scholarly journals Uncharacteristic task-evoked pupillary responses implicate atypical locus coeruleus activity in autism

2019 ◽  
Author(s):  
Michael C. Granovetter ◽  
Charlie S. Burlingham ◽  
Nicholas M. Blauch ◽  
Nancy J. Minshew ◽  
David J. Heeger ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Locus Coeruleus ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Group Differences ◽  
Attentional Demands ◽  
Environmental Stimuli ◽  
Pupillary Responses ◽  
Attentional Engagement ◽  
Task Irrelevant

AbstractAutism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, such as hypersensitivity to environmental stimuli. Attentional engagement is known to be regulated by the locus coeruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether individuals with ASD exhibit a different profile of LC activity compared to typically developing controls under different attentional task demands. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses—an established inverse correlate for baseline LC activity—were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared to controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed only in response to task-relevant and not to task-irrelevant stimuli, providing confirmation that the group differences are specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.Significance StatementIndividuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, such as environmental hypersensitivity and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus coeruleus (LC) activity, as the LC has a critical role in attentional modulation. Elevated LC activity is associated with environmental exploration, while moderate LC activity is associated with focused attention on relevant stimuli. This study shows that, under tightly controlled conditions, task-evoked pupil responses—an LC activity proxy—are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

Autism Spectrum Disorder, Fear Response, and Environmental Exposures

2019 ◽  
pp. 30-51 ◽  
Author(s):  
Theoharis C. Theoharides ◽  
Jaanvi Sant ◽  
Maria-Eleni Giota
Keyword(s):  
Autism Spectrum Disorder ◽  
Mast Cells ◽  
Effective Treatment ◽  
Immune Cells ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Fear Response ◽  
Environmental Stimuli ◽  
Flight Reaction ◽  
Developmental Condition

Autism spectrum disorder (ASD) is a developmental condition characterized by impaired social interactions and communication, as well as by stereotypic movements, that affects 1 in 59 children. ASD is expected to reach 1 in about 40 children by 2020, yet it remains without distinct pathogenesis and effective treatment. Children with ASD respond with high anxiety to almost any unknown stimulus and appear to misread danger/threat signals, and may not experience anxiety in situations where normotypic children do. The authors propose that environmental stimuli stimulate the unique immune cells, known as mast cells (MC), which then trigger microglia, leading to dysfunctional neuronal connectivity in the amygdala. This process lowers or disrupts the “fear response” and leads to an exaggerated “fight-or-flight” reaction. corticotropin-releasing hormone (CRH) could have a synergistic effect with environmental stimuli, especially mycotoxins. Recognizing this association and preventing stimulation of mast cells/microglia could lead to effective treatment of ASD.

Binding of Dopamine D1 Receptor and Noradrenaline Transporter in Individuals with Autism Spectrum Disorder: A PET Study

2020 ◽  
Vol 30 (12) ◽  
pp. 6458-6468
Author(s):  
Manabu Kubota ◽  
Junya Fujino ◽  
Shisei Tei ◽  
Keisuke Takahata ◽  
Kiwamu Matsuoka ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Anterior Cingulate Cortex ◽  
Temporal Cortex ◽  
Autism Spectrum ◽  
D1 Receptor ◽  
Spectrum Disorder ◽  
Anterior Cingulate ◽  
Group Differences ◽  
Significant Group ◽  
Noradrenaline Transporter

Abstract Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the “attention to detail” subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.

scholarly journals Mast Cells, Stress, Fear and Autism Spectrum Disorder

2019 ◽  
Vol 20 (15) ◽  
pp. 3611 ◽  
Author(s):  
Theoharis C. Theoharides ◽  
Maria Kavalioti ◽  
Irene Tsilioni
Keyword(s):  
Autism Spectrum Disorder ◽  
Mast Cells ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Neuronal Connectivity ◽  
Environmental Stimuli ◽  
Flight Reaction ◽  
Developmental Condition ◽  
Synaptic Pruning ◽  
Stimulation Of

