Gene expression and brain imaging association study reveals gene signatures in major depressive disorder.

Major depressive disorder is often characterized by changes in the structure and function of the brain, which are influenced by modifications in gene expression profiles. How the depression-related genes work together within the scope of time and space to cause pathological changes remains unclear. By integrating the brain-wide gene expression data and imaging data in major depressive disorder, we identified gene signatures of major depressive disorder and explored their temporal-spatial expression specificity, network properties, function annotations and sex differences systematically. Based on correlation analysis with permutation testing, we found 345 depression-related genes significantly correlated with functional and structural alteration of brain images in major depressive disorder and separated them by directional effects. The genes with negative effect for grey matter density and positive effect for functional indices are enriched in downregulated genes in the post-mortem brain samples of patients with depression and risk genes identified by genome-wide association studies than genes with positive effect for grey matter density and negative effect for functional indices and control genes, confirming their potential association with major depressive disorder. By introducing a parameter of dispersion measure on the gene expression data of developing human brains, we revealed higher spatial specificity and lower temporal specificity of depression-related genes than control genes. Meanwhile, we found depression-related genes tend to be more highly expressed in females than males, which may contribute to the difference in incidence rate between male and female patients. In general, we found the genes with negative effect have lower network degree, more specialized function, higher spatial specificity, lower temporal specificity and more sex differences than genes with positive effect, indicating they may play different roles in the occurrence and development of major depressive disorder. These findings can enhance the understanding of molecular mechanisms underlying major depressive disorder and help develop tailored diagnostic and treatment strategies for patients of depression of different sex.

Measuring functional connectivity in frequency-domain helps to better characterize brain function.

Resting-state functional connectivity (FC) is widely used in multivariate pattern analysis of functional magnetic resonance imaging (fMRI), including identifying the locations of putative brain functional borders, predicting individual phenotypes, and diagnosing clinical mental diseases. However, limited attention has been paid to the analysis of functional interactions from a frequency perspective. In this study, by contrasting coherence-based and correlation-based FC with two machine learning tasks, we observed that measuring FC in the frequency domain helped to identify finer functional subregions and achieve better pattern discrimination capability relative to the temporal correlation. This study has proven the feasibility of coherence in the analysis of fMRI, and the results indicate that modeling functional interactions in the frequency domain may provide richer information than that in the time domain, which may provide a new perspective on the analysis of functional neuroimaging.

Three-dimensional ranging system based on Fresnel incoherent correlation holography.

We proposed a three-dimensional (3D) ranging system based on Fresnel incoherent correlation holography (FINCH). Distinct from the displacement measurement based on coherent digital holography (DH), our system simultaneously achieves a 3D range measurement using incoherent illumination. The observation range is obtained by the holographic reconstruction, while the in-plane range is determined using the two-dimensional digital imaging correlation (2D-DIC) technique. Experimental results on the resolution target demonstrate precise 3D ranging determination and improved measurement accuracy.

Frequency-specific segregation and integration of human cerebral cortex: An intrinsic functional atlas.

The cognitive and behavioral functions of the human brain are supported by its frequency multiplexing mechanism. However, there is limited understanding of the dynamics of the functional network topology. This study aims to investigate the frequency-specific topology of the functional human brain using 7T rs-fMRI data. Frequency-specific parcellations were first performed, revealing frequency-dependent dynamics within the frontoparietal control, parietal memory, and visual networks. An intrinsic functional atlas containing 456 parcels was proposed and validated using stereo-EEG. Graph theory analysis suggested that, in addition to the task-positive vs. task-negative organization observed in static networks, there was a cognitive control system additionally from a frequency perspective. The reproducibility and plausibility of the identified hub sets were confirmed through 3T fMRI analysis, and their artificial removal had distinct effects on network topology. These results indicate a more intricate and subtle dynamics of the functional human brain and emphasize the significance of accurate topography.

Edge enhancement in three-dimensional vortex imaging based on FINCH by Bessel-like spiral phase modulation.

