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.

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.

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.

Gyral Hinges Account for the Highest Cost and the Highest Communication Capacity in a Corticocortical Network.

Prior studies reported the global structure of brain networks exhibits the "small-world" and "rich-world" attributes. However, the underlying structural and functional architecture highlighted by these graph theory findings hasn't been explicitly related to the morphology of the cortex. This could be attributed to the lower resolution of used folding patterns, such as gyro-sulcal patterns. By defining a novel gyral folding pattern, termed gyral hinge (GH), which is the conjunction of ordinary gyri from multiple directions, we found GHs possess the highest length and cost in the white matter fiber connective network, and the shortest paths in the network tend to travel through GHs in their middle part. Based on these findings, we would hypothesize GHs could reside in the centers of a network core, thereby accounting for the highest cost and the highest communication capacity in a corticocortical network. The following results further support our hypothesis: 1) GHs possess stronger functional network integration capacity. 2) Higher cost is found on the connection with GHs to hinges and GHs to GHs. 3) Moving GHs introduces higher extra network cost. Our findings and hypotheses could reveal a profound relationship among the cortical folding patterns, axonal wiring architectures, and brain functions.

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.

Multi-timepoint pattern analysis: Influence of personality and behavior on decoding context-dependent brain connectivity dynamics.

Behavioral traits are rarely considered in task-evoked functional magnetic resonance imaging (MRI) studies, yet these traits can affect how an individual engages with the task, and thus lead to heterogeneity in task-evoked brain responses. We aimed to investigate whether interindividual variation in behavior associates with the accuracy of predicting task-evoked changes in the dynamics of functional brain connectivity measured with functional MRI. We developed a novel method called multi-timepoint pattern analysis (MTPA), in which binary logistic regression classifiers were trained to distinguish rest from each of 7 tasks (i.e., social cognition, working memory, language, relational, motor, gambling, emotion) based on functional connectivity dynamics measured in 1,000 healthy adults. We found that connectivity dynamics for multiple pairs of large-scale networks enabled individual classification between task and rest with accuracies exceeding 70%, with the most discriminatory connections relatively unique to each task. Crucially, interindividual variation in classification accuracy significantly associated with several behavioral, cognition and task performance measures. Classification between task and rest was generally more accurate for individuals with higher intelligence and task performance. Additionally, for some of the tasks, classification accuracy improved with lower perceived stress, lower aggression, higher alertness, and greater endurance. We conclude that heterogeneous dynamic adaptations of functional brain networks to changing cognitive demands can be reliably captured as linearly separable patterns by MTPA. Future studies should account for interindividual variation in behavior when investigating context-dependent dynamic functional connectivity.

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.

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.

Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort.

The heterogeneity of schizophrenia has defied efforts to derive reproducible and definitive anatomical maps of structural brain changes associated with the disorder. We aimed to map deviations from normative ranges of brain structure for individual patients and evaluate whether the loci of individual deviations recapitulated group-average brain maps of schizophrenia pathology. For each of 48 white matter tracts and 68 cortical regions, normative percentiles of variation in fractional anisotropy (FA) and cortical thickness (CT) were established using diffusion-weighted and structural MRI from healthy adults (n = 195). Individuals with schizophrenia (n = 322) were classified as either within the normative range for healthy individuals of the same age and sex (5-95% percentiles), infra-normal (<5% percentile) or supra-normal (>95% percentile). Repeating this classification for each tract and region yielded a deviation map for each individual. Compared to the healthy comparison group, the schizophrenia group showed widespread reductions in FA and CT, involving virtually all white matter tracts and cortical regions. Paradoxically, however, no more than 15-20% of patients deviated from the normative range for any single tract or region. Furthermore, 79% of patients showed infra-normal deviations for at least one locus (healthy individuals: 59 ± 2%, p < 0.001). Thus, while infra-normal deviations were common among patients, their anatomical loci were highly inconsistent between individuals. Higher polygenic risk for schizophrenia associated with a greater number of regions with infra-normal deviations in CT (r = -0.17, p = 0.006). We conclude that anatomical loci of schizophrenia-related changes are highly heterogeneous across individuals to the extent that group-consensus pathological maps are not representative of most individual patients. Normative modeling can aid in parsing schizophrenia heterogeneity and guiding personalized interventions.

