Overlapping and Distinct Cognitive Impairments in Attention-Deficit/Hyperactivity and Autism Spectrum Disorder without Intellectual Disability

“Multiple Comparisons A false discovery rate correction for multiple comparisons was applied (Benjamini and Hochberg 1995).”

“It provides a secure web-based and intuitive interface and export capabilities (Harris et al. 2009).”

“Diffusionmodel There is increasing recognition that many psychiatric symptom dimensions are shared across existing diagnostic boundaries, and the extent to which this indicates shared liability or etiology across disorders remains a major question (Insel et al. 2010; Sanislow et al. 2010).”

“1998), Conner’s Rating Scale, 3rd edition (Conners 2008), and the Strengths and Difficulties Questionnaire (Goodman 2001), and an in-person semi-structured diagnostic interview (Kiddie Schedule for Affective Disorders and Schizophrenia, KSADS; Puig-Antich and Ryan 1986), while the child completed IQ screening and brie…”

“Although there is heterogeneity in the ADHD population (Fair et al. 2012; Nigg et al. 2005), at the group level relatively consistent impairments have been found in individuals with ADHD in each of these domains (Huang-Pollock et al. 2012; Kofler et al. 2013; Willcutt et al. 2005).”

“Head-to-head comparisons of children with ASD and ADHD have yielded conflicting results as to whether executive function impairments and differences in reward processing are more pronounced in ADHD (Happe et al. 2006; Nyden et al. 2010) or in ASD (Geurts et al. 2004; Pennington and Ozonoff 1996).”

“Cognitive abilities develop rapidly over middle childhood and adolescence(Best and Miller 2010; Karalunas et al. 2017; Miller et al. 2013) and whether the ASD and ADHD groups show distinct trajectories of cognitive development is unable to be evaluated in this cross-sectional study.”

“Multiple cognitive domains have been proposed as relevant in ADHD and, to a lesser extent, in ASD, including: 1) response inhibition (Logan 1994; Nigg 2000); 2) interference control; 3) working memory (Baddeley 1996; De Luca et al. 2003; Engle 2002; Kane et al. 2007; Unsworth and Engle 2007), 4)…”

“Deficits in several aspects of executive function have also been found in individuals with ASD relative to controls, particularly in set-shifting (Hill 2004; Ozonoff and Jensen 1999; Sanders et al. 2008).”

“…inhibition (Logan 1994; Nigg 2000); 2) interference control; 3) working memory (Baddeley 1996; De Luca et al. 2003; Engle 2002; Kane et al. 2007; Unsworth and Engle 2007), 4) set-shifting and 5) reward valuation, particularly delayed reward discounting (Demurie et al. 2012; Hulst et al. 2017;…”

“Delayed Reward Valuation Delayed reward valuation was assessed using a computerized delay discounting questionnaire, based on the task described by Mitchell (1999) and Wilson et al. (2011).”

“Although there is heterogeneity in the ADHD population (Fair et al. 2012; Nigg et al. 2005), at the group level relatively consistent impairments have been found in individuals with ADHD in each of these domains (Huang-Pollock et al. 2012; Kofler et al. 2013; Willcutt et al. 2005).”

“Deficits in several aspects of executive function have also been found in individuals with ASD relative to controls, particularly in set-shifting (Hill 2004; Ozonoff and Jensen 1999; Sanders et al. 2008).”

“Working Memory Children completed a computerized version of a spatial working memory task identical to the spatial span task from the CANTAB (De Luca et al. 2003).”

“However, other studies also suggest that individuals with ADHD and ASD perform similarly (Geurts et al. 2004; Raymaekers et al. 2007; Semrud-Clikeman et al. 2010).”

“…measures of executive functioning, reaction time (RT) measures are of increasing interest in both ADHD and ASD as a window into the intersection of bottomup information processing and cognitive control (Karalunas et al. 2014; Kofler et al. 2013; Rommelse et al. 2011; van der Meer et al. 2012).”

“Head-to-head comparisons of children with ASD and ADHD have yielded conflicting results as to whether executive function impairments and differences in reward processing are more pronounced in ADHD (Happe et al. 2006; Nyden et al. 2010) or in ASD (Geurts et al. 2004; Pennington and Ozonoff 1996).”

