Early adversity and brain response to faces in young adulthood

Early stressors play a key role in shaping interindividual differences in vulnerability to various psychopathologies, which according to the diathesis‐stress model might relate to the elevated glucocorticoid secretion and impaired responsiveness to stress. Furthermore, previous studies have shown that individuals exposed to early adversity have deficits in emotion processing from faces. This study aims to explore whether early adversities associate with brain response to faces and whether this association might associate with the regional variations in mRNA expression of the glucocorticoid receptor gene (NR3C1). A total of 104 individuals drawn from the Northern Finland Brith Cohort 1986 participated in a face‐task functional magnetic resonance imaging (fMRI) study. A large independent dataset (IMAGEN, N = 1739) was utilized for reducing fMRI data‐analytical space in the NFBC 1986 dataset. Early adversities were associated with deviant brain response to fearful faces (MANCOVA, P = 0.006) and with weaker performance in fearful facial expression recognition (P = 0.01). Glucocorticoid receptor gene expression (data from the Allen Human Brain Atlas) correlated with the degree of associations between early adversities and brain response to fearful faces (R² = 0.25, P = 0.01) across different brain regions. Our results suggest that early adversities contribute to brain response to faces and that this association is mediated in part by the glucocorticoid system. Hum Brain Mapp 38:4470–4478, 2017. © 2017 Wiley Periodicals, Inc.     

Hormonal contraceptives,menstrual cycle and brain response to faces

Both behavioral and neuroimaging evidence support a female advantage in the perception of human faces. Here we explored the possibility that this relationship may be partially mediated by female sex hormones by investigating the relationship between the brain’s response to faces and the use of oral contraceptives, as well as the phase of the menstrual cycle. First, functional magnetic resonance images were acquired in 20 young women [10 freely cycling and 10 taking oral contraception (OC)] during two phases of their cycle: mid-cycle and menstruation. We found stronger neural responses to faces in the right fusiform face area (FFA) in women taking oral contraceptives (vs freely cycling women) and during mid-cycle (vs menstruation) in both groups. Mean blood oxygenation level-dependent response in both left and right FFA increased as function of the duration of OC use. Next, this relationship between the use of OC and FFA response was replicated in an independent sample of 110 adolescent girls. Finally in a parallel behavioral study carried out in another sample of women, we found no evidence of differences in the pattern of eye movements while viewing faces between freely cycling women vs those taking oral contraceptives. The imaging findings might indicate enhanced processing of social cues in women taking OC and women during mid-cycle.     

Individual differences in alexithymia and brain response to masked emotion faces

Alexithymia is considered a dimensional personality trait that refers to a cluster of deficits in the recognition, differentiation, and verbalization of emotions. Research on the neurobiology of alexithymia has focused hitherto on impairments in the controlled processing of emotional information. In the present study automatic brain reactivity to facial emotion was investigated as a function of alexithymia (as assessed by the 20-Item Toronto Alexithymia Scale - TAS-20). During 3 T fMRI scanning, pictures of sad, happy, and neutral facial expression masked by neutral faces were presented to 33 healthy women. A priori regions of interest in the whole brain analysis were cerebral structures that are known to be crucially involved in the emotion perception from the face. Independently from trait anxiety and depression TAS-20 alexithymia was negatively correlated with activation to masked sad and happy faces in several regions of interest (in particular, insula, superior temporal gyrus, middle occipital and parahippocampal gyrus). In addition, the TAS-20 score was negatively correlated with response of the left amygdala to masked sad faces. A reduced automatic reactivity of the amygdala and visual occipito-temporal areas could implicate less automated engagement in the encoding of emotional stimuli in high alexithymia. In addition, a low spontaneous insular and amygdalar responsivity in high alexithymia individuals could be related to an attenuation of basic emotional experiences which may contribute to problems in identifying and differentiating one's feelings.     

Regional variation in brain capillary density and vascular response to ischemia

Differences in brain neuroarchitecture have been extensively studied and recent results demonstrated that regional differences in the physiological properties of glial cells are equally common. Relatively little is known on the topographic differences in vascular supply, distribution and density of brain capillaries in different CNS regions. We developed a simple method consisting of intravascular injection of fluorescent dyes coupled to immunocytochemical techniques that allows for simultaneous observation of glia–neuronal–vascular interactions in immersion-fixed brain specimens from small rodents. This technique permits quantitative evaluation of regional differences in glial/neuronal distribution and the study of their relationship to vascular densities. Variations of this technique also allow the detection of abnormal microvasculature (i.e. ‘leaky’ vessels), a useful feature for studies of blood–brain barrier function in health and disease. By use of quantitative confocal microscopy, the three-dimensional geometry of cortical and hippocampal structures revealed remarkable differences in vascularization between cortical gray/white matter junction, and hippocampal formation (CA1 and CA3 regions). Significant differences were also observed within the same investigative region: CA1 was characterized by low capillary density compared to neighboring CA3. Following an ischemic insult, CA1 vessels had more extensive blood–brain barrier leakage than CA3 vessels. We conclude that in addition to neuronal and glial heterogeneity, cortical structures are also endowed with region-specific vascular patterns characterized by distinct pathophysiological responses.     

