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The zona incerta (ZI) is a subcortical structure primarily investigated in rodents that is implicated in various behaviors, ranging from motor control to survival-associated activities, partly due to its integration in multiple neural circuits. In the current study, we used diffusion magnetic resonance imaging tractography to segment the ZI and gain insight into its connectivity in various circuits in humans. We performed probabilistic tractography in 7T diffusion MRI on 178 participants from the Human Connectome Project to validate the ZI's anatomical subdivisions and their respective tracts. K-means clustering segmented the ZI based on each voxel's connectivity profile. We further characterized the connections of each ZI subregion using probabilistic tractography with each subregion as a seed. We identified 2 dominant clusters that delineated the whole ZI into rostral and caudal subregions. The caudal ZI primarily connected with motor regions, while the rostral ZI received a topographic distribution of projections from prefrontal areas, notably the anterior cingulate and medial prefrontal cortices. We generated a probabilistic ZI atlas that was registered to a patient-participant's magnetic resonance imaging scan for placement of stereoencephalographic leads for electrophysiology-guided deep brain stimulation to treat their obsessive-compulsive disorder. Rostral ZI stimulation improved the patient's core symptoms (mean improvement 21%). We present a tractography-based atlas of the rostral and caudal ZI subregions constructed using high-resolution diffusion magnetic resonance imaging from 178 healthy participants. Our work provides an anatomical foundation to explore the rostral ZI as a novel target for deep brain stimulation to treat refractory obsessive-compulsive disorder and other disorders associated with dysfunctional reward circuitry. [ABSTRACT FROM AUTHOR]

This study aims to reveal the association between sleep quality and crystallized intelligence (Gc), fluid intelligence (Gf), and the underlying brain structural basis. Using the data from the Human Connectome Project (N = 1087), we performed mediation analysis to explore whether regional brain structure related to sleep quality mediate the association between sleep quality and intellectual abilities, and further examined whether socioeconomic status (i.e., income and education level) moderate the mediation effect. Results showed that poorer sleep quality was associated with lower Gc rather than Gf, and worse sleep quality was associated with smaller volume and surface area in temporal lobe, including inferior temporal gyrus and middle temporal gyrus. Notably, temporal lobe structures mediated the association between sleep quality and Gc rather than Gf. Furthermore, socioeconomic status (i.e., income and education level) moderated the mediating effect, showing low socioeconomic status has a more significant mediating effect with stronger association between sleep quality and Gc as well as stronger association between temporal lobe structure and Gc in low socioeconomic status group. These findings suggest that individuals with higher socioeconomic status are less susceptible to the effect of sleep quality on Gc. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) is a noninvasive and in-vivo imaging technique essential for measuring brain activity. Functional connectivity is used to study associations between brain regions, either while study subjects perform tasks or during periods of rest. In this paper, we propose a rigorous definition of task-evoked functional connectivity at the population level (ptFC). Importantly, our proposed ptFC is interpretable in the context of task-fMRI studies. An algorithm for estimating the ptFC is provided. We present the performance of the proposed algorithm compared to existing functional connectivity frameworks using simulations. Lastly, we apply the proposed algorithm to estimate the ptFC in a motor-task study from the Human Connectome Project. [ABSTRACT FROM AUTHOR]

Systemic physiological dynamics, such as heart rate variability (HRV) and respiration volume per time (RVT), are known to account for significant variance in the blood oxygen level dependent (BOLD) signal of resting-state functional magnetic resonance imaging (rsfMRI). However, synchrony between these cardiorespiratory changes and the BOLD signal could be due to neuronal (i.e., autonomic activity inducing changes in heart rate and respiration) or vascular (i.e., cardiorespiratory activity facilitating hemodynamic changes and thus the BOLD signal) effects and the contributions of these effects may differ spatially, temporally, and spectrally. In this study, we characterize these brain-body dynamics using a wavelet analysis in rapidly sampled rsfMRI data with simultaneous pulse oximetry and respiratory monitoring of the Human Connectome Project. Our time-frequency analysis across resting-state networks (RSNs) revealed differences in the coherence of the BOLD signal and heartbeat interval (HBI)/RVT dynamics across frequencies, with unique profiles per network. Somatomotor (SMN), visual (VN), and salience (VAN) networks demonstrated the greatest synchrony with both systemic physiological signals when compared to other networks; however, significant coherence was observed in all RSNs regardless of direct autonomic involvement. Our phase analysis revealed distinct frequency profiles of percentage of time with significant coherence between BOLD and systemic physiological signals for different phase offsets across RSNs, suggesting that the phase offset and temporal order of signals varies by frequency. Lastly, our analysis of temporal variability of coherence provides insight on potential influence of autonomic state on brain-body communication. Overall, the novel wavelet analysis enables an efficient characterization of the dynamic relationship between cardiorespiratory activity and the BOLD signal in spatial, temporal, and spectral dimensions to inform our understanding of autonomic states and improve our interpretation of the BOLD signal.

Aging is the basis of neurodegeneration and dementia that affects each endemic in the body. Normal aging in the brain is associated with progressive slowdown and disruptions in various abilities such as motor ability, cognitive impairment, decreasing information processing speed, attention, and memory. With the aggravation of global aging, more research focuses on brain changes in the elderly adult. The graph theory, in combination with functional magnetic resonance imaging (fMRI), makes it possible to evaluate the brain network functional connectivity patterns in different conditions with brain modeling. We have evaluated the brain network communication model changes in three different age groups (including 8 to 15 years, 25 to 35 years, and 45 to 75 years) in lifespan pilot data from the human connectome project (HCP). Initially, Pearson correlation-based connectivity networks were calculated and thresholded. Then, network characteristics were compared between the three age groups by calculating the global and local graph measures. In the resting state brain network, we observed decreasing global efficiency and increasing transitivity with age. Also, brain regions, including the amygdala, putamen, hippocampus, precuneus, inferior temporal gyrus, anterior cingulate gyrus, and middle temporal gyrus, were selected as the most affected brain areas with age through statistical tests and machine learning methods. Using feature selection methods, including Fisher score and Kruskal–Wallis, we were able to classify three age groups using SVM, KNN, and decision-tree classifier. The best classification accuracy is in the combination of Fisher score and decision tree classifier obtained, which was 82.2%. Thus, by examining the measures of functional connectivity using graph theory, we will be able to explore normal age-related changes in the human brain, which can be used as a tool to monitor health with age. [ABSTRACT FROM AUTHOR]

