title: Reorganization of functionally connected brain subnetworks in high-functioning autism.
abstract: Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson's correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default-mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter-individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism.
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
authors.forename: Enrico
authors.initials: E
authors.lastname: Glerean
authors.affiliation: Department of Computer Science, Aalto University, Espoo, Finland.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Pan
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.|Faculty of Arts, Psychology and Theology, Åbo Akademi University, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Salmi
authors.affiliation: Department of Computer Science, Aalto University, Espoo, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kujala
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
authors.forename: Juha M
authors.initials: JM
authors.lastname: Lahnakoski
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Roine
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.|Turku PET Centre and Department of Psychology, University of Turku, Turku, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Nummenmaa
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.|Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Leppämäki
authors.affiliation: Neuropsychiatric Rehabilitation and Medical Centre Neuromental, Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Nieminen-von Wendt
authors.affiliation: Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Tani
authors.affiliation: Department of Computer Science, Aalto University, Espoo, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Saramäki
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Sams
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland.|Advanced Magnetic Imaging (AMI) Centre, Aalto NeuroImaging, Aalto University, Espoo, Finland.
authors.forename: Iiro P
authors.initials: IP
authors.lastname: Jääskeläinen
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016208:Databases, Factual; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009039:Motion Perception / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity; D010775:Photic Stimulation; D015203:Reproducibility of Results; D012146:Rest; D012720:Severity of Illness Index; D055815:Young Adult
keywords: autism spectrum disorder; fMRI; functional connectivity; graph theory; intersubject similarity; network modularity