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Cognitive psychophysiology in anxiolytic drug research
656
Abstrnct~
DlOL PSYCHIATRY 1996;39:500-666
an inter-detion bctw~en medicalion ilnd cither sronps or tasks sUllSests that the visual processinS deticits we hnw identified are unaffected by medication status. and llpparently reflect schizophrenic patients' enduring cognitive deficiencies. The results of the effects of medication on delayed recall, (Le.,on STVM) arc consistent with working memory deficits identified in other paradigms. Patients showed marked amplitude reductions in the NI-N2 region compared to controls, but not in P3. Perfonnance on DEPOT correlated with this reduction in thc negative brain potential. These findings indicate that medicOlted patients can be used in future studies of deficit specification. This replication also strengthens confidence in the utility of thc DEPOT paradigm for testing schizophrenic patients' cognitive deficits.
529. RELATIONSHIP BETWEEN SPECTRAL CHARACTERISTICS OF RESTING EEG AND P50 GATING G.A. Light l , M.A. Geyer', B. Clementz', S.B. Schwarzkopf2 , & D.L. Braff l
related potentials (ERPs). In the tirst study. IS healthy subjects, aged 22-35 ycars, received ornl single doses uf 0.1, 0.2 and 0.4 mg 01 surielone - a cydopyrrolone derivative - and I mg of the bcnzodiazepinc :llpmzolam. In the second study, 20 healthy subjects, aged 22 - 34 years received oral single doses of 2, 10 and 20 mg of 5·20499 - a presynaptic 5HT IA receptor agonist - and 20 mg of buspirone. ERPs were recorded in an auditory odd-ball paradigm before and 3 huurs after drug intake. Seventeen EEG leads and venical and horizontal EOGs were recorded. NI. P2 and P300 (P3b) Illlencies were detected and amplitude maps were calculated. The main effects on the ERPs were a reduction of NI amplitude aftcr 0.4 mg suriclone, and more pronounced arler alprazolam: a reduction of P2 amplitude after alprazolam; a reduction of P300 amplitude after 0.4 mg sundonc, and more pronounced ufter alpruzolam; II marked P300 latency prolongation after alprazolam. Concerning Nl and Pl. alprazolam seemed to have an inhibitory influence on stimulusinduced cortical arousaL Conceming P300, the highest dose of suric10ne had less effect than
I Department of Psychiatry, Universily of California. San Diego. La Jolla. CA 92093-0804: 2Department of Psychilltry. University of Rocnc!'tcr. Roche!\ler. NY 14627
Gating lind inhibitory deficits ar~ pre!'ent in schizophrcnill pali~nL" and have becn measured by a conditioning-test P50 auditory evoked potential parad!gm. In this parndigm. the eMly positive wave occurring ubout 50 milliseconds after stimulus delivery (P50 component) is measured in response to enth of two dicks that IIrc typically scparJtcd by u 500 millisecond interstimulus interval. The PSO response to the fil1it (conditioning) click is typt<:ully large and thc second (test) elitk elicits a P50 wuve that is nonnally inhibited or gated in IImplitude. This phenomenon has been rcl'crrcd to liS PSO suppression or PSO gating and represents celllT:l1 inhihition thatllwy prevent sensory inundation. Failure to inhibit or gate sensory infonnntion is rurthcr thouslit to lead to stimulus overload resulting in cognitive frngmentation anu psychotic symptoms. Preliminary rcsults have shown that scnizophrenia p,ltients havc abnonnal baseline speetl'lll EEG patlcms und show abnormal changes of these EEG tharactcristics IICross a PSO gating lest session. These findings sU!lgest that dynamic alter-Jtions in the seneral state of activation of the brain may be occurring during PSO test ses!\ions. This raises the question of whether variance in PSO measures can be accounted for by the ongoing changes in the resting EEG sampled before the session and in the middle of the sessinn. Data will be presented on the relationship between spectral characteristics of the resting EEG and PSO measures of central inhibition.
530. COGNITIVE PSYCHOPHYSIOLOGY IN ANXIOLYTIC DRUG RESEARCH H.Y. Semlitsch, P. Anderer, & B. Saletu Psychiatric University Clinic. Vien",l The aim of our placebo-controlled. double-blind studies wus to investigate the cffects of different anxiolytic drugs on cognition using event-
531. PSYCHIATRIC CORRELATES OF EEG ASYMMETRIES IN MAJOR DEPRESSION G.P. Lee l , T.M. Brown l •2 , D. Sharon l , & S.L. Haverstock l •2 'Thc Medicul Collegll of Georgia and "'VA Medical Center. Augusl3. GA 30912
Recent EEG investigations have ~usgested that there is a relative hyperactivation of right. lind hypoactivalion of left, anterior brain regions in depressed paticnts when compared with nonnals. To determine if these EEG chllnSes lire specific to depression. and whether there are associated psychiatric symptoms, we compared resting quantitative EEGs and severnl psychiatric rating scales in 34 patients with major depression. 23 patients with other psychiatric disorders. and 11 nannal controls. Diagnoses were obtained using the StruclUred Clinical Interview for DSM-Ill-R. Rating scules used with patients included Mini Mental Status Examination, Hamilton Depression Scale, Modified Spielberger State An:
Abstrnct~
DlOL PSYCHIATRY 1996;39:500-666
an inter-detion bctw~en medicalion ilnd cither sronps or tasks sUllSests that the visual processinS deticits we hnw identified are unaffected by medication status. and llpparently reflect schizophrenic patients' enduring cognitive deficiencies. The results of the effects of medication on delayed recall, (Le.,on STVM) arc consistent with working memory deficits identified in other paradigms. Patients showed marked amplitude reductions in the NI-N2 region compared to controls, but not in P3. Perfonnance on DEPOT correlated with this reduction in thc negative brain potential. These findings indicate that medicOlted patients can be used in future studies of deficit specification. This replication also strengthens confidence in the utility of thc DEPOT paradigm for testing schizophrenic patients' cognitive deficits.