We present CiftiStorm, an electrophysiological source imaging (ESI) pipeline incorporating recently developed methods to improve forward and inverse solutions. The CiftiStorm pipeline produces Human Connectome Project (HCP) and megconnectome-compliant outputs from dataset inputs with varying degrees of spatial resolution. The input data can range from low-sensor-density electroencephalogram (EEG) or magnetoencephalogram (MEG) recordings without structural magnetic resonance imaging (sMRI) to high-density EEG/MEG recordings with an HCP multimodal sMRI compliant protocol. CiftiStorm introduces a numerical quality control of the lead field and geometrical corrections to the head and source models for forward modeling. For the inverse modeling, we present a Bayesian estimation of the cross-spectrum of sources based on multiple priors. We facilitate ESI in the T1w/FSAverage32k high-resolution space obtained from individual sMRI. We validate this feature by comparing CiftiStorm outputs for EEG and MRI data from the Cuban Human Brain Mapping Project (CHBMP) acquired with technologies a decade before the HCP MEG and MRI standardized dataset. [ABSTRACT FROM AUTHOR]

As a novel measure for irregularity and complexity of the spontaneous fluctuations of brain activities, brain entropy (BEN) has attracted much attention in resting-state functional magnetic resonance imaging (rs-fMRI) studies during the last decade. Previous studies have shown its associations with cognitive and mental functions. While most previous research assumes BEN is approximately stationary during scan sessions, the brain, even at its resting state, is a highly dynamic system. Such dynamics could be characterized by a series of reoccurring whole-brain patterns related to cognitive and mental processes. The present study aims to explore the time-varying feature of BEN and its potential links with general cognitive ability. We adopted a sliding window approach to derive the dynamical brain entropy (dBEN) of the whole-brain functional networks from the HCP (Human Connectome Project) rs-fMRI dataset that includes 812 young healthy adults. The dBEN was further clustered into 4 reoccurring BEN states by the k-means clustering method. The fraction window (FW) and mean dwell time (MDT) of one BEN state, characterized by the extremely low overall BEN, were found to be negatively correlated with general cognitive abilities (i.e., cognitive flexibility, inhibitory control, and processing speed). Another BEN state, characterized by intermediate overall BEN and low within-state BEN located in DMN, ECN, and part of SAN, its FW, and MDT were positively correlated with the above cognitive abilities. The results of our study advance our understanding of the underlying mechanism of BEN dynamics and provide a potential framework for future investigations in clinical populations. [ABSTRACT FROM AUTHOR]

Recent studies have established the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state as a key measure of local cortical brain function. Here, we sought to extend that line of research by evaluating TBOLD in 70 cortical areas with respect to corresponding brain volume, age, and sex across the lifespan in 1,344 healthy participants including 633 from the Human Connectome Project (HCP)—Development cohort (294 males and 339 females, age range 8–21 yr) and 711 healthy participants from HCP-Aging cohort (316 males and 395 females, 36–90 yr old). In both groups, we found that 1) TBOLD increased with age, 2) volume decreased with age, and 3) TBOLD and volume were highly significantly negatively correlated, independent of age. The inverse association between TBOLD and volume was documented in nearly all 70 brain areas and for both sexes, with slightly stronger associations documented for males. The strong correspondence between TBOLD and volume across age and sex suggests a common influence such as chronic neuroinflammation contributing to reduced cortical volume and increased TBOLD across the lifespan. NEW & NOTEWORTHY: We report a significant negative association between resting functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) signal turnover (TBOLD) and cortical gray matter volume across the lifespan, such that TBOLD increased whereas volume decreased. We attribute this association to a hypothesized chronic, low-grade neuroinflammation, probably induced by various neurotropic pathogens, including human herpes viruses known to be dormant in the brain in a latent state and reactivated by stress, fever, and various environmental exposures, such as ultraviolet light. [ABSTRACT FROM AUTHOR]

Understanding the complex mechanisms of the brain can be unraveled by extracting the Dynamic Effective Connectome (DEC). Recently, score-based Directed Acyclic Graph (DAG) discovery methods have shown significant improvements in extracting the causal structure and inferring effective connectivity. However, learning DEC through these methods still faces two main challenges: one with the fundamental impotence of high-dimensional dynamic DAG discovery methods and the other with the low quality of fMRI data. In this paper, we introduce Bayesian Dynamic DAG learning with M-matrices Acyclicity characterization (BDyMA) method to address the challenges in discovering DEC. The presented dynamic DAG enables us to discover direct feedback loop edges as well. Leveraging an unconstrained framework in the BDyMA method leads to more accurate results in detecting high-dimensional networks, achieving sparser outcomes, making it particularly suitable for extracting DEC. Additionally, the score function of the BDyMA method allows the incorporation of prior knowledge into the process of dynamic causal discovery which further enhances the accuracy of results. Comprehensive simulations on synthetic data and experiments on Human Connectome Project (HCP) data demonstrate that our method can handle both of the two main challenges, yielding more accurate and reliable DEC compared to state-of-the-art and traditional methods. Additionally, we investigate the trustworthiness of DTI data as prior knowledge for DEC discovery and show the improvements in DEC discovery when the DTI data is incorporated into the process.

