Neural Mechanism of Physical Exercise in Enhancing Executive and Social Functions in Adolescents
Phase: NA
Conditions: Broad Autism Phenotype
Sponsor: The University of Hong Kong

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exercise Training to Enhance Executive and Social Functions 
May 17th, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Background 
Executive function and social functioning  
Executive functions (EF) refer to goal-directed cognitive processes consisting of three major components 
including cognitive flexibility (mental flexibility), inhibition (inhibitory control) and working memory 
(Diamond, 2013). These components interact with each other and play a crucial role in a range of life 
outcomes including mental and physical health (Barch, 2005; Miller, Barnes, & Beaver, 2011), school and 
job success (Bailey, 2007; Duncan et al., 2007) and marital harmony (Eakin et al., 2004). In addition, higher 
EF is associated with better problem solving, reasoning and planning skills (Diamond, 2013) as well as 
social functions. 
 
Relationship between executive and social function and autism spectrum disorder 
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by social communication 
and interaction impairments, as well as restricted and repetitive patterns of behavior (American Psychiatric 
Association, 2013). Individuals with ASD have EF impairments which are linked to the restricted and 
repetitive behaviors that characterise this condition (Robinson et al., 2009). The prevalence of ASD is 
increasing with as many as 1 in 68 individuals (CDC, 2018), which further augments the burden to the ASD 
individuals, their families and society (Baron-Cohen et al., 2009; World Health Organization, 2005a). Hence, 
it is essential to investigate the underlying mechanism of ASD and design a cost-effective training that can 
be widely adopted in the community to reduce impairments arising from ASD symptoms.  
 
Importantly, ASD traits occur on a continuum, and increasingly there is recognition of a broader autism 
phenotype (BAP) (e.g., see Dawson et al., 2002) in those that show sub-clinical symptoms. Similarly, these 
individuals also show impairments in executive function (e.g., Hill, 2004) and social functions, making this 
group an important target for the development and implementation of interventions. As such, we can deliver 
appropriate training at an earlier stage to prevent associated impairments in those with ASD traits. Therefore, 
instead of ASD, the present study examines the individuals with BAP. 
 
The role of physical exercise on executive and social function in autistic individuals 
Given EF impairments along with social function deficits are found in the sub-clinical individuals with BAP 
(Hill, 2004), is the training pertaining to ASD applicable to these individuals? In prior literature, physical 
exercise (PE) has been proved to enhance EF (Best, 2010) and social functions (Sowa & Meulenbroek, 
2012). For instance, regular PE can enhance cerebral blood flow and increase the formation of new blood 
vessels in a number of brain regions that are involved in EF and social functions (e.g., Colcombe & Kramer, 
2003). More specifically, PE is shown to enhance the performance of EF in healthy children and pre-
adolescents (Best, 2010) and those with ASD (Lang et al., 2010).  For example, Lang et al. (2010) and 
Lochbaum and Crews (2003) found that PE including jogging significantly decreased the repetitive and off-
task behaviors and the level of aggression in individuals with ASD. Nevertheless, although PE is shown to 
be beneficial to reduce the symptoms and EF as well as social impairments in ASD, whether it produces the 
same positive outcomes on enhancing EF and social functions in the non-clinical population remains to be 
answered.  
 
To address the research questions listed above, this proposed study aims to investigate whether PE training 
enhances the EF and social functions in the adolescents with BAP.  
                                       
 
 
                                   Research plan and methodology 
Participants 

 
 
To detect possible differences between the means of the primary measure with a power of 80%, eighty 
adolescents from secondary schools in Hong Kong and Australia will be recruited in this study (Hopkins et 
al., 2009). Written informed consent will be obtained from all participants. For participants who are below 
18 years old, the consent from their parents or guardians will be obtained. Based on their self-reported 
autistic traits measured by Autism- Spectrum Quotient- Adolescent Version (details listed below), they will 
be categorized into two groups: 1) typically developing group (low ASD traits) and 2) BAP group (high 
ASD traits). To be included in the study, they must meet the following criteria: a) age ranges from 7 to 20; 
b) studying at one of the primary and secondary schools in Hong Kong; c) have never been diagnosed with 
ASD or any other disorder listed in the Fifth Edition of Diagnostic and Statistical Manual of Mental 
Disorders (DSM-V); and d) are not currently under any psychiatric medications or therapies.  
Randomization. This study consists of a double-blind, and randomized controlled trial (RCT).  After 
obtaining the informed consent, participants will be randomized into two conditions (1. physical exercise 
(PE) training group or 2. control group) using urn randomization, a covariate adaptive randomization 
method. A trained research assistant or a fitness trainer will be responsible to monitor and ensure the safety 
of the training process. 
Physical exercise training. The PE training will adapt the exercise training employed by Lochbaum & 
Crews (2003) and Nicholson et al. (2011) since they targeted adolescents with ASD and the protocol of 
training can easily be replicated. The entire PE training lasts for six weeks and participants need to 
participate in a total of 12 sessions. In each session, every participant will be trained to run for 30 minutes on 
a treadmill. According to Exercise and Sports Science Australia (ESSA) exercise intensity guidelines, the 
intensity of running is suggested to be moderate and vigorous (alternating between the two) in this proposed 
study.  
 