“Overall, results confirm some specificity in features contributing to RT differences in ASD and ADHD.”

“…2014)often enough to warrant clinical recognition in the DSM-5, co-occur at rates well above chance (Musser et al. 2014; Rommelse et al. 2011), and have overlapping genetic correlates (Rommelse et al. 2010; Ronald et al. 2008), suggesting they may be different manifestations of a shared liability.”

“…2014)often enough to warrant clinical recognition in the DSM-5, co-occur at rates well above chance (Musser et al. 2014; Rommelse et al. 2011), and have overlapping genetic correlates (Rommelse et al. 2010; Ronald et al. 2008), suggesting they may be different manifestations of a shared liability.”

“Although there is heterogeneity in the ADHD population (Fair et al. 2012; Nigg et al. 2005), at the group level relatively consistent impairments have been found in individuals with ADHD in each of these domains (Huang-Pollock et al. 2012; Kofler et al. 2013; Willcutt et al. 2005).”

“…1) response inhibition (Logan 1994; Nigg 2000); 2) interference control; 3) working memory (Baddeley 1996; De Luca et al. 2003; Engle 2002; Kane et al. 2007; Unsworth and Engle 2007), 4) set-shifting and 5) reward valuation, particularly delayed reward discounting (Demurie et al. 2012;…”

“However, our results suggest important amendments to the shared liability proposal for RT measures (Rommelse et al. 2011).”

“In addition, diffusion model parameters were estimated from the trial-by-trial RT time series using the Fast-dm modeling technique and the downloadable program from the author’s website (Voss and Voss 2007), and as previously published (Huang-Pollock et al. 2012; Karalunas and Huang-Pollock 2013).”

“In addition, diffusion model parameters were estimated from the trial-by-trial RT time series using the Fast-dm modeling technique and the downloadable program from the author’s website (Voss and Voss 2007), and as previously published (Huang-Pollock et al. 2012; Karalunas and Huang-Pollock 2013).”

“…2) interference control; 3) working memory (Baddeley 1996; De Luca et al. 2003; Engle 2002; Kane et al. 2007; Unsworth and Engle 2007), 4) set-shifting and 5) reward valuation, particularly delayed reward discounting (Demurie et al. 2012; Hulst et al. 2017; Mitchell 1999; Sagvolden et al. 1998).”

“RTspeed and variability reflect the influence of multiple interacting processes (Ratcliff 2002) that traditional RT measures, such as mean and standard deviation, do not differentiate.”

“Wider boundary separation is not associated with ADHD (Karalunas et al. 2014; van Mourik et al. 2005), but has been found in ASD (as compared to typical development) in the only other study applying a diffusion model approach in this population (Pirrone et al. 2017).”

“ASD and ADHD are sometimes hypothesized to be different manifestations of a shared liability (van der Meer et al. 2012), and cognitive impairments have been proposed as indicators of this shared risk.”

“up information processing and cognitive control (Karalunas et al. 2014; Kofler et al. 2013; Rommelse et al. 2011; van der Meer et al. 2012).”

“Response Inhibition Response inhibition was evaluated based on a tracking version of the stop task (Logan 1994; Nigg 1999).”

“…difficulty with response inhibition and delayed reward discounting, whereas those with ASD may have more trouble with set-shifting and working memory (Corbett et al. 2009; Demurie et al. 2012; Gargaro et al. 2011; Happe et al. 2006; Hulst et al. 2017; Ozonoff and Jensen 1999; Sinzig et al. 2008).”

“Processes not directly related to the response decision, such as stimulus encoding and motor response, are modeled by non-decision time (Ratcliff 2006).”

“However, other studies also suggest that individuals with ADHD and ASD perform similarly (Geurts et al. 2004; Raymaekers et al. 2007; Semrud-Clikeman et al. 2010).”

“Delayed Reward Valuation Delayed reward valuation was assessed using a computerized delay discounting questionnaire, based on the task described by Mitchell (1999) and Wilson et al. (2011).”