Despite the connectome or network "era", the variety of individual facets (e.g., cognition, personality, mental health) are typically studied as separate watertight compartments. This study adopted advanced methodological approaches to (i) highlight a network depicting distinct domains of human mind and behavior, and to (ii) delineate their possible direct influences. Through an Exploratory Graph Analysis on the Human Connectome Project's database, we found a network composed by seven separate but related domains - Mental Health, Externalizing problems, High-level Cognitive Functions, Basic Cognitive Functions, Substances use/abuse, Reward Delay Discounting and Pain - unveiling a low dimensionality of human mind and behavior. Finally, by applying Bayesian Networks on this model, we observed that some facets have also specific and oriented relationships, while other facets are instead independent from each other. In such a way, we drew a potential architecture of individual's facets that can pave the way for future neuroimaging studies and clinical practice. [ABSTRACT FROM AUTHOR]

Non‐negligible idiosyncrasy due to interindividual differences is an ongoing issue in resting‐state functional MRI (rfMRI) analysis. We show that a deep neural network (DNN) can be employed for individual identification by learning important features from the time‐varying functional connectivity (FC) of rfMRI in the Human Connectome Project. We employed the trained DNN to identify individuals from an independent dataset acquired at our institution. The results revealed that the DNN could successfully identify 300 individuals with an error rate of 2.9% using 15 s time‐window and 870 individuals with an error rate of 6.7%. A trained DNN with nonlinear hidden layers led to the proposal of the "fingerprint of FC" (fpFC) as representative edges of individual FC. The fpFCs for individuals exhibited commonly important and individual‐specific edges across time‐window lengths (from 5 min to 15 s). Furthermore, the utility of our model for another group of subjects was validated, supporting the feasibility of our technique in the context of transfer learning. In conclusion, our study offers an insight into the discovery of the intrinsic mode of the human brain using whole‐brain resting‐state FC and DNNs. [ABSTRACT FROM AUTHOR]

In a segregated society, marked by a historical background of inequalities, there is a consistent under-representation of ethnic and racial minorities in biomedical research, causing disparities in understanding genetic and acquired diseases as well as in the effectiveness of clinical treatments affecting different groups. The repeated inclusion of small and non-representative samples of the population in neuroimaging research has led to generalization bias in the morphological characterization of the human brain. A few brain morphometric studies between Whites and African Americans have reported differences in orbitofrontal volumetry and insula cortical thickness. Nevertheless, these studies are mostly conducted in small samples and populations with cognitive impairment. For this reason, this study aimed to identify brain morphological variability due to racial identity in representative samples. We hypothesized that, in neurotypical young adults, there are differences in brain morphometry between participants with distinct racial identities. We analyzed the Human Connectome Project (HCP) database to test this hypothesis. Brain volumetry, cortical thickness, and cortical surface area measures of participants identified as Whites (n = 338) or African Americans (n = 56) were analyzed. Non-parametrical permutation analysis of covariance between these racial identity groups adjusting for age, sex, education, and economic income was implemented. Results indicated volumetric differences in choroid plexus, supratentorial, white matter, and subcortical brain structures. Moreover, differences in cortical thickness and surface area in frontal, parietal, temporal, and occipital brain regions were identified between groups. In this regard, the inclusion of sub-representative minorities in neuroimaging research, such as African American persons, is fundamental for the comprehension of human brain morphometric diversity and to design personalized clinical brain treatments for this population. [ABSTRACT FROM AUTHOR]

We present CiftiStorm, an electrophysiological source imaging (ESI) pipeline incorporating recently developed methods to improve forward and inverse solutions. The CiftiStorm pipeline produces Human Connectome Project (HCP) and megconnectome-compliant outputs from dataset inputs with varying degrees of spatial resolution. The input data can range from low-sensor-density electroencephalogram (EEG) or magnetoencephalogram (MEG) recordings without structural magnetic resonance imaging (sMRI) to high-density EEG/MEG recordings with an HCP multimodal sMRI compliant protocol. CiftiStorm introduces a numerical quality control of the lead field and geometrical corrections to the head and source models for forward modeling. For the inverse modeling, we present a Bayesian estimation of the cross-spectrum of sources based on multiple priors. We facilitate ESI in the T1w/FSAverage32k high-resolution space obtained from individual sMRI. We validate this feature by comparing CiftiStorm outputs for EEG and MRI data from the Cuban Human Brain Mapping Project (CHBMP) acquired with technologies a decade before the HCP MEG and MRI standardized dataset.

The n-back task is a widely used behavioral task for measuring working memory and the ability to inhibit interfering information. We develop a novel model of the commonly used 2-back task using the cognitive psychometric framework provided by Multinomial Processing Trees. Our model involves three parameters: a memory parameter, corresponding to how well an individual encodes and updates sequence information about presented stimuli; a decision parameter corresponding to how well participants execute choices based on information stored in memory; and a base-rate parameter corresponding to bias for responding yes or no. We test the parameter recovery properties of the model using existing 2-back experimental designs, and demonstrate the application of the model to two previous data sets: one from social psychology involving faces corresponding to different races (Stelter and Degner, British Journal of Psychology 109:777-798, 2018), and one from cognitive neuroscience involving more than 1000 participants from the Human Connectome Project (Van Essen et al., Neuroimage 80:62-79, 2013). We demonstrate that the model can be used to infer interpretable individual-level parameters. We develop a hierarchical extension of the model to test differences between stimulus conditions, comparing faces of different races, and comparing face to non-face stimuli. We also develop a multivariate regression extension to examine the relationship between the model parameters and individual performance on standardized cognitive measures including the List Sorting and Flanker tasks. We conclude by discussing how our model can be used to dissociate underlying cognitive processes such as encoding failures, inhibition failures, and binding failures.