Control group. Participating adolescents in the control group will not receive any treatments. They are 
considered as waitlist controls.  
 
Measures 
The following self-reported measures will be administered at the baseline, post-training and 1-year follow-
up. 
Demographics. A simple demographic questionnaire will be used to gather participants personal 
information, including age, gender, current medication or therapy, and medical history of the participant and 
his/her family members. Besides, the blood pressure and heart rate of the participants will be assessed by 
electrocardiogram. 
Autistic traits. The Autism-Spectrum Quotient-Adolescent Version (AQ-Adolescent; Baron-Cohen et 
al., 2006) and related self-report scales will be used to measure ASD traits. The AQ- adolescent is a self-
report questionnaire comprising of 50 items assessing five areas, namely social, attention switching, 
attention to detail, communication and imagination. Participants will be asked to rate each item on a four-
point Likert scale. The AQ-Adolescent received an excellent test-retest reliability (r = .92; Baron-Cohen et 
al., 2006) and a good internal consistency (α = .88, Sonié et al., 2013). 
Executive functions and social functions. EF and social functions will be measured using the 
Cambridge Neuropsychological Test Automated Battery (CANTAB).The CANTAB is a computerized test 
battery targeting multiple neuropsychological functions that has been validated in different cultures (De 
Luca et al., 2003). This battery includes Reaction Time, Paired Associates Learning, Spatial Working 
Memory, One Touch Stockings of Cambridge, Multitasking Test, and Emotion Recognition Task. Besides 

 
 
the CANTAB, participant’s psychological well-being including resilience and mental health will be 
measured.  
Implications 
Although the benefits of physical exercise have been studied in the ASD, BAP is under studied in prior 
literature. This proposed study will extend from the current literature to investigate the non-clinical group 
who have autistic traits with a longitudinal and randomized controlled trial design (RCT). The findings of 
this proposed study have multiple levels of significance and implications. For instance, if the hypotheses are 
supported, the PE training which is more cost-effective than psychotherapy in treating EF and social 
functioning deficits and associated impairments can be promoted to school settings. Ultimately, it can be 
incorporated to the curriculum of the primary and secondary schools to reduce BAP and associated 
impairments in the adolescents. Secondly, by examining those with sub- clinical symptoms, this research 
will contribute to early trainings approaches for the condition. Lastly, this proposed study can also help 
promote physical activities among adolescents which can further decrease mental and health issues in Hong 
Kong (MacDonald et al. 2011).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
References 
Alvarez, J. A., & Emory, E. (2006). Executive function and the frontal lobes: A meta-analytic review. 
Neuropsychology Review, 16(1), 17–42. doi:10.1007/s11065-006-9002-x 

 
 
