Brain activation patterns during a selective attention test — a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.     

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.     

Language lateralization in unmedicated patients during an acute episode of schizophrenia: a functional MRI study

In a previous fMRI study of high-functioning outpatients with remitted schizophrenia, we found that healthy subjects and schizophrenia patients showed similar patterns of activation during a verbal fluency task. However, the activation in controls was primarily in Broca's area on the left, while it was more bilateral for schizophrenia patients, implicating a reduced language lateralization in schizophrenia patients. The same fMRI procedure was used in this subsequent study to investigate unmedicated patients during an acute episode of schizophrenia. Schizophrenia patients showed reduced language lateralization in the frontal cortex, because of a more bilateral activation of Broca's area compared with a primarily left hemisphere activation in healthy controls. Furthermore decreased lateralization was correlated to the severity of hallucinations. Although patients with schizophrenia showed a significantly reduced performance on the verbal fluency task when compared with healthy subjects, we were not able to find evidence of decreased language-related activity in the left hemisphere. These results suggest that decreased language lateralization is also evident in unmedicated patients experiencing an acute episode of schizophrenia.     

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

FMRI was used to study cortical activation patterns in nine healthy male subjects and nine high-functioning male schizophrenia patients during a letter verbal fluency task. Both groups showed similar patterns of activation, however, in controls the activation was primarily in the left broca area, while for schizophrenia patients, it was more bilateral. These data indicate that high-functioning schizophrenia patients show a reduced language lateralization of the frontal cortex compared to healthy controls.     

Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.     

偏执型精神分裂症患者Stroop操作的功能磁共振研究

目的利用功能磁共振显像(fMRI)技术探讨精神分裂症患者注意障碍的脑功能基础。方法对14例精神分裂症患者(患者组)和16名正常人(对照组)检测Stroop测验刺激下的fMRI。结果(1)激活脑区计数(个)：Stroopl刺激下,患者组左侧额下回(11/3)、左侧颞上回(6/8)、左侧颞下回(6/8)脑区激活计数均多于对照组(分别为6/10、1/15、1/15),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组左侧前扣带皮质(ACC,4/10)、右侧额中回脑区激活计数(4/10)均少于对照组(分别为12/4、14/2),差异有统计学意义(P＜0.05),患者组左额上回激活计数(9/5)多于对照组(3/ 13),差异有统计学意义(P＜0.05)。(2)激活脑区体积(体素)：Stroop1刺激下,患者组右侧前额叶背外侧区(DLPFC,256±579)、左侧ACC(18±59)激活体积小于对照组(分别为298±597、67±87),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组两侧DLPFC(分别为73±190、80±245)、左侧ACC(17±28)激活体积小于对照组(分别为425±800、414±703、76±98),差异有统计学意义(P＜0.05)。结论精神分裂症患者的注意障碍可能与前额叶、ACC、颞叶神经回路功能障碍密切相关。     

Orienting of attention in unmedicated patients with schizophrenia, prodromal subjects and healthy relatives

In typical orienting of attention tasks subjects have to respond as fast as possible to targets which appear in the periphery of the visual field and are preceded by spatial cues (e.g. brightening of a peripheral box where the target may subsequently appear). Reaction times (RT) are facilitated when cue and target appear at the same location (valid cueing) and the cue target interval is short (<250 ms). However, RTs slow down again when the target follows a valid cue after an interval of 250 ms and longer. This latter phenomenon is called Inhibition of Return (IOR) and is thought to reflect an automatic, inhibitory mechanism to protect the organism from redundant and distracting stimuli. Deficits of IOR were repeatedly reported in patients with schizophrenia. However, the role of medications and the nature of the deficit (trait or vulnerability indicator?) were unclear. In the present study we examined 15 unmedicated patients with schizophrenia (age: 31.2+/-11.1, m/f: 11/4, global scores SAPS: 48.33+/-33.09, SANS: 19.22+/-26.16), 29 subjects who were putatively in a prodromal state of psychosis, 30 first-degree relatives, another 8 first-degree relatives who had one child and at least one more relative with schizophrenia, and 50 healthy controls. We found an impairment of IOR only in the unmedicated patient group. In conclusion, blunted IOR in schizophrenia is not secondary to medications. According to this and previous studies blunted IOR may be most probably viewed as a trait cognitive feature of the schizophrenic disorder.     

