What does handedness reveal about ADHD? An

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left-handed(CLH) among the ADHD children compared to controls (4%). ... right-handers have language skills lateralized to the left hemisphere (Knecht et al., ...

Research in Developmental Disabilities 65 (2017) 46–56

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What does handedness reveal about ADHD? An analysis based on CPT performance Eunice N. Simõesa, Ana Lucia Novais Carvalhob, Sergio L. Schmidta,c,d,



Neurology Department, Federal University of the State of Rio de Janeiro, Brazil Fluminense Federal University, Brazil Federal University of Juiz de Fora, Brazil d State University of Rio de Janeiro, Brazil b c



No of reviews 2

Background: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder. Continuous performance Tests (CPTs) aid the diagnosis. Handedness is linked to disabilities. Objectives: 1-To study the association between handedness and ADHD; 2-To verify the usefulness of the CPT in school settings; 3-To exam the relationship between handedness and CPT performance. Method: Each child was classified as right-consistent, left-consistent, or non-consistent. From the sample, 171 controls and 68 ADHDs fulfilled the inclusion criteria. The effect of handedness on the CPT was studied using a paired-sample that matched handedness by age, grade, gender, and ADHD. Results: Left-handed students had a probability of suffering from ADHD 2.88 greater than righthanders. ANOVAs on standardized scores indicated that the ADHD students exhibited higher number of errors and higher variability of reaction times as compared to the controls. Discriminant analysis indicated that these CPT parameters could discriminate ADHD from controls. Repeated ANOVAs showed a significant effect of handedness on commission errors (CE) because left-handers made more CEs than right-handers. Conclusions: 1-The association between ADHD and handedness reflects that left-handers are less lateralized and have decreased interhemispheric connections; 2-The CPT can be used to measure different attention domains in school settings; 3- Left-handers have problems in the impulsive/ hyperactivity domain.

Keywords: CPT ADHD Gender Handedness

What this paper adds? Gender and handedness are associated with several developmental disorders, which has led to many implications for understanding these diseases and their problems’ remediation. Attention-deficit/hyperactivity disorder (ADHD) is an early-onset disease affecting 5% of the population worldwide. Gender and age differences are known to be associated with ADHD. Regarding handedness, the data are controversial. Here, for the first time in ADHD studies, handedness was defined by direction and strength. The diagnosis of ADHD was based on clinical analysis with the aid of the DSM-V. We found a significant prevalence of 12% consistent left-handed(CLH) among the ADHD children compared to controls (4%). The distinct components of attention were assessed with a

⁎ *Corresponding author at: State University of Rio de Janeiro (UERJ), Rua Jardim Botânico, 674, 1 andar, salas 117/118, Jardim Botânico, Rio de Janeiro, RJ CEP 2246100, Brazil. E-mail address: [email protected] (S.L. Schmidt).

http://dx.doi.org/10.1016/j.ridd.2017.04.009 Received 6 August 2016; Received in revised form 19 March 2017; Accepted 11 April 2017 0891-4222/ © 2017 Elsevier Ltd. All rights reserved.

