Voluntary saccades in attention-deficit/hyperactivity disorder: Looking into the relationship between motor impairment and Autism Spectrum Disorder symptoms
Introduction
Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that affects approximately 5.3% of young people worldwide (Polanczyk et al., 2014). The predominant diagnostic features of ADHD, combined type (Attention Deficit Hyperactivity Disorder-Combined Type (ADHD-CT)) are clinically significant levels of inattentiveness and hyperactivity/impulsivity (American Psychiatric Association, 2013). In reality, few children diagnosed with ADHD-CT display these core symptoms in isolation, and many experience co-occurring neurodevelopmental symptoms, including motor impairment (Angold et al., 1999). Up to 50% of young people with ADHD-CT display a wide range of gross and fine motor coordination difficulties, in some cases significant enough to meet criteria for Developmental Coordination Disorder (DCD) (Pitcher et al., 2003, Kaiser et al., 2015).
Motor coordination difficulties are also considered a “cardinal feature” of Autism Spectrum Disorders (ASDs) (p. 1227; Fournier et al., 2010), another highly prevalent neurodevelopmental disorder, found to co-occur at a rate of 20–50% in young people with ADHD-CT (Reiersen et al., 2008, Gillberg, 2003, Grzadzinski et al., 2011, Green et al., 2015). Long recognized as separate disorders in the Diagnostic and Statistical Manual of Mental Disorders, only the most recent revision (DSM-5) allowed for the diagnosis of ADHD-CT and ASD together in the same individual (American Psychiatric Association, 2013). Findings from genetics research suggest ADHD-CT and ASD share genetic influences and have familial linkage (Mulligan et al., 2009, Ronald et al., 2008). Young people diagnosed with ADHD-CT or ASD are also reported to experience similar difficulties with cognition, language, sleep, mood, behavior, and motor functioning (Gillberg, 2010, Grzadzinski et al., 2011), which is the focus of the current study. However, identifying co-occurring ASD in ADHD-CT clinically can be challenging as it currently relies on subjective interpretation of a young person’s behavior, for example, poor social interaction may also be interpreted as inattentiveness (Mayes et al., 2012), and the diagnosis of ADHD may overshadow ASD symptoms (Joshi et al., 2014).
Recent studies suggest that motor impairment in young people with ADHD-CT may be due to co-occurring ASD symptoms. For example, in their population-based study of 851 young people aged 7–19 years, Reiersen et al. (2008) found that young people with ADHD-CT and greater parent-reported motor impairment had increased levels of ASD symptoms compared to those young people with ADHD-CT without motor impairment. However, motor impairment in their study was measured using two questionnaire items relating to accident proneness and clumsiness, which may have been influenced by other factors. Papadopoulos et al. (2013) extended upon these findings using a standardized clinical measure of motor proficiency, the Movement Assessment Battery for Children-2nd edition, in young people aged 7–14 diagnosed with ADHD-CT. They also found that participants with ADHD-CT, but without comorbid ASD symptoms, did not show clinically significant motor impairment, although their findings were preliminary, and their measure was of gross motor function. The presence of motor impairment may therefore serve as a potential marker of co-occurring ASD symptomology in children with ADHD-CT (Dowd et al., 2010). However, sensitive and objective measures of motor impairment are necessary to further investigate the relationship between ASD symptoms and motor impairment in children with ADHD-CT.
Ocular motor paradigms permit a sensitive, non-invasive investigation of motor performance, with a high degree of measurement accuracy (Leigh and Zee, 2006), and have been used extensively to investigate ocular motor behavior in human and non-human primates (Leigh and Kennard, 2004). The ocular motor network is an extensive network of brain regions, spreading across cortical, subcortical and cerebellar regions, making it useful in studying disruption to a wide range of motor and cognitive processes (Leigh and Zee, 2006, Willard and Lueck, 2014). The cerebellum, in particular the dorsal vermis (lobules VI-VII) and underlying fastigial nucleus, plays a critical role in ocular motor control, maintaining saccade accuracy and efficient saccade dynamics, represented experimentally by variables such as the main sequence relationship (saccade velocity for a given amplitude) and trial-to-trial variability (Leigh and Zee, 2006, Robinson and Fuchs, 2001).