“Exclusion of children on non-stimulant medications may also reduce generalizability of results, particularly for the ASD sample because of possible limited efficacy and potential for greater side effects in this diagnostic group (Davis and Kollins 2012).”

“Clinically, recent review of the National Survey of Children’s Health data found that ASD diagnosis is often delayed when ADHD symptoms are also present, and these delays are independent of ASD severity (Miodovnik et al. 2015).”

“Despite conceptually distinct surface phenotypes, ADHD and ASD share overlapping features (Ronald et al. 2014)often enough to warrant clinical recognition in the DSM-5, co-occur at rates well above chance (Musser et al. 2014; Rommelse et al. 2011), and have overlapping genetic correlates (Rommelse…”

“Deficits in several aspects of executive function have also been found in individuals with ASD relative to controls, particularly in set-shifting (Hill 2004; Ozonoff and Jensen 1999; Sanders et al. 2008).”

“Head-to-head comparisons of children with ASD and ADHD have yielded conflicting results as to whether executive function impairments and differences in reward processing are more pronounced in ADHD (Happe et al. 2006; Nyden et al. 2010) or in ASD (Geurts et al. 2004; Pennington and Ozonoff 1996).”

“…2) interference control; 3) working memory (Baddeley 1996; De Luca et al. 2003; Engle 2002; Kane et al. 2007; Unsworth and Engle 2007), 4) set-shifting and 5) reward valuation, particularly delayed reward discounting (Demurie et al. 2012; Hulst et al. 2017; Mitchell 1999; Sagvolden et al. 1998).”

“Cognitive abilities develop rapidly over middle childhood and adolescence(Best and Miller 2010; Karalunas et al. 2017; Miller et al. 2013) and whether the ASD and ADHD groups show distinct trajectories of cognitive development is unable to be evaluated in this cross-sectional study.”

“…impairments appear to be primarily driven by slow drift rates (i.e., slow, inefficient information processing) and to a lesser extent fast non-decision times, but are unrelated to differences in boundary separation (HuangPollock et al. 2012; Karalunas et al. 2014; Karalunas and Huang-Pollock 2013).”

“…ASD share overlapping features (Ronald et al. 2014)often enough to warrant clinical recognition in the DSM-5, co-occur at rates well above chance (Musser et al. 2014; Rommelse et al. 2011), and have overlapping genetic correlates (Rommelse et al. 2010; Ronald et al. 2008), suggesting they may be…”

“…difficulty with response inhibition and delayed reward discounting, whereas those with ASD may have more trouble with set-shifting and working memory (Corbett et al. 2009; Demurie et al. 2012; Gargaro et al. 2011; Happe et al. 2006; Hulst et al. 2017; Ozonoff and Jensen 1999; Sinzig et al. 2008).”

“The only study to-date applying this model in ASD found that children with ASD have wider boundary separations and slower non-decisions times than typically-developing children, but no differences in drift rates (Pirrone et al. 2017).”

“Attention/Arousal A computerized Identical Pairs CPT (CPT-IP), similar to the A-X CPT design used by Nigg et al. (1996) was used to assess attention/arousal.”

“Valuation of delayed rewards was quantified as the discounting gradient (k) because prior publication indicated this best differentiates ADHD and control performance (Mitchell et al. 2015).”

“Cognitive abilities develop rapidly over middle childhood and adolescence(Best and Miller 2010; Karalunas et al. 2017; Miller et al. 2013) and whether the ASD and ADHD groups show distinct trajectories of cognitive development is unable to be evaluated in this cross-sectional study.”

“…2) interference control; 3) working memory (Baddeley 1996; De Luca et al. 2003; Engle 2002; Kane et al. 2007; Unsworth and Engle 2007), 4) set-shifting and 5) reward valuation, particularly delayed reward discounting (Demurie et al. 2012; Hulst et al. 2017; Mitchell 1999; Sagvolden et al. 1998).”

“…using continuous symptom measures supports that impairments in response inhibition (Corbett et al. 2009; Yerys et al. 2013) and arousal (Corbett et al. 2009) in ASD may be driven by comorbid ADHD symptoms, whereas ASD symptoms may contribute unique variance to processing speed (Yerys et al. 2013).”

