The effect of working memory performance on functional MRI in schizophrenia

INTRODUCTION: Studies of prefrontal cortical (PFC) function in schizophrenia have been inconsistent, with studies showing both increased and decreased PFC activation compared to healthy controls. Discrepant findings may be due to task performance effects or demographic differences between samples. We report functional magnetic resonance imaging (fMRI) data comparing subjects with schizophrenia and healthy controls performing a 2-back working memory (WM) task, addressing the effects of task performance. METHODS: Twenty-two controls and 14 patients with DSM-IV schizophrenia, scanned on a Siemens 1.5 T scanner, performed a visual letter 2-back task and control task (CPT-X) during fMRI. Data were analyzed using Statistical Parametric Mapping (SPM)-99. RESULTS: After statistical adjustment for performance differences, persons with schizophrenia showed significantly greater activation than controls in the right medial frontal gyrus and left inferior parietal lobule/medial temporal gyrus region (BA 39/40), and a trend toward greater activation in the left ventrolateral PFC. This pattern was also observed in demographically matched subgroups of participants. CONCLUSIONS: Data are consistent with findings reported in recent studies showing increased PFC and parietal activation in schizophrenia when the effects of reduced WM task performance in patients with schizophrenia are addressed. Further studies are needed to clarify the pathophysiological basis of WM load sensitivity in schizophrenia and its relationship to genes.     

Schizophrenia subgroups differing in dichotic listening laterality also differ in neurometabolism and symptomatology

Schizophrenia patients vary in right ear advantage (REA) on dichotic listening tests for assessing left hemispheric dominance for language processing. The authors examined if patients with low REA differed from other patients in symptoms and in resting brain metabolism. SPECT was conducted during visual fixation for 9 healthy control subjects and 16 schizophrenia patients: 8 with normal and 8 with diminished REA. REA-diminished patients had greater positive symptoms and lower mental status scores (all P<0.05) and had right middle temporal gyrus hypermetabolism. Both schizophrenia groups had decreased right frontal and increased medial temporal lobe metabolism vs. control subjects. REA-diminished patients had right temporal lobe hypermetabolism under a resting condition (eyes open, visual fixation). Results suggest reduced right ear (left hemisphere) advantage for dichotic word perception in schizophrenia is related to a predisposition to overactivate right temporal lobe regions and to positive symptoms. In contrast, the prefrontal-medial temporal imbalance present in both patient groups may typify the schizophrenia syndrome.     

Brain dysfunctions during facial discrimination in schizophrenia: Selective association to affect decoding

Schizophrenia patients exhibit impaired facial affect perception, yet the exact nature of this impairment remains unclear. We investigated neural activity related to processing facial emotional and non-emotional information and complex images in 12 schizophrenia patients and 15 healthy controls using functional magnetic resonance imaging. All subjects performed a facial information processing task with three conditions: matching facial emotion, matching facial identity, and matching complex visual patterns. Patients and controls showed comparable behavioral performance in all task conditions. The neural activation patterns in schizophrenia patients and healthy controls were distinctly different while processing affect-related facial information but not other non-emotional facial features. During emotion matching, orbital frontal cortex and left amydala activations were found in controls but not in patients. When comparing emotion versus identity matching, controls activated the fusiform and middle temporal gyri, left superior temporal gyrus, and right inferior and middle frontal gyrus, whereas schizophrenia patients only activated the middle and inferior frontal gyri, the frontal operculi and the right insular cortex. Our findings suggest that schizophrenia patients and healthy controls may utilize different neural networks when processing facial emotional information.     

Neural correlates of memory organization deficits in schizophrenia. A single photon emission computed tomography study with 99mTc-ethyl-cysteinate dimer during a verbal learning task

Regional cerebral blood flow (rCBF) during a verbal learning task was measured using 99mTc-ethyl-cysteinate dimer and single photon emission computed tomography in 10 patients with schizophrenia and nine normal controls. Verbal repetition was used as a control task. The schizophrenic patients showed failure to spontaneously utilize implicit category information to learn the word lists. In the normal controls, rCBF in the left inferior frontal and left anterior cingulate regions was significantly increased during the verbal learning task, compared with the verbal repetition task. In contrast, there was no significant frontal lobe activation by the verbal learning in the schizophrenic patients. The patients had lower rCBF during the verbal learning task than the controls in the bilateral inferior frontal, left anterior cingulate, right superior frontal, and bilateral middle frontal regions. Activation in the left inferior frontal region was significantly positively correlated with categorical clustering in the task in the controls, but no such correlation was found in the patients. These results indicate that memory organization deficits in schizophrenia may be related to dysfunction in the prefrontal areas, especially in the left inferior frontal region.     

