The association between hyperhomocysteinemia and the prevalence of bilateral carotid atherosclerotic plaques in a middle-aged population.

OBJECTIVE: We conducted a cross-sectional study to investigate the impact of hyperhomocysteinemia (HHcy) on the prevalence of CASP among middle-aged individuals, aiming to provide insights for CASP prevention. METHODS: 1105 subjects were categorized into HHcy group or normal tHcy group based on their plasma total homocysteine (tHcy). All participants underwent carotid artery ultrasonography to assess the presence of unilateral and bilateral CASP. Comparative analyses of demographic and clinical data were conducted between the two groups. Logistic regression and prespecified subgroup analyses were performed to determine whether HHcy independently contributed to bilateral CASP. RESULTS: 132 individuals exhibited bilateral CASP. The prevalence of bilateral CASP was significantly higher in the HHcy group compared to the normal tHcy group (21.55 % vs. 10.82 %, p = 0.003). Univariate logistic analysis showed a significant association between HHcy and the prevalence of bilateral CASP (OR = 2.056, 95 %CI 1.089-3.881, p = 0.026). In all four models of multivariate logistic analysis, HHcy consistently emerged as an independent risk factor for bilateral CASP, with odd ratios of 1.958, 2.047, 2.023, and 2.186. This association remained significant across all five subgroups stratified by age, sex, hypertension, diabetes, and BMI. CONCLUSION: Our studies demonstrated HHcy was an independent risk factor for the prevalence of bilateral CASP in the middle-aged population. Theses results emphasized the importance of addressing HHcy in preventive strategies aimed at mitigating the burden of CASP among middle-aged individuals.

MEET: A Multi-Band EEG Transformer for Brain States Decoding.

OBJECTIVE: Electroencephalography (EEG) is among the most widely used and inexpensive neuroimaging techniques. Compared to the CNN or RNN based models, Transformer can better capture the temporal information in EEG signals and focus more on global features of the brain's functional activities. Importantly, according to the multiscale nature of EEG signals, it is crucial to consider the multi-band concept into the design of EEG Transformer architecture. METHODS: We propose a novel Multi-band EEG Transformer (MEET) to represent and analyze the multiscale temporal time series of human brain EEG signals. MEET mainly includes three parts: 1) transform the EEG signals into multi-band images, and preserve the 3D spatial information between electrodes; 2) design a Band Attention Block to compute the attention maps of the stacked multi-band images and infer the fused feature maps; 3) apply the Temporal Self-Attention and Spatial Self-Attention modules to extract the spatiotemporal features for the characterization and differentiation of multi-frame dynamic brain states. RESULTS: The experimental results show that: 1) MEET outperforms state-of-the-art methods on multiple open EEG datasets (SEED, SEED-IV, WM) for brain states classification; 2) MEET demonstrates that 5-bands fusion is the best integration strategy; and 3) MEET identifies interpretable brain attention regions. SIGNIFICANCE: MEET is an interpretable and universal model based on the multiband-multiscale characteristics of EEG. CONCLUSION: The innovative combination of band attention and temporal/spatial self-attention mechanisms in MEET achieves promising data-driven learning of the temporal dependencies and spatial relationships of EEG signals across the entire brain in a holistic and comprehensive fashion.

Arousal modulates the amygdala-insula reciprocal connectivity during naturalistic emotional movie watching.

Emotional arousal is a complex state recruiting distributed cortical and subcortical structures, in which the amygdala and insula play an important role. Although previous neuroimaging studies have showed that the amygdala and insula manifest reciprocal connectivity, the effective connectivities and modulatory patterns on the amygdala-insula interactions underpinning arousal are still largely unknown. One of the reasons may be attributed to static and discrete laboratory brain imaging paradigms used in most existing studies. In this study, by integrating naturalistic-paradigm (i.e., movie watching) functional magnetic resonance imaging (fMRI) with a computational affective model that predicts dynamic arousal for the movie stimuli, we investigated the effective amygdala-insula interactions and the modulatory effect of the input arousal on the effective connections. Specifically, the predicted dynamic arousal of the movie served as regressors in general linear model (GLM) analysis and brain activations were identified accordingly. The regions of interest (i.e., the bilateral amygdala and insula) were localized according to the GLM activation map. The effective connectivity and modulatory effect were then inferred by using dynamic causal modeling (DCM). Our experimental results demonstrated that amygdala was the site of driving arousal input and arousal had a modulatory effect on the reciprocal connections between amygdala and insula. Our study provides novel evidence to the underlying neural mechanisms of arousal in a dynamical naturalistic setting.

