Reduced source activity of event-related potentials for affective facial pictures in schizophrenia patients

The ability to recognize facial affect is impaired in schizophrenia patients. This study compared source activities of the event-related potentials (ERPs) for affective facial pictures between schizophrenia patients and healthy controls. Twenty-three schizophrenia patients (11 females) and 24 healthy controls (12 females) were recruited. The standardized low-resolution brain electromagnetic tomography (sLORETA) source activities of four ERP components (P100, N170, N250, and P300) were compared between schizophrenia patients and healthy controls in response to fearful, happy, and neutral facial expressions. Group differences of sLORETA source activities were found only for the N170 component in response to the fearful face. Source activities in the middle frontal gyrus and inferior frontal gyrus were lower in schizophrenia patients compared to healthy controls. Source activity in the insula was lower in male schizophrenia patients compared to male healthy controls. Source activities in the superior temporal gyrus, middle temporal gyrus, insula and inferior frontal gyrus were lower in male compared to female schizophrenia patients. However, there was no gender difference on ERP source activities in the healthy controls. These results support the hypothesis that schizophrenia patients have reduced N170 current source density in response to fearful faces. The area exhibiting reduced current source density includes the frontal and temporal cortex. The present results suggest that there may be gender differences in facial affect processing in schizophrenia patients.     

Depression is associated with increased sensitivity to signals of disgust: A functional magnetic resonance imaging study

Emotions of fear and disgust are related to core symptoms of depression. The neurobiological mechanisms of these associations are poorly understood. This functional magnetic resonance imaging study aimed at examining the Blood oxygenation level dependent (BOLD) response to facial expressions of fear and disgust in patients with major depressive disorder.Nine patients in an episode of major depression and nine healthy controls underwent two functional magnetic resonance imaging experiments where they judged the gender of facial identities displaying different degrees (mild, strong) of fear or disgust, intermixed with non-emotional faces.Compared with healthy controls, patients with depression demonstrated greater activation in left insula, left orbito-frontal gyrus, left middle/inferior temporal gyrus, and right middle/inferior temporal gyrus to expressions of strong disgust. Depressed patients also demonstrated reduced activation in left inferior parietal lobe to mildly fearful faces.Enhanced activation to facial expressions of disgust may reflect an emotion processing bias that suggests high relevance of emotion of disgust to depression.     

Functional MRI of facial emotion recognition deficits in schizophrenia and their electrophysiological correlates

Empirical evidence suggests impaired facial emotion recognition in schizophrenia. However, the nature of this deficit is the subject of ongoing research. The current study tested the hypothesis that a generalized deficit at an early stage of face-specific processing (i.e. putatively subserved by the fusiform gyrus) accounts for impaired facial emotion recognition in schizophrenia as opposed to the Negative Emotion-specific Deficit Model, which suggests impaired facial information processing at subsequent stages. Event-related potentials (ERPs) were recorded from 11 schizophrenia patients and 15 matched controls while performing a gender discrimination and a facial emotion recognition task. Significant reduction of the face-specific vertex positive potential (VPP) at a peak latency of 165 ms was confirmed in schizophrenia subjects whereas their early visual processing, as indexed by P1, was found to be intact. Attenuated VPP was found to correlate with subsequent P3 amplitude reduction and to predict accuracy when performing a facial emotion discrimination task. A subset of ten schizophrenia patients and ten matched healthy control subjects also performed similar tasks in the magnetic resonance imaging scanner. Patients showed reduced blood oxygenation level-dependent (BOLD) activation in the fusiform, inferior frontal, middle temporal and middle occipital gyrus as well as in the amygdala. Correlation analyses revealed that VPP and the subsequent P 3a ERP components predict fusiform gyrus BOLD activation. These results suggest that problems in facial affect recognition in schizophrenia may represent flow-on effects of a generalized deficit in early visual processing.     

