Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: a preliminary report

Previous research has found frontal lobe involvement in memory impairment in schizophrenia. In the present study, proton magnetic resonance spectroscopy was performed in 13 young patients with schizophrenia and 13 normal control subjects. Spectra were obtained from a voxel of 2 x 2 x 1.5 cm(3) in the bilateral inferior frontal gyrus and thalamus. Subjects were given a verbal learning task and stimulus category repetition (SCR) was calculated from the performance of the task. Significantly reduced N-acetylaspartate (NAA)/choline-containing compounds ratios were found in the left inferior frontal cortex of patients compared with controls. The total number of words recalled by patients was significantly lower than that recalled by controls. In all subjects, SCR scores were positively correlated with NAA/phosphocreatine ratios of the left inferior frontal cortex, which showed a trend towards a decrease in patients. These results support the notion of metabolic abnormalities in the left inferior frontal region related to verbal memory deficits in patients with schizophrenia.     

Correlation of regional cerebral blood flow equivalents measured by single photon emission computerized tomography with P300 latency and eye movement abnormality in schizophrenia

Single photon emission tomography with the intravenous blood flow marker ^99mTc-exametazime was carried out in 14 acutely ill drug-free schizophrenic patients from whom P300 event-related potential, smooth eye pursuit eye tracking and verbal fluency were measured within a few days of scanning. Smooth pursuit eye movement abnormality correlated significantly with abnormal tracer uptake in superior pre-frontal cortex on the right and left and inferior pre-frontal cortex on the left. Abnormal eye movement was also associated with higher tracer uptake in left anterior cingulate and left posterior cingulate. P300 latency was significantly correlated with higher tracer uptake in left superior pre-frontal and left parietal regions. Verbal fluency performance was negatively correlated with tracer uptake in left frontal region. Eye tracking abnormality in schizophrenia is associated with bilateral frontal lobe disturbance and P300 latency increase with left-sided frontal and temporoparietal dysfunction. There was, however, a significant inverse relation between eye tracking abnormalities and abnormal perfusion in the left anterior cingulate region.     

Brain activation patterns during a selective attention test-a functional MRI study in healthy volunteers and patients with schizophrenia

Functional magnetic resonance imaging was used to compare cortical activation patterns in healthy volunteers with those in patients with schizophrenia during a modified verbal Stroop task. Healthy subjects (n=13) and patients with schizophrenia (n=13) on stable antipsychotic treatment, matched on demographic variables, were included. Patients were preselected on the basis of good performance on a selective attention test. Patients with schizophrenia showed a significantly increased pattern of activation in the left and right inferior frontal cortex and the anterior cingulate cortex. A significant negative correlation between activation of the left prefrontal cortex and accuracy in the modified Stroop test was observed for healthy controls but not schizophrenia patients. Although both groups recruited the prefrontal cortex during the modified Stroop task, for the schizophrenia patients this activation was bilateral, whereas for the controls this activation was primarily in the left hemisphere, suggesting that patients with schizophrenia recruited more prefrontal regions to perform the task with the same accuracy as healthy controls. Our findings of increased activity across multiple areas of the brain, including dorsolateral frontal cortex and anterior cingulate, in patients with schizophrenia who perform relatively well on a task of selective attention give further evidence that task performance may be a confounding factor in the interpretation of neuroimaging results.     

Procedural learning in schizophrenia investigated with functional magnetic resonance imaging

