- Email: [email protected]
Functional imaging with spect of cognitive activity in schizotypals
FRIDAY, MAY 20
245. SPECT DIAMOX RESPONSE AUGMENTED IN COCAINE DEPENDENT PATIENTS K.M. Bell 1,3, C. Widmark 1,3, E. DeMet !,3, & N. Milne2, 3 1University of California, Irvine, Departments of Psychiatry and 2Nuclear Medicine; 3Veterans Affairs Medical Center, Long Beach, CA 90822 The acetazolamide (DIAMOX) challenge paradigm characterizes the vascular reserve of brain tissue in patients with decreased regional cerebral blood flow (CBF). Patients with poor vascular reserve respond with little or no increase in flow after DIAMOX. in contrast, those patients with deafferentation show normal or augmented responses compared to controis. The DIAMOX challenge has distinguished patients suffering from dementia and Alzheimer's Disease from those with multi-infarct dementia. Cocaine abuse is associated with stroke in persons less than 50 years old. Since cocaine abuse diminishes CBF, changes associated with DIAMOX intravenous challenge and 99-m-Tc-HMPAO SPECT were studied in ! 3 subjects: 8 patients with cocaine dependence (COCAINE) and 5 controls (C). Subjects were male, right-handed and of similar age (p-NS). Patients were not on medication; and last use of cocaine was a minimum of 12 days before the scan. Repeated measures ANCOVA, (Huynh-Feldt adjusted degrees of freedom and total transaxial counts as covariate) was significant for Group X Hemisphere X REGION X PRE- OR POST-DIAMOX (F - 1.9; d f - 15,90; p<.05). Post-hoc regional analyses of areas of interest relative to mean cerebeUar flow were examined for changes with DIAMOX administration. ANOVA for cocaine-dependent patients compared with controls showed significantly increased relative CBF to left and right superior temporal, superior parietal, left inferior frontal, right occipital cortex and right caudate. CBF changes with DIAMOX seen in cocaine dependent patients are consistent with deafferentation and a robust vascular response.
246. CORRELATES OF IH-MAGNETIC RESONANCE SPECTROSCOPY IN SCHIZOPHRENIA P. Buckley I, C. Moore 2, H. Long 2, C. Larkin 2, F. Mulvany 2, O. Redmond 2, J.P. Stack 2, J,T. Ennis 2, & J.L. Waddington 3 nDepartment of Psychiatwc, Case Western Reserve University, Cleveland, Ohio, USA; St. John of God Psychiatric ~ervice, Stillorgan, Co. Dublin, Ireland; 3Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland Some structural magnetic resonance imaging (MRI) studies in schizophrenia have noted more abnormalities among male relative to female patients. MRi correlates of putative neurodevelopmental indices such as obstetric complications (OC's), family history of schizophrenia (FI-I), or minor physical anomalies (MPA's) have sometimes been observed. We examined here the relationship of these indices to cerebral function as measured by nil-MR spectroscopy of the left temporal and frontal lobes in 28 patients with DSM III-R schizophrenia and 20 healthy, matched volunteen. Male patients showed a significant reduction in frontal n-acetylaspartate (NAA) values in comparison with male controls (35.1 + 8.0 vs 45.3 + 8.9, p<.01)and female patients (45.9 + 7.2, p<.005); frontal choline values were raised (13<.01)in male patients relative to these groups. Neither OC's, FH, nor MPA's were associated with distinct patterns on tH-
BIOLPSYCHIATRY 683 1994;35:615-747
MRS. However memory function in patients, as assessed by the Weschler Memory Scale-Revised, was related to temporal, but not frontal MRS measures; this pattern was less apparent in controls. Though gender specific patient-control differences were evident, MRS measures proved unrelated to putative neurodevelopmental indices; also they were differentially associated with memory function in patients venus controls. The relative decrement in NAA (which is distributed intrane.uronally) may reflect frontal hypoplasia/dysplasia that predominantly affects male patients.