Reduced reward processing in the brains of Parkinsonian patients

Regional cerebral blood flow (rCBF) in healthy controls and non-demented, non-depressed Parkinsonian patients was measured using H2(15)O PET while subjects performed a prelearned pattern recognition task with delayed response. To investigate differences between the two groups in response to reward, the experimental design consisted of three reinforcement conditions: no reinforcement consisting of nonsense feedback, positive symbolic reinforcement and monetary reward. In the controls, monetary reward activated bilaterally the striatum and anterior cingulate gyrus, as well as unilaterally the left cerebellum, midbrain and medial frontal gyrus. Symbolic reinforcement revealed a similar pattern of activation, except that the striatum and left midbrain showed no activation. The Parkinsonian patients responded to monetary reward with increased activation bilaterally in the cerebellum, medial frontal gyrus, and anterior cingulate gyrus as well as unilaterally in the right fusiform gyrus and midbrain and left caudate nucleus and precentral gyrus. Symbolic reinforcement induced significantly increased rCBF in the right cerebellum only. Compared with symbolic reinforcement, monetary reward produced extended activation of temporoparietal association cortex. The pattern observed in the controls demonstrates the role in reward processing of dopaminergic mesolimbic pathways in the healthy human brain, whereas the pattern in the Parkinsonian patients suggests the involvement of compensatory cortical loops in the diseased brain.     

A SPECT study of apathy in Alzheimer's disease

BACKGROUND/AIMS: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer's Disease (AD). METHODS: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 +/- 6.6 years; MMSE 22.3 +/- 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 +/- 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. RESULTS: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. CONCLUSIONS: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.     

Visual exploration of form and position with identical stimuli: functional anatomy with PET

Visual form and position perception in primates is thought to engage two different sets of cortical visual areas. However, the original concept of two functionally different and anatomically segregated pathways has been challenged by recent investigations. Using identical stimuli in the centre of the visual field with no external cues, we examined whether discrimination of form aspects and position aspects would indeed activate occipito-temporal and occipito-parietal areas, respectively. We measured and localised regional cerebral blood flow (rCBF) changes in the brain with positron emission tomography (PET) and 15O-butanol while the subjects performed four visual tasks: position discrimination (PD), form discrimination (FD), joint form and position discrimination (FPD), and a control task. Discrimination of form contrasted with discrimination of position resulted in rCBF increases in the lateral occipital and fusiform gyri. Discrimination of position contrasted with discrimination of form yielded rCBF increases in the left frontal eye field and middle frontal gyrus. No extra activations were seen when the joint form and position discrimination task was contrasted with either the individual form and position discrimination tasks. When the individual form and position discrimination tasks were contrasted with the control task, form discrimination resulted in activations in both occipito-temporal and occipito-parietal visual cortical regions, as well as in the right middle-frontal gyrus. Position discrimination resulted in activation in occipito-parietal visual cortical regions, the left frontal eye field and the left middle frontal gyrus. These findings are consistent with the view that the processing of visual position information activates occipito-parietal visual regions. On the other hand, the processing of 2D visual form information, in addition to the activation of occipito-temporal neuronal populations, also involves the parietal cortex. Form and position discrimination activated different nonsymmetrical prefrontal fields. Although the visual stimuli were identical, the network of activated cortical fields depended on whether the task was a form discrimination task or a position discrimination task, indicating a strong task dependence of cortical networks underlying form and position discrimination in the human brain. In contrast to former studies, however, these task-dependent macronetworks are overlapping in the posterior parietal cortex, but differentially engage the occipito-temporal and the prefrontal cortex.     