Edge enhancement, as an important part of image processing, has played an essential role in amplitude-contrast and phase-contrast object imaging. The edge enhancement of three-dimensional (3D) vortex imaging has been successfully implemented by Fresnel incoherent correlation holography (FINCH), but the background noise and image contrast effects are still not satisfactory. To solve these issues, the edge enhancement of FINCH by employing Bessel-like spiral phase modulation is proposed and demonstrated. Compared with the conventional spiral phase modulated FINCH, the proposed technique can achieve high-quality edge enhancement 3D vortex imaging with lower background noise, higher contrast and resolution. The significantly improved imaging quality is mainly attributed to the effective sidelobes' suppression in the generated optical vortices with the Bessel-like modulation technique. Experimental results of the small circular aperture, resolution target, and the Drosophila melanogaster verify its excellent imaging performance. Moreover, we also proposed a new method for selective edge enhancement of 3D vortex imaging by breaking the symmetry of the spiral phase in the algorithmic model of isotropic edge enhancement. The reconstructed images of the circular aperture show that the proposed method is able to enhance the edges of the given objects selectively in any desired direction.

Hippocampus Parcellation via Discriminative Embedded Clustering of fMRI Functional Connectivity.

Dividing a pre-defined brain region into several heterogenous subregions is crucial for understanding its functional segregation and integration. Due to the high dimensionality of brain functional features, clustering is often postponed until dimensionality reduction in traditional parcellation frameworks occurs. However, under such stepwise parcellation, it is very easy to fall into the dilemma of local optimum since dimensionality reduction could not take into account the requirement of clustering. In this study, we developed a new parcellation framework based on the discriminative embedded clustering (DEC), combining subspace learning and clustering in a common procedure with alternative minimization adopted to approach global optimum. We tested the proposed framework in functional connectivity-based parcellation of the hippocampus. The hippocampus was parcellated into three spatial coherent subregions along the anteroventral-posterodorsal axis; the three subregions exhibited distinct functional connectivity changes in taxi drivers relative to non-driver controls. Moreover, compared with traditional stepwise methods, the proposed DEC-based framework demonstrated higher parcellation consistency across different scans within individuals. The study proposed a new brain parcellation framework with joint dimensionality reduction and clustering; the findings might shed new light on the functional plasticity of hippocampal subregions related to long-term navigation experience.

Gradient Matching Federated Domain Adaptation for Brain Image Classification.

Federated learning has shown its unique advantages in many different tasks, including brain image analysis. It provides a new way to train deep learning models while protecting the privacy of medical image data from multiple sites. However, previous studies suggest that domain shift across different sites may influence the performance of federated models. As a solution, we propose a gradient matching federated domain adaptation (GM-FedDA) method for brain image classification, aiming to reduce domain discrepancy with the assistance of a public image dataset and train robust local federated models for target sites. It mainly includes two stages: 1) pretraining stage; we propose a one-common-source adversarial domain adaptation (OCS-ADA) strategy, i.e., adopting ADA with gradient matching loss to pretrain encoders for reducing domain shift at each target site (private data) with the assistance of a common source domain (public data) and 2) fine-tuning stage; we develop a gradient matching federated (GM-Fed) fine-tuning method for updating local federated models pretrained with the OCS-ADA strategy, i.e., pushing the optimization direction of a local federated model toward its specific local minimum by minimizing gradient matching loss between sites. Using fully connected networks as local models, we validate our method with the diagnostic classification tasks of schizophrenia and major depressive disorder based on multisite resting-state functional MRI (fMRI), respectively. Results show that the proposed GM-FedDA method outperforms other commonly used methods, suggesting the potential of our method in brain imaging analysis and other fields, which need to utilize multisite data while preserving data privacy.

Altered cerebellar-motor loop in benign adult familial myoclonic epilepsy type 1: The structural basis of cortical tremor.

OBJECTIVE: Cortical tremor/myoclonus is the hallmark feature of benign adult familial myoclonic epilepsy (BAFME), the mechanism of which remains elusive. A hypothesis is that a defective control in the preexisting cerebellar-motor loop drives cortical tremor. Meanwhile, the basal ganglia system might also participate in BAFME. This study aimed to discover the structural basis of cortical tremor/myoclonus in BAFME. METHODS: Nineteen patients with BAFME type 1 (BAFME1) and 30 matched healthy controls underwent T1-weighted and diffusion tensor imaging scans. FreeSurfer and spatially unbiased infratentorial template (SUIT) toolboxes were utilized to assess the motor cortex and the cerebellum. Probabilistic tractography was generated for two fibers to test the hypothesis: the dentato-thalamo-(M1) (primary motor cortex) and globus pallidus internus (GPi)-thalamic projections. Average fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) of each tract were extracted. RESULTS: Cerebellar atrophy and dentate nucleus alteration were observed in the patients. In addition, patients with BAFME1 exhibited reduced AD and FA in the left and right dentato-thalamo-M1 nondecussating fibers, respectively false discovery rate (FDR) correction q < .05. Cerebellar projections showed negative correlations with somatosensory-evoked potential P25-N33 amplitude and were independent of disease duration and medication. BAFME1 patients also had increased FA and decreased MD in the left GPi-thalamic projection. Higher FA and lower RD in the right GPi-thalamic projection were also observed (FDR q < .05). SIGNIFICANCE: The present findings support the hypothesis that the cerebello-thalamo-M1 loop might be the structural basis of cortical tremor in BAFME1. The basal ganglia system also participates in BAFME1 and probably serves a regulatory role.

