Clinical trial NCT03199937: Executive Function Intervention for High School Students With ASD
Official title: Behavioral and Neural Outcomes of a New Executive Function Treatment for Transition-age Youth With ASD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: Autism Spectrum Disorder
Executive Functioning
Intervention
Flexible
Unstuck
Transition
Behavior
High school
Problem Solving
Self-Control
Coping
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
Collaborators: name: Georgetown University
First posted: 2017-06-27
Enrollment: 68
Sex: ALL
Minimum age (years): 14
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this project is to test the effectiveness of a novel school-based intervention targeting executive function skills, including flexibility and planning, in college-track, transition-age youth with ASD. Evaluating treatment change through behavior and brain activity provides important information on how the treatment works and who will best benefit from it.

Detailed description: With half of the $3.2 million lifetime per capita cost of autism spectrum disorder (ASD) attributable to care and productivity loss during adult life, the Interagency Autism Coordinating Committee has identified a pressing need to improve adult outcomes. Even in individuals without intellectual disability who make up 2/3 of children with ASD, as few as 9% reach full functional independence as adults. Failure in college is related to weaknesses in executive function (EF), specifically with flexibility and planning. As such, the transition from high school is a period of amplified risk characterized by poor educational and vocational attainment that persists in adulthood. EF problems are pivotal targets for intervention because they are common, linked to independence, and responsive to treatment in younger children. There are three barriers to treatment outcome research in transition-aged youth with ASD: (1) a lack of proven EF treatments for this age, (2) pervasive failure to generalize skills learned in the clinic to real-world settings, and (3) inadequate objective measures of outcome. This proposal tests the effectiveness of Flexible Futures a new phenotype specific, cognitive behavioral EF intervention to increase flexibility and planning skills for college-track high school students with ASD. It is novel and innovative because its use of translational methods comprehensively evaluates treatment change at the behavioral, cognitive, and neural level.

Cognitive flexibility and planning are impaired in ASD, linked to core ASD symptoms, and embedded in anomalies of brain structure and function. Individuals with ASD fail to activate local cortical regions such as dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) on set-shifting (flexibility) tasks and show global abnormalities in the default mode, salience, and attentional networks associated with EF problems in attending to important information and implementing goal-directed behavior. In typical development, greater segregation between and greater connectivity within these networks is associated with better cognitive and behavioral regulation. Dr. Pugliese aims to determine whether treatment change can be objectively measured in the brain using functional MRI (fMRI). This cutting edge methodology is critical to identifying processes of treatment change at the neural level, consistent with the NIMH Research Domain Criteria framework, and may yield findings that impact the large variety of psychiatric and developmental disorders linked to EF deficits. Specifically, this study aligns with NIMH K23 guidance soliciting proposals for the development of pilot studies of novel treatments eliciting mechanisms of change.

AIM 1: Refine the Flexible Futures treatment manual and test acceptability, feasibility, and effectiveness in a school setting.

Dr. Pugliese will refine the Flexible Futures manual based on expert opinion and feedback from our in-clinic pilot via an iterative process and run a school-based trial comparing Flexible Futures to social skills treatment. It is hypothesized that intervention acceptability, feasibility, and fidelity will reach an 80% benchmark (H1.1) and students who receive Flexible Futures will show improved EF flexibility and planning abilities in laboratory, school, and home settings post-treatment and at 5-month follow up compared to students who receive treatment as usual (H1.2).

AIM 2: Identify neural correlates of treatment change using fMRI.

Task-evoked and resting-state activation of prefrontal cortex networks will be assessed pre-/post-intervention. It is hypothesized that post-treatment, students receiving Flexible Futures will display increased (normalized) DLPFC and ACC activation during a well-established set-shifting task compared to those receiving social skills training (H2.1), and that activation will be positively correlated with behavioral/cognitive measures of EF (H2.2). It is also hypothesized that post-treatment, students receiving Flexible Futures will display increased connectivity within, and decreased connectivity across default mode, salience, and attentional networks compared to the control group (H2.3).

AIM 3: Identify biomarkers of later EF outcomes at the behavioral, cognitive, and neural level.