A cerebral basis for the acquisition and retention of procedural knowledge in schizophrenia was examined with 1.5 T functional MRI during an embedded sequence Serial Reaction Time Task (SRTT) in 10 chronic medicated patients and 15 healthy controls. Comparable procedural learning was observed in both groups, suggesting that the impairment reported in previous schizophrenia samples may not be robust. Consistent with previous fMRI reports, procedural learning in the control group was associated with activity in the dorsal striatum, anterior cingulate, parietal cortex and frontal cortex. Greater procedural learning related activity was observed in the control relative to the schizophrenia group in the bilateral frontal, left parietal and bilateral caudate regions. Patients did not activate frontal or parietal areas while responding to the embedded sequence within the SRTT, but greater activation during procedural learning was observed relative to the control sample in the right anterior cingulate, left globus pallidus and the right superior temporal gyrus. Thus, despite comparable instantiation of procedural learning in schizophrenia, the cerebral activation associated with this cognitive skill was abnormal. The paucity of activity in bilateral frontal cortex, left parietal cortex and bilateral caudate nucleus may represent cerebral dysfunction associated with schizophrenia, whereas the hyperactivation of the right superior temporal gyrus, the right anterior cingulate cortex and the left globus pallidus may represent a compensatory cerebral action capable of facilitating near-normal task performance. The results are thus consistent with a neurodevelopmental pathology impinging on fronto-subcortical circuitry.     

Regional cerebral blood flow in male schizophrenic patients performing an auditory discrimination task

Regional cerebral blood flow (rCBF) was measured in 11 schizophrenic patients amid 10 normal controls, both at rest and while performing an auditory discrimination task. Single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was used for quantitative evaluation of rCBF. The schizophrenic patients showed greater rCBF in the temporal and parietal regions at rest than the controls, but no abnormalities were found in frontal perfusion. During task performance. on the other hand, the patients showed a reduced frontal rCBF. whereas there was no group difference in rCBF in the temporal and parietal regions. In addition, the left> right hemisphere asymmetries of rCBF observed in the controls during task performance were not present in the patients. although there was no group difference in hemisphere laterality in rCBF at rest. These findings suggest that the employment of a cognitive task for neuroimaging studies is useful for detecting abnormalities of brain activation. such as hypofrontality and altered hemisphere laterality. in patients with schizophrenia.     

Gray matter abnormalities in paranoid schizophrenia and their clinical correlations

Numerous imaging studies have shown structural brain abnormalities in schizophrenia. Recently, voxel-based morphometry enabled whole brain analysis beyond the regions of interest (ROI). Regional gray matter concentrations of magnetic resonance (MR) images from 35 patients with paranoid schizophrenia were compared with those from 35 age- and sex-matched controls, and their clinical correlations were explored using voxel-based morphometry. Gray matter concentrations in the patients were significantly reduced in the left insular and dorsolateral prefrontal regions, and bilaterally in the medial frontal, anterior cingulate, inferior frontal and superior temporal regions. On the other hand, gray matter concentrations in the bilateral cerebellum and right striatum were significantly increased in the patients compared with controls. A negative correlation between the score for the severity of 'lack of insight and judgment' and gray matter concentrations in the left posterior and right anterior cingulate and bilateral inferior temporal regions including the lateral fusiform gyri was found. These results suggest the important roles of the paralimbic structures in the pathophysiology of schizophrenia and the involvement of the perceptual and monitoring systems in the mechanism of insight.     

Brain response abnormalities during verbal learning among patients with schizophrenia

Patients with schizophrenia often show verbal learning deficits that have been linked to the pathophysiology of the disorder and result in functional impairment. This study examined the biological basis of these deficits by comparing the brain response of patients with schizophrenia (n=17) to that of healthy comparison participants (n=14) during a verbal paired-associates learning task using functional magnetic resonance imaging (fMRI). Brain response during new word learning was examined within and between groups in two a priori regions of interest, the inferior frontal gyrus and hippocampus, and across the whole brain. In regions of group difference, we also examined the relationship of brain response during learning to later recall of the word pairs. Despite successful matching of levels of word-pair recall, patients' brain response during new learning was abnormal in bilateral regions within the inferior frontal gyrus, a small region in left posterior hippocampus, and other areas within the frontal, parietal and temporal cortex compared with healthy individuals. In some regions, but not in the hippocampus, patients with the most normal brain response also remembered the most word pairs following scanning. Thus, verbal learning deficits found among patients with schizophrenia appear to be related to hypofunction of distributed brain networks.     