529. RELATIONSHIP BETWEEN SPECTRAL CHARACTERISTICS OF RESTING EEG AND P50 GATING G.A. Light l , M.A. Geyer', B. Clementz', S.B. Schwarzkopf2 , & D.L. Braff l
related potentials (ERPs). In the tirst study. IS healthy subjects, aged 22-35 ycars, received ornl single doses uf 0.1, 0.2 and 0.4 mg 01 surielone - a cydopyrrolone derivative - and I mg of the bcnzodiazepinc :llpmzolam. In the second study, 20 healthy subjects, aged 22 - 34 years received oral single doses of 2, 10 and 20 mg of 5·20499 - a presynaptic 5HT IA receptor agonist - and 20 mg of buspirone. ERPs were recorded in an auditory odd-ball paradigm before and 3 huurs after drug intake. Seventeen EEG leads and venical and horizontal EOGs were recorded. NI. P2 and P300 (P3b) Illlencies were detected and amplitude maps were calculated. The main effects on the ERPs were a reduction of NI amplitude aftcr 0.4 mg suriclone, and more pronounced arler alprazolam: a reduction of P2 amplitude after alprazolam; a reduction of P300 amplitude after 0.4 mg sundonc, and more pronounced ufter alpruzolam; II marked P300 latency prolongation after alprazolam. Concerning Nl and Pl. alprazolam seemed to have an inhibitory influence on stimulusinduced cortical arousaL Conceming P300, the highest dose of suric10ne had less effect than
I Department of Psychiatry, Universily of California. San Diego. La Jolla. CA 92093-0804: 2Department of Psychilltry. University of Rocnc!'tcr. Roche!\ler. NY 14627
Gating lind inhibitory deficits ar~ pre!'ent in schizophrcnill pali~nL" and have becn measured by a conditioning-test P50 auditory evoked potential parad!gm. In this parndigm. the eMly positive wave occurring ubout 50 milliseconds after stimulus delivery (P50 component) is measured in response to enth of two dicks that IIrc typically scparJtcd by u 500 millisecond interstimulus interval. The PSO response to the fil1it (conditioning) click is typt<:ully large and thc second (test) elitk elicits a P50 wuve that is nonnally inhibited or gated in IImplitude. This phenomenon has been rcl'crrcd to liS PSO suppression or PSO gating and represents celllT:l1 inhihition thatllwy prevent sensory inundation. Failure to inhibit or gate sensory infonnntion is rurthcr thouslit to lead to stimulus overload resulting in cognitive frngmentation anu psychotic symptoms. Preliminary rcsults have shown that scnizophrenia p,ltients havc abnonnal baseline speetl'lll EEG patlcms und show abnormal changes of these EEG tharactcristics IICross a PSO gating lest session. These findings sU!lgest that dynamic alter-Jtions in the seneral state of activation of the brain may be occurring during PSO test ses!\ions. This raises the question of whether variance in PSO measures can be accounted for by the ongoing changes in the resting EEG sampled before the session and in the middle of the sessinn. Data will be presented on the relationship between spectral characteristics of the resting EEG and PSO measures of central inhibition.
530. COGNITIVE PSYCHOPHYSIOLOGY IN ANXIOLYTIC DRUG RESEARCH H.Y. Semlitsch, P. Anderer, & B. Saletu Psychiatric University Clinic. Vien",l The aim of our placebo-controlled. double-blind studies wus to investigate the cffects of different anxiolytic drugs on cognition using event-
531. PSYCHIATRIC CORRELATES OF EEG ASYMMETRIES IN MAJOR DEPRESSION G.P. Lee l , T.M. Brown l •2 , D. Sharon l , & S.L. Haverstock l •2 'Thc Medicul Collegll of Georgia and "'VA Medical Center. Augusl3. GA 30912
Recent EEG investigations have ~usgested that there is a relative hyperactivation of right. lind hypoactivalion of left, anterior brain regions in depressed paticnts when compared with nonnals. To determine if these EEG chllnSes lire specific to depression. and whether there are associated psychiatric symptoms, we compared resting quantitative EEGs and severnl psychiatric rating scales in 34 patients with major depression. 23 patients with other psychiatric disorders. and 11 nannal controls. Diagnoses were obtained using the StruclUred Clinical Interview for DSM-Ill-R. Rating scules used with patients included Mini Mental Status Examination, Hamilton Depression Scale, Modified Spielberger State An: