Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1

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

doi:10.1038/s41598-022-21907-9

Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1

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

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 11–18 years, 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.

Original language	English
Article number	18297
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-21907-9
Publication status	Published - 1 Dec 2022
Externally published	Yes

Funding

The authors thank the radiographers at the Manchester Clinical Research Facility: Neal Sherratt, Sarah Lehmann and Barry Whitnall for their help and assistance in acquiring the imaging data. The authors also wish to thank the patients and families that participated in this study. This work is supported by the Neurofibromatosis Therapeutic Acceleration Program (NTAP) through a Francis Collins Scholarship to SG. DGE is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). JG is supported by NIHR Senior Investigator Award. JJ is supported by a Beacon Anne McLaren Research Fellowship (University of Nottingham). This article is supported by an Agreement from The Johns Hopkins University School of Medicine and the Neurofibromatosis Therapeutic Acceleration Program (NTAP). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of The Johns Hopkins University School of Medicine. Charlotte J. Stagg is supported by Wellcome Trust.

Funders	Funder number
Wellcome Trust
School of Medicine, Johns Hopkins University
Manchester Biomedical Research Centre	IS-BRC-1215-20007
National Institute for Health and Care Research
University of Nottingham

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title = "Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1",

abstract = "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 11–18 years, 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.",

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AU - Lim, Ben

AU - Vassallo, Grace

AU - Green, Jonathan

AU - Evans, D. Gareth

AU - Stagg, Charlotte J.

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Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1

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