Chunxiang Jiang,1,2 Siqi Cai,1,2 Lijuan Zhang1,2 1Paul. C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaCorrespondence: Lijuan Zhang, Paul. C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, 518055, People’s Republic of China, Tel +86 0755 86392247, Fax +86 0755 86392299, Email lj.zhang@siat.ac.cnPurpose: Functional magnetic resonance imaging (fMRI) has been widely adopted to investigate the neural activity in gray matter (GM) in the field of sleep research, but the neural activity in white matter (WM) has received much less attention. The current study set out to test our hypothesis that WM functional abnormality is associated with poor sleep quality.Participants and Methods: K-means clustering analysis was performed on 78 healthy adults drawn from the Human Connectome Project dataset to extract stable WM functional networks (WM-FNs) and GM-FNs. The differences in functional connectivity within WM-FNs and between WM- and GM-FNs, as well as the power spectrum between good sleep quality group (Pittsburgh Sleep Quality Index (PSQI) < 6, daytime dysfunction = 0) and poor sleep quality group (PSQI > 6, daytime dysfunction > 0) were examined between groups with good and poor sleep quality. Additionally, linear relationships between sleep quality and altered functional characteristics of WM-FNs were evaluated.Results: Functional connectivity between middle and superficial WM-FNs, short- and long-range functional connectivity between WM- and GM-FNs were decreased in poor sleepers and negatively correlated with PSQI score. The mean amplitudes of right sensorimotor WM networks at whole, high and low frequency bands were higher in poor sleepers and were positively correlated with PSQI score.Conclusion: WM functional abnormality is associated with poor sleep quality. The neurobiological mechanisms that underlie the functional alterations of WM-FNs in poor sleepers need to be investigated in future studies.Keywords: human connectome project, sleep quality, white matter, functional connectivity, functional magnetic resonance imaging

In a segregated society, marked by a historical background of inequalities, there is a consistent under-representation of ethnic and racial minorities in biomedical research, causing disparities in understanding genetic and acquired diseases as well as in the effectiveness of clinical treatments affecting different groups. The repeated inclusion of small and non-representative samples of the population in neuroimaging research has led to generalization bias in the morphological characterization of the human brain. A few brain morphometric studies between Whites and African Americans have reported differences in orbitofrontal volumetry and insula cortical thickness. Nevertheless, these studies are mostly conducted in small samples and populations with cognitive impairment. For this reason, this study aimed to identify brain morphological variability due to racial identity in representative samples. We hypothesized that, in neurotypical young adults, there are differences in brain morphometry between participants with distinct racial identities. We analyzed the Human Connectome Project (HCP) database to test this hypothesis. Brain volumetry, cortical thickness, and cortical surface area measures of participants identified as Whites (n = 338) or African Americans (n = 56) were analyzed. Non-parametrical permutation analysis of covariance between these racial identity groups adjusting for age, sex, education, and economic income was implemented. Results indicated volumetric differences in choroid plexus, supratentorial, white matter, and subcortical brain structures. Moreover, differences in cortical thickness and surface area in frontal, parietal, temporal, and occipital brain regions were identified between groups. In this regard, the inclusion of sub-representative minorities in neuroimaging research, such as African American persons, is fundamental for the comprehension of human brain morphometric diversity and to design personalized clinical brain treatments for this population.

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.

Measuring and testing the dependency between multiple random functions is often an important task in functional data analysis. In the literature, a model-based method relies on a model which is subject to the risk of model misspecification, while a model-free method only provides a correlation measure which is inadequate to test independence. In this paper, we adopt the Hilbert–Schmidt Independence Criterion (HSIC) to measure the dependency between two random functions. We develop a two-step procedure by first pre-smoothing each function based on its discrete and noisy measurements and then applying the HSIC to recovered functions. To ensure the compatibility between the two steps such that the effect of the pre-smoothing error on the subsequent HSIC is asymptotically negligible when the data are densely measured, we propose a new wavelet thresholding method for pre-smoothing and to use Besov-norm-induced kernels for HSIC. We also provide the corresponding asymptotic analysis. The superior numerical performance of the proposed method over existing ones is demonstrated in a simulation study. Moreover, in a magnetoencephalography (MEG) data application, the functional connectivity patterns identified by the proposed method are more anatomically interpretable than those by existing methods. [ABSTRACT FROM AUTHOR]

The cerebellum (CB) and basal ganglia (BG) each have topographically distinct functional subregions that are functionally and anatomically interconnected with cortical regions through discrete thalamic loops and with each other via disynaptic connections, with previous work detailing high levels of functional connectivity between these phylogenetically ancient regions. It was posited that this CB-BG network provides support for cortical systems processing, spanning cognitive, emotional, and motor domains, implying that subcortical network measures are strongly related to cortical network measures (Bostan & Strick, 2018); however, it is currently unknown how network measures within distinct CB-BG networks relate to cortical network measures. Here, 122 regions of interest comprising cognitive and motor CB-BG networks and 7 canonical cortical resting-state were used to investigate whether the integration (quantified using global efficiency, GE) of cognitive CB-BG network (CCBN) nodes and their segregation from motor CB-BG network (MCBN) nodes is related to cortical network GE and segregation in 233 non-related, right-handed participants (Human Connectome Project-1200). CCBN GE positively correlated with GE in the default mode, motor, and auditory networks and MCBN GE positively correlated with GE in all networks, except the default mode and emotional. MCBN segregation was related to motor network segregation. These findings highlight the CB-BG network's potential role in cortical networks associated with executive function, task switching, and verbal working memory. This work has implications for understanding cortical network organization and cortical-subcortical interactions in healthy adults and may help in determining biomarkers and deciphering subcortical differences seen in disease states. [ABSTRACT FROM AUTHOR]

The human visual pathway starts from the retina, passes through the retinogeniculate visual pathway, the optic radiation, and finally connects to the primary visual cortex. Diffusion MRI tractography is the only technology that can noninvasively reconstruct the visual pathway. However, complete and accurate visual pathway reconstruction is challenging because of the skull base environment and complex fiber geometries. Specifically, the optic nerve within the complex skull base environment can cause abnormal diffusion signals. The crossing and fanning fibers at the optic chiasm, and a sharp turn of Meyer's loop at the optic radiation, contribute to complex fiber geometries of the visual pathway. A fiber trajectory distribution (FTD) function‐based tractography method of our previous work and several high sensitivity tractography methods can reveal these complex fiber geometries, but are accompanied by false‐positive fibers. Thus, the related studies of the visual pathway mostly applied the expert region of interest selection strategy. However, interobserver variability is an issue in reconstructing an accurate visual pathway. In this paper, we propose a unified global tractography framework to automatically reconstruct the visual pathway. We first extend the FTD function to a high‐order streamline differential equation for global trajectory estimation. At the global level, the tractography process is simplified as the estimation of global trajectory distribution coefficients by minimizing the cost between trajectory distribution and the selected directions under the prior guidance by introducing the tractography template as anatomic priors. Furthermore, we use a deep learning‐based method and tractography template prior information to automatically generate the mask for tractography. The experimental results demonstrate that our proposed method can successfully reconstruct the visual pathway with high accuracy. [ABSTRACT FROM AUTHOR]

