetic resonance imaging (MRI) approaches, such as combining structural MRI, diffusion weighted imaging (DWI), and resting-state functional MRI (rs-fMRI), there is a need to construct integrated brain atlases based on these three imaging modalities. This study constructed a multi-modal brain atlas for a Chinese aging population (n = 180, age: 22–79 years), which consists of a T1 atlas showing the brain morphology, a high angular resolution diffusion imaging (HARDI) atlas delineating the complex fiber architecture, and a rs-fMRI atlas reflecting brain intrinsic functional organization in one stereotaxic coordinate. We employed large deformation diffeomorphic metric mapping (LDDMM) and unbiased diffeomorphic atlas generation to simultaneously generate the T1 and HARDI atlases. Using spectral clustering, we generated 20 brain functional networks from rs-fMRI data. We demonstrated the use of the atlas to explore the coherent markers among the brain morphology, functional networks, and white matter tracts for aging and gender using joint independent component analysis.

Tracing Evolving Networks Using Tensor Factorizations vs. ICA-Based Approaches.

Analysis of time-evolving data is crucial to understand the functioning of dynamic systems such as the brain. For instance, analysis of functional magnetic resonance imaging (fMRI) data collected during a task may reveal spatial regions of interest, and how they evolve during the task. However, capturing underlying spatial patterns as well as their change in time is challenging. The traditional approach in fMRI data analysis is to assume that underlying spatial regions of interest are static. In this article, using fractional amplitude of low-frequency fluctuations (fALFF) as an effective way to summarize the variability in fMRI data collected during a task, we arrange time-evolving fMRI data as a subjects by voxels by time windows tensor, and analyze the tensor using a tensor factorization-based approach called a PARAFAC2 model to reveal spatial dynamics. The PARAFAC2 model jointly analyzes data from multiple time windows revealing subject-mode patterns, evolving spatial regions (also referred to as networks) and temporal patterns. We compare the PARAFAC2 model with matrix factorization-based approaches relying on independent components, namely, joint independent component analysis (ICA) and independent vector analysis (IVA), commonly used in neuroimaging data analysis. We assess the performance of the methods in terms of capturing evolving networks through extensive numerical experiments demonstrating their modeling assumptions. In particular, we show that (i) PARAFAC2 provides a compact representation in all modes, i.e., subjects, time, and voxels, revealing temporal patterns as well as evolving spatial networks, (ii) joint ICA is as effective as PARAFAC2 in terms of revealing evolving networks but does not reveal temporal patterns, (iii) IVA's performance depends on sample size, data distribution and covariance structure of underlying networks. When these assumptions are satisfied, IVA is as accurate as the other methods, (iv) when subject-mode patterns differ from one time window to another, IVA is the most accurate. Furthermore, we analyze real fMRI data collected during a sensory motor task, and demonstrate that a component indicating statistically significant group difference between patients with schizophrenia and healthy controls is captured, which includes primary and secondary motor regions, cerebellum, and temporal lobe, revealing a meaningful spatial map and its temporal change.

Joint independent component analysis for hypothesizing spatiotemporal relationships between longitudinal gray and white matter changes in preclinical Alzheimer's disease.

Characterizing relationships between gray matter (GM) and white matter (WM) in early Alzheimer's disease (AD) would improve understanding of how and when AD impacts the brain. However, modeling these relationships across brain regions and longitudinally remains a challenge. Thus, we propose extending joint independent component analysis (jICA) into spatiotemporal modeling of regional cortical thickness and WM bundle volumes leveraging multimodal MRI. We jointly characterize these GM and WM features in a normal aging (n=316) and an age- and sex-matched preclinical AD cohort (n=81) at each of two imaging sessions spaced three years apart, training on the normal aging population in cross-validation and interrogating the preclinical AD cohort. We find this joint model identifies reproducible, longitudinal changes in GM and WM between the two imaging sessions and that these changes are associated with preclinical AD and are plausible considering the literature. We compare this joint model to two focused models: (1) GM features at the first session and WM at the second and (2) vice versa. The joint model identifies components that correlate poorly with those from the focused models, suggesting the different models resolve different patterns. We find the strength of association with preclinical AD is improved in the GM to WM model, which supports the hypothesis that medial temporal and frontal thinning precedes volume loss in the uncinate fasciculus and inferior anterior-posterior association fibers. These results suggest that jICA effectively generates spatiotemporal hypotheses about GM and WM in preclinical AD, especially when specific intermodality relationships are considered a priori.

Joint structural-functional magnetic resonance imaging features are associated with diagnosis and real-world functioning in patients with schizophrenia

ObjectiveEarlier evidence suggested that structural–functional covariation in schizophrenia patients (SCZ) is associated with cognition, a predictor of functioning. Moreover, studies suggested that functional brain abnormalities of schizophrenia may be related with structural network features. However, only few studies have investigated the relationship between structural–functional covariation and both diagnosis and functioning in SCZ. We hypothesized that structural–functional covariation networks associated with diagnosis are related to real-world functioning in SCZ. MethodsWe performed joint Independent Component Analysis on T1 images and resting-state fMRI-based Degree Centrality (DC) maps from 89 SCZ and 285 controls. Structural-functional covariation networks in which we found a main effect of diagnosis underwent correlation analysis to investigate their relationship with functioning. Covariation networks showing a significant association with both diagnosis and functioning underwent univariate analysis to better characterize group-level differences at the spatial level. ResultsA structural–functional covariation network characterized by frontal, temporal, parietal and thalamic structural estimates significantly covaried with temporo-parietal resting-state DC. Compared with controls, SCZ had reduced structural–functional covariation within this network (pFDR = 0.005). The same measure correlated positively with both social and occupational functioning (both pFDR = 0.042). Univariate analyses revealed grey matter deviations in SCZ compared with controls within this structural–functional network in hippocampus, cerebellum, thalamus, orbito-frontal cortex, and insula. No group differences were found in DC. ConclusionsFindings support the existence of a phenotypical association between group-level differences and inter-individual heterogeneity of functional deficits in SCZ. Given that only the joint structural/functional analysis revealed this association, structural–functional covariation may be a potentially relevant schizophrenia phenotype.