Autism Spectrum Disorder (ASD) is a developmental condition characterized by impaired communication and obsessive behavior that affects 1 in 59 children. ASD is expected to affect 1 in about 40 children by 2020, but there is still no distinct pathogenesis or effective treatments. Prenatal stress has been associated with higher risk of developing ASD in the offspring. Moreover, children with ASD cannot handle anxiety and respond disproportionately even to otherwise benign triggers. Stress and environmental stimuli trigger the unique immune cells, mast cells, which could then trigger microglia leading to abnormal synaptic pruning and dysfunctional neuronal connectivity. This process could alter the “fear threshold” in the amygdala and lead to an exaggerated “fight-or-flight” reaction. The combination of corticotropin-releasing hormone (CRH), secreted under stress, together with environmental stimuli could be major contributors to the pathogenesis of ASD. Recognizing these associations and preventing stimulation of mast cells and/or microglia could greatly benefit ASD patients.

scholarly journals Pupillary Responses to Illusions of Brightness in Autism Spectrum Disorder

i-Perception ◽  
2018 ◽  
Vol 9 (3) ◽  
pp. 204166951877171 ◽  
Author(s):  
Bruno Laeng ◽  
Fredrik Svartdal Færevaag ◽  
Stine Tanggaard ◽  
Stephen von Tetzchner
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Pupillary Responses

scholarly journals Difficulties in Recognising Dynamic but not Static Emotional Body Movements in Autism Spectrum Disorder

2021 ◽  
Author(s):  
Noemi Mazzoni ◽  
Paola Ricciardelli ◽  
Rossana Actis-Grosso ◽  
Paola Venuti
Keyword(s):  
Autism Spectrum Disorder ◽  
Response Times ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Body Motion ◽  
Group Differences ◽  
Cognitive Resources ◽  
Dynamic Stimuli ◽  
Static Images ◽  
Point Light

AbstractIn this study, we investigated whether the difficulties in body motion (BM) perception may led to deficit in emotion recognition in Autism spectrum disorder (ASD). To this aim, individuals with high-functioning ASD were asked to recognise fearful, happy, and neutral BM depicted as static images or dynamic point-light and full-light displays. Results showed slower response times in participants with ASD only in recognising dynamic stimuli, but no group differences in accuracy. This suggests that i) a deficit in action chaining mechanism in ASD may prevent the recognition of dynamic BM automatically and rapidly, ii) individuals with ASD and high cognitive resources can develop alternative—but equally successful—strategies to recognise emotional body expressions. Implications for treatment are discussed

scholarly journals Exploring Expressive Communication Skills in a Cross-Sectional Sample of Individuals With a Dual Diagnosis of Autism Spectrum Disorder and Down Syndrome

2021 ◽  
Vol 126 (2) ◽  
pp. 97-113
Author(s):  
Alexandria Cook ◽  
Emily D. Quinn ◽  
Charity Rowland
Keyword(s):  
Autism Spectrum Disorder ◽  
Down Syndrome ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Group Differences ◽  
Cross Sectional ◽  
Communication Behaviors ◽  
Symbolic Communication ◽  
Expressive Communication ◽  
Comorbid Diagnosis

Abstract Individuals with a comorbid diagnosis of Down syndrome (DS) and autism spectrum disorder (ASD) have been found to exhibit greater deficits in expressive communication than individuals with DS only. We hypothesized that individuals with a comorbid diagnosis (n = 430) would have significantly lower Communication Matrix scores and specifically social communication scores than individuals with DS alone (n = 4,352). In a sample of 4,782 individuals with DS, scores for individuals with a comorbid diagnosis were on average 18.01 points and 7.26 points lower for total score and social score respectively as compared to individuals with DS. Comorbid diagnosis accounted for 10.5% of the variance in communication scores. Between-group differences in referential gestures and symbolic communication behaviors were also observed.

scholarly journals Social attention to activities in children and adults with autism spectrum disorder: effects of context and age