Does hypofrontality expand to global brain area in progression of schizophrenia?: A cross-sectional study between first-episode and chronic schizophrenia

Although to date there have been no conclusive pathophysiological findings in support of the degenerative theory of the etiology of schizophrenia, the results of neuroimaging studies have suggested that progressive changes in the brain do occur during the clinical course of schizophrenia. However, there has been no report on alterations in regional cerebral blood flow (rCBF) under resting condition, which was compared between the first-episode and the chronic patients of schizophrenia and healthy controls. Therefore, in this study, we applied three-dimensional stereotactic surface projection analysis of resting SPECT (3D-SSP SPECT) in patients with first-episode (n = 18) and chronic schizophrenia (n = 23) and age-/sex-matched healthy controls (n = 40). The rCBFs in the middle/inferior/medial frontal gyrus and the anterior cingulate gyrus were significantly decreased in both patient groups, relative to the respective controls (Z > 3.0, P < 0.001, uncorrected). The chronic group showed significant hypoperfused region in the left inferior parietal lobule and middle/inferior temporal gyrus. Furthermore, within-cases comparison between the first-episode and chronic schizophrenia, revealed that the significant hypoperfused regions in the chronic group, compared to the first-episode group, were not only the lateral and medial prefrontal cortex, but also the inferior parietal cortex, posterior part of the temporal lobe, and the cuneus. The present study suggested that the reduction in rCBF occurs in the posterior brain area in addition to the frontal lobe across all clinical stages of schizophrenia.     

首发精神分裂症患者的功能磁共振初步研究

目的 利用血氧水平依赖性(blood oxygenation level-dependent,BOLD)功能磁共振成像(functional magnetic resonance imaging,fMRI)技术探讨首发精神分裂症患者治疗前后认知功能激发图像的特点。方法 13例首发精神分裂症患者入组,用利培酮或氯丙嗪治疗后9例患者复查fMRI。以词语流畅性作业(verbal fluency task,VF)作为任务,采用Block设计,用梯度回波-平面回波成像(GRE-EPI)序列采集数据,经工作站处理后获功能图像。结果 (1)VF激活受试者的额叶(前额叶)、顶叶及颞叶皮层;(2)复查的9例受试者中,7例激活增强,2例激活减弱;(3)治疗后激活增强的7例受试者的双侧额上、中、下回激活有增加趋势,而双侧颞上、中、下回激活有减少趋势(P>0.05);但左额叶背外侧面治疗后的激活明显强于治疗前(P=0.032)。结论 BOLD-fMRI可用于研究人脑的高级认知功能。首发精神分裂症患者治疗前后脑功能图像有明显变化,提示认知缺陷症状是可以治疗的。     

PET study of human voluntary saccadic eye movements in darkness: effect of task repetition on the activation pattern

Using H₂¹⁵O 3D Positron Emission Tomography (PET), regional cerebral blood flow (rCBF) was measured in six human subjects under two different conditions: at rest and while performing self-paced horizontal saccadic eye movements in darkness. These two conditions were repeated four times each. First, the comparison between the four saccadic and four resting conditions was investigated in a group and a single subject analysis. Saccades elicited bilateral rCBF increases in the medial part of the superior frontal gyrus (supplementary eye field), precentral gyrus (frontal eye field), superior parietal lobule, anterior medial part of the occipital lobe involving striate and extrastriate cortex (lingual gyrus and cuneus), and in the right inferior parietal lobule. At the subcortical level, activations were found in the left putamen. These results mainly replicate previous PET findings on saccadic control. Second, the interaction between the experimental conditions and their repetition was examined. When activations throughout repetition of the same saccadic task are compared, the supplementary eye fields show a progressive increase of activation. On the contrary, the activation in the cerebellum, left superior parietal lobule and left occipital cortex progressively decreases during the scanning session. Given the existence of such an interaction, the pattern of activations must be interpreted as a function of task repetition. This may be a factor explaining some apparent mismatch between different studies.     

Color Stroop and negative priming in schizophrenia: An fMRI study

Disturbances in selective attention represent a core characteristic of schizophrenia, whose neural underpinnings have yet to be fully elucidated. Consequently, we recorded brain activation using functional magnetic resonance imaging (fMRI) while 15 patients with schizophrenia and 15 age-matched controls performed a well-established measure of selective attention—the color Stroop negative priming task. We focused on two aspects of performance: overriding pre-potent responses (Stroop effect) and inhibition of prior negatively primed trials (negative priming effect). Behaviorally, controls demonstrated both significant Stroop and negative priming effects, while schizophrenic subjects only showed the Stroop effect. For the Stroop effect, fMRI indicated significantly greater activation in frontal regions–medial frontal gyrus/anterior cingulate gyrus and middle frontal gyrus for controls–but greater activation in medial parietal regions (posterior cingulate gyrus/precuneus) for patients. Negative priming elicited significant activation in right dorsolateral prefrontal cortex for both groups, but also in left dorsolateral prefrontal cortex for patients. These different patterns of fMRI activation may reflect faulty interaction in schizophrenia within networks of brain regions that are vital to selective attention.     

