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

NeuroImage
Jessica R GilbertRosalyn J Moran

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.

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Citations

Jun 25, 2016·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Constantinos Siettos, Jens Starke
Jun 28, 2016·Brain : a Journal of Neurology·Charlotte L RaeJames B Rowe
Sep 23, 2016·Wiley Interdisciplinary Reviews. Cognitive Science·Sandra IglesiasKlaas E Stephan
Jan 26, 2018·Wiley Interdisciplinary Reviews. Cognitive Science·Stefan FrässleKlaas E Stephan
Jan 27, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Zina-Mary ManjalyKlaas Enno Stephan
Apr 3, 2018·Cerebral Cortex·Dimitris A PinotsisEarl K Miller
Nov 30, 2016·Frontiers in Human Neuroscience·Klaas E StephanFrederike H Petzschner
Jun 22, 2021·Frontiers in Psychiatry·Stefan FrässleKlaas E Stephan
Mar 13, 2021·Brain : a Journal of Neurology·Natalie E AdamsJames B Rowe

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Methods Mentioned

BETA
exome sequencing

Software Mentioned

DCM
SPM

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