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fMRI analysis of deviance processing in schizophrenia
172S
BIOL PSYCHIATRY 2000;47:1S–173S
outcomes. The clinical factor consists of measures of symptoms and intrapsychic deficits; the functional factor is comprised of measures of hospitalization, social functioning, independent living, and work functioning; the subjective experience factor consists of measures of self-esteem and satisfaction with life. Outcome was measured every six months over a three-year period. P-technique factor analysis is used to demonstrate the longitudinal character of this three-factor model for measuring outcome in the context of intervention or course studies in schizophrenia. The second objective is to present data from another prospective study using 160 individuals diagnosed with schizophrenia who were selected as they began intensive community-based psychosocial rehabilitation programs. The goal of the study is to examine whether baseline neurocognitive and psychophysiological variables can predict prospective rehabilitative outcomes. Using the three-factor model of outcome discussed above, baseline neurocognitive variables have shown medium and large effect sizes in predicting functional rehabilitation outcomes over a twelve-month period. Data on the specificity of the relationships between neurocognitive variables and distinct functional outcomes will be presented.
564. INDICES OF EARLY DEMENTIA: NEUROPSYCHOLOGICAL AND BEHAVIORAL INDICES R.C. Mohs (1,2), D. Marin (1), C. Green (1), S. Tungold (1) (1) Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY 10029; (2) Department of Psychiatry, Bronx VA Medical Center, Bronx, NY 10468 Identification of the neuropathological, neurobiological and neuropsychological abnormalities most closely associated with the earliest symptoms of Alzheimer’s disease (AD) is crucial to the understanding of the disease process and the development of treatments to affect its progression. Do the classical lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? We examined over 2500 residents of a long-term care facility with the Mini Mental State Examination (MMSE) and conducted follow-up clinical examinations on over 250 volunteers who had MMSE scores ⬎15 and who had no evidence of CNS disease other than mild AD. Patients were assigned a score on the Clinical Dementia Rating (CDR) scale, and those with CDR of 0 (no dementia), 0.5 (questionable dementia) or 1 (mild dementia) were given a battery of neuropsychological tests. All patients were reexamined yearly. The rate of conversion from CDR 0 to 0.5 was 29% and for CDR 0.5 to 1 was 50% after one year. Baseline deficits in delayed recall and naming were predictors of decline from 0 to 0.5, and deficits in memory and executive function predicted decline from CDR 0.5 to 1. The contribution of age and APOE genotype were also examined. The results indicate that memory and language deficits can be measured before clinical evidence of dementia is evident and that executive function deficits emerge early in the course of dementia.
565. INTEGRATED ERP/fMRI ANALYSIS OF DEVIANCE PROCESSING IN SCHIZOPHRENIA B.I. Turetsky (1), J. Raz (2), D. Alsop (3), D. Charbonnier (1), L. Schroeder (1), R.E. Gur (1) (1) Departments of Psychiatry, (2) Biostatistics and (3) Radiology University of Pennsylvania, Philadelphia, PA 19104 The P300 ERP is a physiologic index of cognitive processes, elicited by infrequent novel and task-relevant stimuli. Abnormal P300 is a robust
Saturday Abstracts
marker of information processing deficits associated with both normal aging and neuropsychiatric disturbances, especially schizophrenia. Electrophysiologic studies have clearly established that the scalp-recorded P300 is not a unitary phenomenon. Rather, it is a composite representation of the activity of multiple anatomically and functionally distinct brain regions. ERPs, however, offer relatively poor spatial resolution, so the neuroanatomic sources of the P300 cannot be clearly delineated, even with dense electrode arrays. Functional magnetic resonance imaging (fMRI), in contrast, offers excellent spatial resolution. However, the delayed onset and extended duration of the hemodynamic response yields poor temporal resolution, even with single-trial designs. By combining these two methodologies, a more comprehensive understanding of normal and abnormal information processing can be derived. We have utilized ERP subcomponent decomposition methods and single trial fMRI analytic techniques with random stimulus presentation and short interstimulus intervals to study the oddball and novelty P300 response in healthy individuals and patients with schizophrenia. ERPs reveals frontal, temporal and parietal subcomponents of the oddball P300. fMRI demonstrates convergent activation in anterior cingulate, superior temporal gyrus and inferior parietal lobe. For the novelty P300, fMRI analysis reveals superior temporal, rather than frontal, activity as expected from the ERP data. Schizophrenics show selective deficits of only some of these ERP subcomponent and fMRI hemodynamic activations. Efforts are currently underway to integrate these approaches directly, through simultaneous ERP/fMRI data acquisition and fMRI-guided source localization of dense electode array scalp ERP data using realistic head modeling. The use of these newer approaches will be illustrated. This type of integrated investigation will allow us to identify and probe the integrity of the precise physiologic networks underlying normal and abnormal information processing.