Sex differences in the brain response to affective scenes with or without humans

Recent findings have demonstrated that women might be more reactive than men to viewing painful stimuli (vicarious response to pain), and therefore more empathic [Han, S., Fan, Y., & Mao, L. (2008). Gender difference in empathy for pain: An electrophysiological investigation. Brain Research, 1196, 85–93]. We investigated whether the two sexes differed in their cerebral responses to affective pictures portraying humans in different positive or negative contexts compared to natural or urban scenarios. 440 IAPS slides were presented to 24 Italian students (12 women and 12 men). Half the pictures displayed humans while the remaining scenes lacked visible persons. ERPs were recorded from 128 electrodes and swLORETA (standardized weighted Low-Resolution Electromagnetic Tomography) source reconstruction was performed. Occipital P115 was greater in response to persons than to scenes and was affected by the emotional valence of the human pictures. This suggests that processing of biologically relevant stimuli is prioritized. Orbitofrontal N2 was greater in response to positive than negative human pictures in women but not in men, and not to scenes. A late positivity (LP) to suffering humans far exceeded the response to negative scenes in women but not in men. In both sexes, the contrast suffering-minus-happy humans revealed a difference in the activation of the occipito/temporal, right occipital (BA19), bilateral parahippocampal, left dorsal prefrontal cortex (DPFC) and left amygdala. However, increased right amygdala and right frontal area activities were observed only in women. The humans-minus-scenes contrast revealed a difference in the activation of the middle occipital gyrus (MOG) in men, and of the left inferior parietal (BA40), left superior temporal gyrus (STG, BA38) and right cingulate (BA31) in women (270–290 ms). These data indicate a sex-related difference in the brain response to humans, possibly supporting human empathy.     

Neural response to the visual familiarity of faces

Recognizing personally familiar faces is the result of a spatially distributed process that involves visual perceptual areas and areas that play a role in other cognitive and social functions, such as the anterior paracingulate cortex, the precuneus and the amygdala [M.I. Gobbini, E. Leibenluft, N. Santiago, J.V. Haxby, Social and emotional attachment in the neural representation of faces, Neuroimage 22 (2004) 1628-1635; M.I. Gobbini, J.V. Haxby, Neural systems for recognition of familiar faces, Neuropsychologia, in press; E. Leibenluft, M.I. Gobbini, T. Harrison, J.V. Haxby, Mothers' neural activation in response to pictures of their, and other, children, Biol. Psychiatry 56 (2004) 225-232]. In order to isolate the role of visual familiarity in face recognition, we used fMRI to measure the response to faces characterized by experimentally induced visual familiarity that carried no biographical information or emotional content. The fMRI results showed a stronger response in the precuneus to the visually familiar faces consistent with studies that implicate this region in the retrieval of information from long-term memory and imagery. Moreover, this finding supports the hypothesis of a key role for the precuneus in the acquisition of familiarity with faces [H. Kosaka, M. Omori, T. Iidaka, T. Murata, T. Shimoyama, T. Okada, N. Sadato, Y. Yonekura, Y. Wada, Neural substrates participating in acquisition of facial familiarity: an fMRI study, Neuroimage 20 (2003) 1734-1742]. By contrast, the visually familiar faces evoked a weaker response in the fusiform gyrus, which may reflect the development of a sparser encoding or a reduced attentional load when processing stimuli that are familiar. The visually familiar faces also evoked a weaker response in the amygdala, supporting the proposed role of this structure in mediating the guarded attitude when meeting someone new.     

Task-invariant brain responses to the social value of faces

In two fMRI experiments (n = 44) using tasks with different demands-approach-avoidance versus one-back recognition decisions-we measured the responses to the social value of faces. The face stimuli were produced by a parametric model of face evaluation that reduces multiple social evaluations to two orthogonal dimensions of valence and power [Oosterhof, N. N., & Todorov, A. The functional basis of face evaluation. Proceedings of the National Academy of Sciences, U.S.A., 105, 11087-11092, 2008]. Independent of the task, the response within regions of the occipital, fusiform, and lateral prefrontal cortices was sensitive to the valence dimension, with larger responses to low-valence faces. Additionally, there were extensive quadratic responses in the fusiform gyri and dorsal amygdala, with larger responses to faces at the extremes of the face valence continuum than faces in the middle. In all these regions, participants' avoidance decisions correlated with brain responses, with faces more likely to be avoided evoking stronger responses. The findings suggest that both explicit and implicit face evaluation engage multiple brain regions involved in attention, affect, and decision making.     

