Author name cluster

Seok-Jun Hong

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

12 papers

1 author row

YNIMG Journal 2026 Journal Article

Morphometric dissimilarity in association cortices linked to autism subtype with more severe symptoms

Hongxiu Jiang
Raul Rodriguez-Cruces
Ke Xie
Valeria Kebets
Yezhou Wang
Clara F. Weber
Ying He
Jonah Kember

Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental condition marked by atypical brain connectivity. Understanding ASD neural subtypes at the network level is critical for clarifying its neuroanatomical heterogeneity. Morphometric similarity networks (MSNs), derived from region-to-region similarity across multiple anatomical features, offer a powerful approach for capturing individual-level neural architecture. In this study, MSNs were estimated from seven anatomical features in 348 individuals with ASD and 452 typically developing (TD) controls. Across all ASD participants, the first principal component of MSN values was negatively correlated with social and communication severity. Three ASD subtypes with distinct MSN patterns were identified. Subtype-1, characterized by weaker morphometric similarity values in frontotemporal association regions compared to TD individuals, exhibited the most severe symptoms in social, communication and repetitive behaviors, and displayed hyperconnectivity between the salience and visual networks, and between language and visual networks. Subtype-2 showed greater values of morphometric similarities than TD and less severe social symptoms compared to subtype-1, along with hyperconnectivity between default and salience networks relative to TD. Subtype-3 displayed morphometric similarity values largely comparable to TD and the least severe symptoms out of the three subtypes. Transcriptomic analysis revealed that GABAergic parvalbumin and glutamatergic intratelencephalic-projecting neurons were key cell types differentiating subtypes. These findings suggest the existence of distinct ASD neuroanatomical subtypes defined by regional morphometric similarity, each linked to unique behavioral, functional, and transcriptomic profiles. Morphometric dissimilarity in association regions may serve as a neural signature for ASD subtypes characterized by more severe clinical manifestations.

Details DOI

NeurIPS Conference 2025 Conference Paper

EVAAA: A Virtual Environment Platform for Essential Variables in Autonomous and Adaptive Agents

Sungwoo Lee
Jungmin Lee
Sohee Kim
Hyebhin Yoon
Shinwon Park
Junhyeok Park
Jaehyuk Bae
Seok-Jun Hong

Reinforcement learning (RL) agents have demonstrated strong performance in structured environments, yet they continue to struggle in real-world settings where goals are ambiguous, conditions change dynamically, and external supervision is limited. These challenges stem not primarily from the algorithmic limitations but from the characteristics of conventional training environments, which are usually static, task-specific, and externally defined. In contrast, biological agents develop autonomy and adaptivity by interacting with complex, dynamic environments, where most behaviors are ultimately driven by internal physiological needs. Inspired by these biological constraints, we introduce EVAAA (Essential Variables in Autonomous and Adaptive Agents), a 3D virtual environment for training and evaluating egocentric RL agents endowed with internal physiological state variables. In EVAAA, agents must maintain essential variables (EVs)—e. g. , satiation, hydration, body temperature, and tissue integrity (the level of damage)—within viable bounds by interacting with environments that increase in difficulty at each stage. The reward system is derived from internal state dynamics, enabling agents to generate goals autonomously without manually engineered, task-specific reward functions. Built on Unity ML-Agents, EVAAA supports multimodal sensory inputs, including vision, olfaction, thermoception, collision, as well as egocentric embodiment. It features naturalistic survival environments for curricular training and a suite of unseen experimental testbeds, allowing for the evaluation of autonomous and adaptive behaviors that emerge from the interplay between internal state dynamics and environmental constraints. By integrating physiological regulation, embodiment, continual learning, and generalization, EVAAA offers a biologically inspired benchmark for studying autonomy, adaptivity, and internally driven control in RL agents. Our code is publicly available at https: //github. com/cocoanlab/evaaa

PDF Details

YNIMG Journal 2024 Journal Article

Connectome-wide structure-function coupling models implicate polysynaptic alterations in autism