The nerve fibers are divided into three categories: projection, commissural, and association fibers. This study demonstrated a novel cortical mapping method based on these three fiber categories using MR tractography data. The MR fiber-track data were extracted using the diffusion-weighted 3T-MRI data from 19 individuals' Human Connectome Project dataset. Anatomical MR images in each dataset were parcellated using FreeSurfer software and Brainnetome atlas. The 5 million extracted tracks per subject by MRtrix software were classified based on the basic cortical structure (cortical area in the left and right hemisphere, subcortical area), after the tracks validation procedure. The number of terminals for each categorized track per unit-sized cortical area (1 mm3) was defined as the track-density in that cortical area. Track-density ratio mapping with fiber types was achieved by mapping the density-dependent color intensity for each categorized tracks with a different primary color. The mapping results showed a highly localized, unique density ratio map determined by fiber types. Furthermore, the quantitative group data analysis based on the parcellation information revealed that the majority of nerve fibers in the brain are association fibers, particularly in temporal, inferior parietal, and occipital lobes, while the projection and commissural fibers were mainly located in the superior part of the brain. Hemispheric asymmetries in the fiber density were also observed, such as long association fiber in the Broca's and Wernicke's areas. We believe this new dimensional brain mapping information allows us to further understand brain anatomy, function.

The WU-Minn Human Connectome Project (HCP) is a publicly-available dataset containing state-of-the-art structural magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion MRI (dMRI) for over a thousand healthy subjects. While the planned scope of the HCP included an anatomic connectome, resting-state fMRI (rs-fMRI) forms the bulk of the HCP's current connectomic output. We address this by presenting a full-cortex connectome derived from probabilistic diffusion tractography and organized into the HCP-MMP1.0 atlas. Probabilistic methods and large sample sizes are preferable for whole-connectome mapping as they increase the fidelity of traced low-probability connections. We find that overall, connection strengths are lognormally distributed and decay exponentially with tract length, that connectivity reasonably matches macaque histologic tracing in homologous areas, that contralateral homologs and left-lateralized language areas are hyperconnected, and that hierarchical similarity influences connectivity. We compare the dMRI connectome to existing rs-fMRI and cortico-cortico-evoked potential connectivity matrices and find that it is more similar to the latter. This work helps fulfill the promise of the HCP and will make possible comparisons between the underlying structural connectome and functional connectomes of various modalities, brain states, and clinical conditions.

Visual field maps in human early extrastriate areas (V2 and V3) are traditionally thought to form mirror-image representations which surround the primary visual cortex (V1). According to this scheme, V2 and V3 form nearly symmetrical halves with respect to the calcarine sulcus, with the dorsal halves representing lower contralateral quadrants, and the ventral halves representing upper contralateral quadrants. This arrangement is considered to be consistent across individuals, and thus predictable with reasonable accuracy using templates. However, data that deviate from this expected pattern have been observed, but mainly treated as artifactual. Here, we systematically investigate individual variability in the visual field maps of human early visual cortex using the 7T Human Connectome Project (HCP) retinotopy dataset. Our results demonstrate substantial and principled inter-individual variability. Visual field representation in the dorsal portions of V2 and V3 was more variable than in their ventral counterparts, including substantial departures from the expected mirror-symmetrical patterns. In addition, left hemisphere retinotopic maps were more variable than those in the right hemisphere. Surprisingly, only one-third of individuals had maps that conformed to the expected pattern in the left hemisphere. Visual field sign analysis further revealed that in many individuals the area conventionally identified as dorsal V3 shows a discontinuity in the mirror-image representation of the retina, associated with a Y-shaped lower vertical representation. Our findings challenge the current view that inter-individual variability in early extrastriate cortex is negligible, and that the dorsal portions of V2 and V3 are roughly mirror images of their ventral counterparts.

Our understanding of the structure of the brain and its relationships with human traits is largely determined by how we represent the structural connectome. Standard practice divides the brain into regions of interest (ROIs) and represents the connectome as an adjacency matrix having cells measuring connectivity between pairs of ROIs. Statistical analyses are then heavily driven by the (largely arbitrary) choice of ROIs. In this article, we propose a human trait prediction framework utilizing a tractography-based representation of the brain connectome, which clusters fiber endpoints to define a data-driven white matter parcellation targeted to explain variation among individuals and predict human traits. This leads to Principal Parcellation Analysis (PPA), representing individual brain connectomes by compositional vectors building on a basis system of fiber bundles that captures the connectivity at the population level. PPA eliminates the need to choose atlases and ROIs a priori, and provides a simpler, vector-valued representation that facilitates easier statistical analysis compared to the complex graph structures encountered in classical connectome analyses. We illustrate the proposed approach through applications to data from the Human Connectome Project (HCP) and show that PPA connectomes improve power in predicting human traits over state-of-the-art methods based on classical connectomes, while dramatically improving parsimony and maintaining interpretability. Our PPA package is publicly available on GitHub, and can be implemented routinely for diffusion image data.

