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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Neurodevelopmental Disorders 1/2017

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome

Zeitschrift:
Journal of Neurodevelopmental Disorders > Ausgabe 1/2017
Autoren:
Jun Wang, Lauren E. Ethridge, Matthew W. Mosconi, Stormi P. White, Devin K. Binder, Ernest V. Pedapati, Craig A. Erickson, Matthew J. Byerly, John A. Sweeney
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s11689-017-9191-z) contains supplementary material, which is available to authorized users.

Abstract

Background

Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability.

Methods

We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants.

Results

FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS.

Conclusions

Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability.
Zusatzmaterial
Additional file 1: Table S1. EEG measurements in the combined FXS group and in both the medicated FXS and non-medicated FXS group. (DOCX 14 kb)
11689_2017_9191_MOESM1_ESM.docx
Additional file 2: Figure S1. (A) Scalp topographies of “local coupling”, showing correlations in each electrode between relative power of activity in the theta, and lower and upper alpha power bands and gamma power for FXS and healthy control participants, with significant group differences presented in the bottom row (p < 0.05, corrected), with dark blue reflecting no group difference. (B) Mean and standard error of correlations for all electrodes showing group differences as are plotted in A. * denotes correlations of spectral power in theta and upper alpha bands with gamma band power that are significantly different from zero based on the results of permutation analyses at p < 0.05. (TIF 3754 kb)
11689_2017_9191_MOESM2_ESM.tif
Additional file 3: Figure S2. Scatter plot of each participant’s values of coupling with gamma in theta and alpha band within electrodes for FXS and healthy control participants. Circle denotes female participants, plus (+) denotes male participants. (TIF 321 kb)
11689_2017_9191_MOESM3_ESM.tif
Additional file 4: Cross-frequency amplitude coupling within individual electrodes. (DOCX 19 kb)
11689_2017_9191_MOESM4_ESM.docx
Additional file 5: Figure S3. Scalp topographies of relative power spectrum are presented for male FXS and male healthy control participants per frequency band, with significant group differences presented in the bottom row (p < 0.05, corrected). Relative power represents the percentage of power in each frequency band divided by total power across 1–80 Hz. (TIF 5063 kb)
11689_2017_9191_MOESM5_ESM.tif
Additional file 6: Figure S4. (A) Significant group differences in connectivity strength between male FXS and male healthy control participants based on permutation tests (p < 0.05) show increased connectivity in FXS in the gamma band but reduced connectivity in the alpha (lower and upper) and beta range. (B) Mean and standard error of between-electrode distances for electrode pairs showing group differences (plotted in A) in lower alpha, upper alpha, beta, and gamma bands. * denotes significant differences in connectivity distances with significant group differences between bands at p < 0.05. (C) Bivariate scatter plots depict the relationship between averaged connectivity strength (dbWPLI) and averaged between-electrode distance for FXS (red dots) and Healthy Control participants (black dots). (TIF 3314 kb)
11689_2017_9191_MOESM6_ESM.tif
Additional file 7: Figure S5. (A) Scalp topographies of “global coupling”, showing correlations between activity in the region showing the maximum relative power of activity in the theta, and lower and upper alpha power bands defined as the average of the power in that region of electrodes clusters (marked with *) and gamma power in all other electrodes for male FXS and male healthy control participants. Significant group differences are presented in the bottom row (p < 0.05, corrected), with dark blue reflecting no group difference. (B) Mean and standard error of correlations for all electrodes showing group differences as are plotted in A. * denotes correlations of spectral power in theta and upper alpha bands with gamma band power that are significantly different from zero based on the results of permutation analyses at p < 0.05. (TIF 3306 kb)
11689_2017_9191_MOESM7_ESM.tif
Additional file 8: Figure S6 (A) Scalp topographies of “local coupling”, showing correlations in each electrode between relative power of activity in the theta, and lower and upper alpha power bands and gamma power for male FXS and male healthy control participants, with significant group differences presented in the bottom row (p < 0.05, corrected), with dark blue reflecting no group difference. (B) Mean and standard error of correlations for all electrodes showing group differences as are plotted in A. * denotes correlations of spectral power in theta and upper alpha bands with gamma band power that are significantly different from zero based on the results of permutation analyses at p < 0.05. (TIF 4297 kb)
11689_2017_9191_MOESM8_ESM.tif
Additional file 9: Figure S7. Scatter plots of each participant’s values of power and connectivity in delta, theta, lower alpha, upper alpha, beta bands for FXS and healthy control participants. Circle denotes female participants, plus denotes male participants. (TIF 475 kb)
11689_2017_9191_MOESM9_ESM.tif
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