精神分裂症患者基础及认知激活状态局部脑血流的研究

目的 探讨精神分裂症患者基础及认知激活状态局部脑血流量(rCBF)特点及精神分裂症症状与rCBF之间的关系。方法 患者组为49例未用过抗精神病药治疗的精神分裂患者,对照组为26名正常人。以阳性及阴性症状量表（PANSS）等量表评定患者组疾病严重程度,用双日法进行基础及认知激活状态单光子发射计算机断层扫描（SPECT）脑显像,以威斯康星卡片分类试验（ WCST）为认知激活工具。结果 患者组基础状态时左颞叶外侧部及左右颞叶后下部rCBF比值明显高于对照组（P＝0.050,0.002及0.001)。认知激活状态时与基础状态时比较,对照组左额叶外侧中部及右枕叶上部的血流灌注明显增加（ P＝0.001及0.033);患者组各感兴趣区（region of interest,ROI）血流灌注无明显变化。PANSS阳性量表及阳性症状量靛（SAPS）评分与左颞叶外侧部、右颞枕部、右颞叶后上部、右枕叶上部、右顶叶中部及左右顶叶等ROI的rCBF比值呈正相关。结论 精神分裂症患者可能存在潜在的额叶功能低下,阳性症状的严重程度与一些ROI的血流灌注量有关。     

Clinical symptoms and regional cerebral blood flow in schizophrenia

This study examined the relationship between clinical symptoms and regional cerebral blood flow (rCBF) in schizophrenic patients using single photon emission computed tomography (SPECT). The subjects were 26 medicated schizophrenic patients diagnosed according to DSM-III-R criteria. Clinical symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS), selected items for the Positive and Negative Syndrome Scale (PANSS), and the scale for Schneider's first rank symptoms. Resting rCBF was measured using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT, and relative rCBF distribution was evaluated in nine regions of interest in each hemisphere. Factor analysis of symptom ratings indicated four separate syndromes: psychomotor poverty, alienation (hallucination and disturbance of the self), delusion, and disorganization. Stepwise multiple regression analysis showed the psychomotor poverty syndrome to be correlated with decreased rCBF in bilateral superior frontal areas and increased rCBF in the left thalamus and right basal ganglia. The disorganization syndrome was correlated with increases rCBF in bilateral anterior cingulates and decreased rCBF in bilateral midolle frontal areas. The alienation syndrome was shown related to increased rCBF in the right inferior frontal area and parietal area. Dysfunction in distinctive neural networks involving various prefrontal areas would thus appear to underlie these syndromes in schizophrenia.     

精神分裂症患者局部脑血流研究

目的：了解精神分裂症患者局部脑血流(rCBF)特征，探讨rCBF与临床症状和疗效的关系。方法：采用阳性症状与阴性症状量表(PANSS)评定精神分裂症患者精神症状，应用^99m锝-双半胱乙脂(^99mTc-ECD)，单光子发射计算机断层扫描(SPECT)技术，测量患者治疗前后rCBF，并与11名正常人作对照。结果：治疗前患者组右侧额叶与右侧颞叶rCBF低于对照组；治疗后右侧额叶与右侧颞叶rCBF较治疗前明显增加。治疗前不同脑区rCBF与精神病理症状和疗效均无显著相关。结论：精神分裂症患者存在右侧额叶与颞叶局部脑功能减退，但未发现rCBF与精神病理症状和疗效有关。     

