Look Me in the Eyes: Constraining Gaze in the Eye-region Provokes Abnormally High Subcortical Activation in Autism

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jun 11

PMID 28600558

Citations 42

Authors

Nouchine Hadjikhani

Jakob Asberg Johnels

Nicole R Zurcher

Amandine Lassalle

Quentin Guillon

Loyse Hippolyte

Eva Billstedt

Noreen Ward

Eric Lemonnier

Christopher Gillberg

Affiliations

Soon will be listed here.

Abstract

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.

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References

Liu T, Chen Y, Hsieh J, Chen L . Asymmetric engagement of amygdala and its gamma connectivity in early emotional face processing. PLoS One. 2015; 10(1):e0115677. PMC: 4309641. DOI: 10.1371/journal.pone.0115677. View

Lord C, Risi S, Lambrecht L, Cook Jr E, Leventhal B, DiLavore P . The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000; 30(3):205-23. View

Liddell B, Brown K, Kemp A, Barton M, Das P, Peduto A . A direct brainstem-amygdala-cortical 'alarm' system for subliminal signals of fear. Neuroimage. 2004; 24(1):235-43. DOI: 10.1016/j.neuroimage.2004.08.016. View

Yoon K, Zinbarg R . Threat is in the eye of the beholder: social anxiety and the interpretation of ambiguous facial expressions. Behav Res Ther. 2006; 45(4):839-47. DOI: 10.1016/j.brat.2006.05.004. View

Guillon Q, Hadjikhani N, Baduel S, Roge B . Visual social attention in autism spectrum disorder: insights from eye tracking studies. Neurosci Biobehav Rev. 2014; 42:279-97. DOI: 10.1016/j.neubiorev.2014.03.013. View

Donegan N, Sanislow C, Blumberg H, Fulbright R, Lacadie C, Skudlarski P . Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry. 2003; 54(11):1284-93. DOI: 10.1016/s0006-3223(03)00636-x. View

Thomas K, Drevets W, Dahl R, Ryan N, Birmaher B, Eccard C . Amygdala response to fearful faces in anxious and depressed children. Arch Gen Psychiatry. 2001; 58(11):1057-63. DOI: 10.1001/archpsyc.58.11.1057. View

Celeghin A, de Gelder B, Tamietto M . From affective blindsight to emotional consciousness. Conscious Cogn. 2015; 36:414-25. DOI: 10.1016/j.concog.2015.05.007. View

Leekam S, Libby S, Wing L, Gould J, Taylor C . The Diagnostic Interview for Social and Communication Disorders: algorithms for ICD-10 childhood autism and Wing and Gould autistic spectrum disorder. J Child Psychol Psychiatry. 2002; 43(3):327-42. DOI: 10.1111/1469-7610.00024. View

10.

Baron-Cohen S, Hoekstra R, Knickmeyer R, Wheelwright S . The Autism-Spectrum Quotient (AQ)--adolescent version. J Autism Dev Disord. 2006; 36(3):343-50. DOI: 10.1007/s10803-006-0073-6. View

11.

Morris J, Ohman A, Dolan R . A subcortical pathway to the right amygdala mediating "unseen" fear. Proc Natl Acad Sci U S A. 1999; 96(4):1680-5. PMC: 15559. DOI: 10.1073/pnas.96.4.1680. View

12.

Bird G, Cook R . Mixed emotions: the contribution of alexithymia to the emotional symptoms of autism. Transl Psychiatry. 2013; 3:e285. PMC: 3731793. DOI: 10.1038/tp.2013.61. View

13.

Mendez-Bertolo C, Moratti S, Toledano R, Lopez-Sosa F, Martinez-Alvarez R, Mah Y . A fast pathway for fear in human amygdala. Nat Neurosci. 2016; 19(8):1041-9. DOI: 10.1038/nn.4324. View

14.

Tottenham N, Hertzig M, Gillespie-Lynch K, Gilhooly T, Millner A, Casey B . Elevated amygdala response to faces and gaze aversion in autism spectrum disorder. Soc Cogn Affect Neurosci. 2013; 9(1):106-17. PMC: 3871735. DOI: 10.1093/scan/nst050. View

15.

Schuetze M, Park M, Cho I, MacMaster F, Chakravarty M, Bray S . Morphological Alterations in the Thalamus, Striatum, and Pallidum in Autism Spectrum Disorder. Neuropsychopharmacology. 2016; 41(11):2627-37. PMC: 5026732. DOI: 10.1038/npp.2016.64. View

16.

Rafal R, Koller K, Bultitude J, Mullins P, Ward R, Mitchell A . Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography. J Neurophysiol. 2015; 114(3):1947-62. PMC: 4579293. DOI: 10.1152/jn.01016.2014. View

17.

Somerville L, Kim H, Johnstone T, Alexander A, Whalen P . Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety. Biol Psychiatry. 2004; 55(9):897-903. DOI: 10.1016/j.biopsych.2004.01.007. View

18.

Tottenham N, Tanaka J, Leon A, McCarry T, Nurse M, Hare T . The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Res. 2009; 168(3):242-9. PMC: 3474329. DOI: 10.1016/j.psychres.2008.05.006. View

19.

Strumpf H, Mangun G, Boehler C, Stoppel C, Schoenfeld M, Heinze H . The role of the pulvinar in distractor processing and visual search. Hum Brain Mapp. 2012; 34(5):1115-32. PMC: 6870324. DOI: 10.1002/hbm.21496. View

20.

George N, Driver J, Dolan R . Seen gaze-direction modulates fusiform activity and its coupling with other brain areas during face processing. Neuroimage. 2001; 13(6 Pt 1):1102-12. DOI: 10.1006/nimg.2001.0769. View