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Continuous Performance Test (CPT). Using standardized scores, we found that inattention, impulsivity, and sustained attention could be measured by independent CPT variables. The relationship between these variables and handedness was studied using a matchedpaired design, which required a small number of CLH children. The minimum number of subjects was calculated considering an effect size that is psychologically meaningful and was based on a previous test-retest reliability study. CLH children were found to be more impulsive than right-handers. Our data suggested that impulsivity is associated with abnormal brain laterality and with abnormal interhemispheric connections. Consistency of handedness is important because it refers to the callosal connections, whereas direction refers to brain lateralization. Norms derived from CPTs must be interpreted with caution, especially when CLHs are being tested. The present findings have implications for the understanding of this highly prevalent developmental disorder. 1. Introduction 1.1. ADHD, brain abnormal laterality, and callosal interhemispheric connections Attention-deficit/hyperactivity disorder (ADHD) refers to an early-onset highly prevalent developmental disorder, with an estimated worldwide prevalence of approximately 5% (Polanczyk, Willcutt, Salum, Kieling, & Rohde, 2014). It is characterized by age- inappropriate levels of inattention, motor hyperactivity, and impulsivity, that cause significant interference in at least two environments, such as, social life and academic functioning (American Psychiatric Association, 2013). Genetic and environmental factors are implicated with the etiology of this disease (Shang & Gau, 2014; Willcutt et al., 2011) but the physiopathology of ADHD is not fully understood (Cortese, 2012). In this regard, several investigators have proposed that atypical brain laterality is a core component of this disease (Hale, Brokheimer, McGough, Phillips, & McCracken, 2007; Hale et al., 2014; Silk et al., 2016). Abnormal brain laterality is implicated with other psychiatric illness, such as, autism (Floris et al., 2016), and anxiety (Bruder et al., 2015). The first indication of abnormal brain laterality in ADHD stemmed from observations that unilateral right-sided brain damage produced symptoms reminiscent of this disease (Heilman, Bowers, Valenstein, & Watson, 1986). Previous studies have suggested that ADHD is, at least in part, related to a right hemisphere dysfunction (e.g., Sandson, Bachna, & Morin, 2000). More recently, ADHD was associated with anomalous hemispheric asymmetries in major fibre tracts of the frontostriatal system (Silk et al., 2016). Alteration of the right superior longitudinal fasciculus has also been demonstrated in children and adults with ADHD (Chiang, Chen, Lo, Tseng, & Gau, 2015). Several studies have reported that the development of the corpus callosum is associated with the establishment of brain asymmetries (e.g., Lent & Schmidt, 1992). Callosal abnormalities have been described in ADHD (e.g., Semrud-Clikeman et al., 1994). A previous study reported that disrupted callosal growth is related to the abnormalities in development of prefrontal cortex asymmetry and concluded that abnormalities in interhemispheric connections are found in ADHD patients (Gilliam et al., 2011). The question that remained to be clarified is the possible relationship between brain laterality and handedness as well as between handedness and ADHD. 1.2. Handedness as a proxy to cerebral asymmetries: relationship with ADHD Humans show a strong bias toward using one hand rather than the other for manual activities. In fact, roughly 90% of humans are right-handed (Ellis, Ellis, & Marshall, 1988). The preference most people show in using one hand over the other to perform motor tasks must originate in the cerebral cortex (McManus, 1984). There are several examples of cerebral lateralization of cognitive functions such as language and visuospatial skills (Groen, Whitehouse, Badcock, & Bishop, 2012). It is well known that over 90% of right-handers have language skills lateralized to the left hemisphere (Knecht et al., 2000; Mellet, 2014). Thus, handedness is considered as an indirect measure of cerebral asymmetry and is commonly used as a proxy for cerebral lateralization because it is a cheap and easy measure. Departures from right-handedness have been linked to disabilities, such as, schizophrenia (Hirnstein & Hugdahl, 2014), dyslexia (Brandler & Paracchini, 2014), autism (Lindell & Hudry, 2013), and stuttering (Kushner, 2012). Concerning ADHD, the data are highly controversial. A previous study reported that ADHD was not exclusively related to the prevalence of non-right-handedness (Reid & Norvilitis, 2000). In contrast, other investigators found a higher than expected proportion of left-handedness in children with ADHD (Rodriguez & Waldenström, 2008). Another study reported that mixed- handedness was associated to increased risk for ADHD (Rodriguez, Kaakinen, Moilanen, Taanila, & McGough, 2010). More recently, it was reported that left-handedness was not associated with higher parent-reported ADHD (Ghanizadeh, 2013). Part of the controversy may be related to the definition of handedness. As ADHD is related to both abnormal brain laterality (Hale et al., 2009) and disrupted interhemispheric connections (Gilliam et al., 2011), the definition of handedness should consider these two factors. 1.3. Definition of handedness Different approaches have been taken to measure hand preference, ranging from motor performance measurements to self-report inventories assessing hand choice across various manual activities (Oldfield, 1971). Brain asymmetries may be indirectly assessed by the direction of handedness since left-handers exhibit less cerebral asymmetry and more abnormal brain laterality than right-handers (Bishop, 1990; Schmidt, Oliveira, Rocha, & Abreu-Villaça, 2000). However, ADHD is related not only to abnormal brain laterality but also to callosal connections (Gilliam et al., 2011). Therefore, simply classifying the subjects into left or right-handers seems to be insufficient to clarify the controversy regarding handedness and 47