Sex-differential brain activation during exposure to female and male faces

Sex-discriminating facial features are examples of visual information involved in guiding social behavior. We used functional magnetic resonance imaging (fMRI) to assess brain responses in face-relevant brain areas in men and women during exposure to neutral male and female faces. An increased fMRI signal was found in the left amygdala and adjacent anterior temporal regions in men, but not in women, during exposure to faces of the opposite versus the same sex. These data indicate that the relationship between the sex of the subject and the sex of the face affects activity in the inferior temporal lobe. The sex-differential nature of this activation pattern may reflect sex differences in cognitive style and attentional processes when confronting faces of the opposite sex.     

Response of face-selective brain regions to trustworthiness and gender of faces

Neuropsychological and neuroimaging studies have demonstrated a role for the amygdala in processing the perceived trustworthiness of faces, but it remains uncertain whether its responses are linear (with the greatest response to the least trustworthy-looking faces), or quadratic (with increased fMRI signal for the dimension extremes). It is also unclear whether the trustworthiness of the stimuli is crucial or if the same response pattern can be found for faces varying along other dimensions. In addition, the responses to perceived trustworthiness of face-selective regions other than the amygdala are seldom reported. The present study addressed these issues using a novel set of stimuli created through computer image-manipulation both to maximise the presence of naturally occurring cues that underpin trustworthiness judgments and to allow systematic manipulation of these cues. With a block-design fMRI paradigm, we investigated neural responses to computer-manipulated trustworthiness in the amygdala and core face-selective regions in the occipital and temporal lobes. We asked whether the activation pattern is specific for differences in trustworthiness or whether it would also track variation along an orthogonal male-female gender dimension. The main findings were quadratic responses to changes in both trustworthiness and gender in all regions. These results are consistent with the idea that face-responsive brain regions are sensitive to face distinctiveness as well as the social meaning of the face features.     

Cultural specificity in amygdala response to fear faces

The human amygdala robustly activates to fear faces. Heightened response to fear faces is thought to reflect the amygdala's adaptive function as an early warning mechanism. Although culture shapes several facets of emotional and social experience, including how fear is perceived and expressed to others, very little is known about how culture influences neural responses to fear stimuli. Here we show that the bilateral amygdala response to fear faces is modulated by culture. We used functional magnetic resonance imaging to measure amygdala response to fear and nonfear faces in two distinct cultures. Native Japanese in Japan and Caucasians in the United States showed greater amygdala activation to fear expressed by members of their own cultural group. This finding provides novel and surprising evidence of cultural tuning in an automatic neural response.     

Regional brain perfusion changes during standard and microburst vagus nerve stimulation in dogs

PurposeVagus nerve stimulation (VNS) is an effective adjunctive treatment for refractory epilepsy in humans, but its mechanism of action (MOA) and optimal stimulation parameters are still unknown. Functional neuroimaging studies could provide better insight into the brain structures involved in the activity of VNS, but have not yet been described in dogs. The aim of this study was to investigate the effect of acute VNS on the regional cerebral blood flow (rCBF) in dogs using micro-SPECT (μ-SPECT). Additionally, a novel stimulation paradigm (microburst VNS) was used and compared with standard VNS.MethodsA VNS Therapy^® System was implanted in ten Beagle dogs. μ-SPECT was performed after sham, standard and microburst VNS in a randomized, cross-over study. Nineteen volumes of interest (VOIs) were semi-quantitatively analysed and perfusion indices (PIs) were calculated. Furthermore, a rostro-caudal gradient (R-C), an asymmetry index (AI) and a cortical-subcortical index (Co-SCo) were determined. The SPECT results after standard and microburst VNS were compared pairwise with sham stimulation.ResultsAcute standard VNS did not cause significant rCBF alterations. Acute microburst VNS caused a significant hypoperfusion in the left frontal lobe (P = 0.023) and in the right parietal lobe (P = 0.035). Both stimulation paradigms did not cause changes in R-C, AI nor Co-SCo.ConclusionsMicroburst VNS is more potent than standard VNS to modulate the rCBF in the dog. Our results promote further research towards the antiepileptic effect of microburst VNS in dogs and humans.     

