title: A model of functional brain connectivity and background noise as a biomarker for cognitive phenotypes: application to autism.
abstract: We present an efficient approach to discriminate between typical and atypical brains from macroscopic neural dynamics recorded as magnetoencephalograms (MEG). Our approach is based on the fact that spontaneous brain activity can be accurately described with stochastic dynamics, as a multivariate Ornstein-Uhlenbeck process (mOUP). By fitting the data to a mOUP we obtain: 1) the functional connectivity matrix, corresponding to the drift operator, and 2) the traces of background stochastic activity (noise) driving the brain. We applied this method to investigate functional connectivity and background noise in juvenile patients (n = 9) with Asperger's syndrome, a form of autism spectrum disorder (ASD), and compared them to age-matched juvenile control subjects (n = 10). Our analysis reveals significant alterations in both functional brain connectivity and background noise in ASD patients. The dominant connectivity change in ASD relative to control shows enhanced functional excitation from occipital to frontal areas along a parasagittal axis. Background noise in ASD patients is spatially correlated over wide areas, as opposed to control, where areas driven by correlated noise form smaller patches. An analysis of the spatial complexity reveals that it is significantly lower in ASD subjects. Although the detailed physiological mechanisms underlying these alterations cannot be determined from macroscopic brain recordings, we speculate that enhanced occipital-frontal excitation may result from changes in white matter density in ASD, as suggested in previous studies. We also venture that long-range spatial correlations in the background noise may result from less specificity (or more promiscuity) of thalamo-cortical projections. All the calculations involved in our analysis are highly efficient and outperform other algorithms to discriminate typical and atypical brains with a comparable level of accuracy. Altogether our results demonstrate a promising potential of our approach as an efficient biomarker for altered brain dynamics associated with a cognitive phenotype.
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Luis García
authors.initials: LG
authors.lastname: Domínguez
authors.forename: José Luis Pérez
authors.initials: JL
authors.lastname: Velázquez
authors.forename: Roberto Fernández
authors.initials: RF
authors.lastname: Galán
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology*; D002648:Child; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*; D010641:Phenotype
chemical_list: D015415:Biomarkers