Baseline data will be combined across participants to provide a comprehensive EF profile in transition-age youth and identify predictors of later EF and global outcomes. It is hypothesized that baseline measures of EF (behavioral/ cognitive); DLPFC/ACC activation; and greater connectivity within and greater segregation between salience, attentional and default mode networks (neural) will all predict EF outcome and adaptive function. (H3.1).

Significance: Establishing the first effective school-based EF treatment for high-schoolers will provide critical and generalizable transition-related support, and a model for treatment in other prevalent disorders with known EF deficits (e.g. ADHD, anxiety). This training award will launch me toward Dr. Pugliese's ultimate career goals of 1) developing and implementing innovative interventions personalized for specific cognitive profiles, 2) developing school-based treatments to overcome disparities in access to healthcare; and 3) utilizing treatment studies as vehicles to identify biomarkers and provide insight into neural correlates of treatment change.

Eligibility criteria: Inclusion Criteria:

* College-track high school students
* Ages 14-22
* Verbal IQ estimate of ≥ 90 on the Wechsler Abbreviated Intelligence Scale-2
* Clinical diagnosis of ASD OR school classification of autism confirmed by clinical impressions and the Social Responsiveness Scale-Revised total score ≥ 65. If the research staff feels that clinical impressions indicate a diagnosis, but parent report is below threshold, the Autism Diagnostic Observation Schedule-2 will be completed.

Exclusion Criteria:

* Bipolar disorder, schizophrenia, or major depression that is currently preventing from participation in classroom activities
* MRI exclusion: contraindication (metal implant or medical device) for MRI

