Mapping Insular Subdivisions through SEEG and FC: Validation in Non-Insular Epilepsy Patients

Poster No:

1757 

Submission Type:

Abstract Submission 

Authors:

Chen Yi-Hsiu1, Pei-Lin Lee2, Kun-Hsien Chou3, Yi-Hsuan Liu4, Lee Cheng-Chia1, Cheng-Chen Chou5, Lin Ching-Po6

Institutions:

1Taipei Veterans General Hospital, Taipei, Taiwan, 2National Yang Ming Chiao Tung University, Taipei, N/A, 3Brain research center, National Yang Ming Chiao Tung University, Taipei, Taiwan, 4Institute of Neuroscience, Taipei, other, 5Department of Neurology Neurological Institute,Taipei Veterans General Hospital, Taipei, Taiwan, 6Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

First Author:

Chen Yi-Hsiu  
Taipei Veterans General Hospital
Taipei, Taiwan

Co-Author(s):

Pei-Lin Lee  
National Yang Ming Chiao Tung University
Taipei, N/A
Kun-Hsien Chou  
Brain research center, National Yang Ming Chiao Tung University
Taipei, Taiwan
Yi-Hsuan Liu  
Institute of Neuroscience
Taipei, other
Lee Cheng-Chia  
Taipei Veterans General Hospital
Taipei, Taiwan
Cheng-Chen Chou  
Department of Neurology Neurological Institute,Taipei Veterans General Hospital
Taipei, Taiwan
Lin Ching-Po  
Department of Education and Research, Taipei City Hospital
Taipei, Taiwan

Introduction:

The insular cortex, located deep within the brain, serves as a critical hub for integrating diverse brain function. While classical studies emphasized its role in visceral-somatic processing, recent intracranial electroencephalography investigations have revealed its involvement in a broader spectrum of functions, including pain processing, auditory response, and gustatory sensation [1,2]. Advanced neuroimaging analyses have proposed varying numbers of functional subdivisions within the insula, with a comprehensive meta-analysis of 1,768 studies suggesting four distinct parcellations [3]. However, a critical gap exists in validating these neuroimaging-based subdivisions with direct neurophysiological evidence. Therefore, this study aims to bridge this gap by integrating stereo-electroencephalography (SEEG) mapping with resting-state functional connectivity analysis to validate and characterize insular subdivisions.

Methods:

We collected rs-fMRI data and SEEG mapping results from 16 epilepsy patients with non-insular seizure onset who underwent SEEG implantation, leveraging this unique patient population to validate insular function in the absence of local pathology. SEEG contact locations were verified through co-registration of post-implantation CT with pre-operative MRI. Only SEEG contacts located within the insula were selected as seeds for subsequent analyses. For functional connectivity analysis, the rs-fMRI data underwent standard preprocessing procedures, followed by brain parcellation into 400 cortical regions defined by Yeo et al. [5] as target ROIs. After excluding regions located near the insular (defined by Harvard-Oxford subcortical atlas [4]), 353 cortical ROIs remained for analysis. To identify common connectivity patterns, we performed one-sample t-tests on the FC maps across all patients. Next, we employed K-means clustering to classify the insular seeds based on their FC patterns, aiming to identify distinct functional subdivisions within the insula. For clinical validation, we extracted SEEG mapping results (assessed by neurologists) from each insular contact and visualized them as word clouds to represent the functions elicited by electrical stimulation within each identified subdivision.

Results:

Using SEEG-guided functional connectivity analysis, we identified three distinct subdivisions within the insula: the dorsal anterior insula (dAI), ventral anterior insula (vAI), and posterior insula (PI). The dAI was connected to frontal cortex and dorsal anterior cingulate cortex (dACC), linked to cognitive processing and visceral sensation. The vAI connected to superior temporal cortex and ventral anterior cingulate cortex (vACC), associated with social-emotional and gustatory functions, while the PI connected to pericentral lobules, related to sensorimotor functions. SEEG stimulation validated these findings, with the dAI eliciting facial sensations and emotional responses, the vAI inducing dysesthesia and gustatory sensations, and the PI triggering limb-related sensations.
Supporting Image: OHBMfig1.png
   ·Figure1. Demographics of SEEG contacts.
Supporting Image: OHBMfig2.png
   ·Figure2. Insular functional subdivisions and the corresponding SEEG mapping results.
 

Conclusions:

By integrating SEEG-guided functional connectivity analysis with electrical stimulation mapping in patients with preserved insular function, we have provided robust evidence for three distinct functional subdivisions within the human insula: dAI, vAI, and PI. Each subdivision exhibited distinct connectivity patterns: dAI with cognitive and visceral processing, vAI with social-emotional and gustatory functions, and PI with sensorimotor functions. SEEG stimulation validated these findings through consistent clinical responses. Our multimodal approach establishes a more precise map of insular organization, advancing both basic neuroscience understanding and clinical applications in insular-related pathologies.

Brain Stimulation:

Direct Electrical/Optogenetic Stimulation

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural) 2
fMRI Connectivity and Network Modeling

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Subcortical Structures 1

Novel Imaging Acquisition Methods:

BOLD fMRI

Keywords:

FUNCTIONAL MRI
Sub-Cortical
Other - SEEG

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

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Please indicate which methods were used in your research:

Functional MRI
Other, Please specify  -   electrophysiology

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

AFNI
SPM
FSL
Free Surfer

Provide references using APA citation style.

[1] Isnard, J., Guénot, M., Sindou, M., & Mauguière, F. (2004). Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study. Epilepsia, 45(9), 1079–1090. https://doi.org/10.1111/j.0013-9580.2004.68903.x
[2] Stephani C, Fernandez-Baca Vaca G, Maciunas R, Koubeissi M, Lüders HO. Functional neuroanatomy of the insular lobe. Brain Struct Funct. 2011 Jun;216(2):137-49. doi: 10.1007/s00429-010-0296-3. Epub 2010 Dec 14. PMID: 21153903; PMCID: PMC3097350.
[3] Kurth F et al. (2010). ‘A link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis’, Brain Struct Funct, vol. 214, pp. 519-34.

[4] Nikos Makris, Jill M. Goldstein, David Kennedy, Steven M. Hodge, Verne S. Caviness, Stephen V. Faraone, Ming T. Tsuang, and Larry J. Seidman. Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophrenia Research, 83(2-3):155–171, April 2006. doi:10.1016/j.schres.2005.11.020.

[5]Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., Roffman, J. L., Smoller, J. W., Zöllei, L., Polimeni, J. R., Fischl, B., Liu, H., & Buckner, R. L. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of neurophysiology, 106(3), 1125–1165. https://doi.org/10.1152/jn.00338.2011

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