Magnetic resonance imaging of mediodorsal, pulvinar, and centromedian nuclei of the thalamus in patients with schizophrenia

BACKGROUND: Postmortem and magnetic resonance imaging (MRI) data have suggested volume reductions in the mediodorsal (MDN) and pulvinar nuclei (PUL) of the thalamus. The centromedian nucleus (CMN), important in attention and arousal, has not been previously studied with MRI. METHODS: A sample of 41 patients with schizophrenia (32 men and 9 women) and 60 healthy volunteers (45 men and 15 women) underwent assessment with high-resolution 1.2-mm thick anatomical MRI. Images were differentiated to enhance the edges and outline of the whole thalamus, and the MDN, PUL, and CMN were outlined on all slices by a tracer masked to diagnostic status. RESULTS: Significantly smaller volumes of the MDN and PUL were found in patients with schizophrenia compared with controls. Volume relative to brain size was reduced in all 3 nuclei; differences in relative reduction did not differ among the nuclei. The remainder of the thalamic volume (whole thalamus minus the volume of the 3 delineated nuclei) was not different between schizophrenic patients and controls, indicating that the volume reduction was specific to these nuclei. Volume relative to brain size was reduced in all 3 nuclei and remained significant when only patients who had never been exposed to neuroleptic medication (n = 15) were considered. For the MDN, women had larger relative volumes than men among controls, but men had larger volumes than women among schizophrenic patients. CONCLUSIONS: Three association regions of the thalamus that have reciprocal connectivity to schizophrenia-associated regions of the cortex have significantly smaller volumes on MRI in patients with schizophrenia.     

The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.

Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life.     

Relative glucose metabolic rate higher in white matter in patients with schizophrenia

OBJECTIVE: There is increasing evidence demonstrating that circuits involving the frontal lobe, striatum, temporal lobe, and cerebellum are abnormal in individuals with schizophrenia, which suggests that metabolic activity in the white matter connecting these areas should be investigated. METHOD: The authors obtained [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) on 170 subjects. Participants were 103 normal volunteers and 67 unmedicated patients with schizophrenia (N=61) or schizoaffective disorder (N=6). The images were coregistered and warped to standard space for significance probability mapping. RESULTS: Compared with normal volunteers, patients showed higher relative metabolic rates in the frontal white matter, corpus callosum, superior longitudinal fasciculus, and white matter core of the temporal lobe. Elevated activity in white matter was most pronounced in the center of large white matter tracts, especially the frontal parts of the brain and the internal capsule. The white matter elevation did not appear to be entirely related to changes in gray matter/white matter brain proportions, whole brain metabolic rate bias, or excess head motion in patients, but this cannot be ruled out without absolute glucose determinations. Patients also showed significantly lower relative glucose metabolism in the frontal and temporal lobes, caudate nucleus, cingulate gyrus, and mediodorsal nucleus of the thalamus relative to normal volunteers, which is consistent with earlier studies. CONCLUSIONS: In comparisons of unmedicated schizophrenia patients with normal volunteers, relative metabolic increases are apparent in white matter in patients with schizophrenia as well as decreases in gray matter. Inefficiency in brain circuitry, defects in white matter leading to enhanced energy need, white matter damage, and alterations in axon packing density are among the possible explanations for these schizophrenia-related findings of relatively increased metabolism in white matter.     

Regional brain glucose metabolism: correlations to biochemical measures and anxiety in patients with schizophrenia.

Regional brain glucose metabolism in 20 patients with schizophrenia (DSM-III) was investigated by positron emission tomography (PET) with uniformly labeled 11C-glucose as the tracer. Monoamine metabolites were analyzed in cerebrospinal fluid (CSF) and serum, and prolactin was analyzed in serum. Intensity of anxiety was rated directly after the PET study. Ten healthy volunteers served as controls. In the patients, weak positive and negative relationships were found between homovanillic acid in CSF and prolactin in serum, respectively, and regional metabolic rates. In all subjects, positive correlations were found between the level of anxiety and the regional glucose metabolism. In the controls, positive correlations were found between anxiety and the frontal/parietal ratios of the left hemisphere, whereas anxiety scores of the patients correlated negatively to relative metabolic rates of the right medial frontal cortex and the left thalamus. These observations may indicate alterations in the neuronal systems participating in the initiation of anxiety and arousal in schizophrenia.     