247. A PET ACTIVATION STUDY OF SELECTIVE ATI'ENDING DURING A STROOP TASK S.F. Taylor I, S. Kornblum !,2, E. Lauber2, S. Minoshima 3, & R.A. Koeppe 3 t Univ. of Michigan Dept. of Psychiatry, Ann Arbor, MI 4810901 ! 6; 2Univ, of Michigan Dept. of Psychology; 3Univ. of Michigan Dept. of Internal Medicine, Div. of Nuclear Medicine The Stmop task requires subjects to name the color of words spelling colors different than the color-to-be-named. Since the Stroop has been a preferred paradigm in the study of selective attention, an understanding of the underlying functional neuroanatomy could make the task an ideal behavioral probe for disorders which present with disturbed attention, such as schizophrenia. We used PET to study regional CBF changes occurring with performance of the Stroop task and two control conditions: naming the color of letter-like stimuli ("false fonts") and naming the color of non-color words. Eight, healthy male subjects were scanned twice in each condition, and data were acquired with a Siemens ECAT Exact PET camera after injection of 50 mCi of [O- 15]H20 for each scan. Relative counts were normalized to gray matter activity, and the image arrays were transformed into stereotactic space with automated computer routines to facilitate intersubject averaging and statistical analysis. Averaged images of voxel-by-voxel changes were expressed as Z-scores and thresholded for significant change between the Stroop task and each of the control conditions. Compared to either control condition, we did not find any activation in the anterior cingulate during the Stroop task, as had been previously reported for a variation of this task (pardo et al., 1990). We did fred significant activation in the left parietal region (Brodman's area 40/7) in the Stroop minus false font comparison, with activity during the non-color word condition falling between these two conditions. We interpret activation in this region as a part of a distributed network organizing selective attending. We also found right prefrontal activation (BA 46), but only with the neutral words as the control condition.
248. FUNCTIONAL IMAGING WITH SPECT OF COGNITIVE ACTIVITY IN SCHIZOTYPALS R.L. Trestman 1'2, M. Buchsbaum 2, B. Siegel l'2, M. Losonczy 2.3, C. Schaefer t, & L.J. Siever 1'2 1Bronx VA Medical Center, Bronx NY; 2Mt. Sinai Medical Center, New York NY; 3FDR VA Medical Center, Montrose NY Schizophrenic patients have demonstrated a reduced rCBF (by SPECT) in the prefrontal cortex during prefrontal lobe cognitive activation with the Wisconsin Card Sorting Test (WCST) vers]~.a control task; this contrasts with normal controls, who demonstrate an increase in prefrontal rCBF (Weinberger et al 1986, 1988). Consistent with a schizophrenia spectrum hypothesis, Schizotypal Personality Disorder (SPD) patients are hypothe-
684
BIOLPSYCHIATRY 1994;35:615-747
sized to be able to compensate for cognitive/perceptual impairment by alternative strategies that are less efficient than those used by normal controis. Subjects are medically healthy males, with IRB informed consent, and are DSM-In-R SPD (n-7) or normal controls (n-5). Subjects are studied on 2 days, one week apart at the same time of day, with tasks counterbalanced. An autcm,~:~ cognitive activation task known to be sensitive to frontal dysfuncti~it Cthe WCST) is compared to a symbol matching task (SMT); 99mTc- HMPAO is infused and registered on a Medimatic 564. Results with this preliminary data set suggest that, compared to normal controls, SPD patients: 1) may increase flow in the dorsolateral prefrontal cortex (DLPFC) in response to WCST, particularly the left DLPFC; 2) appear to have a dissociation of performance from rCBF in the left DLPFC while left DLPFC rCBF in normals is inversely related to rate of perseverative errors; 3) the ratio of rCBF in the DLPFC to the occipital lobe increases significantly during the WCST compared to the SMT only in SPD patients. These results are consistent with the possibility that SPD patients use inefficient strategies to compensate for an underlying prefrontal neurecognitive deficit; these strategies may rely on increasing prefrontal gCBF.
