Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Autism
Published in: Molecular Autism 1/2016

Open Access 01-12-2016 | Research

Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study

Authors: Annika Rausch, Wei Zhang, Koen V. Haak, Maarten Mennes, Erno J. Hermans, Erik van Oort, Guido van Wingen, Christian F. Beckmann, Jan K. Buitelaar, Wouter B. Groen

Published in: Molecular Autism | Issue 1/2016

Login to get access

Abstract

Background

Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls.

Methods

We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions.

Results

Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei.

Conclusions

These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways.
Appendix
Available only for authorised users
Literature
1.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR®. Washington (DC): American Psychiatric Publisher; 2000.
2.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington (DC): American Psychiatric Publisher; 2013.
3.
Verhoeven JS, De Cock P, Lagae L, Sunaert S. Neuroimaging of autism. Neuroradiology. 2010;52(1):3–14.PubMedCrossRef
4.
Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ. Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb Cortex. 2007;17(4):951–61.PubMedPubMedCentralCrossRef
5.
6.
7.
Ashwin C, Chapman E, Colle L, Baron-Cohen S. Impaired recognition of negative basic emotions in autism: a test of the amygdala theory. Soc Neurosci. 2006;1(3-4):349–63.PubMedCrossRef
8.
Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C, Williams SC. The amygdala theory of autism. Neurosci Biobehav Rev. 2000;24(3):355–64.PubMedCrossRef
9.
Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron. 2005;48(2):175.PubMedCrossRef
10.
Bellani M, Calderoni S, Muratori F, Brambilla P. Brain anatomy of autism spectrum disorders II. Focus on amygdala. Epidemiol Psychiatr Sci. 2013;22:309–12.PubMedCrossRef
11.
Groen W, Teluij M, Buitelaar J, Tendolkar I. Amygdala and hippocampus enlargement during adolescence in autism. J Am Acad Child Adolesc Psychiatry. 2010;49(6):552–60.PubMed
12.
Green SA, Rudie JD, Colich NL, Wood JJ, Shirinyan D, Hernandez L, et al. Overreactive brain responses to sensory stimuli in youth with autism spectrum disorders. J Am Acad Child Adolesc Psychiatry. 2013;52(11):1158–72.PubMedCrossRef
13.
Tottenham N, Hertzig ME, Gillespie-Lynch K, Gilhooly T, Millner AJ, Casey B. Elevated amygdala response to faces and gaze aversion in autism spectrum disorder. Soc Cogn Affect Neurosci. 2014;9(1):106–17.PubMedPubMedCentralCrossRef
14.
Nacewicz BM, Dalton KM, Johnstone T, Long MT, McAuliff EM, Oakes TR, et al. Amygdala volume and nonverbal social impairment in adolescent and adult males with autism. Arch Gen Psychiatry. 2006;63(12):1417–28.PubMedCrossRef
15.
Schumann CM, Barnes CC, Lord C, Courchesne E. Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biol Psychiatry. 2009;66(10):942–9.PubMedPubMedCentralCrossRef
16.
Courchesne E, Pierce K. Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol. 2005;15(2):225–30.PubMedCrossRef
17.
Anderson JS, Druzgal TJ, Froehlich A, DuBray MB, Lange N, Alexander AL, et al. Decreased interhemispheric functional connectivity in autism. Cereb Cortex. 2011;21(5):1134–46.PubMedPubMedCentralCrossRef
18.
Travers BG, Adluru N, Ennis C, Tromp DP, Destiche D, Doran S, et al. Diffusion tensor imaging in autism spectrum disorder: a review. Autism Res. 2012;5(5):289–313.PubMedPubMedCentralCrossRef
19.
Di Martino A, Zuo X-N, Kelly C, Grzadzinski R, Mennes M, Schvarcz A, et al. Shared and distinct intrinsic functional network centrality in autism and attention-deficit/hyperactivity disorder. Biol Psychiatry. 2013;74(8):623–32.PubMedPubMedCentralCrossRef
