- Email: [email protected]
Proton magnetic resonance spectroscopy of basal ganglia in chronic schizophrenia
686
BIOLPSYCHIATRY
FRIDAE MAY 20
1994;35:615--747
coltex (Bmdmann's areas (BA) 9 and 32) in the depressed PD group compaged to those with PD alone and compared to a group of normal controls who had been scanned as part of an earlier study. This regional disturbance overlaps that observed in an earlier study, usingidentical methods, of patients with primary depression. A direct comparison of results from PD-depressed and wimary-dewessed patients revealed no differences between these two groups in BA 9 and 32. The findings indicate that medial wefmntal cortex is a common area of nenral dysfunction in the manifestation of both primary depression and depression in PD.
257. PROTON MAGNETIC RESONANCE SPECTROSCOPY OF BASAL GANGLIA IN CHRONIC SCHIZOPHRENIA T. Fujimoto I, T. Nakano I, T. Takanol, K. YamadaI, T. Fukuzako l, & H. Akimoto2 tSouth Japan Health Science Centre, Fujimoto Hospital, Miyakonojo Japan; 2Matsuzawa Hospital Recently, studies with proton magnetic resonance spectroscopy have shown an abnormality of cerebral metabolism in the dorsolateral prefrontal cortex(l) and temporal lohe(2) in schizophrenia. We studied proton MR spectra in the left basal ganglia region in patients with chronic schizopluenia. Fourteen male patients with chronic schizophrenia aged 28 to 46 years and eleven normal controls aged 23 to 63 years were studied. All of the patients were under antipsychotic medication. The proton spectrum in the voxei size of 2.5X 2.5X 2.5 cm3 was acquired t,~;ng 2.OT MRS. Peaks of N-aeetyl aspartate (NAA, CH3), glutamate (Glu, F-CH2), NAA (~-CH2), creatine (Cr, N-CH3) and phosphocreatine (l~r, N-CH3), choline (Cho, N-(CH3)3), giycin (Gly, CH2) and inositol (Ins, H4, H6), Olu(wCH) and glutamine (Gin, wCH), and PCr(N-CH a) and Cr(N-CH2) were acquired, The above 8 peaks were added to obtain the total peak heights, and the peak ratio(%) of each individual peak height to total peak heights was determined. In the left basal ganlia, significant decreases of peaks(%) in Glu(F-CH2)(Pg0.01) and PCr/Cr(N-CH2)(P<0.05) were ob. served in the patients, as compared to normal subjects. Significant increases of peaks(%) in Cho(N-(CH3)3) (P<0.01) and PC~'/O(NCH3XP~.05) were shown in the patients. These results demonstrate an abnormality of metabolism in the cerebral basal ganglia in patients with schizophrenia under antipsychotic medication, and the usefulness of proton MRS in the study of schizophrenia. References: (I)Stanley et al, SMRM, 1941, 1992. (2)Yurgelan-Todd et al, Bioi Psychiatry, 33, 45A, 1993.
258. THE ROLE OF THE FRONTAL LOBE DURING MAZE LEARNING ASSESSED USING PET J.D. Van Horn, J. Gold, G. Esposito, J.L. Ostrem, D. R. Weinberger & K.F. Berman Unit on PET, National Institutes of Health, NIMWCBDB, Bldg. !0 Rm. 4N-317, 9000 Rockville Pike, Bethesda, MD 20892 Maze learning involves cognitive abilities such as planning, sequencing, goal setting, and knowledge of previous actions, all believed to be functions of the prefrontal cortex (PFC). Patients known to have PFC damage have shown poor maze learning performance, particularly when there is right sided insult. Deficits in maze learning performance have also been observed in hippocampal patients. This study sought to investigate brain function underlying maze learning by measuring tCBF with the Oxygen-
15 water PET method during three conditions; !) a naive performance of a maze task consisting of a 10xl0 matrix of small circles presented on a computer through which subjects had to maneuver a small square; 2) performance of the same task following training to perfect/near perfect performance; and 3) a sensorimotor control task involving the pursuit of a target square around the 10xl0 matrix, thus having the same motor and sensory features as the actual maze task. For the naive trial Statistical Parametric Mapping (SPM) demonstrated a strikingly lateralized pattern with predominantly right hemisphere activation of the superior and inferior dorsolateral PFC, orbital FFC, middle and inferior temporal gyri, and parietotemporal cortex. Following training, this pattern was dramatically altered, showing bilateral activation in primary visual cortex, parietal lobe, and left hippocampal gyms, but showing little evidence of frontal activity. Our findings support an important role for the right hemisphere in knowi. edge acquisition during complex spatial tasks such as maze learning. These results also provide additional information about the relative roles of the PFC and h ippecampus in the acquisition and performance of cognitive tasks.