249. SPECT FINDINGS IN NARCOLEPSY S. Shettar, S. Parikh, J.M. Mountz, R. Acton, & C. Inampudl University of Alabama at Birmingham, Birmingham, AL 352330018 Narcolepsy is a neumlngical condition manifested by a tetrad of symptoms, most commonly excessive daytime sleepiness and often by other symptoms such as sleep paralysis, cataplexy & hypnngngic hallucinations. Sometimes symptoms of narcolepsy overlap with depression, schizophrenia-like psychosis and attention deficit disorder and cerebral blood flow studies have been evaluated in the latter disorders. To test the hypothesis that functional abnormalities Involving the frontal or anterior temporal lobes may be present in narcolepsy, regional cerebral blood flow (rCBF) studies in eight patients were performed. Eight chug free patients (M-4;F,-4)aged (18-50 yrs) were diagnosed clinically as narcoleptics by standard polysonmography and multiple sleep latency test. Each underwent 99mTc hexmethyl-pmpyleneamine oxime (99mTc-HMPAO) high resolution brain SPELT imaging. Region of Interest (R01) for analysis were defined using a reference system which defined cortical circumferential R01 at slice levels parallel to and sequentially above the canthomeatal line at +3.5cm, +5.5cm & +7.5cm. The cortex was subdivided in twelve In equal angular regions using a computer automated edge detection program. The caudate nucleus & thalami were also evaluated by reference to an anatomic scan. Regional CBF values were obtained by normalizing cortical counts to both whole brain and cerebellar counts. A onesample t-test revealed a significant decrease in mean tCBF of the R-anterior temporal (p-.001) & R-posterior frontal (p-.043) regions compat~ to normals. A two-sample t-test revealed a significant decrease in mean rCBF of the R-anterior temporal (p-.048) and R-posterior frontal (p-.044) regions of patients with cutaplexy compared to those without. A similar significant decrease In mean rCBF of R-anterior temporal (p-.043) & Rposterior frontal (p-.029) was found between patients with sleepparalysis comparcd to those without, in conclusion, this study suggests that regional decreases In frontal and anterior temporal lobe ~ B F occurs in patients with narcolepsy, and may provide a method to better understand the underlying pathophysiology.
FRIDAE, MAY 20
250. ORBITAL FRONTAL CORTEX METABOLISM AND OBSESSIONALITY IN NORMAL VOLUNTEERS L.W. Kraft, N. Kusubov, R. Tang, M. Young, & T.E. Nordahl University of California, Davis Medical School, Department of Psychiatry, Sacramento, CA 95817 Three studies have demonstrated orbital frontal hypermetabolism in unmedicated patients with obsessive-compulsive disorder (OCD). Another study has found a significant correlation in normal controls between neuroticism and orbital frontal metabolism. We decided to test for correlation between orbital frontal and basal ganglia metabolism with obsessive symptoms in normal controls. Ten normal volunteers (9 males, I females, mean age 31.2 + 12.0 yrs) underwent FDG-PET scans and were administered the Symptom Checklist 90 (SCL-90) which includes an assessment of obsessive-compulsive symptoms. Correlations between the SCL-90 obsessive-compulsive subscale and regional orbital frontal cortical metabolism were significant (r-.82, p<0.005) for the left orbital frontal gyms, but not (r-0.035, N$) for the right orbital frontal gyms. No significant correlations were noted for basal ganglia metabolism and obsessive compulsive symptoms. These preliminary findings further support the linkage of orbital frontal cortex and the symptoms seen in obsessive-compulsive disorder.