“However, other studies also suggest that individuals with ADHD and ASD perform similarly (Geurts et al. 2004; Raymaekers et al. 2007; Semrud-Clikeman et al. 2010).”

“Diffusion modeling has been previously used successfully in the analysis of go-trials of a stop task in adults (Verbruggen and Logan, 2009) and in our own work in both ADHD and autism spectrum disorders (Karalunas et al., 2018; Karalunas and Huang-Pollock, 2013; Karalunas et al., 2012a).”

“Yet, the eventual aim is to use the VR-EAL to assess cognitive impairments in healthy aging and dementias (Anderson & Craik, 2017) or attention-deficit/hyperactivity disorder and autism (Karalunas et al., 2018).”

“This was not unexpected, given the overlapping nature of how disabilities may affect individuals (Merikangas et al. , 2007; Karalunas et al. , 2018).”

“…directly comparing children with ASD and ADHD showed similarities during early development in attention, response inhibition, working memory, verbal fluency, preparatory processes, and concept formation, with some differences more likely to be quantitative rather than qualitative 145,191,192 .”

“It is also possible that standard cognitive performance metrics are too multi-factorially determined and use of computational parameters that distinguish different aspects of information processing would yield more informative profiles (47, 48).”

“Studies in which ADHD and ASD traits were controlled indicate that, at least response inhibition and response variability, may be more strongly associated with ADHD than with ASD traits (Karalunas et al., 2018; Schachar et al., 2022).”

“This variability in the relationship between EF and ASD has also been demonstrated, but whether this is due to comorbid ASD+ADHD remains unclear (Karalunas et al., 2018).”

“, 2010), although the ASD effects may be attributable to comorbid ADHD (Karalunas et al., 2018).”

“In this study, accuracy and RT remained unchanged in ASD and controls while the decision thresholds were significantly higher (Karalunas et al., 2018; Iuculano et al., 2020).”

“In both the Karalunas et al. (2018) and Powell et al. (2019) studies, ASD groups did not differ from age-matched neuro-typical groups on non-decision parameters, which suggests that motor skills did not contribute directly to group differences.”

“Youths with either ADHD or ASD demonstrated impaired performance on tests intended to measure inhibitory control compared to neurotypically developing peers 49,65,66,68 .”

“Nevertheless, to further examine how the LC-NE system modulates attention and task performance future studies should examine other, and more sensitive measures of (disorder-specific) response execution in addition to RT (Karalunas et al., 2018).”

“…less systematic changes in RT, such as attention-de fi cit/hyperactivity disorder, also show less consistent changes in NDT, some reporting a decrease (see Karalunas et al., 2014, for instance), an increase (Merkt et al., 2013) or no changes (e.g., Fosco et al., 2017; Karalunas et al., 2018).”

“In addition, the cognitive weaknesses observed in ADHD are commonly associated with multiple forms of psychopathology (Bloemen et al., 2018; Karalunas et al., 2018; Martel et al., 2017; White et al., 2017), yet it is not clear how strongly these impairments are correlated with disorders when ADHD is also controlled (N…”

“Overall, there is continued interest in cognitive performance measures and particularly computational performance parameters as potential transdiagnostic risk markers for psychopathology (Ferrante et al., 2019; Karalunas et al., 2018; Wiecki et al., 2015).”

“Only five studies reported performance on the stop-signal task (SST), a widely used measure of response inhibition (Albajara Sáenz et al., 2020; Karalunas et al., 2018; Kuijper et al., 2015, 2017; Van Hulst et al., 2018).”

“…evidence for greater discounting of future rewards in ASD (e.g., Carlisi et al., 2017; Chantiluke et al., 2014; Murphy et al., 2017), but others have found no group differences (e.g., Antrop et al., 2006; Demurie et al., 2012; Karalunas et al., 2018 & Kouklari, Tsermentseli, & Monks, in press).”

“…Working Group of The Psychiatric Genomics Consortium, 2017; Grove et al., 2019), despite the fairly well-replicated association of SHANK genes with ASD in previous association and animal studies, cited above (Peça et al., 2011; Won et al., 2012; Leblond et al., 2014; Connolly et al., 2017).”

