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150. Cognitive function and QEEG: Stimulant effects among ADHD children
TbursdayAbstracts
200p,gPO.When given in slow infusions over 80 or 120 minutes, clonidine 1.5~glkg produced concentrationdependentreductions in SEMpeakvelocity,accelerationanddeceleration.Thereweresignificant linearrelationshipsbetweenthe administeredclonidinedose, or plasma clonidineconcentration,andtheirSEMeffectsin mostsubjects.In a pilot analysis,femalepatients,recoveredfroma majordepressiveepisodeand still taking SSRIS, showed reduced dose-responsescompared with controls(depressed= –43*29”/seclpgikg; controls = –93*26°1secl I@g; r = 3.3; d~ = 12; p= O.006).These results supportthe further developmentof this approachas a challengetest of central a2-adrenoceptorfunctionin humans.
150. COGNITIVE FUNCTION AND QEEG: STIMULANT EFFECTS AMONG ADHD CHILDREN S. Loo, B. Camp, P. Teale & M. Reite Universityof ColoradoHealthSciencesCenter,Denver,Colorado80262 Recentquantitativeelectroencepbalography (QEEG)studieshave found that children with Attention-DeficitHyperactivityDisorder (ADHD) have an excess of theta (associatedwith drowsinessand undersrousaf) and diminishedbeta activity (associatedwith highermentafprocesses) when compared to normal children. Psychostimulantsare the most commonlyused medicationin the managementof ADHD,however,the neural mechanismthrough which stimulants achieve its effects are largely unknown.The present study used QEEGto record changesin brainactivityassociatedwitha double-blind,placebo-controlledadministration of MPH.Subjectswereeightchildrenwith a primarydiagnosis of ADHD,aged8- to 13-yearsold.Brainelcctricrdactivitywasrecorded with7 electrodesin the frontal,centralandmidlineareasduringbaseline and cognitiveactivationconditions.Childrenwhose performanceimprovedonmedicationcomparedto placeboona ContinuousPerformance Test (CPT)were classifiedas responders(N=5), while childrenwhose scoresdid not improvewereclassifiedas nonresponders(N=3). Results of repeated-measuresanalysesof varianceindicatesignificantinteraction effects of responderstatus and medicationeffects on QEEGmeasures. Respondersexhibitedglobaland focafreductionsof theta and alpha as wellas increasedbetain thefrontalregions,whilenonrespondersshowed the oppositepattern (P<.05). These preliminarytindings indicatethat stimulants may differentiallychange brain elcctricaJ activity among children with ADHD.Furthermore,the data suggest that the primary effect of MPH among respondersis to increase cortical arousal by decreasingslow-wave(i.e., theta, alpha) activityrather than increasing highermentalactivity(i.e., beta).
151. THE ETIOLOGIC ROLE OF SYMPATHOADRENAL HYPERACTIVITY IN N.M.S. R.J. Gurrera HarvardMedicalSchool,BostonMA 02115and Brockton-West RoxburyDVAMC,BrocktonMA 02401 Neurolepticmalignantsyndrome(NMS)is remarkablefor its unpredictableoccurrenceandfluidclinicalcourse.Thereis littledirectevidenceto supporteitherof thetwoleadinghypothesesregardingtheetiologyof this disorder,namelyhypothalamicdopamineantagonismand direct myotoxicaction,anddespitethe identificationof putativerisk factorsthereis no consensusregardingwhichpatientsare at immediaterisk for NMS. This potentiallyfatal disorder remains poorly understood,difficult to
BIOLPSYCHIATRY 1998:43 :1S-133S
45s
prevent,and lackingany provenmanagementstrategy.In this paperthe author explores the idea that the pathophysiologicsignificance of autonomicdysfunction,a prominent and ubiquitousfeature of this disorder,has beenrelativelyoverlookedin the searchfor an expkmation of NMS.In orderto evaluatethe explanatorypowerof this hypothesis, human and animal studies pertinent to mammalianthermoregulation, sympathetic nervous system (SNS) organization and function, and striated muscle physiologywere reviewed.Collectively,these studies stronglysupportthe followingsynthesisand conclusions:Mammalian homcothermyis the result of coordinatedthermoeffectoractivitythat is normallyregulatedby corticalandhypothalamicinputs,buteachlevelof the neumxisretainsits (earlier,evolution~) capacityfor someindependent thermoregulatoryfunction, and is predisposed to autonomous activitywhenhigher(inhibitory)regulatorycontrolsarc lost.The SNSis the primary regulatory influence for all thermocffcctors,including thermogenesisin fat and muscle tissue. In addition, adrenoceptors modulatemusclecontractilityvia effectson intracellularcalcium;alterationsin intracellularcrdciumcan producechangesin muscletone and metabolism;and a varietyof catecholamineexcess states are associated withelevatedserumCPK.Theprominenceandprevalenceof autonomic dysfunctionand hyperactivityin NMSstronglysuggestthat a disruption of normal hierarchical SNS regulation is central to this disorder. Moreover,spinaldopamine-D2receptorstonicallyinhibitSNS activity, which suggestsa mechanismby which neurolepticscould destabilize SNSfunctionandprecipitateNMS.Oneimplicationof this modelis that elevatedCPK,in theabsenceof NMS,mightidentifyspecificindividuals who are predisposedto this type of SNSdysfunction.