Deep neural networks (DNNs) have been adopted widely as classifiers for functional magnetic resonance imaging (fMRI) data, advancing beyond traditional machine learning models. Consequently, transfer learning of the pre-trained DNN becomes crucial to enhance DNN classification performance, specifically by alleviating an overfitting issue that occurs when a substantial number of DNN parameters are fitted to a relatively small number of fMRI samples. In this study, we first systematically compared the two most popularly used, unsupervised pretraining models for resting-state fMRI (rfMRI) volume data to pre-train the DNNs, namely autoencoder (AE) and restricted Boltzmann machine (RBM). The group in-brain mask used when training AE and RBM displayed a sizable overlap ratio with Yeo's seven functional brain networks (FNs). The parcellated FNs obtained from the RBM were fine-grained compared to those from the AE. The pre-trained AE and RBM served as the weight parameters of the first of the two hidden DNN layers, and the DNN fulfilled the task classifier role for fMRI (tfMRI) data in the Human Connectome Project (HCP). We tested two transfer learning schemes: (1) fixing and (2) fine-tuning the DNN's pre-trained AE or RBM weights. The DNN with transfer learning was compared to a baseline DNN, trained using random initial weights. Overall, DNN classification performance from the transfer learning proved superior when the pre-trained RBM weights were fixed and when the pre-trained AE weights were fine-tuned (average error rates: 14.8% for fixed RBM, 15.1% fine-tuned AE, and 15.5% for the baseline model) compared to the alternative scenarios of DNN transfer learning schemes. Moreover, the optimal transfer learning scheme between the fixed RBM and fine-tuned AE varied according to seven task conditions in the HCP. Nonetheless, the computational load reduced substantially for the fixed-weight-based transfer learning compared to the fine-tuning-based transfer learning (e.g., the number of weight parameters for the fixed-weight-based DNN model reduced to 1.9% compared with a baseline/fine-tuned DNN model). Our findings suggest that weight initialization at the DNN's first layer using RBM-based pre-trained weights provides the most promising approach when the whole-brain fMRI volume supports associated task classification. We believe that our proposed scheme could be applied to a variety of task conditions to improve their classification performance and to utilize computational resources efficiently using our AE/RBM-based pre-trained weights compared to random initial weights for DNN training.

Major depressive disorder (MDD) has been associated with changes in functional brain connectivity. Yet, typical analyses of functional connectivity, such as spatial independent components analysis (ICA) for resting‐state data, often ignore sources of between‐subject variability, which may be crucial for identifying functional connectivity patterns associated with MDD. Typically, methods like spatial ICA will identify a single component to represent a network like the default mode network (DMN), even if groups within the data show differential DMN coactivation. To address this gap, this project applies a tensorial extension of ICA (tensorial ICA)—which explicitly incorporates between‐subject variability—to identify functionally connected networks using functional MRI data from the Human Connectome Project (HCP). Data from the HCP included individuals with a diagnosis of MDD, a family history of MDD, and healthy controls performing a gambling and social cognition task. Based on evidence associating MDD with blunted neural activation to rewards and social stimuli, we predicted that tensorial ICA would identify networks associated with reduced spatiotemporal coherence and blunted social and reward‐based network activity in MDD. Across both tasks, tensorial ICA identified three networks showing decreased coherence in MDD. All three networks included ventromedial prefrontal cortex, striatum, and cerebellum and showed different activation across the conditions of their respective tasks. However, MDD was only associated with differences in task‐based activation in one network from the social task. Additionally, these results suggest that tensorial ICA could be a valuable tool for understanding clinical differences in relation to network activation and connectivity. [ABSTRACT FROM AUTHOR]

Brain decoding, aiming to identify the brain states using neural activity, is important for cognitive neuroscience and neural engineering. However, existing machine learning methods for fMRI‐based brain decoding either suffer from low classification performance or poor explainability. Here, we address this issue by proposing a biologically inspired architecture, Spatial Temporal‐pyramid Graph Convolutional Network (STpGCN), to capture the spatial–temporal graph representation of functional brain activities. By designing multi‐scale spatial–temporal pathways and bottom‐up pathways that mimic the information process and temporal integration in the brain, STpGCN is capable of explicitly utilizing the multi‐scale temporal dependency of brain activities via graph, thereby achieving high brain decoding performance. Additionally, we propose a sensitivity analysis method called BrainNetX to better explain the decoding results by automatically annotating task‐related brain regions from the brain‐network standpoint. We conduct extensive experiments on fMRI data under 23 cognitive tasks from Human Connectome Project (HCP) S1200. The results show that STpGCN significantly improves brain‐decoding performance compared to competing baseline models; BrainNetX successfully annotates task‐relevant brain regions. Post hoc analysis based on these regions further validates that the hierarchical structure in STpGCN significantly contributes to the explainability, robustness and generalization of the model. Our methods not only provide insights into information representation in the brain under multiple cognitive tasks but also indicate a bright future for fMRI‐based brain decoding. [ABSTRACT FROM AUTHOR]

Resting-state (rs) fMRI has been widely used to examine brain-wide large-scale spatiotemporal architectures, known as resting-state networks (RSNs). Recent studies have focused on the temporally evolving characteristics of RSNs, but it is unclear what temporal characteristics are reflected in the networks. To address this issue, we devised a novel method for voxel-based visualization of spatiotemporal characteristics of rs-fMRI with a time scale of tens of seconds. We first extracted clusters of dominant activity-patterns using a region-of-interest approach and then used these temporal patterns of the clusters to obtain voxel-based activation patterns related to the clusters. We found that activation patterns related to the clusters temporally evolved with a characteristic temporal structure and showed mutual temporal alternations over minutes. The voxel-based representation allowed the decoding of activation patterns of the clusters in rs-fMRI using ameta-analysis of functional activations. The activation patterns of the clusters were correlated with behavioral measures. Taken together, our analysis highlights a novel approach to examine brain activity dynamics during rest. [ABSTRACT FROM AUTHOR]