Attenuated frontal activation in schizophrenia may be task dependent

Functional magnetic resonance imaging was used to examine the neural correlates of two linguistic tasks in schizophrenia. METHOD: Five dextral male schizophrenic patients and five volunteers matched for demographic variables and task performance participated. Echoplanar images were acquired over 5 min at 1.5 T while subjects performed two paced, covert tasks; (1) verbal fluency: silent generation of words beginning with an aurally presented cue letter, contrasted with silent repetition of the aurally presented word 'rest'; (2) semantic decision: deciding whether a visually presented cue word was 'living or non-living' and silently articulating the response, contrasted with rest. Both tasks entailed language processing; only verbal fluency requires the intrinsic generation of verbal material. Between-group differences in the mean power of experimental response to the semantic decision task were identified by a one-way analysis of covariance (ANCOVA), with a measure of stimulus-correlated motion as a covariate. Voxels demonstrating a significant interaction between task and group were identified using a two-way ANCOVA. RESULTS: In controls, both tasks were associated with activation of prefrontal cortex. In patients with schizophrenia there was a significantly reduced power of response in several prefrontal regions during verbal fluency relative to controls, a difference that was not evident for the semantic decision task. There was a significant group x task interaction in the left inferior frontal gyrus, left dorsolateral prefrontal cortex and the supplementary motor area at voxel and regional levels of analysis. CONCLUSIONS: Attenuation of frontal activation during cognitive task performance in schizophrenia does not represent a fixed deficit in frontal function, but may depend on the specific cognitive demands of the experimental task employed.     

The relationship between regional cerebral blood flow and the Wisconsin Card Sorting Test in negative schizophrenia

The purpose of this study was to explore the relationship between regional cerebral blood flow (rCBF) and problem-solving thinking in negative schizophrenia. Twenty-one negative schizophrenic patients and 12 normal controls were studied with single photon emission computed tomography (SPECT). Measures of regional cerebral blood flow (rCBF) were taken both at rest and during a prefrontal activation task using Wisconsin Card Sorting Test (WCST). Compared with controls, poor performances on the WCST of total trials category (TT), perseverative errors (PE) and non-perseverative errors (NE) were found in negative schizophrenic (P < 0.05). During WCST activation, patients showed interhemispheric differences in the prefrontal region, but under rest conditions, no such differences manifested. The negative schizophrenia group had a significantly lower rCBF change rate in profrontal lobe during stimulant WCST than those in normal controls (P < 0.05). The negative schizophrenic patient has executive function deficits and lower rCBF perfusion in left profrontal lobes, which suggest that the negative schizophrenic patient has dysfunction of the left profrontal region.     

Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI

This study examined regional structural changes in the whole brain in 45 medicated patients with schizophrenia (23 males and 22 females), comparing with 42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was conducted using statistical parametric mapping (SPM). Compared with the controls, relative gray matter in the patients was significantly reduced in the left superior temporal, left middle and inferior frontal, right inferior frontal, and bilateral anterior cingulate and medial temporal areas. Gray matter reductions in the left superior temporal and prefrontal areas were found predominantly in the male patients, while the anterior cingulate gray mater reduction was more striking in the female patients. On the contrary, significant gray matter increases in the patients were found in the parietal areas and the cerebellum. In the white matter, significant reduction was found in the bilateral anterior limbs of the internal capsule and the superior occipitofrontal fasciculus, whereas the bilateral parietal white matter showed significant increases. These results suggest that a pathological process in schizophrenia predominantly affects the fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting bundles, which was first found in this study, may imply morphological substrates for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in schizophrenia.     