American Psychological Association. (2013). Diagnostic and statistical manual of mental disorders.  
Washington, DC: Author. 
Anderson, S. W., Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1999). Impairment of social and  
moral behavior related to early damage in human prefrontal cortex. Nature Neuroscience, 2(11), 
1032. 
Bailey, C. E. (2007). Cognitive accuracy and intelligent executive function in the brain and in business. 
Annals of the New York Academy of Sciences, 1118, 122–141. doi:10.1196/annals.1412.011 
Banich, M. T., Milham, M. P., Atchley, R., Cohen, N. J., Webb, A., Wszalek, T., . . . Brown, C. (2000). 
Prefrontal regions play a predominant role in imposing an attentional ‘set’: Evidence from fMRI. 
Cognitive Brain Research, 10(1–2), 1–9. doi:10.1016/S0926-6410(00)00015-X 
Barch, D. M. (2005). The cognitive neuroscience of schizophrenia. Annual Review of Psychology, 1, 321–
353. doi:10.1146/annurev.clinpsy.1.102803.143959 
Baron-Cohen, S., Hoekstra, R. A., Knickmeyer, R., & Wheelwright, S. (2006). The Autism-Spectrum 
Quotient (AQ)—Adolescent version. Journal of Autism and Developmental Disorders, 36(3), 343–
350. doi:10.1007/s10803-006-0073-6 
Baron-Cohen, S., Scott, F. J., Allison, C., Williams, J., Bolton, P., Matthews, F. E., & Brayne, C. (2009). 
Prevalence of autism-spectrum conditions: UK school-based population study. British Journal of 
Psychiatry, 194(6), 500–509. doi:10.1192/bjp.bp.108.059345 
Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I. The ‘Reading the Mind in the Eyes’ Test revised  
version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. 
J Child Psychol Psychiatry. 2001; 42: 241–251. 
Best, J. R. (2010). Effects of physical activity on children’s executive function: Contributions of 
experimental research on aerobic exercise. Developmental Review, 30(4), 331–551. 
doi:10.1016/j.dr.2010.08.001 
Bradley, M. M., and P. J. Lang. 1999. Affective norms for English words (ANEW): stimuli, instruction  
manual and affective ratings. Technical report C-1, The Center for Research in Psychophysiology, 
University of Florida, Gainesville, FL. 
Carper, R. A., & Courchesne, E. (2005). Localized enlargement of the frontal cortex in early autism. 
Biological Psychiatry, 57(2), 126–133. doi:10.1016/j.biopsych.2004.11.005 
Centers for Disease Control and Prevention (CDC), & Developmental Disabilities Monitoring Network  
Surveillance 2014 Year Principal Investigators. (2018). Prevalence of autism spectrum disorder 
among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, 
united states, 2014. Morbidity and Mortality Weekly Report. Surveillance Summaries,  67(6), 1–23. 
Colcombe, S., & Kramer, A. F. (2003). Fitness effects on the cognitive function of older adults: A meta- 
analytic study. Psychological Science, 14(2), 125–130. doi:10.1111/1467-9280.t01-1-01430 
Compton, R. J., Banich, M. T., Milham, M. P., Heller, W., Miller, G. A., Scalf, P. E., ... & Kramer, A. (2000).  
Paying attention to emotion: An fMRI investigation. Journal of Cognitive Neuroscience, 54-54. 
Damasio, A. R. (1994). Descartes’ error: Emotion, reason, and the human. New York: Avon Books. 
Dawson, G., Webb, S., Schellenberg, G. D., Dager, S., Friedman, S., Aylward, E., &  
           Richards, T. (2002). Defining  the broader phenotype of autism: Genetic, brain, and    
           behavioral perspectives. Development and Psychopathology, 14(3), 581-611. 
De Luca, C. R., Wood, S. J., Anderson, V., Buchanan, J. A., Proffitt, T. M., Mahony, K., & Pantelis, C.  
(2003). Normative data from the CANTAB. I: development of executive function over the 
lifespan. Journal of clinical and experimental neuropsychology, 25(2), 242-254. 
Diamond, A. (2013). Executive Functions. Annual Review of Psychology, 64, 135–168.  
doi:10.1146/annurev-psych-113011-143750 
Duncan, G. J., Dowsett, C. J., Claessens, A., Magnuson, K., Huston, A. C., Klebanov, P., . . . Japel, C. 
(2007). School readiness and later achievement. Developmental Psychology, 43(6), 1428-1446. 
doi:10.1037/0012-1649.43.6.1428 

 
 
