Patients with autism spectrum disorders display reproducible functional connectivity alterations

被引：98

作者：

Holiga, Stefan ^{[1
]}

Hipp, Joerg F. ^{[1
]}

Chatham, Christopher H. ^{[1
]}

Garces, Pilar ^{[1
]}

Spooren, Will ^{[1
]}

D'Ardhuy, Xavier Liogier ^{[1
]}

Bertolino, Alessandro ^{[1
,2
]}

Bouquet, Celine ^{[1
]}

Buitelaar, Jan K. ^{[3
]}

Bours, Carsten ^{[3
]}

Rausch, Annika ^{[3
]}

Oldehinkel, Marianne ^{[3
,4
,5
]}

Bouvard, Manuel ^{[6
]}

Amestoy, Anouck ^{[6
]}

Caralp, Mireille ^{[7
]}

Gueguen, Sonia ^{[8
]}

Ly-Le Moal, Myriam ^{[9
]}

Houenou, Josselin ^{[10
,11
]}

Beckmann, Christian F. ^{[3
]}

Loth, Eva ^{[12
]}

Murphy, Declan ^{[12
]}

Charman, Tony ^{[12
]}

Tillmann, Julian ^{[12
,13
]}

Laidi, Charles ^{[10
]}

Delorme, Richard ^{[14
,15
]}

Beggiato, Anita ^{[14
,15
]}

Gaman, Alexandru ^{[10
]}

Scheid, Isabelle ^{[10
]}

Leboyer, Marion ^{[10
]}

d'Albis, Marc-Antoine ^{[10
,11
]}

Sevigny, Jeff ^{[1
]}

Czech, Christian ^{[1
]}

Bolognani, Federico ^{[1
,16
]}

Honey, Garry D. ^{[1
]}

Dukart, Juergen ^{[1
,17
,18
]}

机构：

[1] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, Grenzacherstr 124, CH-4070 Basel, Switzerland

[2] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, I-70121 Bari, Italy

[3] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav,Ctr Cognit Neur, NL-6525 EN Nijmegen, Netherlands

[4] Monash Univ, Brain & Mental Hlth Lab, Monash Inst Cognit & Clin Neurosci, Clayton, Vic 3800, Australia

[5] Monash Univ, Sch Psychol Sci, Clayton, Vic 3800, Australia

[6] Hop Charles Perrens Bordeaux, Pole Univ Psychiat Enfant & Adolescent, F-33076 Bordeaux, France

[7] INSERM, Natl Biobank Infrastruct, F-75013 Paris, France

[8] INSERM, Dept Clin Res, F-75014 Paris, France

[9] Inst Roche, F-92100 Boulogne, France

[10] Univ Paris Est, Hop Univ Mondor, DHU PePSY,Psychiat Translat,Fdn FondaMental, Pole Psychiat,Fac Med,INSERM,U955,IMRB,Equipe 15, F-94000 Creteil, France

[11] CEA Saclay, NeuroSpin, UNIACT Lab, Psychiat Team, F-91191 Gif Sur Yvette, France

[12] Kings Coll London, Inst Psychiat Psychol & Neurosci, De Crespigny Pk,Denmark Hill, London SE5 8AF, England

[13] Univ Vienna, Dept Appl Psychol Hlth Dev Enhancement & Interven, A-1010 Vienna, Austria

[14] Robert Debre Hosp, AP HP, Child & Adolescent Psychiat Dept, Paris, France

[15] Pasteur Inst, F-75019 Paris, France

[16] Therachon AG, Aeschenvorstadt 36, CH-4051 Basel, Switzerland

[17] Res Ctr Julich, Inst Neurosci & Med Brain & Behav INM 7, D-52428 Julich, Germany

[18] Heinrich Heine Univ Dusseldorf, Fac Med, Inst Syst Neurosci, D-40223 Dusseldorf, Germany

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2019年 / 11卷 / 481期

关键词：

RESTING-STATE NETWORKS; BRAIN; CHILDREN; OVERCONNECTIVITY; METAANALYSIS; ADOLESCENTS; ATTENTION; PROJECT; SIGNAL; MRI;

D O I：

10.1126/scitranslmed.aat9223

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Despite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here, we addressed these questions in four large ASD cohorts. Using rs-fMRI, we identified functional connectivity alterations associated with ASD. We tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status, and clinical symptom severity. Our results showed reproducible patterns of ASD-associated functional hyper- and hypoconnectivity. Hypoconnectivity was primarily restricted to sensory-motor regions, whereas hyperconnectivity hubs were predominately located in prefrontal and parietal cortices. Shifts in cortico-cortical between-network connectivity from outside to within the identified regions were shown to be a key driver of these abnormalities. This reproducible pathophysiological phenotype was partially associated with core ASD symptoms related to communication and daily living skills and was not affected by age, sex, or medication status. Although the large effect sizes in standardized cohorts are encouraging with respect to potential application as a treatment and for patient stratification, the moderate link to clinical symptoms and the large overlap with healthy controls currently limit the usability of identified alterations as diagnostic or efficacy readout.

引用

页数：12

共 61 条

[1] Decreased Interhemispheric Functional Connectivity in Autism [J].