精神分裂症患者记忆围棋子位置时的脑激活区域

BACKGROUND： Go, a traditional Chinese chess-like game, requires many unknown functions of the brain including attention, imaging, problem solving and processing of spatial working memory. To date, it remains uncertain whether the intellectual activities required to play Go are related to the frontal lobe. OBJECTIVE： To investigate various patterns of brain region activity while schizophrenic patients and normal subjects engaged in memorizing piece placement in the Chinese game of Go. Spatial working memory was measured in order to validate whether the prefrontal lobe participates in this memory process.
DESIGN, TIME AND SETTING： Non-randomized, concurrent control trial was performed at Second Xiangya Hospital of Central South University, between May and December 2004.
PARTICIPANTS： A total of nine Chinese schizophrenic patients with no brain or bodily diseases and not undergoing electroshock treatment, who were in accordance with the DSM-Ⅳ criteria for schizophrenia, as well as thirteen healthy staffs and students with matched age, sex, and education were included. Patients and control subjects had no neurological disorders or mental retardation. In addition, all participants were right-handed. METHODS： The cognitive task for functional magnetic resonance imaging was a block design experiment. Both groups were asked to remember the placement of pieces in the Chinese game of Go on a computer screen. A brain activation map was analyzed in SPM99.
MAIN OUTCOME MEASURES： Brain responses were compared with regard to activation region size, volume, and asymmetry indices. RESULTS： Compared with the control group, the reaction time was significantly delayed in schizophrenics performing the working memory task （P 〈 0.05）. When performing the tasks, normal subjects showed significant activation of the bilateral dorsolateral prefrontal lobe with left dominance; the asymmetry indices were： frontal lobe, ＋0.32; temporal lobe, 0.58; parietal lobe, 0.41 ; and occipital lobe, 0.34. On the other hand, schizophrenics showed right dominance and had a broader activation region of the prefrontal lobe （asymmetry indices： frontal lobe, 0.10; temporal lobe, ＋0.38; parietal lobe, ＋0.24; and occipital lobe, 0.00）. When comparing the normal group subtracted with the schizophrenic group, no significant lateralization was found in the frontal lobes but significant activation was found in the left anterior central gyrus, left middle frontal gyrus and in both sides of the cingulate gyrus. Comparing the schizophrenic group subtracted with the normal group, there was significant right lateralization of the frontal lobe and abnormally activated regions on both sides of the anterior central gyrus, middle frontal gyrus, left inferior frontal gyrus, right medial frontal gyrus and the right insular lobe. CONCLUSION： Different brain activation regions are involved in memorizing the placement of pieces in Chinese Go between schizophrenia and healthy subjects. Schizophrenics showed right dominance and border activation range, indicating that the prefrontal cortex plays an important role in memory information processing and resource allocation when remembering piece placement in the game of Go.     

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.     

A Tc-99m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome

Twenty-nine patients with DSM-IV diagnoses of schizophrenia were categorized into deficit syndrome (n=14) and non-deficit syndrome (n=15) subgroups on the basis of the Schedule for the Deficit Syndrome. The patients, who had all been free of antipsychotic medication for at least 3 weeks, and 17 sex- and age-matched normal controls were studied with single-photon emission computed tomography with Tc-99m HMPAO. Age at onset, Brief Psychiatric Rating Scale (BPRS) total scores, BPRS positive symptom subscores and duration of illness were similar between the two schizophrenic subgroups. As expected, the deficit patients had more negative symptoms than the non-deficit patients. There were no statistically significant correlations between clinical parameters and regional cerebral blood flow (rCBF) values. The deficit syndrome subgroup showed diminished rCBF in the frontal regions bilaterally, right parietal regions and right superior temporal region compared with the control groups. Deficit patients showed significantly lower rCBF perfusion ratios in the right superior and inferior frontal cortex than did the non-deficit patients. No differences were detected between the controls and the non-deficit schizophrenic patients in terms of rCBF perfusion indices. The results of the present study confirm previous reports of different patterns of rCBF in deficit vs. non-deficit schizophrenic subgroups.     

Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation

Procedural learning (PL) is a type of rule-based learning in which performance facilitation occurs with practice on task without the need for conscious awareness. Schizophrenic patients have often (though not invariably) been found to show impaired PL. We performed functional magnetic resonance imaging (fMRI) during a blocked, periodic sequence-learning task with groups of: (i) healthy subjects, and (ii) schizophrenic patients on conventional antipsychotics. Healthy subjects showed significant PL, but patients did not. In healthy subjects, PL was associated with increased activation in the striatum, thalamus, cerebellum, precuneus, medial frontal lobe, and cingulate gyrus. The power of activation in the thalamus, striatum, precuneus, cingulate gyrus and BA 6 was related to the magnitude of PL in these subjects. No regions, except the anterior inferior gyrus, were significantly activated in patients. The caudate nucleus, thalamus, precuneus, and sensorimotor regions were activated significantly differently between the two groups. The findings demonstrate the involvement of the striatum, cerebellum, thalamus, cingulate gyrus, precuneus, and sensorimotor regions in PL. Further fMRI studies of PL in normal subjects treated with conventional antipsychotics, drug na?ve patients, and patients given atypical antipsychotics would help to clarify the roles of schizophrenic disease processes and antipsychotic medication in impaired PL and associated brain abnormalities in schizophrenia.     