抑郁症患者情绪图片刺激早期低频脑磁图研究

目的：探讨抑郁症患者给予视觉情绪图片刺激早期0～100ms、100～200ms、200～300ms3个时段8～30Hz的神经磁场激活特征。方法：8例抑郁症患者及12例健康右利手对照者,在给予国际情绪图片库（IAPS）正性、中性、负性情绪图片刺激同时记录脑磁图信号,使用SPM8b软件进行数据分析：设两样本t检验P〈0.01（未校正）和K值≥10个体素范围为差异有统计学意义。结果：与对照组相比,抑郁组在正性情绪图片刺激下,100～200ms内的左侧额下回,右侧的终板旁回、额内侧回、海马回激活增强。在中性情绪图片刺激下,抑郁组在0～100ms的右侧豆状核、岛叶、额上回,左内侧额叶,100～200ms内的右侧岛叶、豆状核壳核及屏状核,左侧额下回、额上回、颞上回,200～300ms内的右侧岛叶、豆状核、尾状核体激活增强。负性情绪图片刺激下抑郁组在0～100ms内的右侧颞上回、岛叶、尾状核头部、额中下回激活增强,100～200ms内的右侧额中回、尾状核体,200～300ms内右额下回激活增强。此外还比较一致的发现抑郁组在楔前叶、后扣带回等顶叶脑区激活降低。结论：抑郁个体起注意调节功能的顶叶脑区如楔前叶功能不足,对视觉皮质向前部脑区情绪信息颞叶底部传递通路抑制不足,腹侧前额皮质、岛叶过度的激活,可能是抑郁症的一个发病基础。     

Facial Emotion Processing in Schizophrenia: A Meta-analysis of Functional Neuroimaging Data

Background: People with schizophrenia have difficulty with emotion perception. Functional imaging studies indicate regional brain activation abnormalities in patients with schizophrenia when processing facial emotion. However, findings have not been entirely consistent across different studies. Methods: Activation likelihood estimation (ALE) meta-analyses were conducted to examine brain activation during facial emotion processing in patients with schizophrenia, controls, and patients compared with controls. Secondary meta-analyses were performed to assess the contribution of task design and illness chronicity to the results reported. Results: When processing facial expressions of emotions, both patients with schizophrenia and healthy controls activated the bilateral amygdala and right fusiform gyri. However, the extent of activation in these regions was generally much more limited in the schizophrenia samples. When directly compared with controls, the extent of activation in bilateral amygdala, parahippocampal gyrus and fusiform gyrus, right superior frontal gyrus, and lentiform nucleus was significantly less in patients. Patients with schizophrenia, but not controls, activated the left insula. A relative failure to recruit the amygdala in patients occurred regardless of whether the task design was explicit or implicit, while differences in fusiform activation were evident in explicit, not implicit, tasks. Restricting the analysis to patients with chronic illness did not substantially change the results. Conclusions: A marked underrecruitment of the amygdala, accompanied by a substantial limitation in activation throughout a ventral temporal-basal ganglia-prefrontal cortex “social brain” system may be central to the difficulties patients experience when processing facial emotion.     

Neural mechanism for judging the appropriateness of facial affect

Questions regarding the appropriateness of facial expressions in particular situations arise ubiquitously in everyday social interactions. To determine the appropriateness of facial affect, first of all, we should represent our own or the other's emotional state as induced by the social situation. Then, based on these representations, we should infer the possible affective response of the other person. In this study, we identified the brain mechanism mediating special types of social evaluative judgments of facial affect in which the internal reference is related to theory of mind (ToM) processing. Many previous ToM studies have used non-emotional stimuli, but, because so much valuable social information is conveyed through nonverbal emotional channels, this investigation used emotionally salient visual materials to tap ToM. Fourteen right-handed healthy subjects volunteered for our study. We used functional magnetic resonance imaging to examine brain activation during the judgmental task for the appropriateness of facial affects as opposed to gender matching tasks. We identified activation of a brain network, which includes both medial frontal cortex, left temporal pole, left inferior frontal gyrus, and left thalamus during the judgmental task for appropriateness of facial affect compared to the gender matching task. The results of this study suggest that the brain system involved in ToM plays a key role in judging the appropriateness of facial affect in an emotionally laden situation. In addition, our result supports that common neural substrates are involved in performing diverse kinds of ToM tasks irrespective of perceptual modalities and the emotional salience of test materials.     

Neural bases of different cognitive strategies for facial affect processing in schizophrenia

OBJECTIVE: To examine the neural basis and dynamics of facial affect processing in schizophrenic patients as compared to healthy controls. METHOD: Fourteen schizophrenic patients and fourteen matched controls performed a facial affect identification task during fMRI acquisition. The emotional task included an intuitive emotional condition (matching emotional faces) and a more cognitively demanding condition (labeling emotional faces). Individual analysis for each emotional condition, and second-level t-tests examining both within-, and between-group differences, were carried out using a random effects approach. Psychophysiological interactions (PPI) were tested for variations in functional connectivity between amygdala and other brain regions as a function of changes in experimental conditions (labeling versus matching). RESULTS: During the labeling condition, both groups engaged similar networks. During the matching condition, schizophrenics failed to activate regions of the limbic system implicated in the automatic processing of emotions. PPI revealed an inverse functional connectivity between prefrontal regions and the left amygdala in healthy volunteers but there was no such change in patients. Furthermore, during the matching condition, and compared to controls, patients showed decreased activation of regions involved in holistic face processing (fusiform gyrus) and increased activation of regions associated with feature analysis (inferior parietal cortex, left middle temporal lobe, right precuneus). CONCLUSIONS: Our findings suggest that schizophrenic patients invariably adopt a cognitive approach when identifying facial affect. The distributed neocortical network observed during the intuitive condition indicates that patients may resort to feature-based, rather than configuration-based, processing and may constitute a compensatory strategy for limbic dysfunction.     

