Preserved function of the fusiform face area in schizophrenia as revealed by fMRI

Many lines of evidence suggest that individuals with schizophrenia suffer from face processing deficits. However, the specificity of these deficits and the neural dysfunction underlying them remain unclear. To address these questions, we evaluated the functional status of a critical region for face processing, the fusiform face area (FFA), in subjects with schizophrenia. Fourteen schizophrenia patients and 10 healthy control subjects participated in an fMRI experiment to determine the functional status of the FFA by viewing a series of faces and exemplars of other object categories, while completing a low-level task designed to verify their engagement with the stimuli. Behavioral performance and activation of the FFA were equivalent between groups. Thirteen of 14 patients and all control subjects displayed FFA activation. Furthermore, the degree of FFA activation, as measured by FFA volume and magnitude of activity, was similar between groups. The FFA, a critical region in the neural system subserving the perceptual processing of faces, appears to be intact in schizophrenia. These results call into question the presence of a specific face processing deficit in schizophrenia.     

Association between amygdala response to emotional faces and social anxiety in autism spectrum disorders

Difficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD.     

The asymmetry of the fusiform face area is a stable individual characteristic that underlies the left-visual-field superiority for faces

Recognition of faces is better when faces are presented in the left than right-visual-field. Furthermore, this perceptual asymmetry is a stable individual characteristic. Although it has been commonly assumed that the right hemispheric dominance for face processing underlies this left-visual-field superiority in face recognition, this neural-behavioral association has never been directly demonstrated. Here we applied functional MRI (fMRI) to measure the magnitude of the asymmetric response to faces for each subject. To determine whether the asymmetric neural response to faces is stable across sessions, subjects returned for a second fMRI session. In addition, subjects performed a behavioral experiment outside the scanner where they had to recognize centrally presented chimeric faces, which presented different identities in the right- and left-visual-field. This task yielded a measure of the magnitude of the left-visual-field bias for each subject. Our findings show that the magnitude of the asymmetry of the face-selective area in the fusiform gyrus (FFA) is highly consistent for each individual across scans. We then show that the behavioral left-visual-field asymmetry, measured outside the scanner, was strongly and specifically correlated with the asymmetry of the FFA across subjects, but not with other face-specific or nearby object-general regions. Our findings provide the first empirical evidence for the prevalent idea that perceptual asymmetries in face recognition are associated with the well-known hemispheric asymmetry for faces. We conclude that the FFA asymmetry is a highly stable individual characteristic that underlies the well-established left-visual-field superiority for face recognition.     

Experimental manipulation of face-evoked activity in the fusiform gyrus of individuals with autism

Much research has been carried out to understand how human brains make sense of another agent in motion. Current views based on human adult and monkey studies assume a matching process in the motor system biased toward actions performed by conspecifics and present in the observer's motor repertoire. However, little is known about the neural correlates of action cognition in early ontogeny. In this study, we examined the processes involved in the observation of full body movements in 4-month-old infants using functional near-infrared spectroscopy to measure localized brain activation. In a 2?×?2 design, infants watched human or robotic figures moving in a smooth, familiar human-like manner, or in a rigid, unfamiliar robot-like manner. We found that infant premotor cortex responded more strongly to observe robot-like motion compared with human-like motion. Contrary to current views, this suggests that the infant motor system is flexibly engaged by novel movement patterns. Moreover, temporal cortex responses indicate that infants integrate information about form and motion during action observation. The response patterns obtained in premotor and temporal cortices during action observation in these young infants are very similar to those reported for adults. These findings thus suggest that the brain processes involved in the analysis of an agent in motion in adults become functionally specialized very early in human development.     

Disturbed spatial cognitive processing of body-related stimuli in a case of a lesion to the right fusiform gyrus

The fusiform gyrus (FG) is well known as one of the main neural sites of human face and body processing. We report the case of a young male patient with epilepsy and a circumscribed lesion in the right FG who presented with isolated impairments in spatial cognitive processing of body-related stimuli. However, he did not show any clinical signs of prosopagnosia. In particular, handling/processing of body and face stimuli was impaired, when stimuli were presented in unconventional views and orientations, thus requiring additional spatial cognitive operations. In this case study, we discuss the patient’s selective impairment from the view of current empirical and theoretical work on the segregation of functions in the FG.     