Originating from a series of morphometric studies conducted in the 1980s, it appears a widely held belief in cognitive neuroscience that the corpus callosum is larger in left or mixed handers than in right handers (RH). However, a recent meta-analysis challenges this belief by not finding significant differences in corpus callosum size between handedness groups. Yet, relying on the available published data, the meta-analysis was not able to account for a series of factors potential influencing its outcome, such as confounding effects of brain size differences and a restricted spatial resolution of previous callosal segmentation strategies. To address these remaining questions, we here analysed N = 1057 participants' midsagittal corpus callosum of from the Human Connectome Project (HCP 1200 Young Adults) to compare handedness groups based on consistency (e.g., consistent RH vs. mixed handers, MH) and direction of hand preference (e.g., dominant RH vs. dominant left handers). A possible relevance of brain-size differences was addressed by analysing callosal variability by both using forebrain volume (FBV) as covariate and utilising relative area (callosal area/thickness divided by FBV) as a dependent variable. Callosal thickness was analysed at 100 measuring points along the structure to achieve high spatial resolution to detect subregional effects. However, neither of the conducted analyses was able to find significant handedness-related differences in the corpus callosum and the respective effect-sizes estimates were small. For example, comparing MH and consistent RH, the effect sizes for difference in callosal area were below a Cohen's d = 0.1 (irrespective of how FBV was included), and narrow confidence intervals allowed to exclude effects above |d| = 0.2. Analysing thickness, effect sizes were below d = 0.2 with confidence intervals not extending above |d| = 0.3. In this, the possible range of population effect sizes of hand preference on callosal morphology appears well below the effects commonly reported for factors like age, sex, or brain size. Effects on cognition or behaviour accordingly can be considered small, questioning the common practise to attribute performance differences between handedness groups to differences in callosal architecture.

Introduction: Males and females tend to exhibit small but reliable differences in personality traits and indices of psychopathology that are relatively stable over time and across cultures. Previous work suggests that sex differences in brain structure account for differences in domains of cognition. Methods: We used data from the Human Connectome Project (N = 1098) to test whether sex differences in brain morphometry account for observed differences in the personality traits neuroticism and agreeableness, as well as symptoms of internalizing and externalizing psychopathology. We operationalized brain morphometry in three ways: omnibus measures (e.g., total gray matter volume), Glasser regions defined through a multi‐modal parcellation approach, and Desikan regions defined by structural features of the brain. Results: Most expected sex differences in personality, psychopathology, and brain morphometry were observed, but the statistical mediation analyses were null: sex differences in brain morphometry did not account for sex differences in personality or psychopathology. Conclusions: Men and women tend to exhibit meaningful differences in personality and psychopathology, as well as in omnibus morphometry and regional morphometric differences as defined by the Glasser and Desikan atlases, but these morphometric differences appear unrelated to the psychological differences. [ABSTRACT FROM AUTHOR]

How variable is the functionally defined structure of early visual areas in human cortex and how much variability is shared between twins? Here we quantify individual differences in the best understood functionally defined regions of cortex: V1, V2, V3. The Human Connectome Project 7T Retinotopy Dataset includes retinotopic measurements from 181 subjects (109 female, 72 male), including many twins. We trained four “anatomists” to manually define V1-V3 using retinotopic features. These definitions were more accurate than automated anatomical templates and showed that surface areas for these maps varied more than threefold across individuals. This threefold variation was little changed when normalizing visual area size by the surface area of the entire cerebral cortex. In addition to varying in size, we find that visual areas vary in how they sample the visual field. Specifically, the cortical magnification function differed substantially among individuals, with the relative amount of cortex devoted to central vision varying by more than a factor of 2. To complement the variability analysis, we examined the similarity of visual area size and structure across twins. Whereas the twin sample sizes are too small to make precise heritability estimates (50 monozygotic pairs, 34 dizygotic pairs), they nonetheless reveal high correlations, consistent with strong effects of the combination of shared genes and environment on visual area size. Collectively, these results provide the most comprehensive account of individual variability in visual area structure to date, and provide a robust population benchmark against which new individuals and developmental and clinical populations can be compared. [ABSTRACT FROM AUTHOR]

The brain‐age‐gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine‐learning models to neuroimaging data and is considered a biomarker of brain health. Understanding sex differences in brainAGE is a significant step toward precision medicine. Global and local brainAGE (G‐brainAGE and L‐brainAGE, respectively) were computed by applying machine learning algorithms to brain structural magnetic resonance imaging data from 1113 healthy young adults (54.45% females; age range: 22–37 years) participating in the Human Connectome Project. Sex differences were determined in G‐brainAGE and L‐brainAGE. Random forest regression was used to determine sex‐specific associations between G‐brainAGE and non‐imaging measures pertaining to sociodemographic characteristics and mental, physical, and cognitive functions. L‐brainAGE showed sex‐specific differences; in females, compared to males, L‐brainAGE was higher in the cerebellum and brainstem and lower in the prefrontal cortex and insula. Although sex differences in G‐brainAGE were minimal, associations between G‐brainAGE and non‐imaging measures differed between sexes with the exception of poor sleep quality, which was common to both. While univariate relationships were small, the most important predictor of higher G‐brainAGE was self‐identification as non‐white in males and systolic blood pressure in females. The results demonstrate the value of applying sex‐specific analyses and machine learning methods to advance our understanding of sex‐related differences in factors that influence the rate of brain aging and provide a foundation for targeted interventions. [ABSTRACT FROM AUTHOR]

Joint and Individual Variation Explained (JIVE) is a model that decomposes multiple datasets obtained on the same subjects into shared structure, structure unique to each dataset, and noise. JIVE is an important tool for multimodal data integration in neuroimaging. The two most common algorithms are R.JIVE, an iterative approach, and AJIVE, which uses principal angle analysis. The joint structure in JIVE is defined by shared subspaces, but interpreting these subspaces can be challenging. In this paper, we reinterpret AJIVE as a canonical correlation analysis of principal component scores. This reformulation, which we call CJIVE, (1) provides an intuitive view of AJIVE; (2) uses a permutation test for the number of joint components; (3) can be used to predict subject scores for out-of-sample observations; and (4) is computationally fast. We conduct simulation studies that show CJIVE and AJIVE are accurate when the total signal ranks are correctly specified but, generally inaccurate when the total ranks are too large. CJIVE and AJIVE can still extract joint signal even when the joint signal variance is relatively small. JIVE methods are applied to integrate functional connectivity (resting-state fMRI) and structural connectivity (diffusionMRI) fromthe Human Connectome Project. Surprisingly, the edges with largest loadings in the joint component in functional connectivity do not coincide with the same edges in the structural connectivity, indicating more complex patterns than assumed in spatial priors. Using these loadings, we accurately predict joint subject scores in new participants. We also find joint scores are associated with fluid intelligence, highlighting the potential for JIVE to reveal important shared structure. [ABSTRACT FROM AUTHOR]

