Neurofibromatosis 1
Conditions
Brief summary
Intellectual impairment, particularly working memory deficits are a significant cause of morbidity in children with Neurofibromatosis type (NF1) with long-term implications on academic and occupational functioning. Whilst significant discoveries have been made in Nf1 animal models in trying to find treatments for these conditions, human translational studies have not been successful. This mechanistic experimental study will investigate the neural mechanisms underlying working memory deficits in NF1. In particular, we will investigate how individual differences in inhibitory neurotransmitter GABA relate to performance on working memory tests. Further, we will investigate the use of a novel, experimental intervention called transcranial Direct Current Stimulation (tDCS);known to modulate GABA. Using a randomized, crossover design in a cohort of 30 adolescents aged 11-17 years, we will apply real or sham tDCS to the dorsolateral prefrontal cortex (DLPFC). State-of-art real time imaging techniques such as Magnetic Resonance Spectroscopy (MRS) and task based functional MRI (fMRI) will be used to investigate the effect of tDCS on GABA concentration, changes in functional plasticity and working memory. We expect that results from this study will help elucidate the neural mechanisms underlying working memory deficits in people with NF1 and show biologic activity for a novel, low-cost intervention that can be used for cognitive remediation in NF1. This kind of focused mechanism trial method is a highly promising approach to understanding the complex neural system pathology in a multifactorial neurodevelopmental condition like NF1.
Interventions
OTHERTranscranial direct current stimulation
tDCS is a form of non-invasive brain stimulation. tDCS is an established research tool for non-invasive modulation of neuroplasticity. It uses low-intensity DC currents to modulate spontaneous neuronal network activity by altering the resting membrane potential. Anodal tDCS has been shown to increase cortical excitability, reduce regional levels of GABA enhance LTP and synaptic plasticity.
Sponsors
University of Manchester
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Single-blind cross over experimental trial
Eligibility
Sex/Gender
ALL
Age
11 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Meets National Institute of Health NF1 diagnostic criteria 2. Children aged 11-17 years 3. Written informed consent/assent
Exclusion criteria
1. No history of intracranial pathology other than asymptomatic optic pathway glioma or other asymptomatic and untreated NF1-associated white matter lesion 2. No history of epilepsy or any major mental illness 3. No MRI contraindications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Corsi Block task | immediately after the intervention | memory span task |
Countries
United Kingdom
Outcome results
None listed