Time course of gamma‐band oscillation associated with face processing in the inferior occipital gyrus and fusiform gyrus: A combined fMRI and MEG study

Debate continues over whether the inferior occipital gyrus (IOG) or the fusiform gyrus (FG) represents the first stage of face processing and what role these brain regions play. We investigated this issue by combining functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in normal adults. Participants passively observed upright and inverted faces and houses. First, we identified the IOG and FG as face‐specific regions using fMRI. We applied beamforming source reconstruction and time–frequency analysis to MEG source signals to reveal the time course of gamma‐band activations in these regions. The results revealed that the right IOG showed higher gamma‐band activation in response to upright faces than to upright houses at 100 ms from the stimulus onset. Subsequently, the right FG showed greater gamma‐band response to upright faces versus upright houses at around 170 ms. The gamma‐band activation in the right IOG and right FG was larger in response to inverted faces than to upright faces at the later time window. These results suggest that (1) the gamma‐band activities occurs rapidly first in the IOG and next in the FG and (2) the gamma‐band activity in the right IOG at later time stages is involved in configuration processing for faces. Hum Brain Mapp 38:2067–2079, 2017. © 2017 Wiley Periodicals, Inc.     

When seeing depends on knowing: Adults with Autism Spectrum Conditions show diminished top-down processes in the visual perception of degraded faces but not degraded objects

Behavioural, neuroimaging and neurophysiological approaches emphasise the active and constructive nature of visual perception, determined not solely by the environmental input, but modulated top-down by prior knowledge. For example, degraded images, which at first appear as meaningless ‘blobs’, can easily be recognized as, say, a face, after having seen the same image un-degraded. This conscious perception of the fragmented stimuli relies on top-down priming influences from systems involved in attention and mental imagery on the processing of stimulus attributes, and feature-binding [Dolan, R. J., Fink, G. R., Rolls, E., Booth, M., Holmes, A., Frackowiak, R. S. J., et al. (1997). How the brain learns to see objects and faces in an impoverished context. Nature, 389, 596-599]. In Autism Spectrum Conditions (ASC), face processing abnormalities are well-established, but top-down anomalies in various domains have also been shown. Thus, we tested two alternative hypotheses: (i) that people with ASC show overall reduced top-down modulation in visual perception, or (ii) that top-down anomalies affect specifically the perception of faces. Participants were presented with sets of three consecutive images: degraded images (of faces or objects), corresponding or non-corresponding grey-scale photographs, and the same degraded images again. In a passive viewing sequence we compared gaze times (an index of focal attention) on faces/objects vs. background before and after viewers had seen the undegraded photographs. In an active viewing sequence, we compared how many faces/objects were identified pre- and post-exposure. Behavioural and gaze tracking data showed significantly reduced effects of prior knowledge on the conscious perception of degraded faces, but not objects in the ASC group. Implications for future work on the underlying mechanisms, at the cognitive and neurofunctional levels, are discussed.     

The effect of gaze direction on the processing of facial expressions in children with autism spectrum disorder: An ERP study

This study investigated the neural basis of the effect of gaze direction on facial expression processing in children with and without ASD, using event-related potential (ERP). Children with ASD (10-17-year olds) and typically developing (TD) children (9-16-year olds) were asked to determine the emotional expressions (anger or fearful) of a facial stimulus with a direct or averted gaze, and the ERPs were recorded concurrently. In TD children, faces with a congruent expression and gaze direction in approach-avoidance motivation, such as an angry face with a direct gaze (i.e., approaching motivation) and a fearful face with an averted gaze (i.e., avoidant motivation), were recognized more accurately and elicited larger N170 amplitudes than motivationally incongruent facial stimuli (an angry face with an averted gaze and a fearful face with a direct gaze). These results demonstrated the neural basis and time course of integration of facial expression and gaze direction in TD children and its impairment in children with ASD.     

The time course of social-emotional processing in early childhood: ERP responses to facial affect and personal familiarity in a Go-Nogo task