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ADHD. In this regard, previous studies reported that consistency of handedness reflects interhemispheric connections rather than brain laterality (Propper, Pierce, Geisler, Christman, & Bellorado, 2012). In addition, other investigators have reported differences between consistent left-handers and other groups in the performance of some cognitive tasks (Hardier & Wright, 2014). Therefore, it is possible to hypothesize that the prevalence of ADHD will be higher in consistent left-handers. 1.4. The assessment of attention by a continuous performance test (CPT) Attention performance is frequently measured using continuous performance task. Since the finding that demonstrated that CPTs are highly sensitive to brain dysfunction (Rosvold, Mirsky, Sarason, & Beck, 1956), these tests have been usually used to differentiate ADHD from control subjects (Epstein et al., 2003). The variables derived from the CPTs, include: mean hit reaction time (RT), signal detection measures, errors of omission and commission (Uno et al., 2006). Children with ADHD had greater variation in their reaction times and made more omission and commission errors (Epstein et al., 2003; Uno et al., 2006). Consequently, the CPTs are regarded as an effective ADHD assessment tool for children’s attentional deficits (Monden et al., 2015; Riccio, Reynolds, Lowe, & Moore, 2002). However, because certain CPTs exhibit false positives and negatives, there are concerns about their utility as a tool for distinguishing ADHD children from the general population (Hinshaw, Carte, Fan, Jassy, & Owens, 2007). In Brazil, the Continuous Visual Attention Test (CVAT) is most commonly used for neurological conditions such as dementias (Schmidt et al., 2008), and fibromyalgia (Schmidt, Alvarenga, Manhães, & Schmidt, 2017) as well as in clinical trials (Avellar et al., 2016). The CVAT is approved for clinical use in Brazil (Schmidt & Manhães, 2004). It has robust internal consistency and construct validity. The standardized scores of the CVAT were based on more than 1000 subjects, which incorporated students from different places in the country. The CVAT is a typical go/no go task and is simpler than other CPTs, such as the Conner’s test (Conners, 2002), because it does not involve letters. It does not depend on IQ, and there is no learning effect in the event of a retest. Although the CVAT has been used in ADHD research (Schmidt, Simões, & Carvalho, 2016), its utility for discriminating between ADHD and the general population in school settings remains to be proved. Therefore, the present study tested the CVAT on healthy and ADHD students to evaluate if this instrument is an effective ADHD assessment tool for students’ attentional deficits. The present study also investigated the effect of handedness on the performance of the CVAT since a previous functional neuroimaging study showed that the performance depends on brain asymmetry (Schmidt et al., 2008). This investigation is of clinical relevance because of all of the available norms of the CPTs, including the CVAT, do not take handedness into account. Considering the clinical utility, the popularity of the CPTs, and the fact that the CPTs measure a cognitive domain that is related to brain asymmetries, the study of the association between handedness and CVAT's performance is clinically and theoretically needed. 1.5. Hypotheses to be tested As consistency of handedness is associated with decreased inter-hemispheric interaction, left-handers are less strongly lateralized than right-handers, and ADHD is related to abnormalities in both brain lateralization and interhemispheric connections; we hypothesized that ADHD would be more probable to occur in consistent left −handers as compared to right-handers. Considering that the CVAT is a convenient method to measure attention performance, it is expected that ADHD children will exhibit significant deficits in the parameters of the test that are associated to specific impairments in the different domains associated with ADHD (inattention, impulsivity, and sustained attention). Moreover, it is expected that certain parameters of the test will be able to discriminate healthy controls from ADHD students. Finally, it is hypothesized that consistent left-handers should exhibit inferior performance on the CVAT task as compared to righthanders. 1.6. Objectives 1st: To study the association between handedness and ADHD in students of the elementary and junior high school levels naïve of any medication; 2nd: To identity the usefulness of the CVAT in school settings, particularly the utility of the CVAT in discriminating between ADHD and healthy control students via discriminant accuracy; 3rd: To examine a possible relationship between the direction of handedness and CPT variables in healthy controls and ADHD students that are consistent handers. To the best of the authors’ knowledge, this is the first study to examine the association of direction of handedness with the severity of inattention and hyperactivity in consistent-handed subjects. Moreover, this is the first study that addresses the question of how handedness is associated with CPT’s performance. 2. Methods 2.1. Participants and samples Participation in the research was voluntary. Parents and school principals signed informed consents. This study was carried out under institutional approval, by the law (Declaration of Helsinki). After approval of the project by the ethical committees, educational authorities of the State of Rio de Janeiro and four selected 48

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Fig. 1. The teachers were oriented to select participants with ADHD without other comorbidities and a corresponding number of healthy controls. Based on the teachers’ judgments, they decided to answer the questionnaires of 337 students (A). Then, the questionnaires were analysed by one investigator who recruited 262 participants for a clinical interview (B). After the clinical interview (conducted by another investigator), 239 students were enrolled to continue the study (C). All the 239 students completed the handedness assessment (D), and 229 completed the CVAT (E). Handedness assessments and administration of the CVAT were conducted by a third investigator, blind to the diagnoses of the students. From the 229 students who completed the CVAT, 14 right-handed subjects were randomly selected to be paired with the 14 left-handed subjects found in the total sample. The pairs were matched individually on presence or absence of ADHD, grade, gender, and age. These 14 matched pairs (n = 28) were used to study the effect of handedness on the performance of the CVAT (F). The investigator who selected the 28 students was blind to the CVAT performance. CVAT = Continuous Visual Attention Test; CRH = Consistent Right-Hander; CLH = Consistent Left-Hander.

