P119 Computational modeling of the cumulative neuroplastic effects of repeated direct current stimulation
Linda-Iris JosephTomy1, Elif Köksal-Ersöz2,3,MehmetAlihanKayabas1, Pascal Benquet1, Fabrice Wendling1 ¹UnivRennes, INSERM, LTSI – UMR 1099, Rennes F-35000, France ²InriaLyonResearchCentre, Villeurbanne 69603, France ³CophyTeam, Lyon NeuroscienceResearchCenter, INSERM UMRS 1028, CNRS UMR 5292, Université Claude Bernard Lyon 1, Bron 69500, France *Email:malihankayabas@gmail.com Introduction
Metaplasticitymodulates theneuroplasticabilityofneurons/synapsesin orderto maintain it withinafunctionalphysiological range.In conditionssuch asepilepsy, where neuroplasticitymayevolve pathologically, this metaplastic property of synapseswould also bedisrupted[1].Transcranial direct current stimulation (tDCS)isa non-invasivetechniquethatcan modulateneuroplasticity.Repeatedsessions oftDCScanimprove the likelihood of inducingseizure reduction in patients with refractory epilepsy[2].TheeffectoftDCSon neuroplasticityhas also been shown todependon the ongoingneuronalactivity andneuroplastic propertiesofthe stimulated brain regions.
Methods Computational modeling[3]was usedtoidentify‘functional’ and‘dysfunctional’ metaplastic conditions.The modelconsistedof an epileptogeniczone(EZ)connectedto anirritatedzone (IZ).We assumedthe potentiation threshold(ϴp)discriminatedbetween the‘functional’and‘dysfunctional’metaplastic conditions.We evaluated the variation in connectivity strengthbyinitiatingthe modelfrom depressed and potentiated states for the metaplastic conditionsfordifferent frequencies of interictal activity from the EZ.Theeffectof repeatedtDCSwasinvestigated.Variations in connectivity strengthfor different frequencies ofongoing neuronalactivitywere assessedby plottingthe frequency response function (FRF). Results In the‘functional’metaplastic condition, the connectivity strength from EZ to IZwasprevented from being potentiated orevolved towards depression.Whereas, in the ‘dysfunctional’ metaplastic condition, theconnectivity strength tendedto evolve towards potentiation.Further,a decrease in ϴpled totheexpansion of epileptic activity in this network.Under repetitivetDCSapplication,weobserveda downwardshift inthe FRF, suggesting that repetitivetDCScould promotelong term depression. Discussion In thisstudy, we exploredhow functional and dysfunctionalmetaplasticconditions affect neuroplasticityin an epileptic network.Theimpact of varying ϴpto switch between thesemetaplasticconditionsreflectedthe relationship betweenmetaplasticityandepileptogenicity, as also seen in animal studies [1].Based on the variationsin the FRF observed here, it may be possible to designtDCSprotocolsto depressthe connectivityfromthe EZ to other IZs. Thismay thenimprovestimulationoutcomes.
Acknowledgements This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (No 855109). References ● https://doi.org/10.1371/journal.pcbi.1012666
