The dynamic of basal ganglia activity with a multiple covariance method: influences of Parkinson's disease

Abstract

The closed-loopcortico-subcortical pathways of basal gangliahavebeenextensivelyused todescribe thephysiologyof these centresandtojustifythefunctionaldisordersofbasalgangliadiseases.Thisapproachjustifiessomeexperimentalandclinicaldata butnotothers,andfurthermore, itdoesnot includeanumberofsubcorticalcircuitsthatmayproduceamorecomplexbasalgangliadynamicthanthatexpectedforclosed-looplinearnetworks.Thisworkstudiedthefunctionalconnectivityofthemainregions ofthebasalgangliamotorcircuitwithmagneticresonanceimagingandanewmethod(functionalprofilemethod),whichcananalyse themultiplecovariantactivityofhumanbasalganglia.The functionalprofilemethodidentifiedthemost frequent covariant functional status (profiles)of thebasal gangliamotorcircuit,orderingthemaccordingtotheir relative frequencyandidentifying themostfrequentsuccessionsbetweenprofiles(profiletransitions).Thefunctionalprofilemethodclassifiedprofilesasinputprofiles thataccept theinformationcomingfromothernetworks,outputprofiles involvedintheoutputofprocessedinformationtoother networksandhighlyinterconnectedinternalprofilesthataccept transitionsfrominputprofilesandsendtransitionstooutputprofiles.Profiletransitionsshowedapreviouslyunobservedfunctionaldynamicofhumanbasalganglia,suggestingthatthebasalgangliamotorcircuitmayworkasadynamicmultiplecovariancenetwork.Thenumberof internalprofilesandinternal transitions showedastrikingdecrease inpatientswithParkinson’sdisease, afactnotobservedfor inputandoutputprofiles.This suggests thatbasalgangliaofpatientswithParkinson’sdiseaserespondtorequirementscomingfromotherneuronalnetworks,butbecause the internal processingof information isdrasticallyweakened, its responsewill be insufficient andperhaps alsoself-defeating. Thesemarkedeffectswere foundinpatientswithfewmotordisorders, suggestingthat the functionalprofilemethodmaybean earlyproceduretodetectthefirststagesoftheParkinson’sdiseasewhenthemotordisordersarenotveryevident.Themultiplecovarianceactivityfoundpresentsacomplementarypointofviewtothecortico-subcorticalclosed-loopmodelofbasalganglia.The functionalprofilemethodmaybeeasilyappliedtootherbrainnetworks,anditmayprovideadditionalexplanationsfortheclinical manifestationsofotherbasalgangliadisorders.