152. THE P3 RESPONSE TO NOVEL AND TARGET AUDITORY STIMULI R.J. Gurrera, B.F. O’Donnell, J.S. Kwon & R.W. McCarley HarvardMedicalSchool,BostonMA 02115and Brockton-West RoxburyDVAMC,BrocktonMA 02401 P3a and P3b componentsof the auditory event-relatedpotential are evokedby novel non-targetand target (task-relevant)stimuli, respectively. These responses appmr to be associated with the cognitive functions of orientationand attention, and originate in anatomically distinctbrain regions:P3a is generatedby frontaland medialtemporal lobe structures,whereassuperiortemporafgyms activityunderliesboth P3a and P3b components.In the present study P3 responsesto target tones (15%), frequent tones (70Yo),and novel sounds (15%) were obtainedusinga standardauditoryoddballparadigmto whichthe third, novelstimuluswas added.Subjectswerenormalvolunteers(N=21) and medicatedDSM-IVschizophrenics(N= 16).A 64-charmelhigh-density electrode“net”wasusedto collectdataat 6 sites(3 anterior,3 posterior); oneelectrodepaircorrespondsto Fz andCz,andtheothertwopairsflank thiscentralpair oneither side.Comparedto schizophrenics,normalshad a largeramplituderesponseto the novelstimulusat Cz (p=.004), but no groupdifferenceswere found at any other leads under either stimulus condition.A 2(group) x 3(left,center,right)x 2(anterior,posterior)x 2(novel,target)repeatedmeasuresMANOVArevealeda 4-wayinteractionof groupx literality x anterior-posteriorx stimulus(p=.012),a main effectfor stimulus(p=.001), and a stimulusx anterior-posteriorinteraction (p=.039). Controlshad a greater responseto novel, comparedto target,stimulieverywhereexceptat the leftposteriorsite (pairedsamples t z 2,28, ps .033),butschizophrenicsshowedno stimuluseffectat snY lead (pairedsamplest s 1.75, p = .1). These findingsare consistent with a role for frontallobe structuresin generatingthe P3 responseto novelstimuli,andsuggestthatthisresponsemechanismmaybe defective in schizophrenia.Theabsenceof distinctelectrophysiologicresponsesto novel and target stimuli in schizophrenicscould be due to impaired attentionalcapacity,an attenuatedorientingreflex, or both.
200p,gPO.When given in slow infusions over 80 or 120 minutes, clonidine 1.5~glkg produced concentrationdependentreductions in SEMpeakvelocity,accelerationanddeceleration.Thereweresignificant linearrelationshipsbetweenthe administeredclonidinedose, or plasma clonidineconcentration,andtheirSEMeffectsin mostsubjects.In a pilot analysis,femalepatients,recoveredfroma majordepressiveepisodeand still taking SSRIS, showed reduced dose-responsescompared with controls(depressed= –43*29”/seclpgikg; controls = –93*26°1secl I@g; r = 3.3; d~ = 12; p= O.006).These results supportthe further developmentof this approachas a challengetest of central a2-adrenoceptorfunctionin humans.
150. COGNITIVE FUNCTION AND QEEG: STIMULANT EFFECTS AMONG ADHD CHILDREN S. Loo, B. Camp, P. Teale & M. Reite Universityof ColoradoHealthSciencesCenter,Denver,Colorado80262 Recentquantitativeelectroencepbalography (QEEG)studieshave found that children with Attention-DeficitHyperactivityDisorder (ADHD) have an excess of theta (associatedwith drowsinessand undersrousaf) and diminishedbeta activity (associatedwith highermentafprocesses) when compared to normal children. Psychostimulantsare the most commonlyused medicationin the managementof ADHD,however,the neural mechanismthrough which stimulants achieve its effects are largely unknown.The present study used QEEGto record changesin brainactivityassociatedwitha double-blind,placebo-controlledadministration of MPH.Subjectswereeightchildrenwith a primarydiagnosis of ADHD,aged8- to 13-yearsold.Brainelcctricrdactivitywasrecorded with7 electrodesin the frontal,centralandmidlineareasduringbaseline and cognitiveactivationconditions.Childrenwhose performanceimprovedonmedicationcomparedto placeboona ContinuousPerformance Test (CPT)were classifiedas responders(N=5), while childrenwhose scoresdid not improvewereclassifiedas nonresponders(N=3). Results of repeated-measuresanalysesof varianceindicatesignificantinteraction effects of responderstatus and medicationeffects on QEEGmeasures. Respondersexhibitedglobaland focafreductionsof theta and alpha as wellas increasedbetain thefrontalregions,whilenonrespondersshowed the oppositepattern (P<.05). These preliminarytindings indicatethat stimulants may differentiallychange brain elcctricaJ activity among children with ADHD.Furthermore,the data suggest that the primary effect of MPH among respondersis to increase cortical arousal by decreasingslow-wave(i.e., theta, alpha) activityrather than increasing highermentalactivity(i.e., beta).