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dzmitry A. Kaliukhovich ◽  
Nikolay V. Manyakov ◽  
Abigail Bangerter ◽  
Seth Ness ◽  
Andrew Skalkin ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Biological Indicators ◽  
Biological Indicator ◽  
Autism Spectrum ◽  
Activity Monitoring ◽  
Spectrum Disorder ◽  
Group Differences ◽  
Control Group ◽  
Activity Area ◽  
Mutual Gaze

Abstract Background Diminished visual monitoring of faces and activities of others is an early feature of autism spectrum disorder (ASD). It is uncertain whether deficits in activity monitoring, identified using a homogeneous set of stimuli, persist throughout the lifespan in ASD, and thus, whether they could serve as a biological indicator (“biomarker”) of ASD. We investigated differences in visual attention during activity monitoring in children and adult participants with autism compared to a control group of participants without autism. Methods Eye movements of participants with autism (n = 122; mean age [SD] = 14.5 [8.0] years) and typically developing (TD) controls (n = 40, age = 16.4 [13.3] years) were recorded while they viewed a series of videos depicting two female actors conversing while interacting with their hands over a shared task. Actors either continuously focused their gaze on each other’s face (mutual gaze) or on the shared activity area (shared focus). Mean percentage looking time was computed for the activity area, actors’ heads, and their bodies. Results Compared to TD participants, participants with ASD looked longer at the activity area (mean % looking time: 58.5% vs. 53.8%, p < 0.005) but less at the heads (15.2% vs. 23.7%, p < 0.0001). Additionally, within-group differences in looking time were observed between the mutual gaze and shared focus conditions in both participants without ASD (activity: Δ = − 6.4%, p < 0.004; heads: Δ = + 3.5%, p < 0.02) and participants with ASD (bodies: Δ = + 1.6%, p < 0.002). Limitations The TD participants were not as well characterized as the participants with ASD. Inclusion criteria regarding the cognitive ability [intelligence quotient (IQ) > 60] limited the ability to include individuals with substantial intellectual disability. Conclusions Differences in attention to faces could constitute a feature discriminative between individuals with and without ASD across the lifespan, whereas between-group differences in looking at activities may shift with development. These findings may have applications in the search for underlying biological indicators specific to ASD. Trial registration ClinicalTrials.gov identifier NCT02668991.

Eye Movements Reveal no Immediate “WOW” (“Which One's Weird”) Effect in Autism Spectrum Disorder

2012 ◽  
Vol 65 (6) ◽  
pp. 1139-1150 ◽  
Author(s):  
Valerie Benson ◽  
Monica S. Castelhano ◽  
Sheena K. Au-Yeung ◽  
Keith Rayner
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Group Differences ◽  
Target Region ◽  
Processing Theory ◽  
Complex Information ◽  
Adult Participants ◽  
Complex Information Processing ◽  
The Difference

Autism spectrum disorder (ASD) and typically developed (TD) adult participants viewed pairs of scenes for a simple “spot the difference” (STD) and a complex “which one's weird” (WOW) task. There were no group differences in the STD task. In the WOW task, the ASD group took longer to respond manually and to begin fixating the target “weird” region. Additionally, as indexed by the first-fixation duration into the target region, the ASD group failed to “pick up” immediately on what was “weird”. The findings are discussed with reference to the complex information processing theory of ASD (Minshew & Goldstein, 1998).

scholarly journals Investigating the Mechanisms Driving Referent Selection and Retention in Toddlers at Typical and Elevated Likelihood for Autism Spectrum Disorder

2021 ◽  
pp. 1-13
Author(s):  
Teodora GLIGA ◽  
Alex SKOLNICK ◽  
Ute LIERSCH ◽  
Tony CHARMAN ◽  
Mark H JOHNSON ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Corrective Feedback ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Group Differences ◽  
Lexical Knowledge ◽  
New Words ◽  
Memory Traces ◽  
Referent Selection ◽  
Referent Choice

Abstract It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al., 2013). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words.

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