259. THE NEURAL BASIS OF ABSTRACT REASONING: AN INVESTIGATION OF TWO PROBLEM SOLVING TASKS WITH PET J.L. Ostrem, K.F. Berman, V.S. Mattay, J.D. Van Horn, G. Esposito, & D.R. Weinberger Unit on PET, Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIH, Building 10, 4N-317, 9000 Rockviile Pike, Bethesda, MD 20892 in this study we investigated the neural mechanisms subserving higher order cognition. Subjects were ten pairs of normal monozygotic twins (five male, five female; mean age 27). Regional cerebral blood flow (rCBF) was measured using the oxygen-15 PET method while subjects performed two abstract reasoning, problem solving tasks - the Wisconsin Card Sorting Task (WCS) and Raven's Progressive Matrices (RAV) - and two sensorimotor control tasks. Both abstract reasoning tasks are thought to involve the use of working memory, but RAV is a considerably more difficult task and may require the use of additional cognitive operations including longer-term parallel processing to complete the task. The data were analyzed with 1) a hypothesis driven approach using MRl-based regions of interest (ROI) and 2) a data driven approach using Statistical Parametric Mapping (SFM). Common to both tasks was activation of a network of regions including the inferior frontal gyms (areas 46 and 9), a region involved in working memory; the occipital lobe, which may reflect visual processing; and the inferior parietal Iobule (areas 40 and 7), which may be involved in mediating attention. Several interesting differences between the two tasks were also noted. With regard to the frontal lobe, the SPM analysis suggested that, while performance of RAV mainly activated dorsolateral prefrontal cortex (DLPFC), the WCS activated not only DLPFC, but orbital frontal areas as well. Additionally, the posterior activation seen with RAV was more significantly robust and extended more superiorly. Of particular interest, RAV activated the hippocampus while the activity in this region during WCS was relatively suppres~d, suggesting that RAV, a more complex task, may require not only working memory, but also longer-term memory mechanisms. During the WCS, task performance was positively correlated with activation of the left inferior frontal gyros (BA 9/46) (Rs-4).43, p,.O.05)and negatively correlated with left hippocampal activation (Rs=-0.41, p,-.¢37). These relationships were not found w!.~,~.~AV,suggesting that, although these two abstract reasoning problem solving tasks involve some common neural circuitry, the degree of success in performing the WCS may depend on the relative levels of recruitment of DLPFC and hippocampus, while other or additional regions may be more relevant to successful performance during RAV. These results demonstrate the utility of PET to assess the neural networks undedying higher-order cognition.
BIOLPSYCHIATRY
FRIDAE MAY 20
1994;35:615--747
coltex (Bmdmann's areas (BA) 9 and 32) in the depressed PD group compaged to those with PD alone and compared to a group of normal controls who had been scanned as part of an earlier study. This regional disturbance overlaps that observed in an earlier study, usingidentical methods, of patients with primary depression. A direct comparison of results from PD-depressed and wimary-dewessed patients revealed no differences between these two groups in BA 9 and 32. The findings indicate that medial wefmntal cortex is a common area of nenral dysfunction in the manifestation of both primary depression and depression in PD.
257. PROTON MAGNETIC RESONANCE SPECTROSCOPY OF BASAL GANGLIA IN CHRONIC SCHIZOPHRENIA T. Fujimoto I, T. Nakano I, T. Takanol, K. YamadaI, T. Fukuzako l, & H. Akimoto2 tSouth Japan Health Science Centre, Fujimoto Hospital, Miyakonojo Japan; 2Matsuzawa Hospital Recently, studies with proton magnetic resonance spectroscopy have shown an abnormality of cerebral metabolism in the dorsolateral prefrontal cortex(l) and temporal lohe(2) in schizophrenia. We studied proton MR spectra in the left basal ganglia region in patients with chronic schizopluenia. Fourteen male patients with chronic schizophrenia aged 28 to 46 years and eleven normal controls aged 23 to 63 years were studied. All of the patients were under antipsychotic medication. The proton spectrum in the voxei size of 2.5X 2.5X 2.5 cm3 was acquired t,~;ng 2.OT MRS. Peaks of N-aeetyl aspartate (NAA, CH3), glutamate (Glu, F-CH2), NAA (~-CH2), creatine (Cr, N-CH3) and phosphocreatine (l~r, N-CH3), choline (Cho, N-(CH3)3), giycin (Gly, CH2) and inositol (Ins, H4, H6), Olu(wCH) and glutamine (Gin, wCH), and PCr(N-CH a) and Cr(N-CH2) were acquired, The above 8 peaks were added to obtain the total peak heights, and the peak ratio(%) of each individual peak height to total peak heights was determined. In the left basal ganlia, significant decreases of peaks(%) in Glu(F-CH2)(Pg0.01) and PCr/Cr(N-CH2)(P<0.05) were ob. served in the patients, as compared to normal subjects. Significant increases of peaks(%) in Cho(N-(CH3)3) (P<0.01) and PC~'/O(NCH3XP~.05) were shown in the patients. These results demonstrate an abnormality of metabolism in the cerebral basal ganglia in patients with schizophrenia under antipsychotic medication, and the usefulness of proton MRS in the study of schizophrenia. References: (I)Stanley et al, SMRM, 1941, 1992. (2)Yurgelan-Todd et al, Bioi Psychiatry, 33, 45A, 1993.