151. THE ETIOLOGIC ROLE OF SYMPATHOADRENAL HYPERACTIVITY IN N.M.S. R.J. Gurrera HarvardMedicalSchool,BostonMA 02115and Brockton-West RoxburyDVAMC,BrocktonMA 02401 Neurolepticmalignantsyndrome(NMS)is remarkablefor its unpredictableoccurrenceandfluidclinicalcourse.Thereis littledirectevidenceto supporteitherof thetwoleadinghypothesesregardingtheetiologyof this disorder,namelyhypothalamicdopamineantagonismand direct myotoxicaction,anddespitethe identificationof putativerisk factorsthereis no consensusregardingwhichpatientsare at immediaterisk for NMS. This potentiallyfatal disorder remains poorly understood,difficult to
BIOLPSYCHIATRY 1998:43 :1S-133S
45s
prevent,and lackingany provenmanagementstrategy.In this paperthe author explores the idea that the pathophysiologicsignificance of autonomicdysfunction,a prominent and ubiquitousfeature of this disorder,has beenrelativelyoverlookedin the searchfor an expkmation of NMS.In orderto evaluatethe explanatorypowerof this hypothesis, human and animal studies pertinent to mammalianthermoregulation, sympathetic nervous system (SNS) organization and function, and striated muscle physiologywere reviewed.Collectively,these studies stronglysupportthe followingsynthesisand conclusions:Mammalian homcothermyis the result of coordinatedthermoeffectoractivitythat is normallyregulatedby corticalandhypothalamicinputs,buteachlevelof the neumxisretainsits (earlier,evolution~) capacityfor someindependent thermoregulatoryfunction, and is predisposed to autonomous activitywhenhigher(inhibitory)regulatorycontrolsarc lost.The SNSis the primary regulatory influence for all thermocffcctors,including thermogenesisin fat and muscle tissue. In addition, adrenoceptors modulatemusclecontractilityvia effectson intracellularcalcium;alterationsin intracellularcrdciumcan producechangesin muscletone and metabolism;and a varietyof catecholamineexcess states are associated withelevatedserumCPK.Theprominenceandprevalenceof autonomic dysfunctionand hyperactivityin NMSstronglysuggestthat a disruption of normal hierarchical SNS regulation is central to this disorder. Moreover,spinaldopamine-D2receptorstonicallyinhibitSNS activity, which suggestsa mechanismby which neurolepticscould destabilize SNSfunctionandprecipitateNMS.Oneimplicationof this modelis that elevatedCPK,in theabsenceof NMS,mightidentifyspecificindividuals who are predisposedto this type of SNSdysfunction.
152. THE P3 RESPONSE TO NOVEL AND TARGET AUDITORY STIMULI R.J. Gurrera, B.F. O’Donnell, J.S. Kwon & R.W. McCarley HarvardMedicalSchool,BostonMA 02115and Brockton-West RoxburyDVAMC,BrocktonMA 02401 P3a and P3b componentsof the auditory event-relatedpotential are evokedby novel non-targetand target (task-relevant)stimuli, respectively. These responses appmr to be associated with the cognitive functions of orientationand attention, and originate in anatomically distinctbrain regions:P3a is generatedby frontaland medialtemporal lobe structures,whereassuperiortemporafgyms activityunderliesboth P3a and P3b components.In the present study P3 responsesto target tones (15%), frequent tones (70Yo),and novel sounds (15%) were obtainedusinga standardauditoryoddballparadigmto whichthe third, novelstimuluswas added.Subjectswerenormalvolunteers(N=21) and medicatedDSM-IVschizophrenics(N= 16).A 64-charmelhigh-density electrode“net”wasusedto collectdataat 6 sites(3 anterior,3 posterior); oneelectrodepaircorrespondsto Fz andCz,andtheothertwopairsflank thiscentralpair oneither side.Comparedto schizophrenics,normalshad a largeramplituderesponseto the novelstimulusat Cz (p=.004), but no groupdifferenceswere found at any other leads under either stimulus condition.A 2(group) x 3(left,center,right)x 2(anterior,posterior)x 2(novel,target)repeatedmeasuresMANOVArevealeda 4-wayinteractionof groupx literality x anterior-posteriorx stimulus(p=.012),a main effectfor stimulus(p=.001), and a stimulusx anterior-posteriorinteraction (p=.039). Controlshad a greater responseto novel, comparedto target,stimulieverywhereexceptat the leftposteriorsite (pairedsamples t z 2,28, ps .033),butschizophrenicsshowedno stimuluseffectat snY lead (pairedsamplest s 1.75, p = .1). These findingsare consistent with a role for frontallobe structuresin generatingthe P3 responseto novelstimuli,andsuggestthatthisresponsemechanismmaybe defective in schizophrenia.Theabsenceof distinctelectrophysiologicresponsesto novel and target stimuli in schizophrenicscould be due to impaired attentionalcapacity,an attenuatedorientingreflex, or both.