Bo-yong Park
Oualid Benkarim
Clara F. Weber
Valeria Kebets
Serena Fett
Seulki Yoo
Adriana Di Martino
Michael P. Milham

Autism spectrum disorder (ASD) is one of the most common neurodevelopmental diagnoses. Although incompletely understood, structural and functional network alterations are increasingly recognized to be at the core of the condition. We utilized multimodal imaging and connectivity modeling to study structure-function coupling in ASD and probed mono- and polysynaptic mechanisms on structurally-governed network function. We examined multimodal magnetic resonance imaging data in 80 ASD and 61 neurotypical controls from the Autism Brain Imaging Data Exchange (ABIDE) II initiative. We predicted intrinsic functional connectivity from structural connectivity data in each participant using a Riemannian optimization procedure that varies the times that simulated signals can unfold along tractography-derived personalized connectomes. In both ASD and neurotypical controls, we observed improved structure-function prediction at longer diffusion time scales, indicating better modeling of brain function when polysynaptic mechanisms are accounted for. Prediction accuracy differences (∆prediction accuracy) were marked in transmodal association systems, such as the default mode network, in both neurotypical controls and ASD. Differences were, however, lower in ASD in a polysynaptic regime at higher simulated diffusion times. We compared regional differences in ∆prediction accuracy between both groups to assess the impact of polysynaptic communication on structure-function coupling. This analysis revealed that between-group differences in ∆prediction accuracy followed a sensory-to-transmodal cortical hierarchy, with an increased gap between controls and ASD in transmodal compared to sensory/motor systems. Multivariate associative techniques revealed that structure-function differences reflected inter-individual differences in autistic symptoms and verbal as well as non-verbal intelligence. Our network modeling approach sheds light on atypical structure-function coupling in autism, and suggests that polysynaptic network mechanisms are implicated in the condition and that these can help explain its wide range of associated symptoms.

Details DOI

YNIMG Journal 2024 Journal Article

Whole-brain structural connectome asymmetry in autism

Seulki Yoo
Yurim Jang
Seok-Jun Hong
Hyunjin Park
Sofie L. Valk
Boris C. Bernhardt
Bo-yong Park

Autism spectrum disorder is a common neurodevelopmental condition that manifests as a disruption in sensory and social skills. Although it has been shown that the brain morphology of individuals with autism is asymmetric, how this differentially affects the structural connectome organization of each hemisphere remains under-investigated. We studied whole-brain structural connectivity-based brain asymmetry in individuals with autism using diffusion magnetic resonance imaging obtained from the Autism Brain Imaging Data Exchange initiative. By leveraging dimensionality reduction techniques, we constructed low-dimensional representations of structural connectivity and calculated their asymmetry index. Comparing the asymmetry index between individuals with autism and neurotypical controls, we found atypical structural connectome asymmetry in the sensory and default-mode regions, particularly showing weaker asymmetry towards the right hemisphere in autism. Network communication provided topological underpinnings by demonstrating that the inferior temporal cortex and limbic and frontoparietal regions showed reduced global network communication efficiency and decreased send-receive network navigation in the inferior temporal and lateral visual cortices in individuals with autism. Finally, supervised machine learning revealed that structural connectome asymmetry could be used as a measure for predicting communication-related autistic symptoms and nonverbal intelligence. Our findings provide insights into macroscale structural connectome alterations in autism and their topological underpinnings.

Details DOI

YNIMG Journal 2023 Journal Article

BrainStat: A toolbox for brain-wide statistics and multimodal feature associations

Sara Larivière
Şeyma Bayrak
Reinder Vos de Wael
Oualid Benkarim
Peer Herholz
Raul Rodriguez-Cruces
Casey Paquola
Seok-Jun Hong

Analysis and interpretation of neuroimaging datasets has become a multidisciplinary endeavor, relying not only on statistical methods, but increasingly on associations with respect to other brain-derived features such as gene expression, histological data, and functional as well as cognitive architectures. Here, we introduce BrainStat - a toolbox for (i) univariate and multivariate linear models in volumetric and surface-based brain imaging datasets, and (ii) multidomain feature association of results with respect to spatial maps of post-mortem gene expression and histology, task-based fMRI meta-analysis, as well as resting-state fMRI motifs across several common surface templates. The combination of statistics and feature associations into a turnkey toolbox streamlines analytical processes and accelerates cross-modal research. The toolbox is implemented in both Python and MATLAB, two widely used programming languages in the neuroimaging and neuroinformatics communities. BrainStat is openly available and complemented by an expandable documentation.