“Previous studies have found a set of shared cognitive dysfunctions across ADHD and ASD, such as executive function (EF) and motor function [17].”

“Indeed, a recent study with a large sample using empirical methods to define diagnostic “classes” concluded some cognitive impairment was shared across both disorders while other cognitive deficits appeared to be unique to each diagnostic class (Karalunas et al. 2018).”

“This result is in line with previous studies showing that individuals with ADHD had lower drift-rates than control participants in a range of tasks 44,64,109–111 .”

“…and motivational inhibition would be more impaired among children with singular (ADHD group) and comorbid diagnosis of ADHD (ASD + ADHD), relative to TD children and children with a singular diagnosis of ASD (Bühler et al., 2011; Karalunas et al., 2018; Sonuga-Barke, 2002; Tye et al., 2014).”

“…in social, psychological and cognitive profiles found among autistic people and those with ADHD (Baribeau et al., 2015; de Boer & Pijl, 2016; Karalunas et al., 2018) and the association between ADHD features (inattention, impulsiveness and hyperactivity) and autistic traits (Panagiotidi et…”

“Children presenting with both symptoms exhibit more EF deficits than those with a single diagnosis [31–33].”

“…autistic individuals may also show increased intra-participant variability (Geurts et al., 2008; Karalunas et al., 2014) and a recent study that found lower drift-rates in autistic children (Karalunas et al., 2018), we anticipated that drift-rates may also be reduced in our autistic participants.”

“Along with a significant development on neuroscience, the principles given underlie many indirect evidences for elaboration of etiology and pathogenesis of ADHD (Roohi-Azizi et al., 2017; Karalunas et al., 2018; Van Doren et al., 2018).”

“Delay or impairment of cognitive flexibility and inhibitory control processes are found in developmental disorders such as attention-deficit/ hyperactivity disorder [26, 27] and autism spectrum disorder [27, 28].”

“For detailed description of this sample, see Karalunas et al. [44].”

“IP address: 207.241.231.83, on 07 Nov 2020 at 04:33:23, subject to the Cambridge Core terms of use, available at (Boxhoorn et al., 2018; Karalunas et al., 2018; Velikonja, Fett, & Velthorst, 2019; Willcutt, Sonuga-Barke, Nigg, & Sergeant, 2008).”

“Attention-deficit hyperactivity disorder (ADHD) and ASD are frequently comorbid, have similar genetics and cognitive deficits [182,183].”

“These co-occurring disorders can include sleep problems,(5) gastrointestinal (GI) symptoms,(6) toileting problems,(7) epilepsy,(8) behavior problems,(9,10) mood disorders,(11) fears and phobias,(12) anxiety disorders,(13) and Attention-Deficit/Hyperactivity Disorder (AD/HD).(14) Among co-occurring challenges, individu…”

“…and attention (Follmer, 2018; Holmes et al., 2021; Landerl & Kölle, 2009; Peng & Fuchs, 2016; Peng et al., 2018; Yeniad et al., 2013), leading many children to experience significant challenges at school (Booth & Happé, 2010; Corbett et al., 2009; Karalunas et al., 2018; Rosello et al., 2022).”

“…ADHD across a range of tasks such as those presumed to measure sustained attention (e.g., Baytunca et al., 2018; Huang-Pollock et al., 2012, 2020; Karalunas et al., 2018; Weigard et al., 2020), inhibitory control (e.g., Baytunca et al., 2018; Epstein et al., 2011; Fosco et al., 2018;…”

“As such, there may be signi fi cant overlap in cognitive patterns between the diagnostic groups (Corbett et al., 2009; Karalunas et al., 2018).”

“[1,2] There is a specific behavioral profile in children with autism.[3,4] Children suffering from autism spectrum disorders (ASD) often demonstrate prominent behavioral characteristics such as high aggressiveness, deficient attention, and unresponsiveness along with a few other associated medical problems that can hi…”

“, 2019), and consistent with an extant and growing body of evidence suggesting that children with ASD plus high ADHD symptoms tend to present with generally lower developmental functioning (Karalunas et al., 2018; Antshel and Russo, 2019; Miller et al., 2020; Hong et al., 2021; Reetzke et al., 2021a).”