Distortion correction of functional MRI without reverse phase encoding scans or field maps.

Functional magnetic resonance images (fMRI) acquired using echo planar sequences typically suffer from spatial distortions due to susceptibility induced off-resonance fields, which may cause geometric mismatch with structural images and affect subsequent quantification and localization of brain function. State-of-the art distortion correction methods (for example, using FSL's topup or AFNI's 3dQwarp algorithms) require the collection of additional scans - either field maps or images with reverse phase encoding directions (i.e., blip-up/blip-down acquisitions) - to estimate and correct distortions. However, not all imaging protocols acquire these additional data and thus cannot take advantage of these post-acquisition corrections. In this study, we aim to enable state-of-the art processing of historical or limited datasets that do not include specific sequences for distortion correction by using only the acquired functional data and a single commonly acquired structural image. To achieve this, we synthesize an undistorted image with contrast similar to the fMRI data and use the non-distorted synthetic image as an anatomical target for distortion correction. We evaluate the efficacy of this approach, named SynBOLD-DisCo (Synthetic BOLD contrast for Distortion Correction), and show that this distortion correction process yields fMRI data that are geometrically similar to non-distorted structural images, with distortion correction virtually equivalent to acquisitions that do contain both blip-up/blip-down images. Our method is available as a Singularity container, source code, and an executable trained model to facilitate evaluation and integration into existing fMRI preprocessing pipelines.

Does Exercise Attenuate Disease Progression in People With Parkinson's Disease? A Systematic Review With Meta-Analyses.

INTRODUCTION: Exercise has many benefits for people with Parkinson's disease (PD) and has been suggested to modify PD progression, but robust evidence supporting this is lacking. OBJECTIVE: This systematic review (PROSPERO registration: CRD42020169999) investigated whether exercise may have neuroplastic effects indicative of attenuating PD progression. METHODS: Six databases were searched for randomized controlled trials (RCTs) that compared the effect of exercise to control (no or sham exercise) or to another form of exercise, on indicators of PD progression (eg, brain-derived neurotrophic factor [BDNF], brain activation, "off" Unified Parkinson's Disease Rating Scale [UPDRS] scores). Trial quality was assessed using the Physiotherapy Evidence Database Scale. Random-effects meta-analyses were performed where at least 3 comparable trials reported the same outcome; remaining results were synthesized narratively. RESULTS: Forty-nine exercise trials involving 2104 PD participants were included. Compared to control, exercise improved "off" UPDRS motor scores (Hedge's g -0.39, 95% CI: -0.65 to -0.13, P = .003) and BDNF concentration (Hedge's g 0.54, 95% CI: 0.10-0.98, P = .02), with low to very low certainty of evidence, respectively. Narrative synthesis for the remaining outcomes suggested that compared to control, exercise may have neuroplastic effects. The exercise versus exercise comparisons were too heterogenous to enable pooling of results. DISCUSSION: This review provides limited evidence that exercise may have an attenuating effect on potential markers of PD progression. Further large RCTs are warranted to explore differential effects by exercise type, dose and PD stage, and should report on a core set of outcomes indicative of PD progression.

Building a tissue-unbiased brain template of fiber orientation distribution and tractography with multimodal registration.

PURPOSE: Brain templates provide an essential standard space for statistical analysis of brain structure and function. Despite recent advances, diffusion MRI still lacks a template of fiber orientation distribution (FOD) and tractography that is unbiased for both white and gray matter. Therefore, we aim to build up a set of such templates for better white-matter analysis and joint structural and functional analysis. METHODS: We have developed a multimodal registration method to leverage the complementary information captured by T1 -weighted, T2 -weighted, and diffusion MRI, so that a coherent transformation is generated to register FODs into a common space and average them into a template. Consequently, the anatomically constrained fiber-tracking method was applied to the FOD template to generate a tractography template. Fiber-centered functional connectivity analysis was then performed as an example of the benefits of such an unbiased template. RESULTS: Our FOD template preserves fine structural details in white matter and also, importantly, clear folding patterns in the cortex and good contrast in the subcortex. Quantitatively, our templates show better individual-template agreement at the whole-brain scale and segmentation scale. The tractography template aligns well with the gray matter, which led to fiber-centered functional connectivity showing high cross-group consistency. CONCLUSION: We have proposed a novel methodology for building a tissue-unbiased FOD and anatomically constrained tractography template based on multimodal registration. Our templates provide a standard space and statistical platform for not only white-matter analysis but also joint structural and functional analysis, therefore filling an important gap in multimodal neuroimage analysis.