Details DOI

YNIMG Journal 2022 Journal Article

A whole-brain 3D myeloarchitectonic atlas: Mapping the Vogt-Vogt legacy to the cortical surface

Niels A. Foit
Seles Yung
Hyo Min Lee
Andrea Bernasconi
Neda Bernasconi
Seok-Jun Hong

Building precise and detailed parcellations of anatomically and functionally distinct brain areas has been a major focus in Neuroscience. Pioneer anatomists parcellated the cortical manifold based on extensive histological studies of post-mortem brain, harnessing local variations in cortical cyto- and myeloarchitecture to define areal boundaries. Compared to the cytoarchitectonic field, where multiple neuroimaging studies have recently translated this old legacy data into useful analytical resources, myeloarchitectonics, which parcellate the cortex based on the organization of myelinated fibers, has received less attention. Here, we present the neocortical surface-based myeloarchitectonic atlas based on the histology-derived maps of the Vogt-Vogt school and its 2D translation by Nieuwenhuys. In addition to a myeloarchitectonic parcellation, our package includes intracortical laminar profiles of myelin content based on Vogt-Vogt-Hopf original publications. Histology-derived myelin density mapped on our atlas demonstrated a close overlap with in vivo quantitative MRI markers for myelin and relates to cytoarchitectural features. Complementing the existing battery of approaches for digital cartography, the whole-brain myeloarchitectonic atlas offers an opportunity to validate imaging surrogate markers of myelin in both health and disease.

Details DOI

YNIMG Journal 2022 Journal Article

Diagnosis-informed connectivity subtyping discovers subgroups of autism with reproducible symptom profiles

Hyoungshin Choi
Kyoungseob Byeon
Bo-yong Park
Jong-eun Lee
Sofie L. Valk
Boris Bernhardt
Adriana Di Martino
Michael Milham

Clinical heterogeneity has been one of the main barriers to develop effective biomarkers and therapeutic strategies in autism spectrum disorder (ASD). Recognizing this challenge, much effort has been made in recent neuroimaging studies to find biologically more homogeneous subgroups (called 'neurosubtypes') in autism. However, most approaches have rarely evaluated how much the employed features in subtyping represent the core anomalies of ASD, obscuring its utility in actual clinical diagnosis. To address this, we combined two data-driven methods, 'connectome-based gradient' and 'functional random forest', collectively allowing to discover reproducible neurosubtypes based on resting-state functional connectivity profiles that are specific to ASD. Indeed, the former technique provides the features (as input for subtyping) that effectively summarize whole-brain connectome variations in both normal and ASD conditions, while the latter leverages a supervised random forest algorithm to inform diagnostic labels to clustering, which makes neurosubtyping driven by the features of ASD core anomalies. Applying this framework to the open-sharing Autism Brain Imaging Data Exchange repository data (discovery, n = 103/108 for ASD/typically developing [TD]; replication, n = 44/42 for ASD/TD), we found three dominant subtypes of functional gradients in ASD and three subtypes in TD. The subtypes in ASD revealed distinct connectome profiles in multiple brain areas, which are associated with different Neurosynth-derived cognitive functions previously implicated in autism studies. Moreover, these subtypes showed different symptom severity, which degree co-varies with the extent of functional gradient changes observed across the groups. The subtypes in the discovery and replication datasets showed similar symptom profiles in social interaction and communication domains, confirming a largely reproducible brain-behavior relationship. Finally, the connectome gradients in ASD subtypes present both common and distinct patterns compared to those in TD, reflecting their potential overlap and divergence in terms of developmental mechanisms involved in the manifestation of large-scale functional networks. Our study demonstrated a potential of the diagnosis-informed subtyping approach in developing a clinically useful brain-based classification system for future ASD research.