Altered Functional Network Connectivity of Precuneus and Executive Control Networks in Type 2 Diabetes Mellitus Without Cognitive Impairment.

In epidemiological studies, type 2 diabetes mellitus (T2DM) has been associated with cognitive impairment and dementia, but studies about functional network connectivity in T2DM without cognitive impairment are limited. This study aimed to explore network connectivity alterations that may help enhance our understanding of damage-associated processes in T2DM. MRI data were analyzed from 82 patients with T2DM and 66 normal controls. Clinical, biochemical, and neuropsychological assessments were conducted in parallel with resting-state functional magnetic resonance imaging, and the cognitive status of the patients was assessed using the Montreal Cognitive Assessment-B (MoCA-B) score. Independent component analysis revealed a positive correlation between the salience network and the visual network and a negative connection between the left executive control network and the default mode network in patients with T2DM. The differences in dynamic brain network connectivity were observed in the precuneus, visual, and executive control networks. Internal network connectivity was primarily affected in the thalamus, inferior parietal lobe, and left precuneus. Hemoglobin A1c level, body mass index, MoCA-B score, and grooved pegboard (R) assessments indicated significant differences between the two groups (p < 0.05). Our findings show that key changes in functional connectivity in diabetes occur in the precuneus and executive control networks that evolve before patients develop cognitive deficits. In addition, the current study provides useful information about the role of the thalamus, inferior parietal lobe, and precuneus, which might be potential biomarkers for predicting the clinical progression, assessing the cognitive function, and further understanding the neuropathology of T2DM.

DC-tCNN: A Deep Model for EEG-Based Detection of Dim Targets.

OBJECTIVE: Dim target detection in remote sensing images is a significant and challenging problem. In this work, we seek to explore event-related brain responses of dim target detection tasks and extend the brain-computer interface (BCI) systems to this task for efficiency enhancement. METHODS: We develop a BCI paradigm named Asynchronous Visual Evoked Paradigm (AVEP), in which subjects are required to search the dim targets within satellite images when their scalp electroencephalography (EEG) signals are simultaneously recorded. In the paradigm, stimulus onset time and target onset time are asynchronous because subjects need enough time to confirm whether there are targets of interest in the presented serial images. We further propose a Domain adaptive and Channel-wise attention-based Time-domain Convolutional Neural Network (DC-tCNN) to solve the single-trial EEG classification problem for the AVEP task. In this model, we design a multi-scale CNN module combined with a channel-wise attention module to effectively extract event-related brain responses underlying EEG signals. Meanwhile, domain adaptation is proposed to mitigate cross-subject distribution discrepancy. RESULTS: The results demonstrate the superior performance and better generalizability of this model in classifying the single-trial EEG data of AVEP task in contrast to typical EEG deep learning networks. Visualization analyses of spatiotemporal features also illustrate the effectiveness and interpretability of our proposed paradigm and learning model. CONCLUSION: The proposed paradigm and model can effectively explore ambiguous event-related brain responses on EEG-based dim target detection tasks. SIGNIFICANCE: Our work can provide a valuable reference for BCI-based image detection of dim targets.

Deep Transfer Learning for Cerebral Cortex Using Area-Preserving Geometry Mapping.

Limited sample size hinders the application of deep learning in brain image analysis, and transfer learning is a possible solution. However, most pretrained models are 2D based and cannot be applied directly to 3D brain images. In this study, we propose a novel framework to apply 2D pretrained models to 3D brain images by projecting surface-based cortical morphometry into planar images using computational geometry mapping. Firstly, 3D cortical meshes are reconstructed from magnetic resonance imaging (MRI) using FreeSurfer and projected into 2D planar meshes with topological preservation based on area-preserving geometry mapping. Then, 2D deep models pretrained on ImageNet are adopted and fine-tuned for cortical image classification on morphometric shape metrics. We apply the framework to sex classification on the Human Connectome Project dataset and autism spectrum disorder (ASD) classification on the Autism Brain Imaging Data Exchange dataset. Moreover, a 2-stage transfer learning strategy is suggested to boost the ASD classification performance by using the sex classification as an intermediate task. Our framework brings significant improvement in sex classification and ASD classification with transfer learning. In summary, the proposed framework builds a bridge between 3D cortical data and 2D models, making 2D pretrained models available for brain image analysis in cognitive and psychiatric neuroscience.