Hippocampal Neuronal Integrity and Functional Connectivity Within the Default Mode Network in Mild Cognitive Impairment: A Multimodal Investigation.

Background: In older people with mild cognitive impairment (MCI), the relationship between early changes in functional connectivity and in vivo changes in key neurometabolites is not known. Two established correlates of MCI diagnosis are decreased N-acetylaspartate (NAA) in the hippocampus, indicative of decreased neuronal integrity, and changes in the default mode network (DMN) functional network. If and how these measures interrelate is yet to be established, and such understanding may provide insight into the processes underpinning observed cognitive decline. Objectives: To determine the relationship between NAA levels in the left hippocampus and functional connectivity within the DMN in an aging cohort. Methods: In a sample of 51 participants with MCI and 30 controls, hippocampal NAA was determined using magnetic resonance spectroscopy, and DMN connectivity was quantified using resting-state functional MRI. The association between hippocampal NAA and the DMN functional connectivity was tested within the MCI group and separately within the control group. Results: In the DMN, we showed a significant inverse association between functional connectivity and hippocampal NAA in 20 specific brain connections for patients with MCI. This was despite no evidence of any associations in the healthy control group or group differences in either of these measures alone. Conclusions: This study suggests that decreased neuronal integrity in the hippocampus is associated with functional change within the DMN for those with MCI, in contrast to healthy older adults. These results highlight the potential of multimodal investigations to better understand the processes associated with cognitive decline. Impact statement This study measured activity within the default mode network (DMN) and quantified N-acetylaspartate (NAA), a measure of neuronal integrity, within the hippocampus in participants with mild cognitive impairment (MCI) and healthy controls. In participants with MCI, NAA levels were inversely associated with connectivity between specific regions of the DMN, a relationship not evident in healthy controls. This association was present even in the absence of group differences in DMN connectivity or NAA levels. This research illustrates the possibility of using multiple magnetic resonance modalities for more sensitive measures of early cognitive decline to identify and intervene earlier.

An explainable deep learning framework for characterizing and interpreting human brain states.

Deep learning approaches have been widely adopted in the medical image analysis field. However, a most of existing deep learning approaches focus on achieving promising performances such as classification, detection, and segmentation, and much less effort is devoted to the explanation of the designed models. Similarly, in the brain imaging field, many deep learning approaches have been designed and applied to characterize and predict human brain states. However, these models lack interpretation. In response, we propose a novel domain knowledge informed self-attention graph pooling-based (SAGPool) graph convolutional neural network to study human brain states. Specifically, the dense individualized and common connectivity-based cortical landmarks system (DICCCOL, structural brain connectivity profiles) and holistic atlases of functional networks and interactions system (HAFNI, functional brain connectivity profiles) are integrated with the SAGPool model to better characterize and interpret the brain states. Extensive experiments are designed and carried out on the large-scale human connectome project (HCP) Q1 and S1200 dataset. Promising brain state classification performances are observed (e.g., an average of 93.7% for seven-task classification and 100% for binary classification). In addition, the importance of the brain regions, which contributes most to the accurate classification, is successfully quantified and visualized. A thorough neuroscientific interpretation suggests that these extracted brain regions and their importance calculated from self-attention graph pooling layer offer substantial explainability.

New insights into anatomical connectivity along the anterior-posterior axis of the human hippocampus using in vivo quantitative fibre tracking.