To date, little is known about the neural underpinnings of social-emotional processes in young children. The present study investigated the time course of children's ERP responses to facial expression and personal familiarity, and the effect of these variables on ERP measures of effortful attention in a Go-Nogo task. Dense-array EEG was collected from 48 4-6-year-old children who were presented with pictures of their mothers' and strangers' happy and angry faces. ERPs were scored following face presentation and following a subsequent cue signaling a Go or Nogo response. Responses to face presentation showed early perceptual components that were larger following strangers' faces, suggesting facilitated rapid processing of personally important faces. A mid-latency frontocentral negativity was greatest following angry mothers' faces, indicating increased attentional monitoring and/or recognition memory evoked by an angry parent. Finally a right-lateralized late positive component was largest following angry faces, suggesting extended processing of negatively valenced social stimuli in general. Following the Go-Nogo response cue, a right-lateralized mid-latency negativity thought to measure effortful attention was larger in Nogo than Go trials, and following angry than happy faces, possibly reflecting increased effortful control required in those conditions. The present study suggests that overlapping but differentiated networks for both rapid and elaborative processing of important socio-affective information are established by 4-6 years. Moreover, the extended spatial and temporal distribution of components suggests a pattern of response to social stimuli in which more rapid processes may index personal familiarity, whereas temporally extended processes are sensitive to affective valence on both familiar and unfamiliar faces.     

Enhanced speech perception capabilities in a blind listener are associated with activation of fusiform gyrus and primary visual cortex

Blind individuals may learn to understand ultra-fast synthetic speech at a rate of up to about 25 syllables per second (syl)/s, an accomplishment by far exceeding the maximum performance level of normal-sighted listeners (8–10 syl/s). The present study indicates that this exceptional skill engages distinct regions of the central-visual system. Hemodynamic brain activation during listening to moderately- (8 syl/s) and ultra-fast speech (16 syl/s) was measured in a blind individual and six normal-sighted controls. Moderately-fast speech activated posterior and anterior ‘language zones’ in all subjects. Regarding ultra-fast tokens, the controls showed exclusive activation of supratemporal regions whereas the blind participant exhibited enhanced left inferior frontal and temporoparietal responses as well as significant hemodynamic activation of left fusiform gyrus (FG) and right primary visual cortex. Since left FG is known to be involved in phonological processing, this structure, presumably, provides the functional link betweeen the central-auditory and -visual systems.     

An fMRI study of facial emotion processing in children and adolescents with 22q11.2 deletion syndrome

Background

22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood.

Methods

We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9–17 years) and healthy controls (aged 8–17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls.

Results

Within groups, contrasts showed that individuals significantly activated ‘face responsive’ areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment—social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum.

Conclusions

Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.

Electronic supplementary material

The online version of this article (doi:10.1186/1866-1955-7-1) contains supplementary material, which is available to authorized users.     

Psychometric properties of the French Version of the Social Responsiveness Scale in autism spectrum disorder with or without attention deficit hyperactivity disorder

ObjectivesThe Social Responsiveness Scale (SRS) is an instrument that is commonly used to screen for Autism Spectrum Disorder (ASD). Attention Deficit Hyperactive Disorder (ADHD) frequently occurs with ASD and both disorders share some phenotypic similarities. In the present study, we aimed to determine the psychometric properties of the French version of the Social Responsiveness Scale (SRS) and its 5 subscales (social awareness, social cognition, social communication, social motivation, and autistic mannerisms) to discriminate between children with ADHD and those with ASD (differential diagnosis) and children with ADHD from those with a dual diagnosis of ADHD and ASD (comorbid diagnosis).MethodSRS total scores and the 5 subscores of the SRS were compared between 4 groups of children: ADHD (n = 32), ASD + ADHD (n = 30), ASD (n = 31) and typical neurodevelopment (TD; n = 30) children. The discriminant validity was estimated using the Area Under the ROC Curves (AUC).ResultsSRS Social cognition (AUC = 0.73) and Autistic mannerisms (AUC = 0.70) subscores were the most discriminating for differential diagnosis of ASD and ADHD. SRS total scores (AUC = 0.70), and Social communication (AUC = 0.66) and Autistic mannerisms (AUC = 0.75) subscores were the most discriminating for comorbid diagnosis of ASD among ADHD children.ConclusionThe SRS autistic mannerisms subscore was found to be clinically relevant for both differential diagnosis of ASD and ADHD and comorbid diagnoses of ASD among ADHD children but with a modest discriminant power.     

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders

Background

Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD.

Methods

The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI).

Results

We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation.

Conclusions

These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.     

The relationship of resting cerebral blood flow and brain activation during a social cognition task in adolescents with chronic moderate to severe traumatic brain injury: a preliminary investigation

Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI.     