Discriminating mild traumatic brain injury using sparse dictionary learning of functional network dynamics.

Mild traumatic brain injury (mTBI) is usually caused by a bump, blow, or jolt to the head or penetrating head injury, and carries the risk of inducing cognitive disorders. However, identifying the biomarkers for the diagnosis of mTBI is challenging as evident abnormalities in brain anatomy are rarely found in patients with mTBI. In this study, we tested whether the alteration of functional network dynamics could be used as potential biomarkers to better diagnose mTBI. We propose a sparse dictionary learning framework to delineate spontaneous fluctuation of functional connectivity into the subject-specific time-varying evolution of a set of overlapping group-level sparse connectivity components (SCCs) based on the resting-state functional magnetic resonance imaging (fMRI) data from 31 mTBI patients in the early acute phase (<3 days postinjury) and 31 healthy controls (HCs). The identified SCCs were consistently distributed in the cohort of subjects without significant inter-group differences in connectivity patterns. Nevertheless, subject-specific temporal expression of these SCCs could be used to discriminate patients with mTBI from HCs with a classification accuracy of 74.2% (specificity 64.5% and sensitivity 83.9%) using leave-one-out cross-validation. Taken together, our findings indicate neuroimaging biomarkers for mTBI individual diagnosis based on the temporal expression of SCCs underlying time-resolved functional connectivity.

Few-shot domain-adaptive anomaly detection for cross-site brain images.

Early screening is essential for effective intervention and treatment of individuals with mental disorders. Functional magnetic resonance imaging (fMRI) is a noninvasive tool for depicting neural activity and has demonstrated strong potential as a technique for identifying mental disorders. Due to the difficulty in data collection and diagnosis, imaging data from patients are rare at a single site, whereas abundant healthy control data are available from public datasets. However, joint use of these data from multiple sites for classification model training is hindered by cross-domain distribution discrepancy and diverse label spaces. Herein, we propose few-shot domain-adaptive anomaly detection (FAAD) to achieve cross-site anomaly detection of brain images based on only a few labeled samples. We introduce domain adaptation to mitigate cross-domain distribution discrepancy and jointly align the general and conditional feature distributions of imaging data across multiple sites. We utilize fMRI data of healthy subjects in the Human Connectome Project (HCP) as the source domain and fMRI images from six independent sites, including patients with mental disorders and demographically matched healthy controls, as target domains. Experiments showed the superiority of the proposed method compared with binary classification, traditional anomaly detection methods, and several recognized domain adaptation methods.

Investigation of the effective aperture: towards high-resolution Fresnel incoherent correlation holography.

Fresnel incoherent correlation holography (FINCH) shows great advantages of coherent-light-source-free, high lateral resolution, no scanning, and easy integration, and has exhibited great potential in recording three-dimensional information of objects. Despite the rapid advances in the resolution of the FINCH system, little attention has been paid to the influence of the effective aperture of the system. Here, the effective aperture of the point spread function (PSF) has been investigated both theoretically and experimentally. It is found that the effective aperture is mainly restricted by the aperture of the charge-coupled device (CCD), the pixel size of the CCD, and the actual aperture of the PSF at different recording distances. It is also found that the optimal spatial resolution exists only for a small range of recording distance, while this range would become smaller as the imaging wavelength gets longer, leading to the result that the optimal spatial resolution is solely determined by the actual aperture of the PSF. By further combining the FINCH system with a microscopy system and optimizing the recording distance, a spatial resolution as high as 0.78 µm at the wavelength of 633 nm has been obtained, enabling a much higher quality imaging of unstained living biological cells compared to the commercial optical microscope. The results of this work may provide some helpful insights into the design of high-resolution FINCH systems and pave the way for their application in biomedical imaging.

Machine learning based on clinical characteristics and chest CT quantitative measurements for prediction of adverse clinical outcomes in hospitalized patients with COVID-19.