Eakin, L., Minde, K., Hechtman, L., Ochs, E., Krane, E., Bouffard, R., . . . Looper, K. (2004). The marital 
and family functioning of adults with ADHD and their spouses. Journal of Attention Disorders, 8(1), 
1–10. doi:10.1177/108705470400800101 
Ecker, C., Bookheimer, S. Y., & Murphy, D. G. (2015). Neuroimaging in autism spectrum disorder: Brain 
structure and function across the lifespan. The Lancet Neurology, 14(11), 1121–1134. 
doi:10.1016/S1474-4422(15)00050-2 
Ecker, C., Ronan, L., Feng, Y., Daly, E., Murphy, C., Ginestet, C. E., . . . Murphy, D. G. (2013). Intrinsic 
gray-matter connectivity of the brain in adults with autism spectrum disorder. Proceedings of the 
National Academy of Sciences, 110(32), 13222–13227. doi:10.1073/pnas.1221880110 
Hill, E. L. (2004). Executive dysfunction in autism. Trends in Cognitive Sciences, 8(1), 26-32. 
Hopkins, W., Marshall, S., Batterham, A., & Hanin, J. (2009). Progressive statistics for studies   
          in sports medicine and exercise science. Medicine+ Science in Sports+ Exercise, 41(1),   
          3. 
Lang, R., Koegel, L. K., Ashbaugh, K., Regester, A., Ence, W., & Smith, W. (2010). Physical exercise and 
individuals with autism spectrum disorders: A systematic review. Research in Autism Spectrum 
Disorders, 4, 565–576. doi:10.1016/j.rasd.2010.01.006 
Leger, L. A., Mercier, D., Gadoury, C., & Lambert, J. (1988). The multistage 20 metre shuttle run test for 
aerobic fitness. Journal of Sports Sciences, 6(2), 93–101. doi:10.1080/02640418808729800 
Lochbaum, M., & Crews, D. (2003). Viability of Cardiorespiratory and Muscular Strength Programs for the 
Adolescent With Autism. Complementary Health Practice Review, 8(3), 225–233. 
doi:10.1177/1076167503252917 
MacDonald, M., Esposito, P., & Ulrich, D. (2011). The physical activity patterns of children with    
          autism. BMC Research Notes, 4(1), 422. 
Miller, H. V., Barnes, J. C., & Beaver, K. M. (2011). Self-control and health outcomes in a nationally 
representative sample. American Journal of Health Behavior, 35(1), 15–27. 
doi:10.5993/AJHB.35.1.2 
Nicholson, H., Kehle, T. J., Bray, M. A., & Heest, J. V. (2011). The effects of antecedent physical activity on  
the academic engagement of children with autism spectrum disorder. Psychology in the 
Schools, 48(2), 198-213. 
Ortega, F. B., Artero, E. G., Ruiz, J. R., Vicente-Rodriguez, G., Bergman, P., Hagstromer, M., . . . Castillo, 
M. J. (2008). Reliability of health-related physical fitness tests in European adolescents. The 
HELENA Study. International Journal of Obesity, 32, S49–S57. doi:10.1038/ijo.2008.183 
Robinson, S., Goddard, L., Dritschel, B., Wisley, M., & Howlin, P. (2009). Executive functions in children 
with Autism Spectrum Disorders. Brain and Cognition, 71(3), 362–368. 
doi:10.1016/j.bandc.2009.06.007 
Song, Y., & Hakoda, Y. (2015). An fMRI study of the functional mechanisms of Stroop/reverse-Stroop 
effects. Behavioural Brain Research, 290, 187-196. 
Sonié, S., Kassai, B., Pirat, E., Bain, P., Robinson, J., Gomot, M., . . . Manificat, S. (2013). The French 
version of the autism-spectrum quotient in adolescents: A cross-cultural validation study. Journal of 
Autism and Developmental Disorders, 43(5), 1178–1183. doi:10.1007/s10803-012-1663-0 
Sowa, M., & Meulenbroek, R. (2012). Effects of physical exercise on autism spectrum disorders: a  
meta- analysis. Research in Autism Spectrum Disorders, 6(1), 46-57. 
Stuss, D. T., & Alexander, M. P. (2000). Executive functions and the frontal lobes: A conceptual view. 
Psychological Research, 63(3-4), 289–298. doi:10.1007/s004269900007 
Troyer, A. K., Moscovitch, M., Winocur, G., Alexander, M. P., & Stuss, D. (1998). Clustering and 
switching on verbal fluency: The effects of focal frontal- and temporal-lobe lesions. 
Neuropsychologia, 36(6), 499–504. doi:10.1016/S0028-3932(97)00152-8 
Waiter, G. D., Williams, J. H., Murray, A. D., Gilchrist, A., Perrett, D. I., & Whiten, A. (2004). A voxel-
based investigation of brain structure in male adolescents with autistic spectrum disorder. 
NeuroImage, 22(2), 619-625. doi:10.1016/j.neuroimage.2004.02.029 
World Health Organization. (2005a). Mental health policy and service guidance package: Child and 
adolescent mental health policies and plans (WHO Reference Number. WM 342005ME-1). 
Retrieved from http://www.who.int/mental_health/policy/Childado_mh_module.pdf 

 
 
World Health Organization. (2005b). WHO STEPS surveillance manual: the WHO STEPwise approach to  
chronic disease risk ractor surveillance. Geneva, Switzerland: World Health Organization. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 1 
‘Reading the Mind in the Eyes’’ Task 

 
 
 
In the ‘‘Reading the Mind in the Eyes’’ task, the participants will first see a word labeling either a 
mental/emotional state (e.g., embarrassed) or a gender (e.g., female). The word is then replaced with a 
fixation cross, and then a picture of eyes. Participants will determine whether the eyes depicted the emotion 
or gender labeled by the word choices by pressing corresponding key. 
 
 
 
 
 
Appendix 2 
Montreal Imaging Stress Task (MIST) 
 
 
 
 
 
 
 
 
 
 
 
 
The Montreal Imaging Stress Task (MIST) is a neuroimaging-adapted psychosocial stress task that 
uses mental arithmetic to combine the key situational components for eliciting stress response, including 
presence of social evaluative threat, atmosphere of high achievement, and low controllability.