Blockade of the MEK/ERK pathway with a raf inhibitor prevents activation of pro-inflammatory mediators in cerebral arteries and reduction in cerebral blood flow after subarachnoid hemorrhage in a rat model

Cerebral ischemia that develops after subarachnoid hemorrhage (SAH) carries high morbidity and mortality. Inflammatory mediators are involved in the development of cerebral ischemia through activation of the mitogen-activated protein kinase pathway. We hypothesized that blockade of the MAPkinase/ERK (MEK)/extracellular signal-regulated kinase (ERK) pathway upstream with a specific raf inhibitor would prevent SAH-induced activation of the cerebrovascular inflammatory response. The raf inhibitor SB-386023-b was injected intracisternally in our rat model at 0, 6, or 12 hours after the SAH. After 48 hours, cerebral arteries were harvested, and iNOS, interleukin (IL)-6, IL-1β, matrix metalloproteinase (MMP)-9, tissue inhibitors of metalloproteinase (TIMP)-1, and phosphorylated ERK1/2 were investigated by immunofluorescence, real-time polymerase chain reaction (PCR), and Western blot analysis. Cerebral blood flow (CBF) was measured using autoradiography. Protein levels of MMP-9, TIMP-1, iNOS, IL-6, and IL-1β were increased after SAH, as were mRNA levels of IL-6, MMP-9, and TIMP-1. After SAH, pERK1/2 was increased, but CBF was reduced. Treatment with SB-386023-b at 0 or 6 hours after SAH normalized CBF and prevented SAH-induced upregulation of MMPs, pro-inflammatory cytokines, and pERK1/2 proteins. These results suggested that inhibition of MEK/ERK signal transduction by a specific raf inhibitor administered up to 6 hours after SAH normalized the expression of pro-inflammatory mediators and extracellular matrix-related genes.     

Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress-induced amnesia

We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing.     

An investigation of the impact of facial affect recognition impairments in moderate to severe TBI on fatigue,depression, and quality of life

Individuals with moderate to severe traumatic brain injury (TBI) have been shown to experience significant problems in facial affect recognition (FAR). However, it is not known how these impairments relate to overall functioning and quality of life (QoL) following TBI. The aim of the current study was to test the hypothesis that worse performance on an FAR task would be associated with reduced QoL (related to social and emotional functioning), worse mood, and increased fatigue. Forty-seven individuals with TBI and 27 healthy controls (HCs) completed the facial emotion identification task (FEIT), as well as questionnaires assessing social and emotional QoL, mood, and fatigue. The TBI group performed significantly worse than HCs on the FEIT. A significant relationship between FAR and fatigue and QoL related to social and emotional functioning was documented, but in an unexpected direction: individuals who performed better on the FEIT reported poorer QoL and greater fatigue. Individuals who have better FAR may require increased effort to perform this task, and thus experience greater fatigue and poorer social and emotional QoL.     

Prenatal IL-6 levels and activation of the tryptophan to kynurenine pathway are associated with depressive but not anxiety symptoms across the perinatal and the post-partum period in a low-risk sample

Depression and anxiety symptoms are highly prevalent among women during pregnancy and post-partum. Previous studies suggest that one of the pathophysiological underpinnings could be an enhanced metabolism of tryptophan (Trp) into kynurenine (Kyn) due to increased inflammation. However, the longitudinal changes in the Kyn pathway and the complex interplay with inflammation and stress in women with perinatal depressive or anxiety symptoms are incompletely understood. We examined a cohort of healthy women at 34–36 gestational weeks. One hundred and ten women were assessed for salivary cortisol and 97 participants were also assessed for serum levels of Trp, Kyn and Interleukin 6 (IL-6). Women filled in two screening questionnaires for depressive (Edinburgh Postnatal Depression Scale (EPDS)) and anxiety (State Trait Anxiety Inventory subscale (STAI-S)) symptoms at 34–36 gestational weeks, delivery, 3 and 12 months postpartum. Unexpectedly, lower prenatal Kyn levels were associated with higher depressive symptoms in late pregnancy. Furthermore, prenatal Trp levels and the Kyn/Trp ratio moderate the association between IL-6 levels and depressive symptoms during the perinatal and the post-partum period. We found no interactions between Trp and Kyn biomarkers and cortisol on depressive symptoms. The observed associations were more robustly found for depressive symptoms, whereas weak and non-significant effects were found for the trajectory of anxiety symptoms. Overall, our data support the involvement of the Trp to Kyn pathway and inflammation in the course of depressive but not anxiety symptoms in women from late pregnancy until one-year post-partum, providing new evidence on the mechanisms regulating emotions during pregnancy and after delivery in a low-risk sample.