以妄想为主的男性精神分裂症患者脑局部一致性的功能磁共振研究

目的：探讨男性偏执型精神分裂症患者在静息状态下是否存在脑功能活动异常及其区域。方法：采用病例一对照研究方法,对20例以妄想为主的男性精神分裂症患者（患者组）和20名性别、年龄、受教育程度相匹配的正常对照者（正常对照组）进行功能磁共振成像（fMRI）扫描,分析静息状态下各脑区的局部一致性（regionalhomogeneity,ReHo）的差异。结果：设P〈0．05、体素范围（k值）≥85,与正常对照组比较,患者组双侧额上回、双侧颞中回、左额中回、左中央前回、左小脑脚和右扣带回局部一致性（ReHo值）减低,右颞上回和左颞下回ReHo值增高,而左梭状回ReHo值既有增高也有减低。结论：以妄想为主的男性精神分裂症患者在静息状态下可能存在广泛分布的脑区功能异常。     

Specific motion processing pathway deficit during eye tracking in schizophrenia: a performance-matched functional magnetic resonance imaging study.

BACKGROUND: The neural mechanisms underlying smooth pursuit eye movement (SPEM) abnormalities in schizophrenia are not well understood. Previous evidence suggests that a deficit in the processing of internal representations of object motion (extraretinal motion) contributes to SPEM deficits in patients. Functional magnetic resonance imaging (fMRI) activation was compared between patients and control subjects to determine whether schizophrenia patients exhibit abnormal cerebral activation in regions associated with extraretinal motion processing during SPEM. METHODS: Patients and control subjects were selected based on matched performance in the closed-loop gain. Despite similar performance on closed-loop pursuit gain, patients showed consistent deficits in extraretinal motion based on predictive pursuit. In the magnet, subjects were tested using a traditional smooth-pursuit task that elicits closed-loop response. RESULTS: Patients had reduced pursuit-related activation in several known extraretinal motion processing areas including frontal and supplemental eye fields, medial superior temporal cortex, and anterior cingulate. Patients also showed increased activation in medial occipitotemporal cortex. CONCLUSIONS: These results provide functional anatomic evidence supporting reduced function in the extraretinal motion processing pathway in schizophrenia. Increased activation in medial occipitotemporal cortex suggests an increased dependence on immediate retinal motion information, which may be used to compensate for reduced extraretinal signaling during sustained visual tracking.     

Voxel-based analysis of P300 electrophysiological topography associated with positive and negative symptoms of schizophrenia

Abnormal P300 waveforms of the event-related potentials during the auditory oddball task are one of the most consistent findings in patients with schizophrenia. In the present study, we sought to test the hypothesis that the abnormal P300 waveform results from composite representation of neural activity in anatomically distinct brain regions responsible for the manifestation of positive and negative symptoms. We used the low-resolution brain electromagnetic tomography (LORETA) to obtain current density images of the P300 component from 26 patients with schizophrenia. The statistical parametric mapping (SPM) was applied to the LORETA images in order to identify brain regions that are related with the severity of psychotic symptoms as evaluated by the Brief Psychiatric Rating Scale (BPRS). The BPRS Total score was negatively correlated with the P300 current density in the left superior temporal gyrus (r=-0.615, corrected p=0.009) and that in the right medial frontal region (r=-0.571, corrected p=0.019) by means of SPM single-subject covariates model. These brain regions were included in the region-specific P300 sources as represented by the current density maxima (corrected p<0.05) using SPM one-sample t-test. A subsequent region-of-interest analysis of Pearson correlations revealed specific relationships between the Positive subscale score and the mean current density in the left superior temporal gyrus (r=-0.528, p=0.005) and between the Negative subscale score and the mean current densities in the medial frontal region (r=-0.551, p=0.003) and left superior temporal gyrus (r=-0.499, p=0.009). These results indicate that functional disturbances of neural networks involving the medial prefrontal and superior temporal regions may be responsible for the generation of positive and the negative psychotic symptoms of schizophrenia.     