municipalities were contacted to indicate possible schools and allow them to participate in the research. Then, the principals of ten different junior high and elementary schools (public and private) in four cities of the State of Rio de Janeiro were contacted by the principal investigator (SLS). Together they represent schools that have more than 2000 enrolled students. The parents were also informed of the research, and only students with their parents’ permission to participate were initially considered (25% were dropped from the study because their parents either refused permission or simply did not sign the consent form.) For each school, which had agreed to participate in the research, the principal investigator (SLS) held a meeting for the orientation of the teachers. The teachers were oriented that the objective of the research involved the study of students with ADHD. However, they were blind to the study’s main objective (effect of handedness on attentional performance). Therefore, the teachers were oriented to include as many students with attention deficits without learning disabilities or other psychiatric or neurological disorders as possible and to sample an approximately equal number of healthy controls. After approval by the parents, the teachers were free to select students and were invited to answer a standardized questionnaire about the students that they considered fitted the objective of the study. Initially, the teachers selected 337 students from elementary and junior high schools (Fig. 1A) and filled for each student a standardized questionnaire, which is validated in Brazil (Carvalho, Manhães, & Schmidt, 2012). Then, the teachers’ questionnaires of 337 students were analysed by one of us (SLS). After applying exclusion and inclusion criteria, 262 students were selected for a clinical interview (Fig. 1B) conducted by an experienced neuropsychologist blind to the teachers’ scores (ALN). After the interview, 23 students were excluded. Therefore, the study included 239 children (Fig. 1C). These 239 participants consisted of students recruited in four different cities in the State of Rio de Janeiro, Brazil (Table 1). The cities were characterized by their human development indices (United Nations, 2000). Hand preference was assessed by the other investigator (ENS) who is a licensed clinical neuropsychologist, a graduate student of the master's program in neuroscience, blind to the diagnoses of the participants (Fig. 1D). This sample (n = 239) was used to address the first objective of this study. The analyses of the handedness assessments, which were completed later, indicated a total number of 15 who were consistently left-handed among the 239 participants. For each student, immediately after the handedness assessment, the CVAT was administered by ENS who remained blind to the participant’s diagnosis (ADHD or healthy control). The CVAT was performed with the hand used for writing. From the 239 participants, 6 consistent right-handers, 3 non-consistent handers, and 1 consistent left-hander did not complete the CVAT (Fig. 1E). Thus, this sample (n = 229) was used to address the second objective. Then the 14 consistent left-handed subjects that completed the task were matched with 14 consistent right-handed subjects randomly selected by one of us, blind with respect to the CVAT performance (SLS). The randomly selected consistent right-handed subjects were paired with their respective consistent left-handed pairs considering the presence or absence of ADHD, grade, gender, and age. The results of the CVAT performance of these 28 selected subjects were extracted from the sample that completed the CVAT (n = 229) with the purpose of addressing the third objective of the investigation, which was the study of the effect of handedness on the performance of the CVAT (Fig. 1F).

2.2. Classification of the children into two groups: control and ADHD groups The teachers filled a standardized checklist composed of 58 questions that are rated on a scale reflecting behavioural problems Table 1 Participants. City


Number of Students

Number of Teachers

Petrópolis Rio de Janeiro São Gonçalo São João de Merití Total

0.804 0.842 0.782 0.774

76 26 41 96 239

6 4 10 25 45


(HDI): Human Development Index.


