title: Temporal lobe connects regression and macrocephaly to autism spectrum disorders.
abstract: Interictal electroencephalogram (EEG) abnormalities are frequently associated with autism spectrum disorders (ASD), although their relationship with the clinical features of ASD, particularly the regressive onset, remains controversial. The aim of this study was to investigate whether the characteristics of interictal EEG abnormalities might help to distinguish and predict definite phenotypes within the heterogeneity of ASD. We reviewed the awake and sleep interictal EEGs of 220 individuals with idiopathic ASD, either with or without a history of seizures. EEG findings were analyzed with respect to a set of clinical variables to explore significant associations. A brain morphometry study was also carried out on a subgroup of patients. EEG abnormalities were seen in 154/220 individuals (70%) and were mostly focal (p < 0.01) with an anterior localization (p < 0.001). They were detected more frequently during sleep (p < 0.01), and were associated with a regressive onset of ASD (p < 0.05), particularly in individuals with focal temporal localization (p < 0.05). This association was also stronger in regressive patients with concurrent macrocephaly, together with a relative volumetric reduction of the right temporal cortex (p < 0.05). Indeed, concurrence of temporal EEG abnormalities, regression and macrocephaly might possibly define a distinct endophenotype of ASD. EEG-based endophenotypes could be useful to untangle the complexity of ASD, helping to establish anatomic or pathophysiologic subtypes of the disorder.
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Valvo
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldini
authors.affiliation: National Institute for Nuclear Physics (INFN), Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Retico
authors.affiliation: Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tancredi
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Ferrari
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Calderoni
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Apicella
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Muratori
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy.
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2 - Calambrone, 56128, Pisa, Italy. federico.sicca@fsm.unipi.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Sicca
mesh_terms: D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D002658:Developmental Disabilities / Q000175:diagnosis*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D058627:Megalencephaly / Q000503:physiopathology*; D010641:Phenotype; D012640:Seizures / Q000150:complications / Q000175:diagnosis*; D012890:Sleep; D013702:Temporal Lobe / Q000503:physiopathology*
keywords: Autism; EEG; Macrocephaly; Regression; Temporal lobe