251. CEREBRAL METABOLIC CORRELATES OF MONITORING THE SOURCE OF REMEMBERED INFORMATION P.J. Andreason, D. Hemmer, K. Sirocco, & H. Weingartner National Institute on Alcohol Abuse and Alcoholism, DICBR, Laboratory on Clinical Studies, Bethesda, MD 20892 Patients (n-I 3, 9 men and 4 women) with alcohol dependence were studied with tSF-2- flum-2-deoxygiucose (FDG) positron emission tomngraphy (PET) and cognitive testing in order to explore the neumanatomic correlates of monitoring the source of remembered information. Preliminary work has suggested that many alcoholics demonstrate impaired source monitoring and that this impairment occurs in the absence of other memory dysfunction. Subjects were scanned using FDG PET while performing a continuous auditory performance task (CPT) then within two days after scanning underwent evaluation of memory functions including source monitoring (identification of words as originally presented by either the experimenter or self-generated). Scores on source monitoring correlated positively with left prefrontal (df -12, r - .64, p
245. SPECT DIAMOX RESPONSE AUGMENTED IN COCAINE DEPENDENT PATIENTS K.M. Bell 1,3, C. Widmark 1,3, E. DeMet !,3, & N. Milne2, 3 1University of California, Irvine, Departments of Psychiatry and 2Nuclear Medicine; 3Veterans Affairs Medical Center, Long Beach, CA 90822 The acetazolamide (DIAMOX) challenge paradigm characterizes the vascular reserve of brain tissue in patients with decreased regional cerebral blood flow (CBF). Patients with poor vascular reserve respond with little or no increase in flow after DIAMOX. in contrast, those patients with deafferentation show normal or augmented responses compared to controis. The DIAMOX challenge has distinguished patients suffering from dementia and Alzheimer's Disease from those with multi-infarct dementia. Cocaine abuse is associated with stroke in persons less than 50 years old. Since cocaine abuse diminishes CBF, changes associated with DIAMOX intravenous challenge and 99-m-Tc-HMPAO SPECT were studied in ! 3 subjects: 8 patients with cocaine dependence (COCAINE) and 5 controls (C). Subjects were male, right-handed and of similar age (p-NS). Patients were not on medication; and last use of cocaine was a minimum of 12 days before the scan. Repeated measures ANCOVA, (Huynh-Feldt adjusted degrees of freedom and total transaxial counts as covariate) was significant for Group X Hemisphere X REGION X PRE- OR POST-DIAMOX (F - 1.9; d f - 15,90; p<.05). Post-hoc regional analyses of areas of interest relative to mean cerebeUar flow were examined for changes with DIAMOX administration. ANOVA for cocaine-dependent patients compared with controls showed significantly increased relative CBF to left and right superior temporal, superior parietal, left inferior frontal, right occipital cortex and right caudate. CBF changes with DIAMOX seen in cocaine dependent patients are consistent with deafferentation and a robust vascular response.
246. CORRELATES OF IH-MAGNETIC RESONANCE SPECTROSCOPY IN SCHIZOPHRENIA P. Buckley I, C. Moore 2, H. Long 2, C. Larkin 2, F. Mulvany 2, O. Redmond 2, J.P. Stack 2, J,T. Ennis 2, & J.L. Waddington 3 nDepartment of Psychiatwc, Case Western Reserve University, Cleveland, Ohio, USA; St. John of God Psychiatric ~ervice, Stillorgan, Co. Dublin, Ireland; 3Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland Some structural magnetic resonance imaging (MRI) studies in schizophrenia have noted more abnormalities among male relative to female patients. MRi correlates of putative neurodevelopmental indices such as obstetric complications (OC's), family history of schizophrenia (FI-I), or minor physical anomalies (MPA's) have sometimes been observed. We examined here the relationship of these indices to cerebral function as measured by nil-MR spectroscopy of the left temporal and frontal lobes in 28 patients with DSM III-R schizophrenia and 20 healthy, matched volunteen. Male patients showed a significant reduction in frontal n-acetylaspartate (NAA) values in comparison with male controls (35.1 + 8.0 vs 45.3 + 8.9, p<.01)and female patients (45.9 + 7.2, p<.005); frontal choline values were raised (13<.01)in male patients relative to these groups. Neither OC's, FH, nor MPA's were associated with distinct patterns on tH-
BIOLPSYCHIATRY 683 1994;35:615-747
MRS. However memory function in patients, as assessed by the Weschler Memory Scale-Revised, was related to temporal, but not frontal MRS measures; this pattern was less apparent in controls. Though gender specific patient-control differences were evident, MRS measures proved unrelated to putative neurodevelopmental indices; also they were differentially associated with memory function in patients venus controls. The relative decrement in NAA (which is distributed intrane.uronally) may reflect frontal hypoplasia/dysplasia that predominantly affects male patients.