Public School

58% 100% 120

Private School 100% 100% 42% 119

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(Carvalho et al., 2012). A child was classified into the ADHD group if he (she) got maximum scores in at least six questions related to the domain of impulsivity or hyperactivity, or in the domain of inattention. The classification of children also considered their behaviour in the classroom. Forty-five teachers rated the children. All students were interviewed by one of the authors (ALN). The clinical interview considered the DSM-IV-RT criteria to identify children with ADHD. These criteria remain in the DSM-V. Children with epilepsy, previous history of traumatic brain injury, psychosis, mood disorders, learning disabilities (including dyslexia, dysgraphia, and dyscalculia), or taking any kind of medication were excluded from the study. A particular student was included in the ADHD group if there were not any discrepancies among the rating scale, the qualitative observations by the teachers, and the clinical interview. The control group was composed of children that did not present any behavioural problem. 2.3. Evaluation of hand preference Handedness was observed during the execution of three tasks: 1) writing; 2) taking a sheet of paper on the table; 3) opening a lid of a bottle. These three tasks derived from a previous empirical study of handedness in 1600 subjects using the Edinburgh Inventory (Oldfield, 1971). Then, each child was classified as right consistent, left consistent, or non-consistent. To be consistent, the child had to perform the three tasks with the same hand. 2.4. Evaluation of attention performance: continuous visual attention test (CVAT) All subjects had visual acuity equal to or better than 20/30 in both eyes (glasses were used when needed). The testing equipment consisted of a laptop computer linked to a 13 in. liquid-crystal display. Subjects were seated in front of the computer is such a way as to allow the hands to be placed on keyboard. The hand used to perform the task was the same hand used to write. The distance between the centre of the monitor and the eyes was of approximately 50 cm. The examiner instructed the subject to press the computer's spacebar as fast as possible each time a specific visual target stimulus was displayed on the monitor. The test started with instructions and a practice session. There were six blocks, with three sub-blocks each of 20 trials (two figures presented, whether targets or not). Three blocks had 80% targets. In the other three blocks, 20% of the stimuli were targets. For each block, the sub-blocks had three different inter stimulus time intervals (ISI): 1, 2, or 4 s. The sequence of the ISIs varies between blocks. Each stimulus was displayed for 250 milliseconds. The test took 15 min to complete. Four parameters derived from the test: omission errors (OE), commission errors (CE), reaction time of correct responses (RT), and variability of reaction time (VRT). 2.5. Statistical analysis T-tests for independent samples and chi-square tests were used for examining group differences across demographic variables. The association between handedness and ADHD was investigated with the aid of odds ratios (OD). A logistic equation was calculated and the 90% confidence interval was used to estimate the precision of the OR. The study of the effect of ADHD on the parameters of the CVAT (n = 229) were performed by one-way ANOVAS on the standardized scores of the CVAT. The standard scores derive from the normalization study and were stratified by gender and age. A stepwise discriminant analysis was performed for the four variables of the CVAT to examine if the CVAT accurately distinguished between ADHD and controls participants. The study of the effects of direction of handedness and disease on the parameters of the Continuous Visual Attention Test (CVAT) was conducted using the CVAT performance from a subsample designed to match all the available consistent left-handers (CLH) in the total sample (14 in 239 subjects) with their consistent right handers. The CRH participants were randomly selected to match handedness by age, grade, gender, and attention disorder. Thus, the data on the CVAT from 28 students (14 consistent right-handed and 14 consistent left-handed) were analysed. It should be mentioned that the extraction of the data from this subsample was made from the available performance on the CVAT collected with the sample that completed the test (n = 229). A matching design was used to study the effect of Handedness and the effect of Disease (ADHD). For each parameter of the CVAT, handedness paired matches were compared on performance in the task. In this case, performances were analysed as if there were repeated measurements of the same person. For each parameter of the CVAT (omission errors, commission errors, reaction time, and variability of reaction time), repeated ANOVAs were performed considering Handedness as the repeated within-subjects factor (Right vs. Left) and Disease (Control vs. ADHD) as the between-subjects factor effect. Gender and age were considered as covariates. The null hypothesis (absence of difference) was tested against the hypothesis of a deficit in attention performance in consistent left-handers. Therefore, the significance level was set 5%, one- tailed for all effects and interactions. As repeated ANOVAs are particularly susceptible to violating the assumption of sphericity, we performed Mauchly’s test of sphericity for each ANOVA. For those parameters of the CVAT in which the repeated ANOVAS showed a significant handedness effect, or a significant interaction, post hoc comparisons were performed using pairwise t-tests. Moreover, for each group (controls and ADHD subjects), the following index was calculated: [(T1 − T2)/(T1 + T2)] x 100, where T2 is the performance by the consistent left-hander, and T1 the performance by the respective right-hander matched pair. This ratio corrected a possible scale effect. Statistical analyses were conducted using the software program Statistical Package for the Social Sciences version 19.0 for Windows (SPSS Inc., 2012) 50

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Table 2 Demographic and Clinical Characteristics of the ADHD/Control Group (N = 239).

Age mean (years) SD (years) Gender Male (%) CLH CRH NC

ADHD (N = 68)

Control (N = 171)

11.3 4.1

12.4 3.2

57 (84%) 8 (12%) 39 (57%) 21 (31%)

63 (37%) 7 (4%) 107 (63%) 57 (33%)

CLH: Consistent Left Handers; CRH: Consistent Right Handers; NC: Non-consistent; SD = Standard Deviation.