OBJECTIVES: To develop and validate a machine learning model for the prediction of adverse outcomes in hospitalized patients with COVID-19. METHODS: We included 424 patients with non-severe COVID-19 on admission from January 17, 2020, to February 17, 2020, in the primary cohort of this retrospective multicenter study. The extent of lung involvement was quantified on chest CT images by a deep learning-based framework. The composite endpoint was the occurrence of severe or critical COVID-19 or death during hospitalization. The optimal machine learning classifier and feature subset were selected for model construction. The performance was further tested in an external validation cohort consisting of 98 patients. RESULTS: There was no significant difference in the prevalence of adverse outcomes (8.7% vs. 8.2%, p = 0.858) between the primary and validation cohorts. The machine learning method extreme gradient boosting (XGBoost) and optimal feature subset including lactic dehydrogenase (LDH), presence of comorbidity, CT lesion ratio (lesion%), and hypersensitive cardiac troponin I (hs-cTnI) were selected for model construction. The XGBoost classifier based on the optimal feature subset performed well for the prediction of developing adverse outcomes in the primary and validation cohorts, with AUCs of 0.959 (95% confidence interval [CI]: 0.936-0.976) and 0.953 (95% CI: 0.891-0.986), respectively. Furthermore, the XGBoost classifier also showed clinical usefulness. CONCLUSIONS: We presented a machine learning model that could be effectively used as a predictor of adverse outcomes in hospitalized patients with COVID-19, opening up the possibility for patient stratification and treatment allocation. KEY POINTS: • Developing an individually prognostic model for COVID-19 has the potential to allow efficient allocation of medical resources. • We proposed a deep learning-based framework for accurate lung involvement quantification on chest CT images. • Machine learning based on clinical and CT variables can facilitate the prediction of adverse outcomes of COVID-19.

Dual-branch combination network (DCN): Towards accurate diagnosis and lesion segmentation of COVID-19 using CT images.

The recent global outbreak and spread of coronavirus disease (COVID-19) makes it an imperative to develop accurate and efficient diagnostic tools for the disease as medical resources are getting increasingly constrained. Artificial intelligence (AI)-aided tools have exhibited desirable potential; for example, chest computed tomography (CT) has been demonstrated to play a major role in the diagnosis and evaluation of COVID-19. However, developing a CT-based AI diagnostic system for the disease detection has faced considerable challenges, which is mainly due to the lack of adequate manually-delineated samples for training, as well as the requirement of sufficient sensitivity to subtle lesions in the early infection stages. In this study, we developed a dual-branch combination network (DCN) for COVID-19 diagnosis that can simultaneously achieve individual-level classification and lesion segmentation. To focus the classification branch more intensively on the lesion areas, a novel lesion attention module was developed to integrate the intermediate segmentation results. Furthermore, to manage the potential influence of different imaging parameters from individual facilities, a slice probability mapping method was proposed to learn the transformation from slice-level to individual-level classification. We conducted experiments on a large dataset of 1202 subjects from ten institutes in China. The results demonstrated that 1) the proposed DCN attained a classification accuracy of 96.74% on the internal dataset and 92.87% on the external validation dataset, thereby outperforming other models; 2) DCN obtained comparable performance with fewer samples and exhibited higher sensitivity, especially in subtle lesion detection; and 3) DCN provided good interpretability on the loci of infection compared to other deep models due to its classification guided by high-level semantic information. An online CT-based diagnostic platform for COVID-19 derived from our proposed framework is now available.

Brain parcellation driven by dynamic functional connectivity better capture intrinsic network dynamics.

Until now, dynamic functional connectivity (dFC) based on functional magnetic resonance imaging is typically estimated on a set of predefined regions of interest (ROIs) derived from an anatomical or static functional atlas which follows an implicit assumption of functional homogeneity within ROIs underlying temporal fluctuation of functional coupling, potentially leading to biases or underestimation of brain network dynamics. Here, we presented a novel computational method based on dynamic functional connectivity degree (dFCD) to derive meaningful brain parcellations that can capture functional homogeneous regions in temporal variance of functional connectivity. Several spatially distributed but functionally meaningful areas that are well consistent with known intrinsic connectivity networks were identified through independent component analysis (ICA) of time-varying dFCD maps. Furthermore, a systematical comparison with commonly used brain atlases, including the Anatomical Automatic Labeling template, static ICA-driven parcellation and random parcellation, demonstrated that the ROI-definition strategy based on the proposed dFC-driven parcellation could better capture the interindividual variability in dFC and predict observed individual cognitive performance (e.g., fluid intelligence, cognitive flexibility, and sustained attention) based on chronnectome. Together, our findings shed new light on the functional organization of resting brains at the timescale of seconds and emphasized the significance of a dFC-driven and voxel-wise functional homogeneous parcellation for network dynamics analyses in neuroscience.