A functional magnetic resonance imaging paradigm of expressed emotion in schizophrenia

Chronic exposure to adverse interpersonal environment in schizophrenia is associated with vulnerability to relapse. The construct of expressed emotion (EE) measures the quality of interpersonal environment, of which criticism is a main component. To use functional magnetic resonance imaging and to investigate the neural basis of vulnerability of schizophrenic patients to EE, the effects of critical comments on brain mechanisms in 11 patients with schizophrenia were examined, comparing evoked responses to familiar (key relative) and unfamiliar (matched stranger) critical and neutral commentary. High EE stimuli evoked enhanced activation of brain regions concerned with the processing of aversive social information. Activations in the right BA44, rostral anterior cingulate, middle superior frontal gyrus, bilateral middle frontal gyrus, left temporal pole, left inferior frontal gyrus, and left insula were significantly modulated to familiar criticism. Such a pattern of neural response may represent a putative neural network responsible for mediating High EE in schizophrenia.     

Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron emission tomography study

OBJECTIVE: This study explored the neural circuitry used during recall of unstructured verbal material in schizophrenic patients and healthy volunteer subjects. METHOD: The subjects were 13 healthy volunteers and 14 schizophrenic patients. All patients were free of medication, and all subjects were right-handed. Two experimental cognitive conditions were used: recall of novel and practiced word lists (two 15-item lists from the Rey Auditory Verbal Learning Test). Both active recall tasks were compared with an eyes-closed resting baseline condition. A nonparametric randomization test was used to determine within- and between-group differences in regional cerebral blood flow. RESULTS: Performance on both the practiced and novel memory tasks was nonsignificantly different in the patients and control subjects. During the novel memory task, the patients showed decreased flow in the right anterior cingulate, right thalamus, and bilateral cerebellum (left greater than right) relative to the control subjects. When recalling the practiced word lists, the patients showed decreased flow in the left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left supplementary motor area, left thalamus, left cerebellar regions, anterior vermis, and right cuneus. CONCLUSIONS: Patients with schizophrenia fail to activate cortical-cerebellar-thalamic-cortical circuitry during recall of both well-learned and novel word lists.     

SPECT study of visual fixation in schizophrenia and comparison subjects.

BACKGROUND: The consistent association of impaired eye movements and schizophrenia suggests a relationship between the neurobiology of the illness and visual pursuit systems. Visual fixation (VF), an eye "movement" task at zero velocity, is the simplest such abnormality in schizophrenia patients and their relatives. METHODS: We used a VF task for a functional imaging study. Six neuroleptic-free schizophrenia patients and eight gender and mean age matched comparison subjects had SPECT scans with 20 mCi of Tc99-HMPAO, during VF on a simple blue line intersection. MEDX data saved in ANALYZE format for SPM 95 was used to generate paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. RESULTS: Patients, compared to controls, had increased rCBF in both the parahippocampal gyrus (bilaterally) and in the right fusiform gyrus. They had decreased rCBF in the left frontal cortex, including medial and superior frontal gyri and anterior cingulate. Overall, compared to controls, patients had medial temporal lobe hyperperfusion along with left prefrontal hypoperfusion. CONCLUSIONS: These findings are consistent with the hypothesized imbalance between the medial temporal and frontal lobes that is postulated for schizophrenia. It was of interest that the relative rCBF differences between schizophrenia patients and controls in this small sample were observable with this cognitively non-demanding visual fixation task.