The hippocampus supports multiple cognitive functions including episodic memory. Recent work has highlighted functional differences along the anterior-posterior axis of the human hippocampus, but the neuroanatomical underpinnings of these differences remain unclear. We leveraged track-density imaging to systematically examine anatomical connectivity between the cortical mantle and the anterior-posterior axis of the in vivo human hippocampus. We first identified the most highly connected cortical areas and detailed the degree to which they preferentially connect along the anterior-posterior axis of the hippocampus. Then, using a tractography pipeline specifically tailored to measure the location and density of streamline endpoints within the hippocampus, we characterised where these cortical areas preferentially connect within the hippocampus. Our results provide new and detailed insights into how specific regions along the anterior-posterior axis of the hippocampus are associated with different cortical inputs/outputs and provide evidence that both gradients and circumscribed areas of dense extrinsic anatomical connectivity exist within the human hippocampus. These findings inform conceptual debates in the field and emphasise the importance of considering the hippocampus as a heterogeneous structure. Overall, our results represent a major advance in our ability to map the anatomical connectivity of the human hippocampus in vivo and inform our understanding of the neural architecture of hippocampal-dependent memory systems in the human brain.

The brain allows us to perceive and interact with our environment and to create and recall memories about our day-to-day lives. A sea-horse shaped structure in the brain, called the hippocampus, is critical for translating our perceptions into memories, and it does so in coordination with other brain regions. For example, different regions of the cerebral cortex (the outer layer of the brain) support different aspects of cognition, and pathways of information flow between the cerebral cortex and hippocampus underpin the healthy functioning of memory. Decades of research conducted into the brains of non-human primates show that specific regions of the cerebral cortex anatomically connect with different parts of the hippocampus to support this information flow. These insights form the foundation for existing theoretical models of how networks of neurons in the hippocampus and the cerebral cortex are connected. However, the human cerebral cortex has greatly expanded during our evolution, meaning that patterns of connectivity in the human brain may diverge from those in the brains of non-human primates. Deciphering human brain circuits in greater detail is crucial if we are to gain a better understanding of the structure and operation of the healthy human brain. However, obtaining comprehensive maps of anatomical connections between the hippocampus and cerebral cortex has been hampered by technical limitations. For example, magnetic resonance imaging (MRI), an approach that can be used to study the living human brain, suffers from insufficient image resolution. To overcome these issues, Dalton et al. used an imaging technique called diffusion weighted imaging which is used to study white matter pathways in the brain. They developed a tailored approach to create high-resolution maps showing how the hippocampus anatomically connects with the cerebral cortex in the healthy human brain. Dalton et al. produced detailed maps illustrating which areas of the cerebral cortex have high anatomical connectivity with the hippocampus and how different parts of the hippocampus preferentially connect to different neural circuits in the cortex. For example, the experiments demonstrate that highly connected areas in a cortical region called the temporal cortex connect to very specific, circumscribed regions within the hippocampus. These findings suggest that the hippocampus may consist of different neural circuits, each preferentially linked to defined areas of the cortex which are, in turn, associated with specific aspects of cognition. These observations further our knowledge of hippocampal-dependant memory circuits in the human brain and provide a foundation for the study of memory decline in aging and neurodegenerative diseases.

Accommodating site variation in neuroimaging data using normative and hierarchical Bayesian models.

The potential of normative modeling to make individualized predictions from neuroimaging data has enabled inferences that go beyond the case-control approach. However, site effects are often confounded with variables of interest in a complex manner and can bias estimates of normative models, which has impeded the application of normative models to large multi-site neuroimaging data sets. In this study, we suggest accommodating for these site effects by including them as random effects in a hierarchical Bayesian model. We compared the performance of a linear and a non-linear hierarchical Bayesian model in modeling the effect of age on cortical thickness. We used data of 570 healthy individuals from the ABIDE (autism brain imaging data exchange) data set in our experiments. In addition, we used data from individuals with autism to test whether our models are able to retain clinically useful information while removing site effects. We compared the proposed single stage hierarchical Bayesian method to several harmonization techniques commonly used to deal with additive and multiplicative site effects using a two stage regression, including regressing out site and harmonizing for site with ComBat, both with and without explicitly preserving variance caused by age and sex as biological variation of interest, and with a non-linear version of ComBat. In addition, we made predictions from raw data, in which site has not been accommodated for. The proposed hierarchical Bayesian method showed the best predictive performance according to multiple metrics. Beyond that, the resulting z-scores showed little to no residual site effects, yet still retained clinically useful information. In contrast, performance was particularly poor for the regression model and the ComBat model in which age and sex were not explicitly modeled. In all two stage harmonization models, predictions were poorly scaled, suffering from a loss of more than 90% of the original variance. Our results show the value of hierarchical Bayesian regression methods for accommodating site variation in neuroimaging data, which provides an alternative to harmonization techniques. While the approach we propose may have broad utility, our approach is particularly well suited to normative modeling where the primary interest is in accurate modeling of inter-subject variation and statistical quantification of deviations from a reference model.