258. THE ROLE OF THE FRONTAL LOBE DURING MAZE LEARNING ASSESSED USING PET J.D. Van Horn, J. Gold, G. Esposito, J.L. Ostrem, D. R. Weinberger & K.F. Berman Unit on PET, National Institutes of Health, NIMWCBDB, Bldg. !0 Rm. 4N-317, 9000 Rockville Pike, Bethesda, MD 20892 Maze learning involves cognitive abilities such as planning, sequencing, goal setting, and knowledge of previous actions, all believed to be functions of the prefrontal cortex (PFC). Patients known to have PFC damage have shown poor maze learning performance, particularly when there is right sided insult. Deficits in maze learning performance have also been observed in hippocampal patients. This study sought to investigate brain function underlying maze learning by measuring tCBF with the Oxygen-
15 water PET method during three conditions; !) a naive performance of a maze task consisting of a 10xl0 matrix of small circles presented on a computer through which subjects had to maneuver a small square; 2) performance of the same task following training to perfect/near perfect performance; and 3) a sensorimotor control task involving the pursuit of a target square around the 10xl0 matrix, thus having the same motor and sensory features as the actual maze task. For the naive trial Statistical Parametric Mapping (SPM) demonstrated a strikingly lateralized pattern with predominantly right hemisphere activation of the superior and inferior dorsolateral PFC, orbital FFC, middle and inferior temporal gyri, and parietotemporal cortex. Following training, this pattern was dramatically altered, showing bilateral activation in primary visual cortex, parietal lobe, and left hippocampal gyms, but showing little evidence of frontal activity. Our findings support an important role for the right hemisphere in knowi. edge acquisition during complex spatial tasks such as maze learning. These results also provide additional information about the relative roles of the PFC and h ippecampus in the acquisition and performance of cognitive tasks.
259. THE NEURAL BASIS OF ABSTRACT REASONING: AN INVESTIGATION OF TWO PROBLEM SOLVING TASKS WITH PET J.L. Ostrem, K.F. Berman, V.S. Mattay, J.D. Van Horn, G. Esposito, & D.R. Weinberger Unit on PET, Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, NIH, Building 10, 4N-317, 9000 Rockviile Pike, Bethesda, MD 20892 in this study we investigated the neural mechanisms subserving higher order cognition. Subjects were ten pairs of normal monozygotic twins (five male, five female; mean age 27). Regional cerebral blood flow (rCBF) was measured using the oxygen-15 PET method while subjects performed two abstract reasoning, problem solving tasks - the Wisconsin Card Sorting Task (WCS) and Raven's Progressive Matrices (RAV) - and two sensorimotor control tasks. Both abstract reasoning tasks are thought to involve the use of working memory, but RAV is a considerably more difficult task and may require the use of additional cognitive operations including longer-term parallel processing to complete the task. The data were analyzed with 1) a hypothesis driven approach using MRl-based regions of interest (ROI) and 2) a data driven approach using Statistical Parametric Mapping (SFM). Common to both tasks was activation of a network of regions including the inferior frontal gyms (areas 46 and 9), a region involved in working memory; the occipital lobe, which may reflect visual processing; and the inferior parietal Iobule (areas 40 and 7), which may be involved in mediating attention. Several interesting differences between the two tasks were also noted. With regard to the frontal lobe, the SPM analysis suggested that, while performance of RAV mainly activated dorsolateral prefrontal cortex (DLPFC), the WCS activated not only DLPFC, but orbital frontal areas as well. Additionally, the posterior activation seen with RAV was more significantly robust and extended more superiorly. Of particular interest, RAV activated the hippocampus while the activity in this region during WCS was relatively suppres~d, suggesting that RAV, a more complex task, may require not only working memory, but also longer-term memory mechanisms. During the WCS, task performance was positively correlated with activation of the left inferior frontal gyros (BA 9/46) (Rs-4).43, p,.O.05)and negatively correlated with left hippocampal activation (Rs=-0.41, p,-.¢37). These relationships were not found w!.~,~.~AV,suggesting that, although these two abstract reasoning problem solving tasks involve some common neural circuitry, the degree of success in performing the WCS may depend on the relative levels of recruitment of DLPFC and hippocampus, while other or additional regions may be more relevant to successful performance during RAV. These results demonstrate the utility of PET to assess the neural networks undedying higher-order cognition.