Primary outcomes:
measure: Change in Behavior Rating Inventory of Executive Function (BRIEF)- Self-Report Form (Gioia, Isquith, Guy & Kenworthy, 2000).
timeFrame: On average, 8 and 13 months
measure: Change in Challenge Task (CT) scores
timeFrame: On average, 8 and 13 months
measure: Change in Wechsler Abbreviated Scale of Intelligence- Second Edition (WASI-II, Wechsler, 2011), block design subtest
timeFrame: On average, 8 and 13 months
measure: Change in Delis-Kaplan Executive Functioning System (DKEFS; Delis, Kaplan, and Kramer, 2001), Sorting subtest
timeFrame: On average, 8 and 13 months
measure: Change in Tower of London-Drexel (TOL-DX; Culbertson & Zillmer, 2000) scores
timeFrame: On average, 8 and 13 months
measure: Change in Adaptive Behavior Assessment System-Second Edition (ABAS-2)
timeFrame: On average, 8 and 13 months
measure: Social Responsiveness Scale-Second Edition (SRS-2; Constantino and Gruber 2012)
timeFrame: On average, 8 and 13 months
measure: Change in Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)- Parent Form (Gioia, Isquith, Guy & Kenworthy, 2015).
timeFrame: On average, 8 and 13 months
measure: Flexibility and Planning Interference Scale
timeFrame: On average, 8 and 13 months
measure: The Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP, Swanson, 1992)
timeFrame: On average, 8 and 13 months
measure: Classroom Observations
timeFrame: On average, 8 and 13 months
measure: Cognitive Flexibility Task
timeFrame: On average, 8 and 13 months
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's Research Institute
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: Cara E Pugliese, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pugliese CE, White SW. Brief report: problem solving therapy in college students with autism spectrum disorders: feasibility and preliminary efficacy. J Autism Dev Disord. 2014 Mar;44(3):719-29. doi: 10.1007/s10803-013-1914-8.
citation: Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. 1996 Jan;37(1):51-87. doi: 10.1111/j.1469-7610.1996.tb01380.x.
citation: Frith U. Why we need cognitive explanations of autism. Q J Exp Psychol (Hove). 2012;65(11):2073-92. doi: 10.1080/17470218.2012.697178. Epub 2012 Aug 21.
citation: Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med. 2007 Apr;161(4):343-9. doi: 10.1001/archpedi.161.4.343.
citation: Interagency Autism Coordinating Committee. The 2011 Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research.; 2011.
citation: Farley MA, McMahon WM, Fombonne E, Jenson WR, Miller J, Gardner M, Block H, Pingree CB, Ritvo ER, Ritvo RA, Coon H. Twenty-year outcome for individuals with autism and average or near-average cognitive abilities. Autism Res. 2009 Apr;2(2):109-18. doi: 10.1002/aur.69.
citation: Gobbo K, Shmulsky S. Faculty Experience With College Students With Autism Spectrum Disorders: A Qualitative Study of Challenges and Solutions. Focus Autism Other Dev Disabl. 2013;29(1):13-22. doi:10.1177/1088357613504989.
citation: Taylor JL, Mailick MR. A longitudinal examination of 10-year change in vocational and educational activities for adults with autism spectrum disorders. Dev Psychol. 2014 Mar;50(3):699-708. doi: 10.1037/a0034297. Epub 2013 Sep 2.
citation: Hume K, Loftin R, Lantz J. Increasing independence in autism spectrum disorders: a review of three focused interventions. J Autism Dev Disord. 2009 Sep;39(9):1329-38. doi: 10.1007/s10803-009-0751-2. Epub 2009 May 9.
citation: Hill EL. Executive dysfunction in autism. Trends Cogn Sci. 2004 Jan;8(1):26-32. doi: 10.1016/j.tics.2003.11.003.
citation: Pugliese CE, Anthony L, Strang JF, Dudley K, Wallace GL, Kenworthy L. Increasing adaptive behavior skill deficits from childhood to adolescence in autism spectrum disorder: role of executive function. J Autism Dev Disord. 2015 Jun;45(6):1579-87. doi: 10.1007/s10803-014-2309-1.
citation: Kenworthy L, Anthony LG, Naiman DQ, Cannon L, Wills MC, Luong-Tran C, Werner MA, Alexander KC, Strang J, Bal E, Sokoloff JL, Wallace GL. Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum. J Child Psychol Psychiatry. 2014 Apr;55(4):374-83. doi: 10.1111/jcpp.12161. Epub 2013 Nov 21.