Personalized connectivity-guided DLPFC-TMS for depression: Advancing computational feasibility, precision and reproducibility.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory depression, however, therapeutic outcomes vary. Mounting evidence suggests that clinical response relates to functional connectivity with the subgenual cingulate cortex (SGC) at the precise DLPFC stimulation site. Critically, SGC-related network architecture shows considerable interindividual variation across the spatial extent of the DLPFC, indicating that connectivity-based target personalization could potentially be necessary to improve treatment outcomes. However, to date accurate personalization has not appeared feasible, with recent work indicating that the intraindividual reproducibility of optimal targets is limited to 3.5 cm. Here we developed reliable and accurate methodologies to compute individualized connectivity-guided stimulation targets. In resting-state functional MRI scans acquired across 1,000 healthy adults, we demonstrate that, using this approach, personalized targets can be reliably and robustly pinpointed, with a median accuracy of ~2 mm between scans repeated across separate days. These targets remained highly stable, even after 1 year, with a median intraindividual distance between coordinates of only 2.7 mm. Interindividual spatial variation in personalized targets exceeded intraindividual variation by a factor of up to 6.85, suggesting that personalized targets did not trivially converge to a group-average site. Moreover, personalized targets were heritable, suggesting that connectivity-guided rTMS personalization is stable over time and under genetic control. This computational framework provides capacity for personalized connectivity-guided TMS targets to be robustly computed with high precision and has the flexibly to advance research in other basic research and clinical applications.

Per- and post-remote ischemic conditioning attenuates ischemic brain injury via inhibition of the TLR4/MyD88 signaling pathway in aged rats.

Remote ischemic conditioning (RIC), as an emerging protective method, might be used clinically to prevent ischemia-reperfusion injury (IRI) in ischemic stroke. In this study, we aim to investigate whether RIC performed either during brain ischemia or after reperfusion has a protective effect and further explore the mechanistic basis for the protective effects of RIC against IRI in an aged rat model. We investigated brain IRI in 16-18 months old SD rats. Animals underwent: (i) sham laparotomy, (ii) brain IRI, (iii) brain IRI + RIC during ischemia (IRI + RIperC), or (iv) brain IRI + RIC after reperfusion (IRI + RIpostC). RIC consists of three cycles of 10 min of hind limb ischemia followed by 10 min reperfusion. After 24 h of reperfusion, the infarct size, neurological deficit scores and brain oedema were assessed in all groups. The levels of IL-1ß, IL-6, TNF-α were measured by ELISA. The mRNA and protein expressions of TLR4, MyD88, TRAF6 and NF-κB were detected by RT-PCR and western blot. Both RIperC and RIpostC treatment attenuated the IRI-induced neuronal injury, reflected by reductions in the infarct size, neurological deficit scores and brain oedema. RIperC and RIpostC also can decrease the concentration of IL-1ß, IL-6, TNF-α in IRI. From the results of RT-PCR and western blot, we found that RIC decreased the mRNA and protein expression of TLR4, MyD88, TRAF6 and NF-κB compared to that in the IRI group. The present study suggested that RIC protected aged rats against IRI, and this protective effect might be mediated by inhibiting the TLR-4/MyD88/TRAF-6/NF-κB signaling pathway.

Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD.

BACKGROUND: Despite the effectiveness of methylphenidate for treating ADHD, up to 30% of individuals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD. METHODS: Using a naturalistic observation design selected from a larger cohort, we included 79 drug-naive individuals (aged 6-42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by individuals' responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an individual's response. RESULTS: 63 and 16 individuals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in individuals with ADHD. CONCLUSION: Our results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in individuals with ADHD.

Risk factors and the potential of nomogram for predicting hospital-acquired pressure injuries.

This 1:5 case-control study aimed to identify the risk factors of hospital-acquired pressure injuries (HAPIs) and to develop a mathematical model of nomogram for the risk prediction of HAPIs. Data for 370 patients with HAPIs and 1971 patients without HAPIs were extracted from the adverse events and the electronic medical systems. They were randomly divided into two sets: training (n = 1951) and validation (n = 390). Significant risk factors were identified by univariate and multivariate analyses in the training set, followed by a nomogram constructed. Age, independent movement, sensory perception and response, moisture, perfusion, use of medical devices, compulsive position, hypoalbuminaemia, an existing pressure injury or scarring from a previous pressure injury, and surgery sufferings were considered significant risk factors and were included to construct a nomogram. In both of the training and validation sets, the areas of 0.90 under the receiver operating characteristic curves showed excellent discrimination of the nomogram; calibration plots demonstrated a good consistency between the observed probability and the nomogram's prediction; decision curve analyses exhibited preferable net benefit along with the threshold probability in the nomogram. The excellent performance of the nomogram makes it a convenient and reliable tool for the risk prediction of HAPIs.

Spatio-temporal modeling of connectome-scale brain network interactions via time-evolving graphs.