247. A PET ACTIVATION STUDY OF SELECTIVE ATI'ENDING DURING A STROOP TASK S.F. Taylor I, S. Kornblum !,2, E. Lauber2, S. Minoshima 3, & R.A. Koeppe 3 t Univ. of Michigan Dept. of Psychiatry, Ann Arbor, MI 4810901 ! 6; 2Univ, of Michigan Dept. of Psychology; 3Univ. of Michigan Dept. of Internal Medicine, Div. of Nuclear Medicine The Stmop task requires subjects to name the color of words spelling colors different than the color-to-be-named. Since the Stroop has been a preferred paradigm in the study of selective attention, an understanding of the underlying functional neuroanatomy could make the task an ideal behavioral probe for disorders which present with disturbed attention, such as schizophrenia. We used PET to study regional CBF changes occurring with performance of the Stroop task and two control conditions: naming the color of letter-like stimuli ("false fonts") and naming the color of non-color words. Eight, healthy male subjects were scanned twice in each condition, and data were acquired with a Siemens ECAT Exact PET camera after injection of 50 mCi of [O- 15]H20 for each scan. Relative counts were normalized to gray matter activity, and the image arrays were transformed into stereotactic space with automated computer routines to facilitate intersubject averaging and statistical analysis. Averaged images of voxel-by-voxel changes were expressed as Z-scores and thresholded for significant change between the Stroop task and each of the control conditions. Compared to either control condition, we did not find any activation in the anterior cingulate during the Stroop task, as had been previously reported for a variation of this task (pardo et al., 1990). We did fred significant activation in the left parietal region (Brodman's area 40/7) in the Stroop minus false font comparison, with activity during the non-color word condition falling between these two conditions. We interpret activation in this region as a part of a distributed network organizing selective attending. We also found right prefrontal activation (BA 46), but only with the neutral words as the control condition.
248. FUNCTIONAL IMAGING WITH SPECT OF COGNITIVE ACTIVITY IN SCHIZOTYPALS R.L. Trestman 1'2, M. Buchsbaum 2, B. Siegel l'2, M. Losonczy 2.3, C. Schaefer t, & L.J. Siever 1'2 1Bronx VA Medical Center, Bronx NY; 2Mt. Sinai Medical Center, New York NY; 3FDR VA Medical Center, Montrose NY Schizophrenic patients have demonstrated a reduced rCBF (by SPECT) in the prefrontal cortex during prefrontal lobe cognitive activation with the Wisconsin Card Sorting Test (WCST) vers]~.a control task; this contrasts with normal controls, who demonstrate an increase in prefrontal rCBF (Weinberger et al 1986, 1988). Consistent with a schizophrenia spectrum hypothesis, Schizotypal Personality Disorder (SPD) patients are hypothe-
684
BIOLPSYCHIATRY 1994;35:615-747
sized to be able to compensate for cognitive/perceptual impairment by alternative strategies that are less efficient than those used by normal controis. Subjects are medically healthy males, with IRB informed consent, and are DSM-In-R SPD (n-7) or normal controls (n-5). Subjects are studied on 2 days, one week apart at the same time of day, with tasks counterbalanced. An autcm,~:~ cognitive activation task known to be sensitive to frontal dysfuncti~it Cthe WCST) is compared to a symbol matching task (SMT); 99mTc- HMPAO is infused and registered on a Medimatic 564. Results with this preliminary data set suggest that, compared to normal controls, SPD patients: 1) may increase flow in the dorsolateral prefrontal cortex (DLPFC) in response to WCST, particularly the left DLPFC; 2) appear to have a dissociation of performance from rCBF in the left DLPFC while left DLPFC rCBF in normals is inversely related to rate of perseverative errors; 3) the ratio of rCBF in the DLPFC to the occipital lobe increases significantly during the WCST compared to the SMT only in SPD patients. These results are consistent with the possibility that SPD patients use inefficient strategies to compensate for an underlying prefrontal neurecognitive deficit; these strategies may rely on increasing prefrontal gCBF.
