Amandine Lassalle

An investigation of the ‘female camouflage effect’ in autism using a computerized ADOS-2 and a test of sex/gender differences

BackgroundAutism spectrum conditions (autism) are diagnosed more frequently in boys than in girls. Females with autism may have been under-identified due to not only a male-biased understanding of autism but also females’ camouflaging. The study describes a new technique that allows automated coding of non-verbal mode of communication (gestures) and offers the possibility of objective, evaluation of gestures, independent of human judgment. The EyesWeb software platform and the Kinect sensor during two demonstration activities of ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition) were used.MethodsThe study group consisted of 33 high-functioning Polish girls and boys with formal diagnosis of autism or Asperger syndrome aged 5–10, with fluent speech, IQ average and above and their parents (girls with autism, n = 16; boys with autism, n = 17). All children were assessed during two demonstration activities of Module 3 of ADOS-2, administered in Polish, and coded using Polish codes. Children were also assessed with Polish versions of the Eyes and Faces Tests. Parents provided information on the author-reviewed Polish research translation of SCQ (Social Communication Questionnaire, Current and Lifetime) and Polish version of AQ Child (Autism Spectrum Quotient, Child).ResultsGirls with autism tended to use gestures more vividly as compared to boys with autism during two demonstration activities of ADOS-2. Girls with autism made significantly more mistakes than boys with autism on the Faces Test. All children with autism had high scores in AQ Child, which confirmed the presence of autistic traits in this group. The current communication skills of boys with autism reported by parents in SCQ were significantly better than those of girls with autism. However, both girls with autism and boys with autism improved in the social and communication abilities over the lifetime. The number of stereotypic behaviours in boys significantly decreased over life whereas it remained at a comparable level in girls with autism.ConclusionsHigh-functioning females with autism might present better on non-verbal (gestures) mode of communication than boys with autism. It may camouflage other diagnostic features. It poses risk of under-diagnosis or not receiving the appropriate diagnosis for this population. Further research is required to examine this phenomenon so appropriate gender revisions to the diagnostic assessments might be implemented.

Emotional contagion for pain is intact in autism spectrum disorders

Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.

Fearful, surprised, happy, and angry facial expressions modulate gaze-oriented attention: Behavioral and ERP evidence

The impact of emotions on gaze-oriented attention was investigated in non-anxious participants. A neutral face cue with straight gaze was presented, which then averted its gaze to the side while remaining neutral or expressing an emotion (fear/surprise in Exp.1 and anger/happiness in Exp.2). Localization of a subsequent target was faster at the gazed-at location (congruent condition) than at the non-gazed-at location (incongruent condition). This Gaze-Orienting Effect (GOE) was enhanced for fear, surprise, and anger, compared to neutral expressions which did not differ from happy expressions. In addition, Event Related Potentials (ERPs) to the target showed a congruency effect on P1 for fear and surprise and a left lateralized congruency effect on P1 for happy faces, suggesting that target visual processing was also influenced by attention to gaze and emotions. Finally, at cue presentation, early postero-lateral (Early Directing Attention Negativity (EDAN)) and later antero-lateral (Anterior Directing Attention Negativity (ADAN)) attention-related ERP components were observed, reflecting, respectively, the shift of attention and its holding at gazed-at locations. These two components were not modulated by emotions. Together, these findings show that the processing of social signals such as gaze and facial expression interact rather late and in a complex manner to modulate spatial attention.

Autistic traits influence gaze-oriented attention to happy but not fearful faces

The relationship between autistic traits and gaze-oriented attention to fearful and happy faces was investigated at the behavioral and neuronal levels. Upright and inverted dynamic face stimuli were used in a gaze-cueing paradigm while event related potentials (ERPs) were recorded. Participants responded faster to gazed-at than to non-gazed-at targets, and this gaze orienting effect (GOE) diminished with inversion, suggesting it relies on facial configuration. It was also larger for fearful than happy faces but only in participants with high autism-spectrum quotient (AQ) scores. While the GOE to fearful faces was of similar magnitude regardless of AQ scores, a diminished GOE to happy faces was found in participants with high AQ scores. At the ERP level, a congruency effect on target-elicited P1 component reflected enhanced visual processing of gazed-at targets. In addition, cue-triggered early directing attention negativity and anterior directing attention negativity reflected, respectively, attention orienting and attention holding at gazed-at locations. These neural markers of spatial attention orienting were not modulated by emotion and were not found in participants with high AQ scores. Together, these findings suggest that autistic traits influence attention orienting to gaze and its modulation by social emotions such as happiness.