20.
Khan S, Gramfort A, Shetty NR, Kitzbichler MG, Ganesan S, Moran JM, et al. Local and long-range functional connectivity is reduced in concert in autism spectrum disorders. Proc Natl Acad Sci U S A. 2013;110(8):3107–12.PubMedPubMedCentralCrossRef
21.
Maximo JO, Keown CL, Nair A, Müller R-A. Approaches to local connectivity in autism using resting state functional connectivity MRI. Front Hum Neurosci. 2013;7:605.PubMedPubMedCentralCrossRef
22.
Paakki J-J, Rahko J, Long X, Moilanen I, Tervonen O, Nikkinen J, et al. Alterations in regional homogeneity of resting-state brain activity in autism spectrum disorders. Brain Res. 2010;1321:169–79.PubMedCrossRef
23.
24.
Mottron L, Dawson M, Soulieres I, Hubert B, Burack J. Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception. J Autism Dev Disord. 2006;36(1):27–43.PubMedCrossRef
25.
Samson F, Mottron L, Jemel B, Belin P, Ciocca V. Can spectro-temporal complexity explain the autistic pattern of performance on auditory tasks? J Autism Dev Disord. 2006;36(1):65–76.PubMedCrossRef
26.
Groen WB, van Orsouw L, Ter Huurne N, Swinkels S, van der Gaag R-J, Buitelaar JK, et al. Intact spectral but abnormal temporal processing of auditory stimuli in autism. J Autism Dev Disord. 2009;39(5):742–50.PubMedCrossRef
27.
Foxton JM, Stewart ME, Barnard L, Rodgers J, Young AH, O’Brien G, et al. Absence of auditory ‘global interference’in autism. Brain. 2003;126(12):2703–9.PubMedCrossRef
28.
Pellicano E, Gibson L, Maybery M, Durkin K, Badcock DR. Abnormal global processing along the dorsal visual pathway in autism: a possible mechanism for weak visuospatial coherence? Neuropsychologia. 2005;43(7):1044–53.PubMedCrossRef
29.
Braddick O, Atkinson J, Wattam-Bell J. Normal and anomalous development of visual motion processing: motion coherence and ‘dorsal-stream vulnerability’. Neuropsychologia. 2003;41(13):1769–84.PubMedCrossRef
30.
Bertone A, Mottron L, Jelenic P, Faubert J. Enhanced and diminished visuo-spatial information processing in autism depends on stimulus complexity. Brain. 2005;128(10):2430–41.PubMedCrossRef
31.
Amunts K, Kedo O, Kindler M, Pieperhoff P, Mohlberg H, Shah N, et al. Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anat Embryol (Berl). 2005;210(5-6):343–52.CrossRef
32.
Ball T, Rahm B, Eickhoff SB, Schulze-Bonhage A, Speck O, Mutschler I. Response properties of human amygdala subregions: evidence based on functional MRI combined with probabilistic anatomical maps. PLoS One. 2007;2(3), e307.PubMedPubMedCentralCrossRef
33.
Roy AK, Shehzad Z, Margulies DS, Kelly AC, Uddin LQ, Gotimer K, et al. Functional connectivity of the human amygdala using resting state fMRI. Neuroimage. 2009;45(2):614.PubMedPubMedCentralCrossRef
34.
Pitkänen A, Savander V, LeDoux JE. Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala. Trends Neurosci. 1997;20(11):517–23.PubMedCrossRef
35.
36.
Moreno N, González A. Evolution of the amygdaloid complex in vertebrates, with special reference to the anamnio‐amniotic transition. J Anat. 2007;211(2):151–63.PubMedPubMedCentralCrossRef
37.
Bickart KC, Hollenbeck MC, Barrett LF, Dickerson BC. Intrinsic amygdala–cortical functional connectivity predicts social network size in humans. J Neurosci. 2012;32(42):14729–41.PubMedPubMedCentralCrossRef
38.
Bzdok D, Laird AR, Zilles K, Fox PT, Eickhoff SB. An investigation of the structural, connectional, and functional subspecialization in the human amygdala. Hum Brain Mapp. 2013;34(12):3247–66.PubMedCrossRef
39.
40.