566. THE TEMPORAL RELATIONSHIP OF COGNITIVE AND FUNCTIONAL DECLINE IN POOR OUTCOME SCHIZOPHRENIA J.I. Friedman, P.D. Harvey, T.M. Coleman, L. White, M. Parrella, K.L. Davis Mount Sinai School of Medicine, New York, N.Y. 10029 Deficits in adaptive functioning are common in patients with poor outcome schizophrenia and are correlated with the severity of cognitive impairments (which tend to be more severe in this subset of patients). Progressive cognitive and adaptive decline have been found in geriatric poor outcome schizophrenic patients over a 2.5 year follow-up. Although these declines are intercorrelated, the timing and nature of the relationship between decline in specific cognitive and adaptive functions in poor outcome schizophrenia has not been determined. To determine the timing of functional and cognitive decline a group of schizophrenic patients aged 20 to 90 (N ⫽ 126) was assessed to determine the magnitude of decline over a six-year follow-up. Cognitive functioning was measured with a neuropsychological battery and functional status was rated with the ADAS-L using the self care factor as the outcome measure (toileting, dressing, feeding, ambulation). One way ANOVA demonstrated a significant effect of age on ADAS-L change score with planned comparisons demonstrating significant differences in six year deterioratiuon occurring between the ages of 65–75. To assess the temporal relationship of cognitive and functional change a group of schizophrenic subjects aged 65 or older demonstrating significant functional decline were assessed over three follow-up intervals for a period of 60 months. Changes in cognitive functioning correlated concurrently with functional change during the second follow-up interval, whereas no such relationship existed with cognitive changes in the preceding interval. Changes in Mini Mental Examination, naming, constructional praxis, and word list learning performance were all significantly correlated with change in functional status (all r ⬎ .25, all p ⬍ .05). These findings suggest that
BIOL PSYCHIATRY 2000;47:1S–173S
outcomes. The clinical factor consists of measures of symptoms and intrapsychic deficits; the functional factor is comprised of measures of hospitalization, social functioning, independent living, and work functioning; the subjective experience factor consists of measures of self-esteem and satisfaction with life. Outcome was measured every six months over a three-year period. P-technique factor analysis is used to demonstrate the longitudinal character of this three-factor model for measuring outcome in the context of intervention or course studies in schizophrenia. The second objective is to present data from another prospective study using 160 individuals diagnosed with schizophrenia who were selected as they began intensive community-based psychosocial rehabilitation programs. The goal of the study is to examine whether baseline neurocognitive and psychophysiological variables can predict prospective rehabilitative outcomes. Using the three-factor model of outcome discussed above, baseline neurocognitive variables have shown medium and large effect sizes in predicting functional rehabilitation outcomes over a twelve-month period. Data on the specificity of the relationships between neurocognitive variables and distinct functional outcomes will be presented.
564. INDICES OF EARLY DEMENTIA: NEUROPSYCHOLOGICAL AND BEHAVIORAL INDICES R.C. Mohs (1,2), D. Marin (1), C. Green (1), S. Tungold (1) (1) Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY 10029; (2) Department of Psychiatry, Bronx VA Medical Center, Bronx, NY 10468 Identification of the neuropathological, neurobiological and neuropsychological abnormalities most closely associated with the earliest symptoms of Alzheimer’s disease (AD) is crucial to the understanding of the disease process and the development of treatments to affect its progression. Do the classical lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? We examined over 2500 residents of a long-term care facility with the Mini Mental State Examination (MMSE) and conducted follow-up clinical examinations on over 250 volunteers who had MMSE scores ⬎15 and who had no evidence of CNS disease other than mild AD. Patients were assigned a score on the Clinical Dementia Rating (CDR) scale, and those with CDR of 0 (no dementia), 0.5 (questionable dementia) or 1 (mild dementia) were given a battery of neuropsychological tests. All patients were reexamined yearly. The rate of conversion from CDR 0 to 0.5 was 29% and for CDR 0.5 to 1 was 50% after one year. Baseline deficits in delayed recall and naming were predictors of decline from 0 to 0.5, and deficits in memory and executive function predicted decline from CDR 0.5 to 1. The contribution of age and APOE genotype were also examined. The results indicate that memory and language deficits can be measured before clinical evidence of dementia is evident and that executive function deficits emerge early in the course of dementia.