Gradual changes in microarchitectural properties of cortex and juxtacortical white matter: Observed by anatomical and diffusion MRI.

PURPOSE: Characterization of cerebral cortex is challenged by the complexity and heterogeneity of its cyto- and myeloarchitecture. This study evaluates quantitative MRI metrics, measured across two cortical depths and in subcortical white matter (WM) adjacent to cortex (juxtacortical WM), indicative of myelin content, neurite density, and diffusion microenvironment, for a comprehensive characterization of cortical microarchitecture. METHODS: High-quality structural and diffusion MRI data (N = 30) from the Human Connectome Project were processed to compute myelin index, neurite density index, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from superficial cortex, deep cortex, and juxtacortical WM. The distributional patterns of these metrics were analyzed individually, correlated to one another, and were compared to established parcellations. RESULTS: Our results supported that myeloarchitectonic and the coexisting cytoarchitectonic structures influence the diffusion properties of water molecules residing in cortex. Full cortical thickness showed myelination patterns similar to those previously observed in humans. Higher myelin indices with similar distributional patterns were observed in deep cortex whereas lower myelin indices were observed in superficial cortex. Neurite density index and other diffusion MRI derived parameters provided complementary information to myelination. Reliable and reproducible correlations were identified among the cortical microarchitectural properties and fiber distributional patterns in proximal WM structures. CONCLUSION: We demonstrated gradual changes across the cortical sheath by assessing depth-specific cortical micro-architecture using anatomical and diffusion MRI. Mutually independent but coexisting features of cortical layers and juxtacortical WM provided new insights towards structural organizational units and variabilities across cortical regions and through depth.

GCNs-Net: A Graph Convolutional Neural Network Approach for Decoding Time-Resolved EEG Motor Imagery Signals.

Toward the development of effective and efficient brain-computer interface (BCI) systems, precise decoding of brain activity measured by an electroencephalogram (EEG) is highly demanded. Traditional works classify EEG signals without considering the topological relationship among electrodes. However, neuroscience research has increasingly emphasized network patterns of brain dynamics. Thus, the Euclidean structure of electrodes might not adequately reflect the interaction between signals. To fill the gap, a novel deep learning (DL) framework based on the graph convolutional neural networks (GCNs) is presented to enhance the decoding performance of raw EEG signals during different types of motor imagery (MI) tasks while cooperating with the functional topological relationship of electrodes. Based on the absolute Pearson's matrix of overall signals, the graph Laplacian of EEG electrodes is built up. The GCNs-Net constructed by graph convolutional layers learns the generalized features. The followed pooling layers reduce dimensionality, and the fully-connected (FC) softmax layer derives the final prediction. The introduced approach has been shown to converge for both personalized and groupwise predictions. It has achieved the highest averaged accuracy, 93.06% and 88.57% (PhysioNet dataset), 96.24% and 80.89% (high gamma dataset), at the subject and group level, respectively, compared with existing studies, which suggests adaptability and robustness to individual variability. Moreover, the performance is stably reproducible among repetitive experiments for cross-validation. The excellent performance of our method has shown that it is an important step toward better BCI approaches. To conclude, the GCNs-Net filters EEG signals based on the functional topological relationship, which manages to decode relevant features for brain MI. A DL library for EEG task classification including the code for this study is open source at https://github.com/SuperBruceJia/ EEG-DL for scientific research.

Modeling spatio-temporal patterns of holistic functional brain networks via multi-head guided attention graph neural networks (Multi-Head GAGNNs).