An fMRI Study of the Neural Correlates of Incidental Versus Directed Emotion Processing in Pediatric Bipolar Disorder

ObjectiveTo use functional neuroimaging to probe the affective circuitry dysfunctions underlying disturbances in emotion processing and emotional reactivity in pediatric bipolar disorder (PBD).MethodEqual numbers of controls (HC) and unmedicated patients with euthymia and PBD were matched for age, sex, race, socioeconomic status, and IQ (n = 10 per group; mean age 14.2 years [SD 2.0 years]). The task consisted of a “directed” emotion processing condition where subjects judged whether emotion in facial expression was positive or negative and an “incidental” condition where subjects judged whether faces expressing similar affect were older or younger than 35 years.ResultsRelative to the directed condition, the incidental condition elicited greater activation in the right amygdala and the right insula, the left middle frontal gyrus, and the left posterior cingulate cortex in patients with PBD, in contrast to the HC that showed greater activation in the right superior frontal gyrus. In both incidental and directed conditions, relative to visual fixation, patients with PBD showed less activation in the right prefrontal cortex (superior, middle, and inferior frontal gyri) and the pregenual anterior cingulate cortex and greater activation in the posterior visual and face-processing regions (i.e., right precuneus/cuneus, fusiform gyrus).ConclusionsIncreased amygdala activation observed in patients with PBD elicited by incidental emotional processing relative to directed emotional processing may indicate more intense automatic emotional reactivity. Furthermore, the right prefrontal systems that are believed to modulate affect seem to be less engaged in patients with PBD regardless of whether the emotion processing is incidental or directed, which may signify reduced top-down control of emotional reactivity in PBD.     

Impaired fronto-temporal processing of emotion in schizophrenia.

AIMS: Abnormal emotion processing in schizophrenia affects social and functional outcome. Spatiotemporal brain mechanisms underlying this deficit are unclear. MATERIALS AND METHODS: Event-related potential (ERP) responses to emotional and neutral face processing during an implicit (gender detection) and an explicit (expression detection) task were compared between a group of healthy volunteers (n=10) and a group of patients with schizophrenia (n=10). RESULTS: Whereas patients had normal primary visual cortex responses, the early modulation of occipital, temporal, and frontal responses by emotional expression observed in controls was absent in patients. The occipito-temporal N170 amplitude was reduced in patients relative to controls during expression detection, but not during gender detection. Frontal activity within 180-250ms was reduced in patients compared to controls. As opposed to controls, no significant difference was seen in patients at the right temporal electrode (T6) between amplitudes of long-latency ERPs elicited by distinct emotions during the expression detection task. CONCLUSION: In patients with schizophrenia, abnormal early extraction of expression-related information in the occipito-temporal cortex (before 170ms) impairs structural encoding of facial expressions (N170) and may disrupt motivation- and task-dependent context processing (180-250ms time window) of expression-related facial features. Moreover, top-down neuromodulation from frontal and limbic structures to visual occipito-temporal cortex may not be sufficient to optimize the extraction of expression-specific face features.     

Prefrontal functional dissociation in the semantic network of patients with schizophrenia

We examined whether deficient prefrontal control over the semantic network exists in patients with schizophrenia. Fourteen patients with schizophrenia and 14 healthy controls performed a comparison task, judging semantic congruity according to an abstract category in an event-related functional MRI paradigm. In the control group, prefrontal-temporal networks consisting of the left inferior frontal gyrus and right inferior frontal sulcus converging at the left posterior superior temporal sulcus were identified as activated during semantic demand of incongruence. In the patients with schizophrenia, we observed a loss of the recruitment of the right inferior frontal sulcus and the prefrontal-temporal network. These findings indicate that cognitive modulation of semantic processing may be dysfunctional in patients with schizophrenia.     