2.6. Sample size calculation This study used a matched-subjects design. An advantage of the matched-subjects design over the within-subjects design is that a smaller number of participants are needed. This was particularly relevant in the present study because the percentage of consistent left- handers in the population is very low (less than 7%). The norms and the psychometric properties of the CVAT were used to calculate the minimum sample size (Np) for each parameter of the test. It took into consideration: α = Type I error; for α = 0.05, Zα⁄2 = 1.96; β = Type II error; for β = 0.20, Zβ = 0.84 (power = 1- β = 0.80); and the common standard deviation (σ) based on a previous test-retest reliability study with 200 subjects. The minimum difference accepted was psychologically meaningful and indicated a significant attention deficit for daily life activities. The analyses for each parameter of the CVAT showed that a minimum of six subjects was required for the pairwise comparisons between left-handers and right–handers. 3. Results 3.1. Demography From the initial sample, n = 337, 239 students (Table 2) fulfilled the inclusion criteria and 28% (n = 68) were included in the ADHD group. The ADHD students with comorbidities (n = 63) were excluded from this study. Inclusion criteria for participants in the control group were the absence of academic or behavioural problems. Exclusion criteria were intellectual disability, other chronic conditions, the use of medications, and other primary psychiatric diagnoses (e.g., depression, anxiety, and psychosis). From the initial sample (n = 337), 35 students were excluded of the control group based on the analysis of the teacher’s questionnaires or after the clinical interview. All participants were drug naïve There was not any significant age difference between the two groups. As expected, the percentage of males was significantly higher in the ADHD group as compared to the control group (p < 1%). In the total group (n = 239), handedness assessment showed that sixty-one (61%) was found to be consistent right-handed, 6% consistent left-handed, and 33% no consistent. There was not any association between handedness and gender. Fourteen right-handed subjects were randomly selected to be paired with the 14 left-handed subjects found in the total sample (n = 239). Demographic characteristics of this subsample (Table 3) is very similar with the other one. 3.2. Association between left-handedness and ADHD (n = 239 subjects). Objective 1 Among ADHD children (n = 69), 12% were consistent left-handed, 57% consistent right-handed, and 31% non-consistent. In contrast, among control children (n = 170), only 4% were consistent left-handed. Logistic regression analyses considering the direction of handedness among consistent handers showed that the odds (OD) of a consistent left-handed presenting ADHD was 2.88 Table 3 Subsample for the study of the effect of handedness on attentional performance (n = 28). N (%)

Age mean − years (SD) − years


16 (58%)


12 (42%)


28 (100%)

10.6 (3.9) 11.3 (4.1) 10.9 (4.4)

Number of CLH = number of CRH = number of ADHD = Number of controls = 14. Pairs were matched by age, grade, disease, and gender. CLH = Consistent Left-Hander.


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Fig. 2. Mean standard scores (T-values) of the ADHD group for reaction times (RT), omission errors (OE), commission errors (CE), and variability of RT (VRT). Negative values indicate performances above the mean of the population (zero). In the ADHD subjects, all parameters of the CPT are significantly affected, except RT. Each line represents one standard errors of the mean; (***) = P < 0.001; NS = Non-significant.

times greater than that of a consistent right-hander (OD 2.88, 90% CI: 1.2–7.1). The increased odds (2.88) reached statistical significance (p = 0.025). 3.3. Validity of the CVAT in ADHD (n = 229 subjects). Objective 2 ANOVA(s) on the standardized scores (Fig. 2) indicated the ADHD children exhibited higher commission and omission errors as well higher variability of reaction time as compared to the control group. In contrast, reaction times did not differ between the two groups. The comparison of the averages standardized scores indicated variable between-group CVAT differences. However, it did not indicate which variables of the test effectively discriminate between ADHD and healthy controls. Discriminant analysis showed that commission error was the most reliable variable for discriminating between groups, followed by omission errors and variability of reaction time. The reaction time variable did not influence the predictor variables of the discriminant function. The following equation (D) derived from the discriminant analysis: D = −1.218 + (0.063 * CE) + (0.015 * OE) − (0.001*VRT). Based on this formula, students with D > 0 were classified as ADHD and students with D < 0 were classified as controls with 73.2% accuracy. 3.4. Effect of handedness on attentional performance (CVAT) in the selected subsample (n = 28). Objective 3 Considering the CVAT performance of the selected 28 students, repeated ANOVAs showed a significant effect of handedness for commission errors (F = 4.06, df = 1/12, P = 0.03). This is explained by the higher number of commission errors (CE) in consistent left-handers as compared to consistent right-handers (Fig. 3). There was no significant handedness effect for RT (F = 2.36, df = 1/ 12, P > 10%), omission errors (F = 1.86, df = 1/12, P > 10%), and VRT (F = 0.10, df = 1/12, P > 10%). Interaction between Handedness and Disease did not reach significance for all parameters of the CVAT. For the commission errors, the interaction did not reach significance because the percentage differences between the two groups was very similar (Fig. 4).