联想学习记忆的脑功能磁共振成像

目的 通过脑功能磁共振成像(functional magnetic resonance imaging,fMRI)技术检测健康人脑纹状体边缘区(marginal division of the striatum,MrD)是否参与联想学习记忆的过程.方法 对16名右利手健康志愿者进行一项配对词语联想学习记忆任务的同时,进行fMRI扫描.试验采用组块设计并选用SPM 99软件进行数据分析和脑功能区定位.结果 应用单样本t检验(SPM统计软件将体素的激活强度T值在数值上等于t检验的t值),当统计阈值设为P＜0.005时,左枕叶和左额上、中回在任务编码时被显著激活(最大激活强度分别为T=13.87、9.36),左纹状体边缘区也在该阶段被明显激活(T=5.46);而左顶叶则在记忆提取阶段被显著激活(T=8.73).结论 除皮质外,皮质下结构如MrD也参与了词语联想学习记忆过程.     

Ventral striatal activation during attribution of stimulus saliency and reward anticipation is correlated in unmedicated first episode schizophrenia patients

Patients with schizophrenia show deficits in motivation, reward anticipation and salience attribution. Several functional magnetic resonance imaging (fMRI) investigations revealed neurobiological correlates of these deficits, raising the hypothesis of a common basis in midbrain dopaminergic signaling. However, investigations of drug-na?ve first-episode patients with comprehensive fMRI tasks are still missing. We recruited unmedicated schizophrenia spectrum patients (N=27) and healthy control subjects (N=27) matched for sex, age and educational levels. An established monetary reward anticipation task in combination with a novel task aiming at implicit salience attribution without the confound of monetary incentive was applied. Patients showed reduced right ventral striatal activation during reward anticipation. Furthermore, patients with a more pronounced hypoactivation attributed more salience to neutral stimuli, had more positive symptoms and better executive functioning. In the patient group, a more differentially active striatum during reward anticipation was correlated positively to differential ventral striatal activation in the implicit salience attribution task. In conclusion, a deficit in ventral striatal activation during reward anticipation can already be seen in drug-na?ve, first episode schizophrenia patients. The data suggest that rather a deficit in differential ventral striatal activation than a generally reduced activation underlies motivational deficits in schizophrenia and that this deficit is related to the aberrant salience attribution.     

Depression in patients with schizophrenia during an acute psychotic episode.

There is disagreement about whether depressive symptoms in schizophrenia are part of the basic disease process, or whether they represent adverse effects of treatment with antipsychotic medications. In a sample of initially antipsychotic drug-free acutely hospitalized patients with schizophrenia (N = 104), we measured change in depressive symptoms after 4 weeks of treatment. We also examined the relationship of changes in depressive symptoms to changes in positive and negative schizophrenic symptoms. Depressive symptoms improved after 4 weeks of antipsychotic medication treatment, and their improvement corresponded with improvement in both positive and negative schizophrenic symptoms. These results suggest that depressive symptoms in schizophrenia are related to the disease process itself, at least during acute exacerbations of schizophrenia. Depressive symptoms may be responsive to antipsychotic medications directly or as a secondary response to improvement in positive and negative symptoms.     

A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery

OBJECTIVE: Difficulty with social interactions is a characteristic of schizophrenia. The authors used functional magnetic resonance imaging (fMRI) to investigate brain activation changes during a social cognition paradigm in patients with schizophrenia during and after an acute episode and their association with social and executive function. METHOD: In a longitudinal study design, 14 patients with schizophrenia experiencing an acute episode had an fMRI scan. They returned for a follow-up scan after clinical improvement. Fourteen healthy comparison subjects were also scanned twice with approximately the same time interval between scans as in the patient group. The authors employed a social cognition fMRI paradigm involving empathic and forgivability judgments. Schizophrenia symptoms, social functioning and illness insight scales, and the Wisconsin Card Sorting Test were used to examine whether improvement on these measures was associated with recovery of brain activation in response to the social cognition paradigm. RESULTS: After recovery from the acute episode, patients exhibited increased activation in the left medial prefrontal cortex, which was, in turn, significantly correlated with improved insight and social functioning. Decreased symptom severity and improved performance on the Wisconsin Card Sorting Test were not significantly associated with increased left medial prefrontal cortex activation. CONCLUSIONS: This is the first study to the authors' knowledge to use a social cognition paradigm to reveal improved left medial prefrontal cortex activation in schizophrenia after recovery from an acute episode. These results suggest that restored left medial prefrontal cortex activation may mediate improvement of insight and social functioning in patients with schizophrenia.     