Neural substrates of facial emotion processing using fMRI

We identified human brain regions involved in the perception of sad, frightened, happy, angry, and neutral facial expressions using functional magnetic resonance imaging (fMRI). Twenty-one healthy right-handed adult volunteers (11 men, 10 women; aged 18-45; mean age 21.6 years) participated in four separate runs, one for each of the four emotions. Participants viewed blocks of emotionally expressive faces alternating with blocks of neutral faces and scrambled images. In comparison with scrambled images, neutral faces activated the fusiform gyri, the right lateral occipital gyrus, the right superior temporal sulcus, the inferior frontal gyri, and the amygdala/entorhinal cortex. In comparisons of emotional and neutral faces, we found that (1) emotional faces elicit increased activation in a subset of cortical regions involved in neutral face processing and in areas not activated by neutral faces; (2) differences in activation as a function of emotion category were most evident in the frontal lobes; (3) men showed a differential neural response depending upon the emotion expressed but women did not.     

Cerebral differences in explicit and implicit emotional processing--an fMRI study

The processing of emotional facial expression is a major part of social communication and understanding. In addition to explicit processing, facial expressions are also processed rapidly and automatically in the absence of explicit awareness. We investigated 12 healthy subjects by presenting them with an implicit and explicit emotional paradigm. The subjects reacted significantly faster in implicit than in explicit trials but did not differ in their error ratio. For the implicit condition increased signals were observed in particular in the thalami, the hippocampi, the frontal inferior gyri and the right middle temporal region. The analysis of the explicit condition showed increased blood-oxygen-level-dependent signals especially in the caudate nucleus, the cingulum and the right prefrontal cortex. The direct comparison of these 2 different processes revealed increased activity for explicit trials in the inferior, superior and middle frontal gyri, the middle cingulum and left parietal regions. Additional signal increases were detected in occipital regions, the cerebellum, and the right angular and lingual gyrus. Our data partially confirm the hypothesis of different neural substrates for the processing of implicit and explicit emotional stimuli.     

Age-dependent differences in human brain activity using a face- and location-matching task: an FMRI study

PURPOSE: To evaluate the differences of cortical activation patterns in young and elderly healthy subjects for object and spatial visual processing using a face- and location-matching task. MATERIALS AND METHODS: We performed a face- and a location-matching task in 15 young (mean age: 28 +/- 9 years) and 19 elderly (mean age: 71 +/- 6 years) subjects. Each experiment consisted of 7 blocks alternating between activation and control condition. For face matching, the subjects had to indicate whether two displayed faces were identical or different. For location matching, the subjects had to press a button whenever two objects had an identical position. For control condition, we used a perception task with abstract images. Functional imaging was performed on a 1.5-tesla scanner using an EPI sequence. RESULTS: In the face-matching task, the young subjects showed bilateral (right > left) activation in the occipito-temporal pathway (occipital gyrus, inferior and middle temporal gyrus). Predominantly right hemispheric activations were found in the fusiform gyrus, the right dorsolateral prefrontal cortex (inferior and middle frontal gyrus) and the superior parietal gyrus. In the elderly subjects, the activated areas in the right fronto-lateral cortex increased. An additional activated area could be found in the medial frontal gyrus (right > left). In the location-matching task, young subjects presented increased bilateral (right > left) activation in the superior parietal lobe and precuneus compared with face matching. The activations in the occipito-temporal pathway, in the right fronto-lateral cortex and the fusiform gyrus were similar to the activations found in the face-matching task. In the elderly subjects, we detected similar activation patterns compared to the young subjects with additional activations in the medial frontal gyrus. CONCLUSION: Activation patterns for object-based and spatial visual processing were established in the young and elderly healthy subjects. Differences between the elderly and young subjects could be evaluated, especially by using a face-matching task.     

Crossmodal emotional integration in major depression

Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life, emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects. Subjects rated the expression of happy, neutral and fearful faces while concurrently being exposed to emotional or neutral sounds. Results demonstrated group differences in left inferior frontal gyrus and inferior parietal cortex when comparing incongruent to congruent happy facial conditions, mainly due to a failure of patients to deactivate these regions in response to congruent stimulus pairs. Moreover, healthy subjects decreased activation in right posterior superior temporal gyrus/sulcus and midcingulate cortex when an emotional stimulus was paired with a neutral rather than another emotional one. In contrast, patients did not show such deactivation when neutral stimuli were integrated. These results demonstrate aberrant neural response in audiovisual processing in depression, indicated by failure to deactivate regions involved in inhibition and salience processing when congruent and neutral audiovisual stimuli pairs are integrated, providing a possible mechanism of constant arousal and readiness to act in this patient group.     