Recovery from wernicke's aphasia: A positron emission tomographic study

Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke.     

男性偏执型精神分裂症患者静息态功能磁共振脑自发低频振幅的变化

目的:利用静息态功能性磁共振成像(fMRI)技术观察男性偏执型精神分裂症患者脑自发低频振幅(ALFF)的变化。方法:对36例男性偏执型精神分裂症患者(病例组)和19名年龄、利手、性别、受教育程度相匹配的健康者(对照组)进行静息态fMRI扫描;分析两组全脑各区域ALFF的差异。结果:与对照组比较,病例组双侧额中回、右颞中回、右顶下回、左中央前回ALFF明显减低;右颞上回、双侧颞下回、左枕下回ALFF明显增强(P均0.01)。结论:男性偏执型精神分裂症患者脑部广泛区域存在ALFF异常。     

Reduced regional cerebral blood flow in non-psychotic violent offenders

The present study was designed to replicate previously reported findings of abnormal frontal and/or temporal cerebral blood flow in violent offenders and to control for the influence of major mental disorder (MMD), substance abuse, and current medication. HMPAO-SPECT-CBF and MRI scans from pretrial forensic psychiatric investigations of 21 subjects convicted of impulsive violent crimes were retrospectively re-evaluated. In 16/21 subjects, visual assessment of SPECT scans showed some hypoperfusion in the temporal and/or frontal lobes. MRI showed no corresponding structural damage. Quantified regional cerebral blood flow (rCBF) in defined regions of interest was compared between index cases and 11 healthy control subjects. Index subjects had significant reductions in the right angular gyrus and the right medial temporal gyrus, bilaterally in the hippocampus, and in the left white frontal matter, but they had significantly increased rCBF in the parietal association cortex bilaterally. The aberrations were as frequent and severe among the subjects without MMD, substance abuse, and current medication (n=7) as in the entire group of index subjects.     

Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: a preliminary report

A longer duration of untreated psychosis (DUP) in schizophrenia is reported to lead to a poorer clinical outcome, possibly reflecting a neurodegenerative process after the onset of overt psychosis. However, the effect of DUP on brain morphology in schizophrenia is still poorly understood. In this study, we used magnetic resonance imaging to investigate the relation between DUP and volumetric measurements for the superior temporal sub-regions (Heschl's gyrus, planum temporale, and caudal superior temporal gyrus), the medial temporal lobe structures (hippocampus and amygdala), and the frontal lobe regions (prefrontal area and anterior cingulate gyrus) in a sample of 38 schizophrenia patients (20 males and 18 females) whose illness duration was less than five years. We found a significant negative correlation between DUP and the volume of gray matter in the left planum temporale even after controlling for age, age at illness onset, and duration and dosage of neuroleptic medication. There was no such correlation for the other brain regions including each sub-region of the prefrontal cortex (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus). When subjects were divided into two groups around the median DUP, the long-DUP group had a significantly smaller planum temporale gray matter than the short-DUP group. These findings may reflect a progressive pathological process in the gray matter of the left planum temporale during the initial untreated phase of schizophrenia, whereas abnormalities in the medial temporal regions might be, as has been suggested from previous longitudinal findings, relatively static at least during the early course of the illness.     

Effect of attention on frontal distribution of delta activity and cerebral metabolic rate in schizophrenia

15 patients with schizophrenia and nine normal volunteers had 32 channel topographic EEG recorded for spectral analysis during the uptake of 18-F-deoxyglucose (FDG) for positron emission tomography (PET). Both patients and controls performed the Continuous Performance Test, a visual vigilance task, during FDG uptake. EEG was also obtained during an initial pre-FDG resting period. Each EEG epoch was individually inspected for eye movement artifacts. Analysis confirmed increased delta activity in the frontal region of patients with schizophrenia in comparison to normal controls, and a significant correlation between increased frontal delta and relative reduction in frontal lobe metabolism among patients with schizophrenia. This finding of increased delta is consistent with PET, blood flow and topographic EEG studies of schizophrenia, suggesting reduced frontal activity.