“(5) eQTL annotations used in the TranscriptomeWide Analysis as part of the current study is available at https://github.”

“…conditions, several studies have also reported some overlap in symptoms between ADHD and ASD, including difficulties with attention, behaviour, social communication, sensory sensitivity, and cognitive flexibility/rigidity (Karalunas et al., 2018; Nijmeijer et al., 2009; Ronald et al., 2014).”

“From a research perspective, accurate sample characterization is essential to understanding distinct and common mechanism(s) underlying ASD and/or ADHD (e.g., Ameis et al., 2016; Aoki et al., 2017; Chantiluke et al., 2014; Chien et al., 2017; Karalunas et al., 2018; Ronald et al., 2008; Satterstrom et al., 2019).”

“It is strongly suspected that the overlapping cognitive deficits in ASD and ADHD may further reveal shared etiology [11,15].”

“However, we observed that unique features of timing may indicate differences across neurodevelopmental conditions, extending previous findings in children with ADHD/autism (Karalunas et al., 2018; Raymaekers et al., 2007).”

“To date, this has included the perception of orientation (Pirrone et al., 2017, 2020), motion (Manning et al., 2022), and faces (Powell et al., 2019), crossmodal selective attention (Poole et al., 2021), and inhibitory con-trol (Karalunas et al., 2018).”

“Studies comparing EF profiles among children with ASD and ADHD directly have demonstrated that while both groups show EF impairment (Karalunas et al., 2018; Sinzig et al., 2008; Tye et al., 2014), those with ASD may display more profound and global EF deficits (Corbett et al., 2009; Verté et al.,…”

“For example, one comparison study was unable to identify a reliable difference in cognitive abilities between autistic individuals and individuals with ADHD on measures such as attention and arousal, response inhibition, working memory, interference control, and processing speed [21].”

“Indeed, ADHD and ASD are neurodevelopmental conditions that often coexist and share neurocognitive pathways [71,72].”

“Increased boundary separation in autistic participants has previously been observed (Karalunas et al, 2018; Pirrone et al, 2017; Pirrone et al, 2020; although see Poole, Miles, Gowen & Poliakoff, 2021; Manning et al, 2022), as has a slower and more deliberate decision-making style (Brosnan, Lewton…”

“ASDandanxiousworryon the other hand may share unique differences in boundary separation (i.e., wider boundaries indicative of greater responses caution, Karalunas et al., 2018; White et al., 2010a).”

“Previous studies have demonstrated that individuals with ASD often exhibit difficulties in shifting attention and managing distractions, which are linked to abnormalities in the ventral attention network [60, 61].”

“Thus, our results show that age-related improvements in RT-based tasks occur above and beyond potential confounds related with speed-accuracy tradeoffs, confirming previous findings (Karalunas et al., 2012, 2018).”

“Questions that concern confidence and safety of the application are for the Dependability scale, such as items 5, 16, 18, 21.”

“Individuals on the autism spectrum can also range from very high to very low functioning in many aspects of cognition, such as arousal, attention, and memory (Karalunas et al., 2018).”

“The overlap between ASD and ADHD symptoms [47] makes discriminant validity of the instrument important since up to 60% of children with ADHD show symptoms of Autism [48] and the comorbidity of both disorders is between 2-78% [49].”

“…differences, they show signi fi cant symptom overlap, with comorbidity rates (30 – 80% of ASD children exhibit ADHD symptoms, and 30 – 65% of ADHD children present ASD symptoms) far exceeding random probability, suggesting potential associations in underlying pathological mechanisms [137, 138].”

“We also note that previous studies have reported differences in diffusion modelling parameters in autistic participants (Iuculano et al., 2020; Karalunas et al., 2018; Kirchner et al., 2012; Pirrone et al., 2017, 2020), and this discrepancy could be due to choice of task, task instructions about…”

“…rather than subtle neuropsychological deficits often characteristic of children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD; Karalunas et al., 2018; Kofler et al., 2020; Kofler et al., in press; Snyder et al., 2015).”