citation: Taylor JL, Dove D, Veenstra-VanderWeele J, et al. Comparative Effictiveness Review: Interventions for Adolescents and Young Adults With Autism. 2012;(65).
citation: Dingfelder HE, Mandell DS. Bridging the research-to-practice gap in autism intervention: an application of diffusion of innovation theory. J Autism Dev Disord. 2011 May;41(5):597-609. doi: 10.1007/s10803-010-1081-0.
citation: Kenworthy L, Black DO, Harrison B, della Rosa A, Wallace GL. Are executive control functions related to autism symptoms in high-functioning children? Child Neuropsychol. 2009 Sep;15(5):425-40. doi: 10.1080/09297040802646983.
citation: Solomon M, Ozonoff SJ, Ursu S, Ravizza S, Cummings N, Ly S, Carter CS. The neural substrates of cognitive control deficits in autism spectrum disorders. Neuropsychologia. 2009 Oct;47(12):2515-26. doi: 10.1016/j.neuropsychologia.2009.04.019. Epub 2009 May 4.
citation: Shafritz KM, Dichter GS, Baranek GT, Belger A. The neural circuitry mediating shifts in behavioral response and cognitive set in autism. Biol Psychiatry. 2008 May 15;63(10):974-80. doi: 10.1016/j.biopsych.2007.06.028. Epub 2007 Oct 4.
citation: Vaidya CJ, Gordon EM. Phenotypic variability in resting-state functional connectivity: current status. Brain Connect. 2013;3(2):99-120. doi: 10.1089/brain.2012.0110.
citation: Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 2012 Mar 30;61(3):1-19.
citation: Cidav Z, Lawer L, Marcus SC, Mandell DS. Age-related variation in health service use and associated expenditures among children with autism. J Autism Dev Disord. 2013 Apr;43(4):924-31. doi: 10.1007/s10803-012-1637-2.
citation: Shattuck PT, Narendorf SC, Cooper B, Sterzing PR, Wagner M, Taylor JL. Postsecondary education and employment among youth with an autism spectrum disorder. Pediatrics. 2012 Jun;129(6):1042-9. doi: 10.1542/peds.2011-2864. Epub 2012 May 14.
citation: Taylor JL, Henninger NA. Frequency and correlates of service access among youth with autism transitioning to adulthood. J Autism Dev Disord. 2015 Jan;45(1):179-91. doi: 10.1007/s10803-014-2203-x.
citation: Taylor JL, Henninger NA, Mailick MR. Longitudinal patterns of employment and postsecondary education for adults with autism and average-range IQ. Autism. 2015 Oct;19(7):785-93. doi: 10.1177/1362361315585643. Epub 2015 May 27.
citation: Geurts HM, Verte S, Oosterlaan J, Roeyers H, Sergeant JA. How specific are executive functioning deficits in attention deficit hyperactivity disorder and autism? J Child Psychol Psychiatry. 2004 May;45(4):836-54. doi: 10.1111/j.1469-7610.2004.00276.x.
citation: Hughes C, Russell J, Robbins TW. Evidence for executive dysfunction in autism. Neuropsychologia. 1994 Apr;32(4):477-92. doi: 10.1016/0028-3932(94)90092-2.
citation: Ozonoff S, Pennington BF, Rogers SJ. Executive function deficits in high-functioning autistic individuals: relationship to theory of mind. J Child Psychol Psychiatry. 1991 Nov;32(7):1081-105. doi: 10.1111/j.1469-7610.1991.tb00351.x.
citation: Ozonoff S, Jensen J. Brief report: specific executive function profiles in three neurodevelopmental disorders. J Autism Dev Disord. 1999 Apr;29(2):171-7. doi: 10.1023/a:1023052913110. No abstract available.
citation: Kenworthy L, Yerys BE, Anthony LG, Wallace GL. Understanding executive control in autism spectrum disorders in the lab and in the real world. Neuropsychol Rev. 2008 Dec;18(4):320-38. doi: 10.1007/s11065-008-9077-7. Epub 2008 Oct 28.
citation: Lopata C et al. ABAS-II Ratings and Correlates of Adaptive Behavior in Children with HFASDs. J Dev Phys Disabil. 2012;24:391-402.
citation: Lawson RA, Papadakis AA, Higginson CI, Barnett JE, Wills MC, Strang JF, Wallace GL, Kenworthy L. Everyday executive function impairments predict comorbid psychopathology in autism spectrum and attention deficit hyperactivity disorders. Neuropsychology. 2015 May;29(3):445-53. doi: 10.1037/neu0000145. Epub 2014 Oct 13.
citation: Lounds J, Seltzer MM, Greenberg JS, Shattuck PT. Transition and change in adolescents and young adults with autism: longitudinal effects on maternal well-being. Am J Ment Retard. 2007 Nov;112(6):401-17. doi: 10.1352/0895-8017(2007)112[401:TACIAA]2.0.CO;2.
