Research Horizons


Exploring How Thalamocortical Modulation Impacts Brain Function in Fragile X Syndrome

Child and Adolescent Psychiatry | Top Scientific Achievement
2023 Research Discoveries

Disrupted thalamocortical modulation appears to play a key role in local hyperexcitability in Fragile X Syndrome (FXS). Researchers at Cincinnati Children’s say these new findings will further the understanding of fundamental disease mechanisms in FXS and open the door to future therapeutic and physiological investigations. 

A team led by Ernest Pedapati, MD, MS, and leading FXS expert Craig Erickson, MD, translated findings from well-established knockout animal models into patients to identify tractable treatment targets. Through source modeling of resting-state electroencephalography (EEG) data, the team noted: 

  • Increases in localized gamma activity  
  • Pervasive changes of theta/alpha activity, indicative of disrupted thalamocortical modulation coupled with elevated gamma power  
  • Stepwise moderation of low- and high-frequency abnormalities based on female sex  
  • Relationship of this physiology to intellectual disability and neuropsychiatric symptoms 

Changes in thalamocortical activity are a system-level hypothesis that could explain these EEG findings. These changes, also known as thalamocortical dysrhythmia (TCD), are underexplored in FXS.  

TCD, an electrophysiological model, shows how intrinsic changes in the thalamocortical system form the basis of disease-related pathophysiology. It is used to characterize dysregulation of cortical excitability in other neuropsychiatric conditions such as epilepsy and Parkinson’s disease. 

The changes may contribute to and maintain abnormal cortical states that reduce functional brain connectivity and regional function necessary for optimal brain functions,” says Erickson. 

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Publication Information
Original title: Neocortical localization and thalamocortical modulation of neuronal hyperexcitability contribute to Fragile X Syndrome
Published in: Communications Biology
Publish date: May 11, 2022
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Research By

Craig Erickson, MD
Craig Erickson, MD
Division of Child Psychiatry