Many recent literature studies have revealed interesting dynamics patterns of functional brain networks derived from fMRI data. However, it has been rarely explored how functional networks spatially overlap (or interact) and how such connectome-scale network interactions temporally evolve. To explore these unanswered questions, this paper presents a novel framework for spatio-temporal modeling of connectome-scale functional brain network interactions via two main effective computational methodologies. First, to integrate, pool and compare brain networks across individuals and their cognitive states under task performances, we designed a novel group-wise dictionary learning scheme to derive connectome-scale consistent brain network templates that can be used to define the common reference space of brain network interactions. Second, the temporal dynamics of spatial network interactions is modeled by a weighted time-evolving graph, and then a data-driven unsupervised learning algorithm based on the dynamic behavioral mixed-membership model (DBMM) is adopted to identify behavioral patterns of brain networks during the temporal evolution process of spatial overlaps/interactions. Experimental results on the Human Connectome Project (HCP) task fMRI data showed that our methods can reveal meaningful, diverse behavior patterns of connectome-scale network interactions. In particular, those networks' behavior patterns are distinct across HCP tasks such as motor, working memory, language and social tasks, and their dynamics well correspond to the temporal changes of specific task designs. In general, our framework offers a new approach to characterizing human brain function by quantitative description for the temporal evolution of spatial overlaps/interactions of connectome-scale brain networks in a standard reference space.

Latent source mining in FMRI via restricted Boltzmann machine.

Blind source separation (BSS) is commonly used in functional magnetic resonance imaging (fMRI) data analysis. Recently, BSS models based on restricted Boltzmann machine (RBM), one of the building blocks of deep learning models, have been shown to improve brain network identification compared to conventional single matrix factorization models such as independent component analysis (ICA). These models, however, trained RBM on fMRI volumes, and are hence challenged by model complexity and limited training set. In this article, we propose to apply RBM to fMRI time courses instead of volumes for BSS. The proposed method not only interprets fMRI time courses explicitly to take advantages of deep learning models in latent feature learning but also substantially reduces model complexity and increases the scale of training set to improve training efficiency. Our experimental results based on Human Connectome Project (HCP) datasets demonstrated the superiority of the proposed method over ICA and the one that applied RBM to fMRI volumes in identifying task-related components, resulted in more accurate and specific representations of task-related activations. Moreover, our method separated out components representing intermixed effects between task events, which could reflect inherent interactions among functionally connected brain regions. Our study demonstrates the value of RBM in mining complex structures embedded in large-scale fMRI data and its potential as a building block for deeper models in fMRI data analysis.

Brain-behavior patterns define a dimensional biotype in medication-naïve adults with attention-deficit hyperactivity disorder.

BACKGROUND: Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD. METHODS: We first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype. RESULTS: Adults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain-symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD. CONCLUSIONS: Overall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain-symptom mediators.

Sparse representation of HCP grayordinate data reveals novel functional architecture of cerebral cortex.

The recently publicly released Human Connectome Project (HCP) grayordinate-based fMRI data not only has high spatial and temporal resolution, but also offers group-corresponding fMRI signals across a large population for the first time in the brain imaging field, thus significantly facilitating mapping the functional brain architecture with much higher resolution and in a group-wise fashion. In this article, we adopt the HCP grayordinate task-based fMRI (tfMRI) data to systematically identify and characterize task-based heterogeneous functional regions (THFRs) on cortical surface, i.e., the regions that are activated during multiple tasks conditions and contribute to multiple task-evoked systems during a specific task performance, and to assess the spatial patterns of identified THFRs on cortical gyri and sulci by applying a computational framework of sparse representations of grayordinate brain tfMRI signals. Experimental results demonstrate that both consistent task-evoked networks and intrinsic connectivity networks across all subjects and tasks in HCP grayordinate data are effectively and robustly reconstructed via the proposed sparse representation framework. Moreover, it is found that there are relatively consistent THFRs locating at bilateral parietal lobe, frontal lobe, and visual association cortices across all subjects and tasks. Particularly, those identified THFRs locate significantly more on gyral regions than on sulcal regions. These results based on sparse representation of HCP grayordinate data reveal novel functional architecture of cortical gyri and sulci, and might provide a foundation to better understand functional mechanisms of the human cerebral cortex in the future.

Fusing DTI and fMRI data: a survey of methods and applications.

The relationship between brain structure and function has been one of the centers of research in neuroimaging for decades. In recent years, diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) techniques have been widely available and popular in cognitive and clinical neurosciences for examining the brain's white matter (WM) micro-structures and gray matter (GM) functions, respectively. Given the intrinsic integration of WM/GM and the complementary information embedded in DTI/fMRI data, it is natural and well-justified to combine these two neuroimaging modalities together to investigate brain structure and function and their relationships simultaneously. In the past decade, there have been remarkable achievements of DTI/fMRI fusion methods and applications in neuroimaging and human brain mapping community. This survey paper aims to review recent advancements on methodologies and applications in incorporating multimodal DTI and fMRI data, and offer our perspectives on future research directions. We envision that effective fusion of DTI/fMRI techniques will play increasingly important roles in neuroimaging and brain sciences in the years to come.