citation: Shattuck PT, Steinberg J, Yu J, Wei X, Cooper BP, Newman L, Roux AM. Disability Identification and Self-Efficacy among College Students on the Autism Spectrum. Autism Res Treat. 2014;2014:924182. doi: 10.1155/2014/924182. Epub 2014 Feb 23.
citation: Weisz JR, Ugueto AM, Cheron DM, Herren J. Evidence-based youth psychotherapy in the mental health ecosystem. J Clin Child Adolesc Psychol. 2013;42(2):274-86. doi: 10.1080/15374416.2013.764824. Epub 2013 Feb 12.
citation: Ylvisaker M, Jacobs HE, Feeney T. Positive supports for people who experience behavioral and cognitive disability after brain injury: a review. J Head Trauma Rehabil. 2003 Jan-Feb;18(1):7-32. doi: 10.1097/00001199-200301000-00005.
citation: Oberman L, Pascual-Leone A. Changes in plasticity across the lifespan: cause of disease and target for intervention. Prog Brain Res. 2013;207:91-120. doi: 10.1016/B978-0-444-63327-9.00016-3.
citation: Lee PS, Yerys BE, Della Rosa A, Foss-Feig J, Barnes KA, James JD, VanMeter J, Vaidya CJ, Gaillard WD, Kenworthy LE. Functional connectivity of the inferior frontal cortex changes with age in children with autism spectrum disorders: a fcMRI study of response inhibition. Cereb Cortex. 2009 Aug;19(8):1787-94. doi: 10.1093/cercor/bhn209. Epub 2008 Dec 9.
citation: Huttenlocher PR. Morphometric study of human cerebral cortex development. Neuropsychologia. 1990;28(6):517-27. doi: 10.1016/0028-3932(90)90031-i.
citation: Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL. Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci. 1999 Oct;2(10):861-3. doi: 10.1038/13158. No abstract available.
citation: Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF 3rd, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8174-9. doi: 10.1073/pnas.0402680101. Epub 2004 May 17.
citation: Shonkoff JP. Protecting brains, not simply stimulating minds. Science. 2011 Aug 19;333(6045):982-3. doi: 10.1126/science.1206014.
citation: Yerys BE, Antezana L, Weinblatt R, Jankowski KF, Strang J, Vaidya CJ, Schultz RT, Gaillard WD, Kenworthy L. Neural Correlates of Set-Shifting in Children With Autism. Autism Res. 2015 Aug;8(4):386-97. doi: 10.1002/aur.1454. Epub 2015 Jan 20.
citation: Castellanos FX, Margulies DS, Kelly C, Uddin LQ, Ghaffari M, Kirsch A, Shaw D, Shehzad Z, Di Martino A, Biswal B, Sonuga-Barke EJ, Rotrosen J, Adler LA, Milham MP. Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biol Psychiatry. 2008 Feb 1;63(3):332-7. doi: 10.1016/j.biopsych.2007.06.025. Epub 2007 Sep 21.
citation: Assaf M, Jagannathan K, Calhoun VD, Miller L, Stevens MC, Sahl R, O'Boyle JG, Schultz RT, Pearlson GD. Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients. Neuroimage. 2010 Oct 15;53(1):247-56. doi: 10.1016/j.neuroimage.2010.05.067. Epub 2010 Jun 2.
citation: Doyle-Thomas KA, Lee W, Foster NE, Tryfon A, Ouimet T, Hyde KL, Evans AC, Lewis J, Zwaigenbaum L, Anagnostou E; NeuroDevNet ASD Imaging Group. Atypical functional brain connectivity during rest in autism spectrum disorders. Ann Neurol. 2015 May;77(5):866-76. doi: 10.1002/ana.24391. Epub 2015 Mar 27.
citation: Eilam-Stock T, Xu P, Cao M, Gu X, Van Dam NT, Anagnostou E, Kolevzon A, Soorya L, Park Y, Siller M, He Y, Hof PR, Fan J. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder. Brain. 2014 Jan;137(Pt 1):153-71. doi: 10.1093/brain/awt294.
citation: Jung M, Kosaka H, Saito DN, Ishitobi M, Morita T, Inohara K, Asano M, Arai S, Munesue T, Tomoda A, Wada Y, Sadato N, Okazawa H, Iidaka T. Default mode network in young male adults with autism spectrum disorder: relationship with autism spectrum traits. Mol Autism. 2014 Jun 11;5:35. doi: 10.1186/2040-2392-5-35. eCollection 2014.
citation: Monk CS, Peltier SJ, Wiggins JL, Weng SJ, Carrasco M, Risi S, Lord C. Abnormalities of intrinsic functional connectivity in autism spectrum disorders. Neuroimage. 2009 Aug 15;47(2):764-72. doi: 10.1016/j.neuroimage.2009.04.069. Epub 2009 May 3.
citation: Yerys BE, Gordon EM, Abrams DN, Satterthwaite TD, Weinblatt R, Jankowski KF, Strang J, Kenworthy L, Gaillard WD, Vaidya CJ. Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children. Neuroimage Clin. 2015 Aug 18;9:223-32. doi: 10.1016/j.nicl.2015.07.018. eCollection 2015.