Hypermetabolic pattern in frontal cortex and other brain regions in unmedicated schizophrenia patients

We report results of a FDG–PET study in 10 patients with schizophrenia (6 unmedicated, 4 never medicated) and 12 healthy age–matched controls. The patients met ICD–10 and DSM–IV criteria for schizophrenia and all reported psychotic, "positive" symptoms when tested. Schizophrenic patients had higher absolute CMRGlu values in almost all quantified regions compared to normal subjects. Using the occipital cortex as the reference region patients showed a hyperfrontal metabolic pattern. Other significant regional differences were found with respect to thalamus, striatum and temporal cortex. The finding of a hyperfrontality in un– and never medicated psychotic schizophrenic patients must be discussed in the light of the psychopathological symptoms of patients when tested, a possible disruption of cortico–striato–thalamic feedback loops and recent findings of a hyperfrontality in experimentally induced psychosis (ketamine– and psilocybin–model of schizophrenia).     

Regional cerebral glucose metabolism in never-medicated patients with schizophrenia.

OBJECTIVE: The purpose of this study was to assess regional cerebral glucose metabolism in patients with schizophrenia who had never received antipsychotic medication and whose olfactory identification ability had been assessed. Two hypotheses were examined. First, the patients were compared with normal controls to determine whether differences in regional cerebral metabolism were apparent. Second, regional rates of metabolism were correlated with olfactory ability and the relation between them determined. METHODS: The patient (n = 26) and control (n = 32) subjects were scanned at rest using positron emission tomography (PET) after administration of 18F-fluorodeoxyglucose (FDG). In addition, the University of Pennsylvania Smell Identification Test was administered to each patient. RESULTS: Patients with schizophrenia had reduced rates of glucose metabolism in the right and left thalamus that reached significance if not corrected for multiple comparisons. However, if a Bonferroni correction was applied over the 27 regions of interest, the differences were not significant. Scores on the Smell Identification Test were negatively correlated with 8 regions of interest. When scores were analyzed using multiple regression, the left frontal cortex and the medial parietal cortex were significant predictors. CONCLUSIONS: The finding of reduced metabolism in the thalami is consistent with some of the previous literature, whereas the negative correlations between specific regions and olfactory function are not consistent with studies using activation paradigms.     

Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia

This study examines whether the duration of treatment with antipsychotic drugs influences the regional distribution of cerebral [18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron emission tomography. Two groups of schizophrenic patients are compared with normal volunteers (n = 10). One group (n = 5) consisted of patients treated for one year, and the second (n = 12) of patients medicated for four to 14 years (mean +/- SD duration, 7.4 +/- 3.4 years). The first group was also examined before patients received their first dose ever of antipsychotic medication. One year of medication was not sufficient to alter the schizophrenic profile of cerebral cortical glucose activity but did elevate activity of the corpus striatum. Medication for 7.4 years also did not alter the schizophrenic pattern of frontal hyperactivity and posterior hypoactivity, although deviations from control values appeared less marked than after one year. On the other hand, in patients medicated for 7.4 years, there was perhaps an even greater increase in the activity of the corpus striatum and of the thalamus. Thus, duration of exposure to antipsychotic medication may affect the pattern of cerebral glucose activity; possibly, even longer exposure may contribute to the hypofrontality noted by others, although this can be confounded with the duration of illness as a factor. In considering the biological significance of the observed profile of cortical glucose activity, we introduce the concept of cerebral metabolic tone. We suggest that a disturbance of this tonus may account for some symptoms of schizophrenia and could be consistent with the hypothesis of abnormal developmental changes in the brains of schizophrenics.     

Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task

Previous research indicates that verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. However, the concomitant patterns of regional brain function associated with these deficits in schizophrenia are not well understood. The present study examined verbal-memory performance and simultaneous relative glucose metabolic rates (rGMR) with FDG PET in 20 unmedicated schizophrenia patients who met stringent memory-performance criteria and 32 age- and sex-matched normal volunteers. On a modified version of the California Verbal Learning Test, patients recalled fewer correct words using a semantic-clustering strategy and exhibited more intrusions compared with normal subjects. However, patients had higher serial-ordering strategy scores, indicating their use of a less efficient organizational strategy. Among patients, greater use of the serial-ordering strategy was associated with decreased rGMR in frontal cortex and increased rGMR in temporal cortex. Patients had lower rGMR primarily in frontal and temporal cortex, but not parietal and occipital lobe regions. Patients also exhibited hypofrontality (lower ratio of frontal to occipital rGMR) compared with normal subjects. Among the patients, more severe hypofrontality was associated with increased perseveration errors.     