Heimer L, Van Hoesen GW. The limbic lobe and its output channels: implications for emotional functions and adaptive behavior. Neurosci Biobehav Rev. 2006;30(2):126–47.PubMedCrossRef
41.
42.
Goossens L, Kukolja J, Onur OA, Fink GR, Maier W, Griez E, et al. Selective processing of social stimuli in the superficial amygdala. Hum Brain Mapp. 2009;30(10):3332–8.PubMedCrossRef
43.
Pessoa L, Adolphs R. Emotion processing and the amygdala: from a ‘low road’ to ‘many roads’ of evaluating biological significance. Nat Rev Neurosci. 2010;11(11):773–83.PubMedPubMedCentralCrossRef
44.
45.
Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994;24(5):659–85.PubMedCrossRef
46.
Kort W, Schittekatte M, Dekker P, Verhaeghe P, Compaan E, Bosmans M. Wechsler intelligence scale for children-dutch version. London: Psychological Corporation; 2005.
47.
Wechsler D. WAIS-III Nederlandstalige bewerking: Afname-en scoringshandleiding [WAIS-III Dutch version: User manual]. Lisse, The Netherlands: Swets and Zeitlinger; 2000.
48.
Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9(1):97–113.PubMedCrossRef
49.
Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E. The Autism-Spectrum Quotient (AQ): evidence from Asperger Syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord. 2001;31(1):5–17.PubMedCrossRef
50.
Woodbury-Smith MR, Robinson J, Wheelwright S, Baron-Cohen S. Screening adults for Asperger Syndrome using the AQ: a preliminary study of its diagnostic validity in clinical practice. J Autism Dev Disord. 2005;35(3):331–5.PubMedCrossRef
51.
Poser BA, Versluis MJ, Hoogduin JM, Norris DG. BOLD contrast sensitivity enhancement and artifact reduction with multiecho EPI: parallel‐acquired inhomogeneity‐desensitized fMRI. Magn Reson Med. 2006;55(6):1227–35.PubMedCrossRef
52.
Chang C, Metzger CD, Glover GH, Duyn JH, Heinze H-J, Walter M. Association between heart rate variability and fluctuations in resting-state functional connectivity. Neuroimage. 2013;68:93–104.PubMedPubMedCentralCrossRef
53.
Birn RM, Smith MA, Jones TB, Bandettini PA. The respiration response function: the temporal dynamics of fMRI signal fluctuations related to changes in respiration. Neuroimage. 2008;40(2):644–54.PubMedPubMedCentralCrossRef
54.
Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23:S208–S19.PubMedCrossRef
55.
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE. Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage. 2012;59(3):2142–54.PubMedPubMedCentralCrossRef
56.
Kelly Jr RE, Alexopoulos GS, Wang Z, Gunning FM, Murphy CF, Morimoto SS, et al. Visual inspection of independent components: defining a procedure for artifact removal from fMRI data. J Neurosci Methods. 2010;189(2):233–45.PubMedPubMedCentralCrossRef
57.
Glover GH, Li TQ, Ress D. Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med. 2000;44(1):162–7.PubMedCrossRef
58.
O’Reilly JX, Beckmann CF, Tomassini V, Ramnani N, Johansen-Berg H. Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. Cereb Cortex. 2010;20(4):953–65.PubMedPubMedCentralCrossRef
59.
Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp. 2002;15(1):1–25.PubMedCrossRef
60.
Smith SM, Nichols TE. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage. 2009;44(1):83–98.PubMedCrossRef
61.
IBM Corp. IBM SPSS Statistics for Windows, Version 20.0. Armonk: IBM Corp; 2011.
62.
Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry. 2003;54(5):504–14.PubMedCrossRef
63.
Durston S, Thomas KM, Yang Y, Uluğ AM, Zimmerman RD, Casey B. A neural basis for the development of inhibitory control. Dev Sci. 2002;5(4):F9–F16.CrossRef
64.
Paus T. Mapping brain maturation and cognitive development during adolescence. Trends Cogn Sci. 2005;9(2):60–8.PubMedCrossRef