Details DOI

YNIMG Journal 2020 Journal Article

Cross-species functional alignment reveals evolutionary hierarchy within the connectome

Ting Xu
Karl-Heinz Nenning
Ernst Schwartz
Seok-Jun Hong
Joshua T. Vogelstein
Alexandros Goulas
Damien A. Fair
Charles E. Schroeder

Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we develop a function-based method for cross-species alignment that enables the quantification of homologous regions between humans and rhesus macaques, even when their location is decoupled from anatomical landmarks. Critically, we find cross-species similarity in functional organization reflects a gradient of evolutionary change that decreases from unimodal systems and culminates with the most pronounced changes in posterior regions of the default mode network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default mode network, as the apex of a cognitive hierarchy, has changed in a complex manner during human evolution - even within subnetworks.

Details DOI

YNICL Journal 2020 Journal Article

Microstructural imaging in temporal lobe epilepsy: Diffusion imaging changes relate to reduced neurite density

Gavin P Winston
Sjoerd B Vos
Benoit Caldairou
Seok-Jun Hong
Monika Czech
Tobias C Wood
Stephen J Wastling
Gareth J Barker

PURPOSE: Previous imaging studies in patients with refractory temporal lobe epilepsy (TLE) have examined the spatial distribution of changes in imaging parameters such as diffusion tensor imaging (DTI) metrics and cortical thickness. Multi-compartment models offer greater specificity with parameters more directly related to known changes in TLE such as altered neuronal density and myelination. We studied the spatial distribution of conventional and novel metrics including neurite density derived from NODDI (Neurite Orientation Dispersion and Density Imaging) and myelin water fraction (MWF) derived from mcDESPOT (Multi-Compartment Driven Equilibrium Single Pulse Observation of T1/T2)] to infer the underlying neurobiology of changes in conventional metrics. METHODS: 20 patients with TLE and 20 matched controls underwent magnetic resonance imaging including a volumetric T1-weighted sequence, multi-shell diffusion from which DTI and NODDI metrics were derived and a protocol suitable for mcDESPOT fitting. Models of the grey matter-white matter and grey matter-CSF surfaces were automatically generated from the T1-weighted MRI. Conventional diffusion and novel metrics of neurite density and MWF were sampled from intracortical grey matter and subcortical white matter surfaces and cortical thickness was measured. RESULTS: In intracortical grey matter, diffusivity was increased in the ipsilateral temporal and frontopolar cortices with more restricted areas of reduced neurite density. Diffusivity increases were largely related to reductions in neurite density, and to a lesser extent CSF partial volume effects, but not MWF. In subcortical white matter, widespread bilateral reductions in fractional anisotropy and increases in radial diffusivity were seen. These were primarily related to reduced neurite density, with an additional relationship to reduced MWF in the temporal pole and anterolateral temporal neocortex. Changes were greater with increasing epilepsy duration. Bilaterally reduced cortical thickness in the mesial temporal lobe and centroparietal cortices was unrelated to neurite density and MWF. CONCLUSIONS: Diffusivity changes in grey and white matter are primarily related to reduced neurite density with an additional relationship to reduced MWF in the temporal pole. Neurite density may represent a more sensitive and specific biomarker of progressive neuronal damage in refractory TLE that deserves further study.

Details DOI

YNIMG Journal 2020 Journal Article

Toward a connectivity gradient-based framework for reproducible biomarker discovery

Seok-Jun Hong
Ting Xu
Aki Nikolaidis
Jonathan Smallwood
Daniel S. Margulies
Boris Bernhardt
Joshua Vogelstein
Michael P. Milham