正常人词语流畅性作业的脑功能磁共振成像研究

目的 利用功能磁共振成像(fMRI)技术探讨词语流畅性作业的脑功能定位。方法对18名健康志愿者进行词语流畅性作业的fMRI检查,fMRI用梯度回波-平面回波成像序列采集数据,经工作站处理后获功能图像。结果 经Fisher精确检验法,健康志愿者的双侧额上回、双侧额中回、右侧额下回及右侧扣带回的激活脑区计数,与理想激活脑区计数的差异均无显著性(P>0.05),其余脑区激活计数的差异均有显著性(P<0.05)。结论 双侧额叶背外侧及右侧额叶腹外侧可能参与长时记忆的提取过程,其中额叶背外侧可能参与核查及管理工作,而额叶腹外侧可能参与搜寻特异目标的过程。     

Brain activation patterns in schizophrenic and comparison volunteers during a matched-performance auditory recognition task

OBJECTIVE: The biological characteristics of schizophrenia are often studied by using functional imaging techniques. However, since volunteers with schizophrenia routinely fail to perform as accurately or as quickly as healthy volunteers, it is difficult to ascertain whether a particular deficit in blood flow to a brain region is due to behavior or to the underlying illness. In this report, investigators used an auditory recognition task to assess brain blood flow patterns and behavioral correlates of schizophrenic patient volunteers trained on the task. METHOD: Twelve healthy volunteers and 18 volunteers with schizophrenia were trained to make tone frequency recognitions. Accuracy and stimuli were matched between groups. Participants were required to press a button to indicate whether a briefly presented tone was the high-frequency (1500 Hz) reference tone or one of a lower frequency level (level chosen to elicit an 80% accuracy score). Subjects underwent bolus [(15)O]H(2)O blood flow positron emission tomography during inactive rest, a sensory motor control condition, and the decision task. Blood flow patterns were assessed between conditions and between groups. RESULTS: As a group, the patients with schizophrenia (who performed as quickly and accurately as the comparison subjects) exhibited significantly less change in regional cerebral blood flow (rCBF) to the anterior cingulate and supplementary motor cortices when switching from the sensory motor control to the decision condition. There were also marked between-group differences in correlations between rCBF and response time. Whereas the comparison subjects exhibited progressively greater blood flow to the frontal cortex in association with longer response times, the schizophrenic patients exhibited progressively lower blood flow in conjunction with extended response times. CONCLUSIONS: The failure to appropriately enhance cingulate activity when engaged in a demanding task and the progressive, time-dependent decline in frontal blood flow suggest that patients with schizophrenia are unable to make optimal use of frontocingulate systems when maximally engaged in high-error tasks.     

Changes in neuronal activation with increasing attention demand in healthy volunteers: an fMRI study.

Several lines of evidence suggest that structures involved in mediating attention differentially respond to increasing processing demand. Investigation of differences in neuronal activation, however, has been complicated by methodological inconsistencies and concomitant discrepancies in degree of difficulty and subject effort between disparate tasks. In this study, we utilized fMRI to compare neural activation patterns associated with two related attention tasks associated with different degrees of processing load while controlling for degree of performance difficulty. Healthy volunteers performed two continuous performance tasks, utilizing an identical pairs paradigm (CPT-IP) and a matched simple number recognition paradigm with degraded stimuli (CPT-DS) during a single fMRI scan. Degree of stimulus resolution degradation in the latter CPT was designed to equalize degree of performance difficulty between the two tasks. CPT-IP and CPT-DS were both associated with activation of frontal, limbic, subcortical, and sensory integratory structures. CPT-IP administration was associated with significantly greater activation of left dorsolateral prefrontal cortex, bilateral posterior temporal cortex, bilateral putamen, and thalamus. This study demonstrates both that differing attention tasks are associated with a high degree of functional overlap and that increasing processing demand is associated with increased activation of specific portions of attentional networks.     

Brain activation during semantic judgment of Chinese sentences: A functional MRI study

A functional magnetic resonance imaging (fMRI) study was conducted to investigate whether the anatomic substrates of semantic memory may reflect categorical organization and to determine whether the left middle frontal gyrus (Brodmann area [BA] 9) plays a role in Chinese semantic judgment. Unlike previous studies using a word-retrieval task (e.g., word generation, naming, and word categorization), we used a typical task of semantic knowledge retrieval in cognitive psychology in which subjects were asked to determine whether a sentence describing an attribute of living things or nonliving things was true or not. The experimental conditions evoked extensive activation over several regions of the brain including a very strong activation in the left middle frontal region (BA9 and BA46). Our data show that there is no unique activation associated with living or nonliving things at the statistical threshold used in our study. The results imply that human semantic system is undifferentiated by category at the neural level. Our findings also corroborate and extend the claim that the left middle frontal gyrus plays an important role in reading Chinese at both the sentence and the word level.     