249. SPECT FINDINGS IN NARCOLEPSY S. Shettar, S. Parikh, J.M. Mountz, R. Acton, & C. Inampudl University of Alabama at Birmingham, Birmingham, AL 352330018 Narcolepsy is a neumlngical condition manifested by a tetrad of symptoms, most commonly excessive daytime sleepiness and often by other symptoms such as sleep paralysis, cataplexy & hypnngngic hallucinations. Sometimes symptoms of narcolepsy overlap with depression, schizophrenia-like psychosis and attention deficit disorder and cerebral blood flow studies have been evaluated in the latter disorders. To test the hypothesis that functional abnormalities Involving the frontal or anterior temporal lobes may be present in narcolepsy, regional cerebral blood flow (rCBF) studies in eight patients were performed. Eight chug free patients (M-4;F,-4)aged (18-50 yrs) were diagnosed clinically as narcoleptics by standard polysonmography and multiple sleep latency test. Each underwent 99mTc hexmethyl-pmpyleneamine oxime (99mTc-HMPAO) high resolution brain SPELT imaging. Region of Interest (R01) for analysis were defined using a reference system which defined cortical circumferential R01 at slice levels parallel to and sequentially above the canthomeatal line at +3.5cm, +5.5cm & +7.5cm. The cortex was subdivided in twelve In equal angular regions using a computer automated edge detection program. The caudate nucleus & thalami were also evaluated by reference to an anatomic scan. Regional CBF values were obtained by normalizing cortical counts to both whole brain and cerebellar counts. A onesample t-test revealed a significant decrease in mean tCBF of the R-anterior temporal (p-.001) & R-posterior frontal (p-.043) regions compat~ to normals. A two-sample t-test revealed a significant decrease in mean rCBF of the R-anterior temporal (p-.048) and R-posterior frontal (p-.044) regions of patients with cutaplexy compared to those without. A similar significant decrease In mean rCBF of R-anterior temporal (p-.043) & Rposterior frontal (p-.029) was found between patients with sleepparalysis comparcd to those without, in conclusion, this study suggests that regional decreases In frontal and anterior temporal lobe ~ B F occurs in patients with narcolepsy, and may provide a method to better understand the underlying pathophysiology.
FRIDAE, MAY 20
250. ORBITAL FRONTAL CORTEX METABOLISM AND OBSESSIONALITY IN NORMAL VOLUNTEERS L.W. Kraft, N. Kusubov, R. Tang, M. Young, & T.E. Nordahl University of California, Davis Medical School, Department of Psychiatry, Sacramento, CA 95817 Three studies have demonstrated orbital frontal hypermetabolism in unmedicated patients with obsessive-compulsive disorder (OCD). Another study has found a significant correlation in normal controls between neuroticism and orbital frontal metabolism. We decided to test for correlation between orbital frontal and basal ganglia metabolism with obsessive symptoms in normal controls. Ten normal volunteers (9 males, I females, mean age 31.2 + 12.0 yrs) underwent FDG-PET scans and were administered the Symptom Checklist 90 (SCL-90) which includes an assessment of obsessive-compulsive symptoms. Correlations between the SCL-90 obsessive-compulsive subscale and regional orbital frontal cortical metabolism were significant (r-.82, p<0.005) for the left orbital frontal gyms, but not (r-0.035, N$) for the right orbital frontal gyms. No significant correlations were noted for basal ganglia metabolism and obsessive compulsive symptoms. These preliminary findings further support the linkage of orbital frontal cortex and the symptoms seen in obsessive-compulsive disorder.
251. CEREBRAL METABOLIC CORRELATES OF MONITORING THE SOURCE OF REMEMBERED INFORMATION P.J. Andreason, D. Hemmer, K. Sirocco, & H. Weingartner National Institute on Alcohol Abuse and Alcoholism, DICBR, Laboratory on Clinical Studies, Bethesda, MD 20892 Patients (n-I 3, 9 men and 4 women) with alcohol dependence were studied with tSF-2- flum-2-deoxygiucose (FDG) positron emission tomngraphy (PET) and cognitive testing in order to explore the neumanatomic correlates of monitoring the source of remembered information. Preliminary work has suggested that many alcoholics demonstrate impaired source monitoring and that this impairment occurs in the absence of other memory dysfunction. Subjects were scanned using FDG PET while performing a continuous auditory performance task (CPT) then within two days after scanning underwent evaluation of memory functions including source monitoring (identification of words as originally presented by either the experimenter or self-generated). Scores on source monitoring correlated positively with left prefrontal (df -12, r - .64, p