State-Independent and -Dependent Structural Connectivity Alterations in Depression.

Some brain abnormalities persist at the remission phase, that is, the state-independent abnormalities, which may be one of the reasons for the high recurrence of major depressive disorder (MDD). Hence, it is of great significance to identify state-independent abnormalities of MDD through longitudinal investigation. Ninety-nine MDD patients and 118 healthy controls (HCs) received diffusion tensor imaging scanning at baseline. After 6-month antidepressant treatment, 68 patients received a second scan, among which 59 patients achieved full clinical remission. Differences in whole-brain structural connectivity (SC) between patients with MDD at baseline and HCs were estimated by two-sample t-tests. Masked with significantly changed SCs in MDD, two-sample t-tests were conducted between the remitted MDD subgroup at follow-up and HCs, and paired t-tests were implemented to compare the differences of SC in the remitted MDD subgroup before and after treatment. Significantly decreased SC between the right insula and the anterior temporal cortex (ATC), between the right ATC and the posterior temporal cortex (PTC), between the left ATC and the auditory cortex as well as increased connectivity between the right posterior cingulate cortex (PCC) and the left medial parietal cortex (MPC) were observed in the MDD group compared with the HC group at baseline (p < 0.05, FDR corrected). The decreased connectivity between the right insula and the ATC and increased connectivity between the right PCC and the left MPC persisted in the remitted MDD subgroup at follow-up (p < 0.05, FDR corrected). The decreased SC between the right insula and the ATC and increased SC between the right PCC and left MPC showed state-independent characters, which may be implicated in the sustained negative attention bias and motor retardation in MDD. In contrast, the decreased SC between the right ATC and the PTC and between the left ATC and the auditory cortex seemed to be state-dependent.

A Deep Network Model on Dynamic Functional Connectivity With Applications to Gender Classification and Intelligence Prediction.

Increasing evidence has suggested that the dynamic properties of functional brain networks are related to individual behaviors and cognition traits. However, current fMRI-based approaches mostly focus on statistical characteristics of the windowed correlation time course, potentially overlooking subtle time-varying patterns in dynamic functional connectivity (dFC). Here, we proposed the use of an end-to-end deep learning model that combines the convolutional neural network (CNN) and long short-term memory (LSTM) network to capture temporal and spatial features of functional connectivity sequences simultaneously. The results on a large cohort (Human Connectome Project, n = 1,050) demonstrated that our model could achieve a high classification accuracy of about 93% in a gender classification task and prediction accuracies of 0.31 and 0.49 (Pearson's correlation coefficient) in fluid and crystallized intelligence prediction tasks, significantly outperforming previously reported models. Furthermore, we demonstrated that our model could effectively learn spatiotemporal dynamics underlying dFC with high statistical significance based on the null hypothesis estimated using surrogate data. Overall, this study suggests the advantages of a deep learning model in making full use of dynamic information in resting-state functional connectivity, and highlights the potential of time-varying connectivity patterns in improving the prediction of individualized characterization of demographics and cognition traits.

Enhanced Regional Functional Connectivity Indicates Seizure Onset Zone.

This project aims to explore if stronger functional connectivity (FC) exists in the maximal BOLD response of EEG/fMRI analysis when it is concordant with seizure-onset-zone (SOZ). Twenty-six patients with drug-resistant focal epilepsy who had an EEG/fMRI and later underwent stereo-EEG implantation were included. Different types of IEDs were labeled in scalp EEG and IED-related maximal BOLD responses were evaluated separately, each constituting one study. After evaluating concordance between maximal BOLD and SOZ, twenty-seven studies were placed in the concordant group and eight in the discordant group. We evaluated the local connectivity and ipsilaterally distant connectivity difference between the maximal BOLD and the contralateral homotopic region. Significantly stronger local FC was found for the maximal BOLD in the concordant group (p < 0.05, Bonferroni corrected). 52% of the studies in the concordant group and 13% in the discordant group had a significant difference compared to healthy subjects (p < 0.05, uncorrected). The finding suggests that, when concordant with the SOZ, the maximal BOLD is more likely to have stronger local FC compared to its contralateral counterpart. This asymmetry in functional connectivity may help to noninvasively improve the specificity of EEG/fMRI analysis.