title: Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale.
abstract: Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8-18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the typical group), with autism severity (P < 0.03), and with diagnosis (89% accuracy). A biophysically realistic computational model using data driven feedforward and feedback parameters replicated the magnetoencephalography data faithfully. The direct observation of both abnormally increased and abnormally decreased functional connectivity in autism occurring simultaneously in different functional connectivity streams, offers a potential unifying framework for the unexplained discrepancies in current findings. Given that cortical feedback, whether local or long-range, is intrinsically non-linear, while cortical feedforward is generally linear relative to the stimulus, the present results suggest decreased non-linearity alongside an increased veridical component of the cortical response in autism.
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Sheraz
authors.initials: S
authors.lastname: Khan
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Michmizos
authors.affiliation: 3 Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Tommerdahl
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Ganesan
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Manfred G
authors.initials: MG
authors.lastname: Kitzbichler
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zetino
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Keri-Lee A
authors.initials: KL
authors.lastname: Garel
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA.
authors.forename: Martha R
authors.initials: MR
authors.lastname: Herbert
authors.affiliation: 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA 4 Department of Radiology, MGH, Harvard Medical School, Boston, MA, USA 5 Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.
authors.forename: Matti S
authors.initials: MS
authors.lastname: Hämäläinen
authors.affiliation: 1 Department of Neurology, MGH, Harvard Medical School, Boston, MA, USA 2 A.A. Martinos Centre for Biomedical Imaging, MGH/MIT/Harvard, Boston, MA, USA tal@nmr.mgh.harvard.edu.
authors.forename: Tal
authors.initials: T
authors.lastname: Kenet
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D004569:Electroencephalography / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D015225:Magnetoencephalography; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D013003:Somatosensory Cortex / Q000503:physiopathology*
keywords: autism spectrum disorder; biomarker; coherence; magnetoencephalography; mu-rhythm; steady-state; vibrotactile