Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations
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 neu...
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creator | Gilbert, Jessica R. Symmonds, Mkael Hanna, Michael G. Dolan, Raymond J. Friston, Karl J. Moran, Rosalyn J. |
description | 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.
•Dynamic causal modeling (DCM) for M/EEG includes ion channel parameter estimates.•Parameter estimates from patients with monogenic ion channelopathies were compared.•Synaptic channel abnormality was identified in patients, with specificity above 89%.•DCM could serve as a platform for non-invasively assaying brain molecular dynamics. |
doi_str_mv | 10.1016/j.neuroimage.2015.08.057 |
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•Dynamic causal modeling (DCM) for M/EEG includes ion channel parameter estimates.•Parameter estimates from patients with monogenic ion channelopathies were compared.•Synaptic channel abnormality was identified in patients, with specificity above 89%.•DCM could serve as a platform for non-invasively assaying brain molecular dynamics.</description><identifier>ISSN: 1053-8119</identifier><identifier>EISSN: 1095-9572</identifier><identifier>DOI: 10.1016/j.neuroimage.2015.08.057</identifier><identifier>PMID: 26342528</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acoustic Stimulation ; Adult ; Aged ; Aged, 80 and over ; Auditory Cortex - physiopathology ; Auditory Perception - physiology ; Biomedical research ; Biophysical models ; Brain - physiopathology ; Brain research ; Calcium Channels - genetics ; Channelopathies ; Channelopathies - genetics ; Channelopathies - physiopathology ; Computer Simulation ; Dynamic causal modeling ; Electroencephalography ; Epilepsy ; Evoked Potentials, Auditory ; Female ; Genes ; Humans ; Ion channel signaling ; Ligands ; Magnetoencephalography ; Magnetoencephalography - methods ; Male ; Medical imaging ; Middle Aged ; Models, Neurological ; Mutation ; Neurons - physiology ; Patients ; Potassium ; Potassium Channels, Inwardly Rectifying - genetics ; Schizophrenia ; Synapses - physiology ; Young Adult</subject><ispartof>NeuroImage (Orlando, Fla.), 2016-01, Vol.124 (Pt A), p.43-53</ispartof><rights>2015 The Authors</rights><rights>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jan 1, 2016</rights><rights>2015 The Authors 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-5fc7d43841182088d84ef8a16836740758deb10887146eee1ad214687872027b3</citedby><cites>FETCH-LOGICAL-c540t-5fc7d43841182088d84ef8a16836740758deb10887146eee1ad214687872027b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1735307076?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26342528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gilbert, Jessica R.</creatorcontrib><creatorcontrib>Symmonds, Mkael</creatorcontrib><creatorcontrib>Hanna, Michael G.</creatorcontrib><creatorcontrib>Dolan, Raymond J.</creatorcontrib><creatorcontrib>Friston, Karl J.</creatorcontrib><creatorcontrib>Moran, Rosalyn J.</creatorcontrib><title>Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations</title><title>NeuroImage (Orlando, Fla.)</title><addtitle>Neuroimage</addtitle><description>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.
•Dynamic causal modeling (DCM) for M/EEG includes ion channel parameter estimates.•Parameter estimates from patients with monogenic ion channelopathies were compared.•Synaptic channel abnormality was identified in patients, with specificity above 89%.•DCM could serve as a platform for non-invasively assaying brain molecular dynamics.</description><subject>Acoustic Stimulation</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Auditory Cortex - physiopathology</subject><subject>Auditory Perception - physiology</subject><subject>Biomedical research</subject><subject>Biophysical models</subject><subject>Brain - physiopathology</subject><subject>Brain research</subject><subject>Calcium Channels - genetics</subject><subject>Channelopathies</subject><subject>Channelopathies - genetics</subject><subject>Channelopathies - physiopathology</subject><subject>Computer Simulation</subject><subject>Dynamic causal modeling</subject><subject>Electroencephalography</subject><subject>Epilepsy</subject><subject>Evoked Potentials, Auditory</subject><subject>Female</subject><subject>Genes</subject><subject>Humans</subject><subject>Ion channel signaling</subject><subject>Ligands</subject><subject>Magnetoencephalography</subject><subject>Magnetoencephalography - methods</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Middle Aged</subject><subject>Models, Neurological</subject><subject>Mutation</subject><subject>Neurons - physiology</subject><subject>Patients</subject><subject>Potassium</subject><subject>Potassium Channels, Inwardly Rectifying - genetics</subject><subject>Schizophrenia</subject><subject>Synapses - physiology</subject><subject>Young Adult</subject><issn>1053-8119</issn><issn>1095-9572</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkk2P1DAMhisEYj_gL6BIXLh0iJOmSTkgwYgFpJXgAOcok7gzGbXJkLSD9hfwt0mZZfm4wMmW_Pi1Lb9VRYCugEL7fL8KOKfoR7PFFaMgVlStqJD3qnOgnag7Idn9JRe8VgDdWXWR855S2kGjHlZnrOUNE0ydV98-ptj7wYct-SEZzEB8DMTuTAg4xIOZdh4z-eqnHQkx1D4cTfZHJJtkfCDLCkuzCY64m2BGb4k1cy4yY3Q45BdkbTKSPM1u0Yk9yYUfkGwxIBnnyUxlXn5UPejNkPHxbbysPl-9-bR-V19_ePt-_eq6tqKhUy16K13DVQOgGFXKqQZ7ZaBVvJUNlUI53EApSGhaRATjWMmUVJJRJjf8snp50j3MmxGdxTAlM-hDKoekGx2N139Wgt_pbTzqphWiA1kEnt0KpPhlxjzp0WeLw2ACxjlrkAIYcMHVf6BcdLTlbFF9-he6j3MqzzhRnEoq20KpE2VTzDlhf7c3UL0YQ-_1L2PoxRiaKl2MUVqf_H73XeNPJxTg9QkoP8Ojx6Sz9RgsOp_QTtpF_-8p3wEFbtDA</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Gilbert, Jessica R.</creator><creator>Symmonds, Mkael</creator><creator>Hanna, Michael G.</creator><creator>Dolan, Raymond J.</creator><creator>Friston, Karl J.</creator><creator>Moran, Rosalyn J.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><general>Academic Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>20160101</creationdate><title>Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations</title><author>Gilbert, Jessica R. ; Symmonds, Mkael ; Hanna, Michael G. ; Dolan, Raymond J. ; Friston, Karl J. ; Moran, Rosalyn J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-5fc7d43841182088d84ef8a16836740758deb10887146eee1ad214687872027b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acoustic Stimulation</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Auditory Cortex - physiopathology</topic><topic>Auditory Perception - physiology</topic><topic>Biomedical research</topic><topic>Biophysical models</topic><topic>Brain - physiopathology</topic><topic>Brain research</topic><topic>Calcium Channels - genetics</topic><topic>Channelopathies</topic><topic>Channelopathies - genetics</topic><topic>Channelopathies - physiopathology</topic><topic>Computer Simulation</topic><topic>Dynamic causal modeling</topic><topic>Electroencephalography</topic><topic>Epilepsy</topic><topic>Evoked Potentials, Auditory</topic><topic>Female</topic><topic>Genes</topic><topic>Humans</topic><topic>Ion channel signaling</topic><topic>Ligands</topic><topic>Magnetoencephalography</topic><topic>Magnetoencephalography - methods</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Middle Aged</topic><topic>Models, Neurological</topic><topic>Mutation</topic><topic>Neurons - physiology</topic><topic>Patients</topic><topic>Potassium</topic><topic>Potassium Channels, Inwardly Rectifying - genetics</topic><topic>Schizophrenia</topic><topic>Synapses - physiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gilbert, Jessica R.</creatorcontrib><creatorcontrib>Symmonds, Mkael</creatorcontrib><creatorcontrib>Hanna, Michael G.</creatorcontrib><creatorcontrib>Dolan, Raymond J.</creatorcontrib><creatorcontrib>Friston, Karl J.</creatorcontrib><creatorcontrib>Moran, Rosalyn J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>NeuroImage (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gilbert, Jessica R.</au><au>Symmonds, Mkael</au><au>Hanna, Michael G.</au><au>Dolan, Raymond J.</au><au>Friston, Karl J.</au><au>Moran, Rosalyn J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations</atitle><jtitle>NeuroImage (Orlando, Fla.)</jtitle><addtitle>Neuroimage</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>124</volume><issue>Pt A</issue><spage>43</spage><epage>53</epage><pages>43-53</pages><issn>1053-8119</issn><eissn>1095-9572</eissn><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.
•Dynamic causal modeling (DCM) for M/EEG includes ion channel parameter estimates.•Parameter estimates from patients with monogenic ion channelopathies were compared.•Synaptic channel abnormality was identified in patients, with specificity above 89%.•DCM could serve as a platform for non-invasively assaying brain molecular dynamics.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26342528</pmid><doi>10.1016/j.neuroimage.2015.08.057</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acoustic Stimulation Adult Aged Aged, 80 and over Auditory Cortex - physiopathology Auditory Perception - physiology Biomedical research Biophysical models Brain - physiopathology Brain research Calcium Channels - genetics Channelopathies Channelopathies - genetics Channelopathies - physiopathology Computer Simulation Dynamic causal modeling Electroencephalography Epilepsy Evoked Potentials, Auditory Female Genes Humans Ion channel signaling Ligands Magnetoencephalography Magnetoencephalography - methods Male Medical imaging Middle Aged Models, Neurological Mutation Neurons - physiology Patients Potassium Potassium Channels, Inwardly Rectifying - genetics Schizophrenia Synapses - physiology Young Adult |
title | Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations |
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