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ERP correlates of recognition memory: Abnormalities in schizophrenia
Abstracts
225. P300 LATENCY AND CORTICAL TISSUE VOLUME IN ALCOHOLICS J.M. Pord', D.H. Mathalon', M. 1. Rosenbloon", K.O. Lim1.2, & A. Pfefferbaum 1.2 'Stanford University School of Medicine, Stanford. CA, 94305; ~V APalo Alto Health Care System. Palo AIIO, CA 94304 Since its discovery 30 years ago (Sulton et al., 1965), the P300 component of the event-related brain potential (ERP) has been used in studies of alcoholism as a marker of family history and an index or cognitive abncrmality. Therelationship between P300and bruin structure has been diflicult to establish perhaps because functional abncrmalitlcs reflected in P300 may precede structural changes, suggesting that significant relationships may depend on age, durntion nf i1Tne55. or extent of pathology. We examined whether P300 latency delay in alcoholics W:lS related to structural brain deficits seen on magnetic resonance images (MRl), duration of alcoholic drinking. or intensity of alcohol consumption, ERPs ellcired during an auditory oddball parudlgm and MRl measures of gray ami white matter and cerebral spinal fluid (CSF) volumes were collected from 31 alcoholics and 32 age-matched normal control men. Regional gray and while mauer and CSF volumes were quantified. lnformatlon regarding years of alcoholic drinking and total amount of alcohol consumed was also collected, Because aging affects bothP300latency andbrain structure, MRIandP300latency values were corrected for normal aging. P300 latency was regressed on age, specific MRI values. alcohol consumption intensity (tctal alcohol consumed! duration of alcoholic drinking). ami duration of alcoholic drinking. Within the alcoholics, age-corrected P300 latency was further delayed with age, as well as with a numberof structural variables. P300 latency was not related to drink.ing duration or intensity. The strongest srructural relationship was seen for the temporal-parietal junction: gray and while mutter volume reductions nntl increases in CSF volume were related to increases in P300 latency. These relationships were not seen for NI latency, suggesting thaIa cornpromised tcmporal-parlcml junction is not associuted with generalized ERP slowing, but is specific to P300, in alcoholics, Supported by N1AAA (AA0596S) & Department of Veterans Affairs.
226. ERP CORRELATES OF RECOGNITION MEMORY: ABNORMALITIES IN SCHIZOPHRENIA B. Turetsky, E,A. Colbath, P. Moberg, L.H. Mozely, R.C. OUf, & R.E, Our Depunment of Psychiatry, University of Pennsylvania. Philadelphia. PA 19104 There is growing evidence 10 suggest that patients wilh schizophrenia have learning and memory lmpalrments that nrc evident during initiul presentation, arc relatively stable overthe (OUniC of illness, and represent a selective information processing deficit. Cognitive ERP studies of schizophrenia have focussed on the P300, II physiologic index of Ihe contextual updatlng of working memory, which is reduced in patients. Therehas been littledirectinvestigation of the physiologic correlates of explicit or declarative memory processes. This Sludy examined ERP responses during both acquisition und retrieval phases of a declarative memory task. employing visually presented words as stimuli, Subjects
UIOL PSYCIIIATRY 1996:39:500-666
565
included 42 patients with schizophrenia and 43 healthy corurols, Curren I source denslty transformations were employed to provide topographically locallzcd and reference-free indices of source activity. A "visual memory component" was identifled, which had n right pnrieto-temporal peak, larcncy between 280 antl36Q msccs, and smaller amplitude, during the retrieval phase. to familiar Vii. unfamiliar stimuli. Schizophrenics exhibltcd reduced amplitudes of this right hemisphere "visual memory potential" during acquisitlon, and which was correlated with bothpoorer performance during the subsequent retrieval phase and an independent assessment of verbal memory abilities (CVLT). During retrieval. however, patients exhibited an abnonn..l increase in left parieto-tcmporal source actlvity, This abnormally high left hemisphere activity was correlated with both improved tusk performance and improved CVLT score. It was also correlated with greater auditory oddball P300 amplitude. Nondeficlt patients. with greater positive and fewer negative symptoms, showed greater retrieval abnonnality than deficit patients. These results suggest a model of schizophrenic memory abnormalltles that entails :I primary acquisltion deficit and a partially compensatory overactivatlon, associated with more positive symptomatology, during retrieval. Preliminary data. from longitudinal and family studies of SUbgroups of thesepatients, suggest thatthereis a progressive worsening of the acqulsition impalrmcnt, as wellas a genetic predlspcsition to both the acqulsition and retrieval abnormalities. ERP results will becompared to findings from Xenon and PETblood now studies using l~e same msk and will be further considered in terms of neural network models of memory acquisltion, storage, and retrieval.