Mounting evidence has demonstrated that complex brain function processes are realized by the interaction of holistic functional brain networks which are spatially distributed across specific brain regions in a temporally dynamic fashion. Therefore, modeling spatio-temporal patterns of holistic functional brain networks plays an important role in understanding brain function. Compared to traditional modeling methods such as principal component analysis, independent component analysis, and sparse coding, superior performance has been achieved by recent deep learning methodologies. However, there are still two limitations of existing deep learning approaches for functional brain network modeling. They either (1) merely modeled a single targeted network and ignored holistic ones at one time, or (2) underutilized both spatial and temporal features of fMRI during network modeling, and the spatial/temporal accuracy was thus not warranted. To address these limitations, we proposed a novel Multi-Head Guided Attention Graph Neural Network (Multi-Head GAGNN) to simultaneously model both spatial and temporal patterns of holistic functional brain networks. Specifically, a spatial Multi-Head Attention Graph U-Net was first adopted to model the spatial patterns of multiple brain networks, and a temporal Multi-Head Guided Attention Network was then introduced to model the corresponding temporal patterns under the guidance of modeled spatial patterns. Based on seven task fMRI datasets from the public Human Connectome Project and resting state fMRI datasets from the public Autism Brain Imaging Data Exchange I of 1448 subjects, the proposed Multi-Head GAGNN showed superior ability and generalizability in modeling both spatial and temporal patterns of holistic functional brain networks in individual brains compared to other state-of-the-art (SOTA) models. Furthermore, the modeled spatio-temporal patterns of functional brain networks via the proposed Multi-Head GAGNN can better predict the individual cognitive behavioral measures compared to the other SOTA models. This study provided a novel and powerful tool for brain function modeling as well as for understanding the brain-cognitive behavior associations.

FOD-Net: A deep learning method for fiber orientation distribution angular super resolution.

Mapping the human connectome using fiber-tracking permits the study of brain connectivity and yields new insights into neuroscience. However, reliable connectome reconstruction using diffusion magnetic resonance imaging (dMRI) data acquired by widely available clinical protocols remains challenging, thus limiting the connectome/tractography clinical applications. Here we develop fiber orientation distribution (FOD) network (FOD-Net), a deep-learning-based framework for FOD angular super-resolution. Our method enhances the angular resolution of FOD images computed from common clinical-quality dMRI data, to obtain FODs with quality comparable to those produced from advanced research scanners. Super-resolved FOD images enable superior tractography and structural connectome reconstruction from clinical protocols. The method was trained and tested with high-quality data from the Human Connectome Project (HCP) and further validated with a local clinical 3.0T scanner as well as with another public available multicenter-multiscanner dataset. Using this method, we improve the angular resolution of FOD images acquired with typical single-shell low-angular-resolution dMRI data (e.g., 32 directions, b=1000s/mm2) to approximate the quality of FODs derived from time-consuming, multi-shell high-angular-resolution dMRI research protocols. We also demonstrate tractography improvement, removing spurious connections and bridging missing connections. We further demonstrate that connectomes reconstructed by super-resolved FODs achieve comparable results to those obtained with more advanced dMRI acquisition protocols, on both HCP and clinical 3.0T data. Advances in deep-learning approaches used in FOD-Net facilitate the generation of high quality tractography/connectome analysis from existing clinical MRI environments. Our code is freely available at https://github.com/ruizengalways/FOD-Net.

Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia.

Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = -0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = -0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.

Control energy assessment of spatial interactions among macro-scale brain networks.

Many recent studies have revealed that spatial interactions of functional brain networks derived from fMRI data can well model functional connectomes of the human brain. However, it has been rarely explored what the energy consumption characteristics are for such spatial interactions of macro-scale functional networks, which remains crucial for the understanding of brain organization, behavior, and dynamics. To explore this unanswered question, this article presents a novel framework for quantitative assessment of energy consumptions of macro-scale functional brain network's spatial interactions via two main effective computational methodologies. First, we designed a novel scheme combining dictionary learning and hierarchical clustering to derive macro-scale consistent brain network templates that can be used to define a common reference space for brain network interactions and energy assessments. Second, the control energy consumption for driving the brain networks during their spatial interactions is computed from the viewpoint of the linear network control theory. Especially, the energetically favorable brain networks were identified and their energy characteristics were comprehensively analyzed. Experimental results on the Human Connectome Project (HCP) task-based fMRI (tfMRI) data showed that the proposed methods can reveal meaningful, diverse energy consumption patterns of macro-scale network interactions. In particular, those networks present remarkable differences in energy consumption. The energetically least favorable brain networks are stable and consistent across HCP tasks such as motor, language, social, and working memory tasks. In general, our framework provides a new perspective to characterize human brain functional connectomes by quantitative assessment for the energy consumption of spatial interactions of macro-scale brain networks.