565. INTEGRATED ERP/fMRI ANALYSIS OF DEVIANCE PROCESSING IN SCHIZOPHRENIA B.I. Turetsky (1), J. Raz (2), D. Alsop (3), D. Charbonnier (1), L. Schroeder (1), R.E. Gur (1) (1) Departments of Psychiatry, (2) Biostatistics and (3) Radiology University of Pennsylvania, Philadelphia, PA 19104 The P300 ERP is a physiologic index of cognitive processes, elicited by infrequent novel and task-relevant stimuli. Abnormal P300 is a robust
Saturday Abstracts
marker of information processing deficits associated with both normal aging and neuropsychiatric disturbances, especially schizophrenia. Electrophysiologic studies have clearly established that the scalp-recorded P300 is not a unitary phenomenon. Rather, it is a composite representation of the activity of multiple anatomically and functionally distinct brain regions. ERPs, however, offer relatively poor spatial resolution, so the neuroanatomic sources of the P300 cannot be clearly delineated, even with dense electrode arrays. Functional magnetic resonance imaging (fMRI), in contrast, offers excellent spatial resolution. However, the delayed onset and extended duration of the hemodynamic response yields poor temporal resolution, even with single-trial designs. By combining these two methodologies, a more comprehensive understanding of normal and abnormal information processing can be derived. We have utilized ERP subcomponent decomposition methods and single trial fMRI analytic techniques with random stimulus presentation and short interstimulus intervals to study the oddball and novelty P300 response in healthy individuals and patients with schizophrenia. ERPs reveals frontal, temporal and parietal subcomponents of the oddball P300. fMRI demonstrates convergent activation in anterior cingulate, superior temporal gyrus and inferior parietal lobe. For the novelty P300, fMRI analysis reveals superior temporal, rather than frontal, activity as expected from the ERP data. Schizophrenics show selective deficits of only some of these ERP subcomponent and fMRI hemodynamic activations. Efforts are currently underway to integrate these approaches directly, through simultaneous ERP/fMRI data acquisition and fMRI-guided source localization of dense electode array scalp ERP data using realistic head modeling. The use of these newer approaches will be illustrated. This type of integrated investigation will allow us to identify and probe the integrity of the precise physiologic networks underlying normal and abnormal information processing.
566. THE TEMPORAL RELATIONSHIP OF COGNITIVE AND FUNCTIONAL DECLINE IN POOR OUTCOME SCHIZOPHRENIA J.I. Friedman, P.D. Harvey, T.M. Coleman, L. White, M. Parrella, K.L. Davis Mount Sinai School of Medicine, New York, N.Y. 10029 Deficits in adaptive functioning are common in patients with poor outcome schizophrenia and are correlated with the severity of cognitive impairments (which tend to be more severe in this subset of patients). Progressive cognitive and adaptive decline have been found in geriatric poor outcome schizophrenic patients over a 2.5 year follow-up. Although these declines are intercorrelated, the timing and nature of the relationship between decline in specific cognitive and adaptive functions in poor outcome schizophrenia has not been determined. To determine the timing of functional and cognitive decline a group of schizophrenic patients aged 20 to 90 (N ⫽ 126) was assessed to determine the magnitude of decline over a six-year follow-up. Cognitive functioning was measured with a neuropsychological battery and functional status was rated with the ADAS-L using the self care factor as the outcome measure (toileting, dressing, feeding, ambulation). One way ANOVA demonstrated a significant effect of age on ADAS-L change score with planned comparisons demonstrating significant differences in six year deterioratiuon occurring between the ages of 65–75. To assess the temporal relationship of cognitive and functional change a group of schizophrenic subjects aged 65 or older demonstrating significant functional decline were assessed over three follow-up intervals for a period of 60 months. Changes in cognitive functioning correlated concurrently with functional change during the second follow-up interval, whereas no such relationship existed with cognitive changes in the preceding interval. Changes in Mini Mental Examination, naming, constructional praxis, and word list learning performance were all significantly correlated with change in functional status (all r ⬎ .25, all p ⬍ .05). These findings suggest that