227. ERP AND BEHAVIORAL INDICES OF WORKING MEMORY DYSFUNCTION IN SCHIZOPHRENIA D.C. Javitt, A-M. Shelley, E. Leiderman, L, March, N. Cowan, & W. Ritter Department of Psychiatry, Nllthan Kline Institute for Psychiatric Research. Orangeburg, NY 10962
Deficits in event-related potential (ERPl generation lire among the most consistent and robust indices of brain dysfunction in schlzophrcnln. Mismatch negalivity (MMN) is 11 short latency cognitive ERPellcitcd in the context of an aUditory "oddball" paradigm. in which a sequence of repetitive standard stimuli is interrupted infrequently and unexpectedly by 11 physically deviant. "oddball" stimulus. As opposed to tatercognitive components (e.g., N2,P3).MMN is elicited even by unattended deviants, indicating thnt it indexes a preauentlve stage of auditory information processing. Generation of MMN depends upon the ability of auditory cortex to form and maintain reprcscntetlons of the physical properties of presented stimuli and to compare each newly presented stimulus to the physical representations of the preceding stimuli. The memory system upon which MMN generation is based appears to correspond to the ladcpendently described auditory sensory or "echoic" memory system. which maintain... represenunlons of the physical properties of presented stimuli for periods of 10 - 20 sec. This study investlgated MMN generation and auditory sensory memory function in II group of 15 chronic schizophrenic subjects. compared with 15age-matched controls. Schizophrenic SUbjects showed signineant impairment in both MMN generation and auditory sensory memory. Further, the degree of MMN impalrment correlated with the degree of bebuviorally determined audllOry sensory memory dysfunction. Parallel studies demonstrated that schlzophrcnic subjects showed decreased precision in performance of visual and somatosensory working memory tasks, indicating thatsimilar Impairments may affect nil spheres of working memory performance in schizophrenia.
225. P300 LATENCY AND CORTICAL TISSUE VOLUME IN ALCOHOLICS J.M. Pord', D.H. Mathalon', M. 1. Rosenbloon", K.O. Lim1.2, & A. Pfefferbaum 1.2 'Stanford University School of Medicine, Stanford. CA, 94305; ~V APalo Alto Health Care System. Palo AIIO, CA 94304 Since its discovery 30 years ago (Sulton et al., 1965), the P300 component of the event-related brain potential (ERP) has been used in studies of alcoholism as a marker of family history and an index or cognitive abncrmality. Therelationship between P300and bruin structure has been diflicult to establish perhaps because functional abncrmalitlcs reflected in P300 may precede structural changes, suggesting that significant relationships may depend on age, durntion nf i1Tne55. or extent of pathology. We examined whether P300 latency delay in alcoholics W:lS related to structural brain deficits seen on magnetic resonance images (MRl), duration of alcoholic drinking. or intensity of alcohol consumption, ERPs ellcired during an auditory oddball parudlgm and MRl measures of gray ami white matter and cerebral spinal fluid (CSF) volumes were collected from 31 alcoholics and 32 age-matched normal control men. Regional gray and while mauer and CSF volumes were quantified. lnformatlon regarding years of alcoholic drinking and total amount of alcohol consumed was also collected, Because aging affects bothP300latency andbrain structure, MRIandP300latency values were corrected for normal aging. P300 latency was regressed on age, specific MRI values. alcohol consumption intensity (tctal alcohol consumed! duration of alcoholic drinking). ami duration of alcoholic drinking. Within the alcoholics, age-corrected P300 latency was further delayed with age, as well as with a numberof structural variables. P300 latency was not related to drink.ing duration or intensity. The strongest srructural relationship was seen for the temporal-parietal junction: gray and while mutter volume reductions nntl increases in CSF volume were related to increases in P300 latency. These relationships were not seen for NI latency, suggesting thaIa cornpromised tcmporal-parlcml junction is not associuted with generalized ERP slowing, but is specific to P300, in alcoholics, Supported by N1AAA (AA0596S) & Department of Veterans Affairs.
226. ERP CORRELATES OF RECOGNITION MEMORY: ABNORMALITIES IN SCHIZOPHRENIA B. Turetsky, E,A. Colbath, P. Moberg, L.H. Mozely, R.C. OUf, & R.E, Our Depunment of Psychiatry, University of Pennsylvania. Philadelphia. PA 19104 There is growing evidence 10 suggest that patients wilh schizophrenia have learning and memory lmpalrments that nrc evident during initiul presentation, arc relatively stable overthe (OUniC of illness, and represent a selective information processing deficit. Cognitive ERP studies of schizophrenia have focussed on the P300, II physiologic index of Ihe contextual updatlng of working memory, which is reduced in patients. Therehas been littledirectinvestigation of the physiologic correlates of explicit or declarative memory processes. This Sludy examined ERP responses during both acquisition und retrieval phases of a declarative memory task. employing visually presented words as stimuli, Subjects
UIOL PSYCIIIATRY 1996:39:500-666
565
included 42 patients with schizophrenia and 43 healthy corurols, Curren I source denslty transformations were employed to provide topographically locallzcd and reference-free indices of source activity. A "visual memory component" was identifled, which had n right pnrieto-temporal peak, larcncy between 280 antl36Q msccs, and smaller amplitude, during the retrieval phase. to familiar Vii. unfamiliar stimuli. Schizophrenics exhibltcd reduced amplitudes of this right hemisphere "visual memory potential" during acquisitlon, and which was correlated with bothpoorer performance during the subsequent retrieval phase and an independent assessment of verbal memory abilities (CVLT). During retrieval. however, patients exhibited an abnonn..l increase in left parieto-tcmporal source actlvity, This abnormally high left hemisphere activity was correlated with both improved tusk performance and improved CVLT score. It was also correlated with greater auditory oddball P300 amplitude. Nondeficlt patients. with greater positive and fewer negative symptoms, showed greater retrieval abnonnality than deficit patients. These results suggest a model of schizophrenic memory abnormalltles that entails :I primary acquisltion deficit and a partially compensatory overactivatlon, associated with more positive symptomatology, during retrieval. Preliminary data. from longitudinal and family studies of SUbgroups of thesepatients, suggest thatthereis a progressive worsening of the acqulsition impalrmcnt, as wellas a genetic predlspcsition to both the acqulsition and retrieval abnormalities. ERP results will becompared to findings from Xenon and PETblood now studies using l~e same msk and will be further considered in terms of neural network models of memory acquisltion, storage, and retrieval.
227. ERP AND BEHAVIORAL INDICES OF WORKING MEMORY DYSFUNCTION IN SCHIZOPHRENIA D.C. Javitt, A-M. Shelley, E. Leiderman, L, March, N. Cowan, & W. Ritter Department of Psychiatry, Nllthan Kline Institute for Psychiatric Research. Orangeburg, NY 10962
Deficits in event-related potential (ERPl generation lire among the most consistent and robust indices of brain dysfunction in schlzophrcnln. Mismatch negalivity (MMN) is 11 short latency cognitive ERPellcitcd in the context of an aUditory "oddball" paradigm. in which a sequence of repetitive standard stimuli is interrupted infrequently and unexpectedly by 11 physically deviant. "oddball" stimulus. As opposed to tatercognitive components (e.g., N2,P3).MMN is elicited even by unattended deviants, indicating thnt it indexes a preauentlve stage of auditory information processing. Generation of MMN depends upon the ability of auditory cortex to form and maintain reprcscntetlons of the physical properties of presented stimuli and to compare each newly presented stimulus to the physical representations of the preceding stimuli. The memory system upon which MMN generation is based appears to correspond to the ladcpendently described auditory sensory or "echoic" memory system. which maintain... represenunlons of the physical properties of presented stimuli for periods of 10 - 20 sec. This study investlgated MMN generation and auditory sensory memory function in II group of 15 chronic schizophrenic subjects. compared with 15age-matched controls. Schizophrenic SUbjects showed signineant impairment in both MMN generation and auditory sensory memory. Further, the degree of MMN impalrment correlated with the degree of bebuviorally determined audllOry sensory memory dysfunction. Parallel studies demonstrated that schlzophrcnic subjects showed decreased precision in performance of visual and somatosensory working memory tasks, indicating thatsimilar Impairments may affect nil spheres of working memory performance in schizophrenia.