65.
Williams BR, Ponesse JS, Schachar RJ, Logan GD, Tannock R. Development of inhibitory control across the life span. Dev Psychol. 1999;35(1):205.PubMedCrossRef
66.
Murphy K, Birn RM, Handwerker DA, Jones TB, Bandettini PA. The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? Neuroimage. 2009;44(3):893–905.PubMedPubMedCentralCrossRef
67.
Cole DM, Smith SM, Beckmann CF. Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Front Syst Neurosci. 2010;4:8.PubMedPubMedCentral
68.
Koelsch S, Skouras S, Fritz T, Herrera P, Bonhage C, Küssner MB, et al. The roles of superficial amygdala and auditory cortex in music-evoked fear and joy. Neuroimage. 2013;81:49–60.PubMedCrossRef
69.
Sah P, Faber E, De Armentia ML, Power J. The amygdaloid complex: anatomy and physiology. Physiol Rev. 2003;83(3):803–34.PubMedCrossRef
70.
Qin S, Young CB, Supekar K, Uddin LQ, Menon V. Immature integration and segregation of emotion-related brain circuitry in young children. Proc Natl Acad Sci U S A. 2012;109(20):7941–6.PubMedPubMedCentralCrossRef
71.
Schoenbaum G, Chiba AA, Gallagher M. Changes in functional connectivity in orbitofrontal cortex and basolateral amygdala during learning and reversal training. J Neurosci. 2000;20(13):5179–89.PubMed
72.
Gabard-Durnam LJ, Flannery J, Goff B, Gee DG, Humphreys KL, Telzer E, et al. The development of human amygdala functional connectivity at rest from 4 to 23 years: a cross-sectional study. Neuroimage. 2014;95:193–207.PubMedPubMedCentralCrossRef
73.
Vissers ME, Cohen MX, Geurts HM. Brain connectivity and high functioning autism: a promising path of research that needs refined models, methodological convergence, and stronger behavioral links. Neurosci Biobehav Rev. 2012;36(1):604–25.PubMedCrossRef
74.
Bertone A, Mottron L, Jelenic P, Faubert J. Motion perception in autism: a “complex” issue. J Cogn Neurosci. 2003;15(2):218–25.PubMedCrossRef
75.
Bonda E, Petrides M, Ostry D, Evans A. Specific involvement of human parietal systems and the amygdala in the perception of biological motion. J Neurosci. 1996;16(11):3737–44.PubMed
76.
Gläscher J, Adolphs R. Processing of the arousal of subliminal and supraliminal emotional stimuli by the human amygdala. J Neurosci. 2003;23(32):10274–82.PubMed
77.
McMenamin BW, Marsolek CJ. Can theories of visual representation help to explain asymmetries in amygdala function? Cogn Affect Behav Neurosci. 2013;13(2):211–24.PubMedPubMedCentralCrossRef
78.
Smith SM, Miller KL, Salimi-Khorshidi G, Webster M, Beckmann CF, Nichols TE, et al. Network modelling methods for FMRI. Neuroimage. 2011;54(2):875–91.PubMedCrossRef
Metadata
Title
Altered functional connectivity of the amygdaloid input nuclei in adolescents and young adults with autism spectrum disorder: a resting state fMRI study
Authors
Annika Rausch
Wei Zhang
Koen V. Haak
Maarten Mennes
Erno J. Hermans
Erik van Oort
Guido van Wingen
Christian F. Beckmann
Jan K. Buitelaar
Wouter B. Groen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2016
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-015-0060-x

Other articles of this Issue 1/2016

Molecular Autism 1/2016 Go to the issue

Research

Sex differences in the association between infant markers and later autistic traits

Research

Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity

Research

Deletion and duplication of 16p11.2 are associated with opposing effects on visual evoked potential amplitude

Research

Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment

Short report

Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder

Commentary

Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al.