Look me in the eyes: constraining gaze in the eye-region provokes abnormally high subcortical activation in autism

Individuals with Autism Spectrum Disorder (ASD) seem to have difficulties looking others in the eyes, but the substrate for this behavior is not well understood. The subcortical pathway, which consists of superior colliculus, pulvinar nucleus of the thalamus, and amygdala, enables rapid and automatic face processing. A specific component of this pathway – i.e., the amygdala – has been shown to be abnormally activated in paradigms where individuals had to specifically attend to the eye-region; however, a direct examination of the effect of manipulating the gaze to the eye-regions on all the components of the subcortical system altogether has never been performed. The subcortical system is particularly important as it shapes the functional specialization of the face-processing cortex during development. Using functional MRI, we investigated the effect of constraining gaze in the eye-region during dynamic emotional face perception in groups of participants with ASD and typical controls. We computed differences in activation in the subcortical face processing system (superior colliculus, pulvinar nucleus of the thalamus and amygdala) for the same stimuli seen freely or with the gaze constrained in the eye-region. Our results show that when constrained to look in the eyes, individuals with ASD show abnormally high activation in the subcortical system, which may be at the basis of their eye avoidance in daily life.

Emotional modulation of attention orienting by gaze varies with dynamic cue sequence

ABSTRACT Recent gaze cueing studies using dynamic cue sequences have reported increased attention orienting by gaze with faces expressing fear, surprise or anger. Here, we investigated whether the type of dynamic cue sequence used impacted the magnitude of this effect. When the emotion was expressed before or concurrently with gaze shift, no modulation of gaze-oriented attention by emotion was seen. In contrast, when the face cue averted gaze before expressing an emotion (as if reacting to the object after first localizing it), the gaze orienting effect was clearly increased for fearful, surprised and angry faces compared to neutral faces. Thus, the type of dynamic sequence used, and in particular the order in which the gaze shift and the facial expression are presented, modulate gaze-oriented attention, with maximal modulation seen when the expression of emotion follows gaze shift.

The effect of constraining eye-contact during dynamic emotional face perception-an fMRI study.

Abstract Eye-contact modifies how we perceive emotions and modulates activity in the social brain network. Here, using fMRI, we demonstrate that adding a fixation cross in the eye region of dynamic facial emotional stimuli significantly increases activation in the social brain of healthy, neurotypical participants when compared with activation for the exact same stimuli observed in a free-viewing mode. In addition, using PPI analysis, we show that the degree of amygdala connectivity with the rest of the brain is enhanced for the constrained view for all emotions tested except for fear, and that anxiety and alexithymia modulate the strength of amygdala connectivity for each emotion differently. Finally, we show that autistic traits have opposite effects on amygdala connectivity for fearful and angry emotional expressions, suggesting that these emotions should be treated separately in studies investigating facial emotion processing.

Bumetanide for autism: more eye contact, less amygdala activation

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism.

Hypersensitivity to low intensity fearful faces in autism when fixation is constrained to the eyes

Previous studies that showed decreased brain activation in people with autism spectrum disorder (ASD) viewing expressive faces did not control that participants looked in the eyes. This is problematic because ASD is characterized by abnormal attention to the eyes. Here, we collected fMRI data from 48 participants (27 ASD) viewing pictures of neutral faces and faces expressing anger, happiness, and fear at low and high intensity, with a fixation cross between the eyes. Group differences in whole brain activity were examined for expressive faces at high and low intensity versus neutral faces. Group differences in neural activity were also investigated in regions of interest within the social brain, including the amygdala and the ventromedial prefrontal cortex (vmPFC). In response to low intensity fearful faces, ASD participants showed increased activation in the social brain regions, and decreased functional coupling between the amygdala and the vmPFC. This oversensitivity to low intensity fear coupled with a lack of emotional regulation capacity could indicate an excitatory/inhibitory imbalance in their socio‐affective processing system. This may result in social disengagement and avoidance of eye‐contact to handle feelings of strong emotional reaction. Our results also demonstrate the importance of careful control of gaze when investigating emotional processing in ASD. Hum Brain Mapp 38:5943–5957, 2017.

Influence of anxiety and alexithymia on brain activations associated with the perception of others’ pain in autism

ABSTRACT The circumstances under which empathy is altered in ASD remain unclear, as previous studies did not systematically find differences in brain activation between ASD and controls in empathy-eliciting paradigms, and did not always monitor whether differences were primarily due to ASD “per se”, or to conditions overlapping with ASD, such as alexithymia and anxiety. Here, we collected fMRI data from 47 participants (22 ASD) viewing pictures depicting hands and feet of unknown others in painful, disgusting, or neutral situations. We computed brain activity for painful and disgusting stimuli (vs. neutral) in whole brain and in regions of interest among the brain areas typically activated during the perception of nociceptive stimuli. Group differences in brain activation disappeared when either alexithymia or anxiety – both elevated in the ASD group – were controlled for. Regression analyses indicated that the influence of symptoms was mainly shared between autistic symptomatology, alexithymia and anxiety or driven by unique contributions from alexithymia or anxiety. Our results suggest that affective empathy may be affected in ASD, but that this association is complex. The respective contribution of alexithymia and anxiety to decreased affective empathy of people with ASD may be due to the association of those psychiatric conditions with reduced motor resonance/Theory of Mind.