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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 publication

DOI

10.1016/j.neuroimage.2015.08.057

Type

Journal article

Journal

Neuroimage

Publication Date

01/01/2016

Volume

124

Pages

43 - 53

Keywords

Biophysical models, Channelopathies, Dynamic causal modeling, Ion channel signaling, Magnetoencephalography, Acoustic Stimulation, Adult, Aged, Aged, 80 and over, Auditory Cortex, Auditory Perception, Brain, Calcium Channels, Channelopathies, Computer Simulation, Evoked Potentials, Auditory, Female, Humans, Magnetoencephalography, Male, Middle Aged, Models, Neurological, Mutation, Neurons, Potassium Channels, Inwardly Rectifying, Synapses, Young Adult