EEG and fMRI coupling and decoupling based on joint independent component analysis (jICA)

BackgroundMeaningful integration of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) requires knowing whether these measurements reflect the activity of the same neural sources, i.e., estimating the degree of coupling and decoupling between the neuroimaging modalities. New methodThis paper proposes a method to quantify the coupling and decoupling of fMRI and EEG signals based on the mixing matrix produced by joint independent component analysis (jICA). The method is termed fMRI/EEG-jICA. ResultsfMRI and EEG acquired during a syllable detection task with variable syllable presentation rates (0.25–3 Hz) were separated with jICA into two spatiotemporally distinct components, a primary component that increased nonlinearly in amplitude with syllable presentation rate, putatively reflecting an obligatory auditory response, and a secondary component that declined nonlinearly with syllable presentation rate, putatively reflecting an auditory attention orienting response. The two EEG subcomponents were of similar amplitude, but the secondary fMRI subcomponent was ten folds smaller than the primary one. Comparison to existing methodFMRI multiple regression analysis yielded a map more consistent with the primary than secondary fMRI subcomponent of jICA, as determined by a greater area under the curve (0.5 versus 0.38) in a sensitivity and specificity analysis of spatial overlap. ConclusionfMRI/EEG-jICA revealed spatiotemporally distinct brain networks with greater sensitivity than fMRI multiple regression analysis, demonstrating how this method can be used for leveraging EEG signals to inform the detection and functional characterization of fMRI signals. fMRI/EEG-jICA may be useful for studying neurovascular coupling at a macro-level, e.g., in neurovascular disorders.

Multimodal data fusion of cortical-subcortical morphology and functional network connectivity in psychotic spectrum disorder

Multiple authors have noted overlapping symptoms and alterations across clinical, anatomical, and functional brain features in schizophrenia (SZ), schizoaffective disorder (SZA), and bipolar disorder (BPI). However, regarding brain features, few studies have approached this line of inquiry using analytical techniques optimally designed to extract the shared features across anatomical and functional information in a simultaneous manner. Univariate studies of anatomical or functional alterations across these disorders can be limited and run the risk of omitting small but potentially crucial overlapping or joint neuroanatomical (e.g., structural images) and functional features (e.g., fMRI-based features) which may serve as informative clinical indicators of across multiple diagnostic categories. To address this limitation, we paired an unsupervised multimodal canonical correlation analysis (mCCA) together with joint independent component analysis (jICA) to identify linked spatial gray matter (GM), resting-state functional network connectivity (FNC), and white matter fractional anisotropy (FA) features across these diagnostic categories. We then calculated associations between the identified linked features and trans-diagnostic behavioral measures (MATRICs Consensus Cognitive Battery, MCCB).Component number 4 of the 13 identified displayed a statistically significant relationship with overall MCCB scores across GM, resting-state FNC, and FA. These linked modalities of component 4 consisted primarily of positive correlations within subcortical structures including the caudate and putamen in the GM maps with overall MCCB, sparse negative correlations within subcortical and cortical connection tracts (e.g., corticospinal tract, superior longitudinal fasciculus) in the FA maps with overall MCCB, and negative relationships with MCCB values and loading parameters with FNC matrices displaying increased FNC in subcortical-cortical regions with auditory, somatomotor, and visual regions.

A Multimodal Fusion Analysis of Pretreatment Anatomical and Functional Cortical Abnormalities in Responsive and Non-responsive Schizophrenia.

Background: Antipsychotic medications provide limited long-term benefit to ~30% of schizophrenia patients. Multimodal magnetic resonance imaging (MRI) data have been used to investigate brain features between responders and nonresponders to antipsychotic treatment; however, these analytical techniques are unable to weigh the interrelationships between modalities. Here, we used multiset canonical correlation and joint independent component analysis (mCCA + jICA) to fuse MRI data to examine the shared and specific multimodal features between the patients and healthy controls (HCs) and between the responders and non-responders.Method: Resting-state functional and structural MRI data were collected from 55 patients with drug-naïve first-episode schizophrenia (FES) and demographically matched HCs. Based on the decrease in Positive and Negative Syndrome Scale scores from baseline to the 1-year follow-up, FES patients were divided into a responder group (RG) and a non-responder group (NRG). Gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) maps were used as features in mCCA + jICA.Results: Between FES patients and HCs, there were three modality-specific discriminative independent components (ICs) showing the difference in mixing coefficients (GMV-IC7, GMV-IC8, and fALFF-IC5). The fusion analysis indicated one modality-shared IC (GMV-IC2 and ReHo-IC2) and three modality-specific ICs (GMV-IC1, GMV-IC3, and GMV-IC6) between the RG and NRG. The right postcentral gyrus showed a significant difference in GMV features between FES patients and HCs and modality-shared features (GMV and ReHo) between responders and nonresponders. The modality-shared component findings were highlighted by GMV, mainly in the bilateral temporal gyrus and the right cerebellum associated with ReHo in the right postcentral gyrus.Conclusions: This study suggests that joint anatomical and functional features of the cortices may reflect an early pathophysiological mechanism that is related to a 1-year treatment response.