Brain functional connectivity of male patients in remission after the first episode of schizophrenia

Objectives: Abnormal task‐related activation and connectivity is present in schizophrenia. The aim of this study was the analysis of functional networks in schizophrenia patients in remission after the first episode. Experimental design: Twenty‐nine male patients in remission after the first episode of schizophrenia and 22 healthy controls underwent examination by functional magnetic resonance during verbal fluency tasks (VFT). The functional connectivity of brain networks was analyzed using independent component analysis. Results: The patients showed lower activation of the salience network during VFT. They also showed lower deactivation of the default mode network (DMN) during VFT processing. Spectral analysis of the component time courses showed decreased power in slow frequencies of signal fluctuations in the salience and DMNs and increased power in higher frequencies in the left frontoparietal cortex reflecting higher fluctuations of the network activity. Moreover, there was decreased similarity of component time courses in schizophrenia—the patients had smaller negative correlation between VFT activated and deactivated networks, and smaller positive correlations between DMN subcomponents. Conclusions: There is still an abnormal functional connectivity of several brain networks in remission after the first episode of schizophrenia. The effect of different treatment modalities on brain connectivity, together with temporal dynamics of this functional abnormality should be the objective of further studies to assess its potential as a marker of disease stabilization. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Longitudinal MRI study in schizophrenia patients and their healthy siblings

To investigate whether genetic and/or disease-related factors are involved in progressive structural brain changes in schizophrenia, magnetic resonance imaging scans with a 5-year scan interval were acquired in patients, their same-gender siblings and matched healthy controls. Structural equation modelling was applied to assess disease and familial effects. Whole brain and cerebral grey matter volumes decreased excessively in patients compared with their siblings and the controls, suggesting that the progressive brain loss in schizophrenia may be related to the disease process.     

Spatial selective attention and inhibition in schizophrenia patients during acute psychosis and at 4-month follow-up.

BACKGROUND: Attentional abnormalities may lie at the core of cognitive symptoms in schizophrenia, but it is unclear how they relate to symptoms. The major aim of our study was to understand the relation between spatial attention and clinical symptoms from acute to chronic state. METHODS: Thirty-six acutely psychotic schizophrenia patients and 42 matched control subjects were assessed on three spatial attention measures: target location detection, interference (concurrent inhibition of distractor), and negative priming (subsequent inhibition of distractor). Symptoms were assessed by the Positive and Negative Syndrome Assessment Scale. Four months later, the same subjects were re-tested, and symptoms were re-assessed. RESULTS: Symptoms were significantly reduced at the follow-up. Schizophrenia patients were slower at detecting target location than control subjects, but they improved significantly over time. Schizophrenia patients and control subjects did not differ on the interference task. Negative priming was abolished during acute psychosis, but 4 months later it was restored. Positive symptoms were correlated with reduced negative priming but not with interference, nor with target detection. Negative priming during acute psychosis was significantly correlated with the clinical symptoms at the follow-up. CONCLUSIONS: These results suggest that reduced negative priming may be associated with increased clinical, symptoms especially the positive symptoms.     

Brain activation pattern according to exercise complexity: a functional MRI study

The aim of this study was to compare the areas of brain activation between complex and simple exercises in a unimanual hand and to assess the possibility of an exercise task for paretic hands following stroke. The subjects included 11 healthy right-handed volunteers. The complex exercise was a wooden ball rotation task with the unimanual hand and the simple exercise was a hand grasp task performed during a functional MRI scan. Stronger activation of the left primary sensorimotor cortex, the left premotor area, and the ipsilateral cerebellum emerged when the complex movement was performed. Ipsilateral activity was located in the primary sensory cortex and premotor area, and contralateral activity was shown in the left cerebellum. These results suggest that a unimanual ball rotation task may be appropriate for rehabilitation of a movable paretic hand in an early stage of stroke recovery, which should provide motor and sensory input using external stimuli, while the simple motor task may appropriate in a compensatory stage, and should inhibit the ipsilateral activity due to maladaptive plasticity.     

Brain activation in the processing of Chinese characters and words: a functional MRI study

Functional magnetic resonance imaging was used to identify the neural correlates of Chinese character and word reading. The Chinese stimuli were presented visually, one at a time. Subjects covertly generated a word that was semantically related to each stimulus. Three sorts of Chinese items were used: single characters having precise meanings, single characters having vague meanings, and two-character Chinese words. The results indicated that reading Chinese is characterized by extensive activity of the neural systems, with strong left lateralization of frontal (BAs 9 and 47) and temporal (BA 37) cortices and right lateralization of visual systems (BAs 17-19), parietal lobe (BA 3), and cerebellum. The location of peak activation in the left frontal regions coincided nearly completely both for vague- and precise-meaning characters as well as for two-character words, without dissociation in laterality patterns. In addition, left frontal activations were modulated by the ease of semantic retrieval. The present results constitute a challenge to the deeply ingrained belief that activations in reading single characters are right lateralized, whereas activations in reading two-character words are left lateralized.