Specific brain activation in Japanese and Caucasian people to fearful faces

Different regions of brain activation, as measured by fMRI, were evident in Japanese and Caucasian individuals observing facial expressions categorized as fearful according to Ekman criteria. Activation was evident in the posterior cingulate, supplementary motor cortex and the amygdala in Caucasians, while activation was evident in the right inferior frontal, premotor cortex and left insula and in Japanese individuals. The results suggest that Caucasians respond to fearful faces in a more direct, emotional way, whereas Japanese do not attach an emotional valence to the faces and therefore activate a template matching system to identify facial expressions. The faces widely used as emotional stimuli therefore are not universally perceived, and cultural specificity should be taken into consideration in designing facial tasks.     

An amygdala response to fearful faces with covered eyes

Findings of amygdala responsiveness to the eye region of fearful faces raise the question of whether eye widening is the only facial cue involved. We used fMRI to investigate the differential amygdala response to fearful versus neutral stimuli for faces, eyes, and for faces in which the eye region was masked. For maximum sensitivity, a block design was used, with a region of interest (ROI) centred on the amygdala which included peri-amygdalar areas. Evidence of amygdala responsiveness to fear compared to neutral stimuli was found for whole faces, eye region only, and for faces with masked eyes. The amygdala can therefore use information from facial regions other than the eyes, allowing it to respond differentially to fearful compared to neutral faces even when the eye region is hidden.     

Temporal profile of amygdala gamma oscillations in response to faces

Neuroimaging studies have reported greater activation of the human amygdala in response to faces than to nonfacial stimuli, yet little is known about the temporal profile of this activation. We investigated this issue by recording the intracranial field potentials of the amygdala in participants undergoing preneurosurgical assessment (n = 6). Participants observed faces, mosaics, and houses in upright and inverted orientations using a dummy target detection task. Time-frequency statistical parametric mapping analyses revealed that the amygdala showed greater gamma-band activity in response to faces than to mosaics at 200-300 msec, with a peak at 255 msec. Gamma-band activation with a similar temporal profile was also found in response to faces versus houses. Activation patterns did not differ between upright and inverted presentations of stimuli. These results suggest that the human amygdala is involved in the early stages of face processing, including the modulation of subjective perception of faces.     

Amygdala response to fearful faces in anxious and depressed children.

BACKGROUND: Alterations in amygdala function have been implicated in the pathophysiological characteristics of adult anxiety and depressive disorders. Studies with healthy adults and children, as well as with adults who have amygdala lesions, have found facial expressions of emotion to be useful probes of amygdala activity. Our study examined the amygdala response to fearful and neutral facial expressions in healthy, anxious, and depressed children. We hypothesized that children with anxiety and depression may show atypical amygdala responses to emotional stimuli. METHODS: Twelve children (8-16 years of age) with generalized anxiety or panic disorder and 12 healthy comparison children underwent noninvasive functional magnetic resonance imaging while viewing photographs of fearful and neutral facial expressions. In a second comparison, 5 girls with major depressive disorder were compared with 5 anxious and 5 healthy girls from the previous sample. RESULTS: Children with anxiety disorders showed an exaggerated amygdala response to fearful faces compared with healthy children, whereas depressed children showed a blunted amygdala response to these faces. In addition, the magnitude of the amygdala's signal change between fearful and neutral faces was positively correlated with the severity of everyday anxiety symptoms. CONCLUSIONS: Our results suggest that amygdala function is affected in both anxiety and depression during childhood and adolescence. Moreover, this disruption appears to be specific to the child's own rating of everyday anxiety.     

Amygdala hypersensitivity in response to emotional faces in Tourette's patients

Abstract

Objectives. Tourette's syndrome is characterised by motor and vocal tics as well as a high level of impulsivity and emotional dysregulation. Neuroimaging studies point to structural changes of the basal ganglia, prefrontal cortex and parts of the limbic system. However, there is no link between behavioural symptoms and the structural changes in the amygdala. One aspect of daily social interaction is the perception of emotional facial expressions, closely linked to amgydala function. Methods. We therefore investigated via fMRI the implicit discrimination of six emotional facial expressions in 19 adult Tourette's patients. Results. In comparison to healthy control group, Tourette's patients showed significantly higher amygdala activation, especially pronounced for fearful, angry and neutral expressions. The BOLD-activity of the left amygdala correlated negatively with the personality trait extraversion. Conclusions. We will discuss these findings as a result of either deficient frontal inhibition due to structural changes or a desynchronization in the interaction of the cortico-striato-thalamo-cortical network within structures of the limbic system. Our data show an altered pattern of implicit emotion discrimination and emphasize the need to consider motor and non-motor symptoms in Tourette's syndrome in the choice of both behavioural and pharmacological treatment.     

Amygdala response to faces parallels social behavior in Williams syndrome

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder.