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Altered Connectome Gradient and Its Association with Gene Expression Profiles in Patients with MELAS.

Rong Wang1,2, Qingyun Yu1,3, Chong Sun4

  • 1From the Department of Radiology (R.W., Q.Y., X.L., B.H., L.Y., D.G., Y.L.), Huashan Hospital, Fudan University, Shanghai, China.

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Brain functional gradients are altered in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients during acute stroke-like episodes (SLE). These changes correlate with specific gene expression profiles, offering insights into MELAS neurobiology.

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Area of Science:

  • Neuroscience
  • Systems Neuroscience
  • Medical Imaging

Background:

  • Brain network organization relies on hierarchy.
  • Functional connectivity (FC) gradients offer a novel method to study brain hierarchy.
  • Disruptions in FC gradients in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) during acute stroke-like episodes (SLE) are unknown.

Purpose of the Study:

  • To investigate functional gradient alterations in MELAS patients during acute SLE.
  • To explore the relationship between these gradient changes and gene expression profiles.

Main Methods:

  • Resting-state functional magnetic resonance imaging (rs-fMRI) was used for 31 MELAS patients (acute stage) and 31 healthy controls (HC).
  • Whole-brain voxel-wise FC patterns were analyzed to generate and compare functional gradient values.
  • Spatial correlations between MELAS-related gradient alterations and gene expression profiles were assessed using the Allen Human Brain Atlas.

Main Results:

  • MELAS patients exhibited global principal gradient alterations, including reduced range and variation compared to HC.
  • Patients showed decreased gradient values in the default mode network (DMN) and increased values in the ventral attention network (VAN) and sensorimotor network (SMN).
  • A link was found between MELAS-related gradient changes and gene expression profiles, particularly those related to mitochondria, neurons, and ATPase activity.

Conclusions:

  • Connectome gradient alterations are evident in MELAS patients during the acute SLE stage.
  • These findings link functional brain changes to specific gene expression profiles, illuminating the neurobiological underpinnings of acute SLE in MELAS.