Poor social functioning is an emerging public health problem associated with physical and mental health consequences. Developing prognostic tools is critical to identify individuals at risk for poor social functioning and guide interventions. We aimed to inform prediction models of social functioning by evaluating models relying on bio-behavioral data using machine learning. With data from the Human Connectome Project Healthy Young Adult sample (age 22–35, N = 1,101), we built Support Vector Regression models to estimate social functioning from variable sets of brain morphology to behavior with increasing complexity: 1) brain-only model, 2) brain-cognition model, 3) cognition-behavioral model, and 4) combined brain-cognition-behavioral model. Predictive accuracy of each model was assessed and the importance of individual variables for model performance was determined. The combined and cognition-behavioral models significantly predicted social functioning, whereas the brain-only and brain-cognition models did not. Negative affect, psychological wellbeing, extraversion, withdrawal, and cortical thickness of the rostral middle-frontal and superior-temporal regions were the most important predictors in the combined model. Results demonstrate that social functioning can be accurately predicted using machine learning methods. Behavioral markers may be more significant predictors of social functioning than brain measures for healthy young adults and may represent important leverage points for preventative intervention. [ABSTRACT FROM AUTHOR]

Cognitive architectures (i.e., theorized blueprints on the structure of the mind) can be used to make predictions about the effect of multiregion brain activity on the systems level. Recent work has connected one high‐level cognitive architecture, known as the "Common Model of Cognition," to task‐based functional MRI data with great success. That approach, however, was limited in that it was intrinsically top‐down, and could thus only be compared with alternate architectures that the experimenter could contrive. In this paper, we propose a bottom‐up method to infer a cognitive architecture directly from brain imaging data itself, overcoming this limitation. Specifically, Granger causality modeling was applied to the same task‐based fMRI data to infer a network of causal connections between brain regions based on their functional connectivity. The resulting network shares many connections with those proposed by the Common Model of Cognition but also suggests important additions likely related to the role of episodic memory. This combined top‐down and bottom‐up modeling approach can be used to help formalize the computational instantiation of cognitive architectures and further refine a comprehensive theory of cognition. [ABSTRACT FROM AUTHOR]

Understanding the complex mechanisms of the brain can be unraveled by extracting the Dynamic Effective Connectome (DEC). Recently, score-based Directed Acyclic Graph (DAG) discovery methods have shown significant improvements in extracting the causal structure and inferring effective connectivity. However, learning DEC through these methods still faces two main challenges: one with the fundamental impotence of high-dimensional dynamic DAG discovery methods and the other with the low quality of fMRI data. In this paper, we introduce Bayesian Dynamic DAG learning with M-matrices Acyclicity characterization (BDyMA) method to address the challenges in discovering DEC. The presented dynamic DAG enables us to discover direct feedback loop edges as well. Leveraging an unconstrained framework in the BDyMA method leads to more accurate results in detecting high-dimensional networks, achieving sparser outcomes, making it particularly suitable for extracting DEC. Additionally, the score function of the BDyMA method allows the incorporation of prior knowledge into the process of dynamic causal discovery which further enhances the accuracy of results. Comprehensive simulations on synthetic data and experiments on Human Connectome Project (HCP) data demonstrate that our method can handle both of the two main challenges, yielding more accurate and reliable DEC compared to state-of-the-art and traditional methods. Additionally, we investigate the trustworthiness of DTI data as prior knowledge for DEC discovery and show the improvements in DEC discovery when the DTI data is incorporated into the process. • We introduce BDyMA to discover dynamic causal structure of high-dimensional networks. • We demonstrate the effectiveness of the BDyMA in comparison to both existing method. • We show that our method enhances the intrasubject and intersubject reliability. • We examine the trustworthiness of DTI data as prior knowledge of DEC discovery. [ABSTRACT FROM AUTHOR]

Connectomics is a framework that models brain structure and function interconnectivity as a network, rather than narrowly focusing on select regions-of-interest. MRI-derived connectomes can be structural, usually based on diffusion-weighted MR imaging, or functional, usually formed by examining fMRI blood-oxygen-level-dependent (BOLD) signal correlations. Recently, we developed a novel method for assessing the hierarchical modularity of functional brain networks-the probability associated community estimation (PACE). PACE uniquely permits a dual formulation, thus yielding equivalent connectome modular structure regardless of whether positive or negative edges are considered. This method was rigorously validated using the 1,000 functional connectomes project data set (F1000, RRID:SCR_005361) (1) and the Human Connectome Project (HCP, RRID:SCR_006942) (2, 3) and we reported novel sex differences in resting-state connectivity not previously reported. (4) This study further examines sex differences in regard to hierarchical modularity as a function of age and clinical correlates, with findings supporting a basal configuration framework as a more nuanced and dynamic way of conceptualizing the resting-state connectome that is modulated by both age and sex. Our results showed that differences in connectivity between men and women in the 22-25 age range were not significantly different. However, these same non-significant differences attained significance in both the 26-30 age group (p = 0.003) and the 31-35 age group (p < 0.001). At the most global level, areas of diverging sex difference include parts of the prefrontal cortex and the temporal lobe, amygdala, hippocampus, inferior parietal lobule, posterior cingulate, and precuneus. Further, we identified statistically different self-reported summary scores of inattention, hyperactivity, and anxiety problems between men and women. These self-reports additionally divergently interact with age and the basal configuration between sexes.