Emotions in unmedicated patients with schizophrenia during evaluation with positron emission tomography

OBJECTIVE: Schizophrenia is currently conceptualized as a disease of functional neural connectivity, leading to symptoms that affect aspects of mental activity, including perception, attention, memory, and emotion. The neural substrates of its emotional components have not been extensively studied with functional neuroimaging. Previous neuroimaging studies have examined medicated patients with schizophrenia. The authors measured regional cerebral blood flow (rCBF) during performance of a task that required unmedicated patients to recognize the emotional valence of visual images and to determine whether they were pleasant or unpleasant. METHOD: The authors examined rCBF in 17 healthy volunteers and 18 schizophrenia patients who had not received antipsychotic medications for at least 3 weeks during responses to pleasant and unpleasant visual stimuli. Areas of relative increases or decreases in rCBF were measured by using the [(15)O]H(2)O method. RESULTS: When patients consciously evaluated the unpleasant images, they did not activate the phylogenetically older fear-danger recognition circuit (e.g., the amygdala) used by the healthy volunteers, although they correctly rated them as unpleasant. Likewise, the patients showed no activation in areas of the prefrontal cortex normally used to recognize the images as pleasant and were unable to recognize them as such. Areas of decreased CBF were widely distributed and comprised subcortical regions such as the thalamus and cerebellum. CONCLUSIONS: This failure of the neural systems used to support emotional attribution is consistent with pervasive problems in experiencing emotions by schizophrenia patients. The widely distributed nature of the abnormalities suggests the importance of subcortical nodes in overall dysfunctional connectivity.     

Mapping metabolic brain activation during human volitional swallowing: a positron emission tomography study using [18F]fluorodeoxyglucose.

We have previously shown that labelled water positron emission tomography (H2(15)O PET) can be used to identify regional cerebral blood flow (rCBF) changes in the human brain during volitional swallowing. (18F) fluorodeoxyglucose (FDG PET), by comparison, uses a glucose analogue to quantitatively measure regional cerebral glucose metabolism (rCMRglc) rather than rCBF. The main advantage of FDG PET is improved spatial resolution, and because of its pharmacodynamic properties, activation can be performed external to the scanner, allowing subjects to assume more physiologic positions. We therefore conducted a study of the brain's metabolic response while swallowing in the erect seated position, using FDG PET. Eight healthy male volunteers were studied with a randomised 2 scan paradigm of rest or water swallowing at 20-second intervals for 30 minutes. Data were analysed with SPM99 using multisubject conditions and covariates design. During swallowing, analysis identified increased rCMRglc (P<0.01) in the following areas: left sensorimotor cortex, cerebellum, thalamus, precuneus, anterior insula, left and right lateral postcentral gyrus, and left and right occipital cortex. Decreased rCMRglc were also seen in the right premotor cortex, right and left sensory and motor association cortices, left posterior insula and left cerebellum. Thus, FDG PET can be applied to measure the brain metabolic activity associated with volitional swallowing and has the advantage of normal task engagement. This has implications for future activation studies in patients, especially those suffering swallowing problems after brain injury.     

Positron emission tomography and subcortical glucose metabolism in schizophrenia

Our previous observation of a disturbed subcortical-to-cortical gradient of activity in schizophrenia was further elucidated by examining glucose metabolism in three subcortical structures: lenticular nucleus, caudate nucleus, and thalamus. Local cerebral glucose metabolism was determined with 18F-fluorodeoxyglucose using positron emission tomography (PET) in a sample of 20 unmedicated schizophrenics and 18 normal volunteers. Repeated evaluations were performed for 12 schizophrenics following treatment with psychotropic medications and for 11 controls. Unmedicated schizophrenics had lower cortical and caudate absolute metabolic rates. Subcortical-to-cortical ratios for the lenticular nucleus and thalamus were increased in schizophrenics compared with controls, reflecting a preservation of activity in these structures relative to decreased cortical metabolism. When patients were grouped by length of medication-free period before the initial study, there was a trend for patients who had been medication free less than 6 months to have higher subcortical ratios. However, there were no consistent effects of medication in the subsample of patients whose PET studies were repeated following treatment. The results demonstrate relative hypermetabolism in structures implicated in dopamine pathways. An understanding of the physiological significance of this finding awaits the combined measurement of metabolic activity and neuroreceptors in schizophrenics.     

Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS

OBJECTIVE: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in medicated patients with chronic schizophrenia. METHOD: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 patients with schizophrenia and 21 comparable healthy volunteers. RESULTS: Significantly lower levels of glutamine and glutamate were found in the left anterior cingulate cortex of patients with schizophrenia than in the healthy volunteers. For the schizophrenia patients, the glutamine level in the left thalamus was found to be higher than normal, and there was a significant negative correlation between N-acetylaspartate level and duration of positive symptoms. CONCLUSIONS: Since previous studies have found higher than normal levels of glutamine in the left anterior cingulate of never-treated patients, decreased levels of these metabolites in chronic patients could be related to neurodegeneration or the effects of chronic medication.     

Brain metabolism in patients with schizophrenia before and after acute neuroleptic administration.

Positron emission tomography (PET) with 11C-2-deoxyglucose (11DG) was used to compare regional brain metabolism in four patients with chronic schizophrenia who had no history of psychotropic medication and in 12 normal controls. Patients had a second PET scan after an injection of thiothixene to evaluate the effects of acute neuroleptics on glucose metabolism. The patients showed higher glucose metabolic values than the normals and did not show the metabolic hypofrontality reported in chronic medicated patients with schizophrenia. Administration of the neuroleptic did not have a significant effect in the metabolic pattern of the patients. These results give support to the hypothesis that prolonged medication may contribute to the metabolic hypofrontal pattern seen in patients with schizophrenia.     

Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls

CONTEXT: Tryptophan depletion (TD) is a model used to study the contribution of reduced serotonin transmission to the pathogenesis of major depressive disorder (MDD). Recent studies have not sufficiently addressed the relative contribution of a functional-length triallelic polymorphism in the promoter of the serotonin transporter, 5-HTTLPR, to the behavioral and neural responses to TD in individuals with remitted MDD (rMDD) and controls. OBJECTIVE: To determine the role of 5-HTTLPR on the behavioral and neural responses to TD in medication-free patients with rMDD and individually matched controls. DESIGN: Participants were stratified according to diagnosis and 5-HTTLPR genotypes and underwent TD on one test day and sham depletion on the other test day in a prospective, double-blind, randomized order. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven medication-free patients with rMDD (18 women and 9 men) and 26 controls (17 women and 9 men). INTERVENTIONS: Tryptophan depletion was induced by administration of capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing lactose. Fludeoxyglucose F 18 positron emission tomography was performed 6 hours after TD. Magnetic resonance images were obtained for each participant. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral metabolic rates for glucose and measures of depression using the Hamilton Depression Rating Scale. RESULTS: Behavioral responses to TD are affected by 5-HTTLPR in patients with rMDD and controls. A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex. CONCLUSIONS: Variations in 5-HTTLPR modulate the sensitivity of patients with rMDD and controls to the behavioral effects of TD. In patients with rMDD, variations in triallelic 5-HTTLPR have a direct effect on regulation of regional cerebral metabolic rates for glucose in a corticolimbic circuit that has been implicated in rMDD.     

Glucose hypermetabolism in the thalamus of patients with essential blepharospasm

Essential blepharospasm (EB) is classified as a form of focal dystonia characterized by involuntary spasms of the musculature of the upper face. The basic neurological process causing EB is not known. The purpose of this study was to investigate cerebral glucose metabolism in patients with EB whose symptoms were suppressed by an injection of botulinum-A toxin. Earlier studies were confounded by sensory feedback activities derived from dystonic symptom itself. Cerebral glucose metabolism was examined by positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) in 25 patients (8 men and 17 women; age 52.6 +/- 10.1 years) with EB. The patients were awake but with the spasms suppressed by an injection of botulinum-A toxin. Thirty-eight normal volunteers (14 men and 24 women; age 58.2 +/- 7.3 years) were examined as controls. The difference between the two groups was examined by statistical parametric mapping (SPM99). A significant increase in the glucose metabolism was detected in the thalamus and pons in the EB patients. Hyperactivity in the thalamus may be a key pathophysiological change common to EB and other types of focal dystonia. The activity of the striatum and cerebellum are likely to be sensory dependent.     