citation: Kennedy DP, Redcay E, Courchesne E. Failing to deactivate: resting functional abnormalities in autism. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8275-80. doi: 10.1073/pnas.0600674103. Epub 2006 May 15.
citation: Dawson G, Jones EJ, Merkle K, Venema K, Lowy R, Faja S, Kamara D, Murias M, Greenson J, Winter J, Smith M, Rogers SJ, Webb SJ. Early behavioral intervention is associated with normalized brain activity in young children with autism. J Am Acad Child Adolesc Psychiatry. 2012 Nov;51(11):1150-9. doi: 10.1016/j.jaac.2012.08.018.
citation: Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA. Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):20953-8. doi: 10.1073/pnas.1312857110. Epub 2013 Dec 2.
citation: Voos AC, Pelphrey KA, Tirrell J, Bolling DZ, Vander Wyk B, Kaiser MD, McPartland JC, Volkmar FR, Ventola P. Neural mechanisms of improvements in social motivation after pivotal response treatment: two case studies. J Autism Dev Disord. 2013 Jan;43(1):1-10. doi: 10.1007/s10803-012-1683-9.
citation: Walker HM. Use of evidence-based interventions in schools: where we've been, where we are, and where we need to go. School Psych Rev. 2004;33:398-407.
citation: Kasari C, Lawton K. New directions in behavioral treatment of autism spectrum disorders. Curr Opin Neurol. 2010 Apr;23(2):137-43. doi: 10.1097/WCO.0b013e32833775cd.
citation: Pugliese CE, Anthony LG, Strang JF, Dudley K, Wallace GL, Naiman DQ, Kenworthy L. Longitudinal Examination of Adaptive Behavior in Autism Spectrum Disorders: Influence of Executive Function. J Autism Dev Disord. 2016 Feb;46(2):467-77. doi: 10.1007/s10803-015-2584-5.
citation: J J, HA L, CK W. Subjective culture and social behavior. In: Adamopoulos J, Kashima Y, eds. Social Psychology and Cultural Context. Thousand Oaks, CA: Sage Publications; 1999:95-106.
citation: Wallace GL, Silvers JA, Martin A, Kenworthy LE. Brief report: Further evidence for inner speech deficits in autism spectrum disorders. J Autism Dev Disord. 2009 Dec;39(12):1735-9. doi: 10.1007/s10803-009-0802-8. Epub 2009 Jun 30.
citation: Wechsler D, Zhou X. Wechsler Abbreviated Scale of Intelligence II. NY, New York: The Psychological Corporation: Harcourt Brace & Company; 2011.
citation: Lord C, Rutter M, DiLavore PC, Risi S, Gotham K, Bishop SL. Autism Diagnostic Observation Schedule, 2nd Ed. (ADOS-2). Torrance, CA: Western Psychological Services; 2012.
citation: Rutter M, Bailey A, Berument SK, Le Couteur A, Lord C. Social Communication Questionnaire (SCQ) Manual. Los Angeles, CA: Western Psychological Services; 2003.
citation: Gioia G, Isquith P, Guy S, Kenworthy L. BRIEF: Behavior Rating Inventory of Executive Function. Odessa: Psychological Assessment Resources; 2000.
citation: Sparrow S, Cicchetti D, Balla DA. Vineland Adaptive Behavior Scales Second Edition:Survey Forms Manual. Minneapolis, MN: Pearson; 2005.
citation: Abraha I, Montedori A. Modified intention to treat reporting in randomised controlled trials: systematic review. BMJ. 2010 Jun 14;340:c2697. doi: 10.1136/bmj.c2697.
citation: Jacobson NS, Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. J Consult Clin Psychol. 1991 Feb;59(1):12-9. doi: 10.1037//0022-006x.59.1.12.
citation: Clopper CJ, Pearson ES. The Use of Confidence or Fiducial Limits Illustrated in the Case of the Binomial. Biometrika. 1934;26:404-413.
citation: MATLAB Version 7.10.0. Natick, Massachusettes: The MathWorks Inc.; 2010.
citation: IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corporation; 2013.
citation: Bullmore E, Sporns O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci. 2009 Mar;10(3):186-98. doi: 10.1038/nrn2575. Epub 2009 Feb 4.
citation: Rubinov M, Sporns O. Complex network measures of brain connectivity: uses and interpretations. Neuroimage. 2010 Sep;52(3):1059-69. doi: 10.1016/j.neuroimage.2009.10.003. Epub 2009 Oct 9.
citation: Power JD, Cohen AL, Nelson SM, Wig GS, Barnes KA, Church JA, Vogel AC, Laumann TO, Miezin FM, Schlaggar BL, Petersen SE. Functional network organization of the human brain. Neuron. 2011 Nov 17;72(4):665-78. doi: 10.1016/j.neuron.2011.09.006.
citation: Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc. 1995;57(1):289-300.