Fig. 3. Consistent left-handers make significantly more commission errors than right- handers. Values are means of the raw scores. Each line represents one standard error of the mean; (*) = P < 0.05.


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Fig. 4. Consistent left-handers with ADHD make the greatest number of commission errors while right-handers in the control group make the lowest numbers of errors. Despite the fact that the presence of ADHD causes an increase in the number of commission errors in both right- and left-handers, the proportional difference does not differ from that already exhibited by right- and left-handers in the control group (47% in the control vs 41% in the ADHD group). Values are means of the raw scores. Each line represents one standard error of the mean; LH = consistent left-handed; RH = consistent right-handed.

4. Discussion When the total group was dichotomized by disease (ADHD versus control) and by direction of consistency of handedness (consistent right-handers versus consistent left- handers) we showed that the percentage of consistent left-handed ADHD children (12%) is different from that found in the control group (4%). The analysis of the odds ratio shows that the probability of a consistent left-handed student presenting ADHD is 2.8 times greater than that of a right-hander. Three variables of the CVAT effectively discriminate between ADHD and healthy controls. The commission error variable (CE) is the most reliable variable for discriminating between groups. The repeated ANOVAS show a significant effect of handedness only for the variable CE. The handedness effect is explained by the finding that consistent left-handers make more commission errors than right-handers.

4.1. Prevalence of ADHD (convenient sample) and left-handers (random sample) in the total sample In the present study, the prevalence of students with ADHD is much higher than the figures reported in other studies. The finding of a high prevalence of ADHD in our sample is explained by the fact that teachers biased the sample to incorporate as many students with ADHD as possible. Therefore, for the ADHD data this convenient sample precludes any epidemiological conclusion. In contrast, handedness was randomly selected. For this reason, the handedness effect could be analysed in terms of its association with ADHD.

4.2. Association between handedness and ADHD (objective 1) The confidence interval of the odds ratio indicates that there is a significant association between left-handedness and ADHD in consistent-handers. This finding agrees with previous studies (Rodriguez & Waldenström, 2008) but is not supported by Ghanizadeh (2013). However, this author did not consider the consistency of handedness. Rodriguez and Waldenström (2008) studied the possible relationship between handedness and mental health in a sample of 1714 children. They found a higher than expected proportion of left-handedness in children with attention disorders but only for the subtype with impulsive or hyperactivity behaviour. Although Rodriguez and Waldenström (2008) reported handedness in a large sample, the assessment was done using a questionnaire answered by the mothers. Several studies (Mitsis, McKay, Schulz, Newcorn, & Halperin 2000; Schmidt, Snyder, Roget, & Gray, 2000) have shown that data derived from parents’ reports must be interpreted with caution. Reid and Norvilitis (2000) observed the hand used by the children and concluded that ADHD was not exclusively related to the prevalence of non-right-handedness. However, the sample size was too small, especially regarding the expected number of left-handers. More recently, Ghanizadeh (2013) reported that left- handedness is not associated with higher parent-reported inattentiveness or hyperactivity, but the study relied on parental reports. This author did not take into account consistency of handedness. We suggest that these controversies are explained by the way handedness was assessed and mostly by the fact that consistency of handedness was not assessed in these previous studies. The finding that ADHD is 2.88 times more likely to be developed by CLH students gives further support to the hypothesis that this group is different from the others. Indeed, left-handers show reductions of lateralized functions as compared to right-handers and consistent handers exhibit less interhemispheric interaction than inconsistent handers. Therefore, the greatest prevalence of ADHD in consistent left-handers can be explained by the fact that they exhibit decreased interhemispheric connections and abnormal brain asymmetries.


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4.3. The influence of ADHD on the performance of the CVAT in the total sample (objective 2) All parameters of the CVAT are affected by the presence of attention problems, except reaction time. The effect of attention problems on performance of the CVAT agrees with many other studies that have shown that Continuous Performance Tests (CPTs) demonstrate sensitivity to dysfunction of the attentional system. In this regard, Uno et al. (2006) found a significant difference observed in all measurements, except mean reaction time, between control and ADHD groups. Therefore, the present finding of an effect of attention problems on three parameters of the CVAT, namely omission and commission errors and mean hit reaction time variability, as well as the absence of effect on reaction time, are largely supported by other studies. In addition, the discriminant analysis demonstrates that commission error is the most reliable variable for discriminating between ADHD and controls.