Eeg alpha rhythm and glucose metabolic rate in the thalamus in schizophrenia

Positron emission tomography with uptake of [(18)F]fluorodeoxyglucose (FDG) and quantitative EEG were simultaneously performed in 18 medication-free patients with schizophrenia and in 13 normal volunteers. Subjects performed the Continuous Performance Task (CPT) during FDG uptake. Correlations were calculated between alpha power during the CPT and glucose metabolic rate (GMR) in thalamic regions and between alpha power during the CPT and GMR in occipital cortices. Regression analyses were used to describe the prediction of GMR in the occipital cortices and in the thalamic regions of occipital alpha power. In normal controls, we found (1) significant negative correlations between absolute alpha power and GMR in the left occipital cortex, (2) significant positive correlations between normalized alpha power and GMR in the right and left lateral thalamus and (3) combined effects of GMR in the thalamic regions and the occipital cortices on alpha power, which accounted for 98% of the variance of alpha power. In patients with schizophrenia, we found no significant correlations between alpha power and GMR in the occipital cortices or between alpha power and GMR in the thalamic regions. Correlation coefficients between absolute alpha power and GMR in the left occipital cortex and between normalized alpha power and GMR in the left lateral thalamus were significantly different in normal subjects compared to schizophrenic patients. The present findings provide evidence for involvement of the thalamus in the generation of alpha rhythm in humans. Furthermore, the present results suggest differences in thalamocortical circuits between normal controls and schizophrenic subjects.     

Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography

Measurements of regional cerebral glucose uptake by the 18F-fluorodeoxyglucose technique (18FDG) and positron emission tomography (PET) along with polygraph recordings were made serially during relaxed wakefulness and different stages of nocturnal sleep in two right-handed normal volunteers. During stage III-IV sleep, values declined diffusely in both hemispheric regions (-31%), thalamus (-33%), cerebellum (-33%) and brain stem (-25%). During paradoxical sleep regional values increased diffusely compared with slow wave sleep. Compared to wakefulness, regional metabolic values seemed to increase but the results were more variable from one volunteer to the other. These preliminary data indicate important regional alterations in cerebral metabolism between sleep states.     

Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls

CONTEXT: An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan. OBJECTIVE: To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD. DESIGN: Randomized double-blind crossover study. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean +/- SD age, 34.4 +/- 11.5 years). INTERVENTIONS: We induced TD by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale. RESULTS: Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls. CONCLUSION: The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD.     

From syndrome to illness: delineating the pathophysiology of schizophrenia with PET

The Section on Clinical Brain Imaging of the Laboratory of Cerebral Metabolism has been engaged in studying regional brain metabolism by positron emission tomography (PET) to establish the pathophysiology of schizophrenia. Recent studies have revealed that the fluorodeoxyglucose (FDG) PET methodology can be applied successfully to determine the anatomical substrata of directed attention. In normal controls, the metabolic rate in the middle prefrontal cortex, measured during the ongoing performance of auditory discrimination, is associated with their accuracy of performance. In unmedicated patients with schizophrenia, even those who performed as well as normals, the metabolic rate in the mid-prefrontal cortex was found to be significantly lower than normal. Further, this decreased metabolic rate was unrelated to performance. In medicated patients with schizophrenia, at least part of the metabolic deficit remains, but this deficit appears to be performance-related. These findings suggest several conclusions. The mid-prefrontal cortex and its dopamine neurotransmitter pathway input are important biological determinants of sustained attention. Two types of prefrontal metabolic deficits may contribute to dysfunctional goal-directed behavior and, more speculatively, vulnerability to psychosis in some patients with schizophrenia. One deficit is sensitive to neuroleptics, and thus presumably to a change in the balance of regional brain dopamine input. A second deficit is unaffected by neurolpetic treatment.     

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.