Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations

Jessica R Gilbert, Mkael Symmonds, Michael G Hanna, Raymond J Dolan, Karl J Friston, Rosalyn J Moran

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Clinical assessments of brain function rely upon visual inspection of electroencephalographic waveform abnormalities in tandem with functional magnetic resonance imaging. However, no current technology proffers in vivo assessments of activity at synapses, receptors and ion-channels, the basis of neuronal communication. Using dynamic causal modeling we compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively. Synaptic channel abnormality was identified in both patients (100% sensitivity) with assay specificity above 89%, furnishing estimates of neurotransmitter and voltage-gated ion throughput of sodium, calcium, chloride and potassium. This performance indicates a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings. More broadly, these findings indicate that biophysical models of synaptic channels can be estimated non-invasively, having important implications for advancing human neuroimaging to the level of non-invasive ion channel assays.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalNeuroImage
Volume124
Issue numberPt A
Early online date3 Sep 2015
DOIs
Publication statusPublished - 1 Jan 2016

Fingerprint

Dive into the research topics of 'Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations'. Together they form a unique fingerprint.

Cite this