title: A unique pattern of cortical connectivity characterizes patients with attention deficit disorders: a large electroencephalographic coherence study.
abstract: BACKGROUND
  Attentional disorders (ADD) feature decreased attention span, impulsivity, and over-activity interfering with successful lives. Childhood onset ADD frequently persists to adulthood. Etiology may be hereditary or disease associated. Prevalence is 5% but recognition may be 'overshadowed' by comorbidities (brain injury, mood disorder) thereby escaping formal recognition. Blinded diagnosis by MRI has failed. ADD may not itself manifest a single anatomical pattern of brain abnormality but may reflect multiple, unique responses to numerous and diverse etiologies. Alternatively, a stable ADD-specific brain pattern may be better detected by brain physiology. EEG coherence, measuring cortical connectivity, is used to explore this possibility.
  
  
  METHODS
  Participants: Ages 2 to 22 years; 347 ADD and 619 neurotypical controls (CON). Following artifact reduction, principal components analysis (PCA) identifies coherence factors with unique loading patterns. Discriminant function analysis (DFA) determines discrimination success differentiating ADD from CON. Split-half and jackknife analyses estimate prospective diagnostic success. Coherence factor loading constitutes an ADD-specific pattern or 'connectome'.  RESULTS: PCA identified 40 factors explaining 50% of total variance. DFA on CON versus ADD groups utilizing all factors was highly significant (p≤0.0001). ADD subjects were separated into medication and comorbidity subgroups. DFA (stepping allowed) based on CON versus ADD without comorbidities or medication treatment successfully classified the correspondingly held out ADD subjects in every instance. Ten randomly generated split-half replications of the entire population demonstrated high-average classification success for each of the left out test-sets (overall: CON, 83.65%; ADD, 90.07%). Higher success was obtained with more restricted age sub-samples using jackknifing: 2-8 year olds (CON, 90.0%; ADD, 90.6%); 8-14 year olds (CON, 96.8%; ADD 95.9%); and 14-20 year-olds (CON, 100.0%; ADD, 97.1%). The connectome manifested decreased and increased coherence. Patterns were complex and bi-hemispheric; typically reported front-back and left-right loading patterns were not observed. Subtemporal electrodes (seldom utilized) were prominently involved.  CONCLUSIONS: Results demonstrate a stable coherence connectome differentiating ADD from CON subjects including subgroups with and without comorbidities and/or medications. This functional 'connectome', constitutes a diagnostic ADD phenotype. Split-half replications support potential for EEG-based ADD diagnosis, with increased accuracy using limited age ranges. Repeated studies could assist recognition of physiological change from interventions (pharmacological, behavioral).
authors.affiliation: Department of Neurology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA. fhd@sover.net.
authors.forename: Frank H
authors.identifier: http://orcid.org/0000-0002-6482-9980
authors.initials: FH
authors.lastname: Duffy
authors.affiliation: Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Shankardass
authors.affiliation: Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Gloria B
authors.initials: GB
authors.lastname: McAnulty
authors.affiliation: Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: Heidelise
authors.initials: H
authors.lastname: Als
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D063132:Connectome / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D025341:Principal Component Analysis; D011446:Prospective Studies; D055815:Young Adult
keywords: Attention deficit disorder; Attention deficit/hyperactivity disorder; Autism spectrum disorder; Classification; Coherence; Connectivity; Connectome; Diagnosis; Discriminant analysis; Electroencephalogram; MRI; Medication; Principal component analysis; Spectral analysis; Split-half replication