Differences in cerebellum morphology have consistently been reported in ADHD-CT groups compared to typically developing (TD) groups. Reductions in total cerebellar volume and in the posterior-inferior vermal region of the cerebellum (lobules VIII–X) compared to TD controls have been found by imaging studies (Castellanos et al., 2002, Krain and Castellanos, 2006, Bledsoe et al., 2011). While ocular motor paradigms have been employed in previous studies involving young people diagnosed with ADHD-CT, these have been primarily used as a means to measure frontal–striatal control, evaluating functions such as response inhibition, working memory and attention (for a review see Rommelse et al. (2008)).
Converging evidence from neuroimaging and motor research fields also implicate cerebellum dysfunction as important in the neuropathology of ASD (Tsai et al., 2012). Structural abnormalities have been consistently reported including reductions in vermal lobules VI and VII (Courchesne et al., 1994, Courchesne et al., 1988) and fewer and smaller sized Purkinje cells (Bauman and Kemper, 2005). Furthermore, clear patterns of ocular motor impairment suggestive of cerebellum dysfunction have been found in groups with ASD. For example, young people with ASD with average IQ are found to have saccades with properties that are more variable, with more variable ‘main sequence’ relationships, altered velocity waveforms and more frequently over- and undershooting the visual target (dysmetria), compared to control groups (Johnson et al., 2012, Schmitt et al., 2014, Stanley-Cary et al., 2011).
To the best of our knowledge, no study to date has examined the influence of co-occurring ADHD-CT and ASD symptoms on ocular motor control in groups with ADHD-CT. The aims of the current study are two-fold. The primary aim of this study was to examine the impact of ASD symptoms on ocular motor control in children with ADHD-CT, using a cued saccade paradigm previously found by Stanley-Cary et al. (2011) to be sensitive to cerebellar ocular motor impairment in ASD and dissociate ASD participants from TD controls. Specifically, this task revealed a profile of ocular motor deficits in ASD groups that included more variable response time, more variable final eye position and more variability of the main sequence (Stanley-Cary et al., 2011).
The second aim of the study was to use a dimensional approach to assess the influence of both ADHD-CT and ASD symptoms on volitional saccade performance, ranging from TD/mild levels to clinically severe levels of symptomology. Given previous research suggesting an association between motor impairment and ASD symptoms in children with ADHD-CT (Reiersen et al., 2008), we anticipated that higher levels of ASD symptoms would be associated with increased impairment to ocular motor control.
Section snippets
Participants
This study was approved by the Human Research Ethics Committees of Monash Health and Monash University in Melbourne, Australia. Parents of participants, in accordance with the Declaration of Helsinki, provided informed consent and written assent was also obtained from participants.
Participants were males with a diagnosis of ADHD-CT made by their pediatrician (n = 14) aged between 8 and 14 years, recruited from Private Paediatric Clinics. Inclusion criteria were having met the relevant criteria of
Group characteristics
Means and standard deviations for age, IQ, ADHD-CT symptom and ASD symptom measures are presented in Table 1. Measures of inattentiveness, hyperactivity, ASD symptoms were all significantly greater for ADHD-CT participants compared to the TD group.
Laterality
A mixed-model ANOVA found a significant main effect for laterality of primary saccade amplitude [F(1,26) = 13.76, p = .001]. Post-hoc analyses showed that for both groups saccade amplitudes were larger to the right compared to the left side. There was
Discussion
The current study investigated the integrity of volitional saccades in young people with ADHD-CT and the relationship to ADHD-CT and ASD symptomology using a simple volitional saccade task and measures sensitive to cerebellum impairment. Compared to TD young people, those with ADHD-CT were found to generate saccades that were significantly larger in amplitude (hypermetric), and with an altered main sequence (peak velocity/amplitude) relationship. We found these differences in ocular motor
Conflict of interests
NR is a member of the Australian National Health and Medical Research Council Expert Working Group on ADHD Clinical Practice Points and has contributed to the Therapeutic Guidelines for Developmental Disorders.
Acknowledgments
The authors would like to thank all the children and families who participated in this study. The authors also thank the Melbourne-based Pediatricians and Psychologists who assisted with recruitment for this study.
This study was partially supported by funding from the National Health and Medical Research Council (NHMRC) Project Grant 1004387 and the NARSAD #17343 awarded to J.F.
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