EEG as a translational biomarker and outcome measure in fragile X syndrome

Aisling Kenny, Damien Wright, Andrew C Stanfield, Aisling Kenny, Damien Wright, Andrew C Stanfield

Abstract

Targeted treatments for fragile X syndrome (FXS) have frequently failed to show efficacy in clinical testing, despite success at the preclinical stages. This has highlighted the need for more effective translational outcome measures. EEG differences observed in FXS, including exaggerated N1 ERP amplitudes, increased resting gamma power and reduced gamma phase-locking in the sensory cortices, have been suggested as potential biomarkers of the syndrome. These abnormalities are thought to reflect cortical hyper excitability resulting from an excitatory (glutamate) and inhibitory (GABAergic) imbalance in FXS, which has been the target of several pharmaceutical remediation studies. EEG differences observed in humans also show similarities to those seen in laboratory models of FXS, which may allow for greater translational equivalence and better predict clinical success of putative therapeutics. There is some evidence from clinical trials showing that treatment related changes in EEG may be associated with clinical improvements, but these require replication and extension to other medications. Although the use of EEG characteristics as biomarkers is still in the early phases, and further research is needed to establish its utility in clinical trials, the current research is promising and signals the emergence of an effective translational biomarker.

Conflict of interest statement

Andrew Stanfield has received grant funding from Novartis and Roche, including for trials of mGluR5 antagonists in fragile X syndrome. Aisling Kenny and Damien Wright declare no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1. Example of N1 ERP in…
Fig. 1. Example of N1 ERP in response to standard and deviant tone presentation in auditory oddball task for FXS and for controls.
A The exaggerated N1 amplitude (reported in microvolts (μV), across time (ms)) response to both standard and oddball tones as observed in FXS. B The neurotypical control response; exaggerated N1 amplitude to oddball tone, but attenuated N1 amplitude to the repeated standard tone.

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