Despite myriad demonstrations of feasibility, the high dimensionality of fMRI data remains a critical barrier to its utility for reproducible biomarker discovery. Recent efforts to address this challenge have capitalized on dimensionality reduction techniques applied to resting-state fMRI, identifying principal components of intrinsic connectivity which describe smooth transitions across different cortical systems, so called “connectivity gradients”. These gradients recapitulate neurocognitively meaningful organizational principles that are present in both human and primate brains, and also appear to differ among individuals and clinical populations. Here, we provide a critical assessment of the suitability of connectivity gradients for biomarker discovery. Using the Human Connectome Project (discovery subsample=209; two replication subsamples= 209 × 2) and the Midnight scan club (n = 9), we tested the following key biomarker traits – reliability, reproducibility and predictive validity – of functional gradients. In doing so, we systematically assessed the effects of three analytical settings, including i) dimensionality reduction algorithms (i. e. , linear vs. non-linear methods), ii) input data types (i. e. , raw time series, [un-]thresholded functional connectivity), and iii) amount of the data (resting-state fMRI time-series lengths). We found that the reproducibility of functional gradients across algorithms and subsamples is generally higher for those explaining more variances of whole-brain connectivity data, as well as those having higher reliability. Notably, among different analytical settings, a linear dimensionality reduction (principal component analysis in our study), more conservatively thresholded functional connectivity (e. g. , 95–97%) and longer time-series data (at least ≥20mins) was found to be preferential conditions to obtain higher reliability. Those gradients with higher reliability were able to predict unseen phenotypic scores with a higher accuracy, highlighting reliability as a critical prerequisite for validity. Importantly, prediction accuracy with connectivity gradients exceeded that observed with more traditional edge-based connectivity measures, suggesting the added value of a low-dimensional and multivariate gradient approach. Finally, the present work highlights the importance and benefits of systematically exploring the parameter space for new imaging methods before widespread deployment.

Details DOI

YNICL Journal 2020 Journal Article

Unsupervised machine learning reveals lesional variability in focal cortical dysplasia at mesoscopic scale

Hyo M. Lee
Ravnoor S. Gill
Fatemeh Fadaie
Kyoo H. Cho
Marie C. Guiot
Seok-Jun Hong
Neda Bernasconi
Andrea Bernasconi

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a prevalent cause of surgically amenable epilepsy. While cellular and molecular biology data suggest that FCD lesional characteristics lie along a spectrum, this notion remains to be verified in vivo. We tested the hypothesis that machine learning applied to MRI captures FCD lesional variability at a mesoscopic scale. METHODS: We studied 46 patients with histologically verified FCD Type II and 35 age- and sex-matched healthy controls. We applied consensus clustering, an unsupervised learning technique that identifies stable clusters based on bootstrap-aggregation, to 3 T multicontrast MRI (T1-weighted MRI and FLAIR) features of FCD normalized with respect to distributions in controls. RESULTS: Lesions were parcellated into four classes with distinct structural profiles variably expressed within and across patients: Class-1 with isolated white matter (WM) damage; Class-2 combining grey matter (GM) and WM alterations; Class-3 with isolated GM damage; Class-4 with GM-WM interface anomalies. Class membership was replicated in two independent datasets. Classes with GM anomalies impacted local function (resting-state fMRI derived ALFF), while those with abnormal WM affected large-scale connectivity (assessed by degree centrality). Overall, MRI classes reflected typical histopathological FCD characteristics: Class-1 was associated with severe WM gliosis and interface blurring, Class-2 with severe GM dyslamination and moderate WM gliosis, Class-3 with moderate GM gliosis, Class-4 with mild interface blurring. A detection algorithm trained on class-informed data outperformed a class-naïve paradigm. SIGNIFICANCE: Machine learning applied to widely available MRI contrasts uncovers FCD Type II variability at a mesoscopic scale and identifies tissue classes with distinct structural dimensions, functional and histopathological profiles. Integrating in vivo staging of FCD traits with automated lesion detection is likely to inform the development of novel personalized treatments.

Details DOI

YNIMG Journal 2018 Journal Article

Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study

Boris C. Bernhardt
Fatemeh Fadaie
Reinder Vos de Wael
Seok-Jun Hong
Min Liu
Marie C. Guiot
David A. Rudko
Andrea Bernasconi

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT1 anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT1 increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT1 suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks.

Details DOI