The alteration of cortical microstructure similarity in drug-resistant epilepsy correlated with mTOR pathway genes
Hang Cao1, Penghu Wei2, Yuda Huang1
1Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun St, Beijing, 100053, China.
Background:
Drug-resistant epilepsy (DRE) is associated with distributed laminar disruptions due to cytoarchitectonic pathologies, which may be characterized by multimodal MRI approaches such as morphometric similarity networks (MSNs). However, the genetic and histological underpinning of MSN alterations in DRE remains poorly understood, hampering its clinical application.
Methods:
We enrolled 60 patients with DRE and 23 controls, acquiring T1 and diffusion spectrum imaging data with a 3.0T GE SIGNA Premier scanner. Morphometric similarity networks (MSNs) were constructed and analyzed to identify microstructure similarity differences between patients and controls. Subsequently, patient-specific MSN alteration patterns were associated with gene expression using the GAMBA tool, and layer-specific neuronal signature mapping were also applied. During these analyses, sex and age were adjusted as covariates and multiple comparisons corrections were applied when appropriate.
Findings:
We observed widespread MSN changes in patients with DRE and identified five distinct MSN alteration patterns. Major patterns presented pattern-specific associations with expressions of epilepsy-related genes, particularly involving the mTOR pathway. Histological analysis confirmed the presence of cortical microstructure changes in areas with MSN alterations and revealed cellular abnormalities matching the aforementioned genetic risks.
Interpretation:
Our findings highlight the potential of quantifying laminar-related microstructure integrity using MSN to uncover the cytoarchitectonic changes in the pathophysiology of DRE. This approach may facilitate the identification of genetic and histological underpinnings of MSN alterations in DRE, ultimately aiding in the development of targeted therapeutic strategies.
Fundings:
The National Natural Science Foundation of China, the Ministry of Science and Technology of the People's Republic of China, and the Beijing Municipal Health Commission.
Insights
Morphometric similarity networks reveal widespread changes in drug-resistant epilepsy (DRE). These alterations link to genetic and histological factors, offering new therapeutic targets for DRE.
Area of Science:
- Neuroimaging
- Epilepsy Research
- Computational Neuroscience
Background:
- Drug-resistant epilepsy (DRE) involves disrupted brain structure.
- Morphometric similarity networks (MSNs) show promise in characterizing these disruptions.
- The genetic and histological basis of MSN alterations in DRE is not well understood.
Purpose of the Study:
- To investigate the genetic and histological underpinnings of MSN alterations in DRE.
- To explore the potential of MSNs for understanding DRE pathophysiology.
Main Methods:
- Acquired T1 and diffusion spectrum imaging data from 60 DRE patients and 23 controls.
- Constructed and analyzed morphometric similarity networks (MSNs).
- Associated patient-specific MSN patterns with gene expression and performed layer-specific neuronal signature mapping.
Main Results:
- Identified five distinct MSN alteration patterns in DRE patients.
- Observed pattern-specific associations with epilepsy-related gene expression, notably the mTOR pathway.
- Histological analysis confirmed cortical microstructure changes and cellular abnormalities linked to genetic risks.
Conclusions:
- MSNs can quantify laminar microstructure integrity in DRE.
- This approach may uncover cytoarchitectonic changes in DRE pathophysiology.
- Findings may aid in identifying genetic/histological underpinnings and developing targeted therapies for DRE.
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