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Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1

Garg, Shruti; Williams, Steve; Jung, JeYoung; Pobric, Gorana; Nandi, Tulika; Lim, Ben; Vassallo, Grace; Green, Jonathan; Evans, D. Gareth; Stagg, Charlotte J.; Parkes, Laura M.; Stivaros, Stavros

Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1 Thumbnail


Shruti Garg

Steve Williams

Gorana Pobric

Tulika Nandi

Ben Lim

Grace Vassallo

Jonathan Green

D. Gareth Evans

Charlotte J. Stagg

Laura M. Parkes

Stavros Stivaros


Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as autism. GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can modulate GABA and working memory in NF1. Thirty-one NF1 adolescents 11–18years, were recruited to this single-blind sham-controlled cross-over randomized trial. AtDCS or sham stimulation was applied to the left Dorsolateral Prefrontal Cortex (DLPFC) and MR Spectroscopy was collected before and after intervention in the left DLPFC and occipital cortex. Task-related functional MRI was collected before, during, and after stimulation. Higher baseline GABA+ in the left DLPFC was associated with faster response times on baseline working memory measures. AtDCS was seen to significantly reduced GABA+ and increase brain activation in the left DLPFC as compared to sham stimulation. Task performance was worse in the aTDCS group during stimulation but no group differences in behavioural outcomes were observed at the end of stimulation. Although our study suggests aTDCS modulates inhibitory activity in the DLPFC, further work is needed to determine whether repeated sessions of atDCS and strategies such as alternating current stimulation offer a better therapeutic approach.

Journal Article Type Article
Acceptance Date Oct 5, 2022
Online Publication Date Oct 31, 2022
Publication Date Oct 31, 2022
Deposit Date Nov 10, 2022
Publicly Available Date Nov 10, 2022
Journal Scientific Reports
Electronic ISSN 2045-2322
Peer Reviewed Peer Reviewed
Volume 12
Issue 1
Article Number 18297
Public URL
Publisher URL


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