The Effects of Pharmaceutical Intervention on Neural Connectivity and Complexity in Fragile X Syndrome

Auger, Emma

The Effects of Pharmaceutical Intervention on Neural Connectivity and Complexity in Fragile X Syndrome

dc.contributor.advisor	Ethridge, Lauren
dc.contributor.author	Auger, Emma
dc.contributor.committeeMember	Wenger, Michael
dc.contributor.committeeMember	Song, Hairong
dc.contributor.committeeMember	Markham, Michael
dc.contributor.committeeMember	Pan, Chongle
dc.date.accessioned	2023-12-14T20:07:27Z
dc.date.available	2023-12-14T20:07:27Z
dc.date.issued	2023-12-15
dc.date.manuscript	2023-12-07
dc.description.abstract	This study aims to investigate the effects of targeted pharmaceutical interventions on brain networks in individuals with Fragile X Syndrome (FXS). Focusing on three drugs tested in phase 2 clinical trials – (1) a metabatropic glutamate receptor-5 (mGluR5) antagonist in children with FXS, (2) single-dose racemic baclofen in adolescents and adults, and (3) a PDE4D allosteric inhibitor in adolescents and adults. Previous studies suggested increased gamma connectivity, decreased alpha connectivity, and decreased complexity in FXS, which may be reversed with targeted treatment. However, none of the three drugs examined showed a significant reversal of these phenotypes. Some brain network measurements did show interesting patterns, which give insight into how the drug mechanisms affect brain function including: sedation effects on connectivity with racemic baclofen and potential minor changes in gamma connectivity with the mGluR-5 antagonist. Additionally, these measures provided insight into brain function within FXS populations. Specifically with increased alpha connectivity for males with FXS compared to females. While connectivity measures show promise in identifying potential drug effects, challenges in achieving consistent significance in small populations are evident. Unfortunately, the small effect sizes and variability within both connectivity and entropy measures indicated that these measures are not robust enough to use as primary outcome measurements in FXS clinical trials given the small populations. Rather, they may be used more effectively in larger studies examining differences between populations or how pharmaceutical interventions work on a large scale rather than in determining individual change. This study underscores the need for further research to understand the unique dynamics of FXS, emphasizing the importance of considering gender, age, and measurement in clinical trials and future investigations.	en_US
dc.identifier.uri	https://hdl.handle.net/11244/340049
dc.language	en_US	en_US
dc.subject	EEG	en_US
dc.subject	Functional Connectivity	en_US
dc.subject	Entropy	en_US
dc.subject	Fragile X Syndrome	en_US
dc.thesis.degree	Ph.D.	en_US
dc.title	The Effects of Pharmaceutical Intervention on Neural Connectivity and Complexity in Fragile X Syndrome	en_US
ou.group	Dodge Family College of Arts and Sciences::Department of Psychology	en_US