Working memory processing of facial images in schizophrenia: fMRI investigation

Impaired processing of facial information is one of the broad ranges of cognitive deficits seen in patients with schizophrenia. This study aimed to elucidate the differences in brain activities involved in the process of facial working memory (images of neutral faces as mnemonic content) between schizophrenic patients and healthy comparison subjects using functional magnetic resonance imaging (fMRI). Group comparison analysis revealed aberrant activities from the patient group in several cortical areas, including the left fusiform gyrus, right superior frontal gyrus, bilateral middle frontal gyri/insula, and left middle temporal gyrus. A decreased level of activity in the left fusiform gyrus, along with performance reduction, implicates abnormal processing of facial information in schizophrenia.     

Reduced activation in the mirror neuron system during a virtual social cognition task in euthymic bipolar disorder

Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the ‘mirror neuron system’, including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.     

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.     

精神分裂症首次发病患者额顶网络功能连接与面孔情绪识别能力的关系

目的:探讨首发精神分裂症患者在静息状态下额顶网络的功能连接特点,及其与面孔情绪识别能力的相关性。方法:对37例首发未用药的精神分裂症患者(患者组)和30名年龄、性别、利手、受教育程度与患者相匹配的健康者(正常对照组)进行静息态功能磁共振(f MRI)扫描,收集两组的一般临床特征,并采用面孔情绪测试评价被试的面孔情绪认知功能;以双侧背外侧前额叶(DLPFC)为种子点比较两组间额顶网络功能连接的差异,并分析与面孔情绪认知功能的相关性。结果:与正常对照组相比,患者组DLPFC与左顶下小叶(t=-3.243,Alphasim校正P0.05)、左额下回(t=-3.151,Alphasim校正P0.05)、左额中回(t=-3.151,Alphasim校正P0.05)、双侧尾状核(t=-4.325,Alphasim校正P0.05)、左颞中回(t=-3.120,Alphasim校正P0.05)的功能连接减低;与双侧扣带回中部(t=2.731,Alphasim校正P0.05)、右中央前回(t=3.991,Alphasim校正P0.05)、右岛叶(t=3.991,Alphasim校正P0.05)功能连接增强。患者组额-顶通路的功能连接与面孔情绪认知障碍呈正相关(r=0.501,P0.05)。结论:首发精神分裂症患者额顶网络的功能连接存在异常,其中DLPFC-顶下小叶通路的功能连接降低可能影响患者面孔情绪识别能力。     

Social brain dysfunctions in schizophrenia: a review of neuroimaging studies

Several studies have indicated that schizophrenic patients show impaired performance in various aspects of social cognition, including theory of mind, emotion processing, and agency judgments. Neuroimaging studies that have compared patients and healthy subjects during such mental activity indicate an abnormal hemodynamic response in the medial prefrontal cortex, the prefrontal cortex, the amygdala, the inferior parietal lobe, i.e., a set of regions known to be critically involved in social cognition. This paper addresses a number of issues raised by schizophrenia research into theory of mind, emotion perception and self-agency with regards to the neural systems that mediate social cognition. In healthy subjects, typical brain patterns are associated with theory of mind, emotion perception and self-agency; some activated clusters overlap, while others are distinct. For instance, activations in the paracingulate gyrus are almost systematically associated with theory of mind tasks, while the amygdala is mainly involved in emotion perception tasks. Additional foci are frequently found activated during those tasks: superior temporal sulcus, inferior frontal area. Moreover, the inferior parietal lobe is thought to contribute to agency judgments. In the light of the data on brain abnormalities and neurochemical dysfunctions in schizophrenia, we discuss the interaction of social cognitive dysfunction with the supposed information processing abnormalities caused by dopamine dysregulation.     

Social brain dysfunctions in schizophrenia: A review of neuroimaging studies

Several studies have indicated that schizophrenic patients show impaired performance in various aspects of social cognition, including theory of mind, emotion processing, and agency judgments. Neuroimaging studies that have compared patients and healthy subjects during such mental activity indicate an abnormal hemodynamic response in the medial prefrontal cortex, the prefrontal cortex, the amygdala, the inferior parietal lobe, i.e., a set of regions known to be critically involved in social cognition. This paper addresses a number of issues raised by schizophrenia research into theory of mind, emotion perception and self-agency with regards to the neural systems that mediate social cognition. In healthy subjects, typical brain patterns are associated with theory of mind, emotion perception and self-agency; some activated clusters overlap, while others are distinct. For instance, activations in the paracingulate gyrus are almost systematically associated with theory of mind tasks, while the amygdala is mainly involved in emotion perception tasks. Additional foci are frequently found activated during those tasks: superior temporal sulcus, inferior frontal area. Moreover, the inferior parietal lobe is thought to contribute to agency judgments. In the light of the data on brain abnormalities and neurochemical dysfunctions in schizophrenia, we discuss the interaction of social cognitive dysfunction with the supposed information processing abnormalities caused by dopamine dysregulation.