4.4. Effect of handedness on the performance of the CVAT (objective 3) A significant handedness effect was found to be restricted to one parameter, i.e. commission errors. Left-handers with attention problems showed greater impairment in commission errors as compared to control right-handers. When the control group was analysed separately, the handedness effect remained for the commission errors. There was an increase in commission errors in the ADHD group for both right and left-handers but control left-handed children already presented a higher number of commission errors as compared to control right-handers. When the indices were used, it become clear that handedness affects the percentage of commission errors in both control and ADHD subjects. Regarding the effect of direction of handedness, left-handers are thought to have less marked hemispheric asymmetries than righthanders (Bishop, 1990; Schmidt, Oliveira, Krahe, & Filgueiras, 2000). The present data suggest that left-handed subjects show greater problems on CPT performance as compared to right-handed subjects because they do not present the patterns of brain asymmetries that are needed for the neural processing of attention. The lack of lateralization should result in poor integration of the lateralized attention processes (Sainburg, 2014). It has been proposed that two unilateral control systems (for example, speech and spatialattention) perform best if different hemispheres control them (Kosslyn, 1987). In addition, the crowding hypothesis states that attention performance can be crowded out if language involves regions in the same hemisphere (Cai, Van der Haegen, & Brysbaert, 2013; Sainburg, 2014). Regarding the effect of consistency of handedness, consistent handers may present difficulties in the interhemispheric interaction (Luders et al., 2010; Propper et al., 2012). In this regard, a previous study showed that left-handers who were unable to change their preferred writing hand had a lower quality of psychological and physical well-being on various measures (Porac & Searleman, 2002). It is possible to speculate that the left-handers who attempt to change their preferred writing hand but are unsuccessful would be among the consistent left-handed group as defined in the present study. Therefore, the finding that strong left-handers show difficulties on the performance of the CVAT may be explained by the fact that they show less hemispheric asymmetries and less interhemispheric interactions than right-handers. The handedness effect was found only for commission errors (CE). This parameter of the CVAT is related to both inattention and impulsivity. The discriminant analysis gives further support that CE is the most reliable variable related to ADHD. The present data are supported by a previous study that found a significant relationship between behavioural inhibition and consistency of left handedness (Hardier & Wright, 2014). Anatomical asymmetries for impulsive control have been described in both normal (Liu, Zubieta, & Heitzeg, 2012) and ADHD subjects (Dang et al., 2016). Therefore, these studies support the hypothesis that consistent lefthanders show greater problems in the impulsive–hyperactivity domain as compared to right-handers.

4.5. Limitations We cannot exclude the possibility that developmental coordination problems influenced our data. In fact, ADHD is supposed to be a right hemisphere dysfunction (Sandston et al., 2000) and right brain pathology may affect the control of the left hand (Rommelse et al., 2007). About 30.6% of children with developmental coordination disorders are left-handed, and 13.3% are ambidextrous (Goez & Zelnik, 2008). As the rate of left-handed subjects with developmental coordination disorders is higher than the general population, this variable may explain our findings because we cannot exclude the possibility that our left- handed ADHD children exhibit motor coordination problems. A further study should be conducted using the assessment of motor coordination with the aid of a larger sample size. This is particularly relevant after the results described recently by Ghanizadeh (2013). This author suggested that ADHD is independent of hand–use preference when the analysis of the results is adjusted for covariant factors such as motor coordination. It is clear from previous studies that any changes in behaviour associated with left handedness are subtle. Therefore, the small sample size is another limitation of the present study. The present investigation tried to overcome this limitation using a matchedsubjects design. Finally, it should be mentioned that impulsivity is considered a multifaceted construct and there are different laboratory behavioural measures of impulsivity to assess the various components of the construct (Dougherty, Mathias, & Marsh, 2005). Therefore, it would be of interest to apply different laboratory behavioural measures of impulsivity rather than relying only on commission errors in the CVAT.


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4.6. Conclusions The probability of a left-handed student presenting ADHD is 2.8 times greater than that of a right-hander. The CVAT is useful in school settings as a valid instrument for helping diagnosis of ADHD students. The present investigation supports the hypothesis that consistent left-handers show greater problems in the impulsive/ hyperactivity domain as compared to right-handers. The handedness effect is exhibited even by the healthy control students. Thus, caution is necessary in the interpretation of the normative data on visual CPT (s), especially for left-handed subjects. Further investigation is needed to verify if left-handed ADHD children exhibit developmental coordination disorders. Remediation of the problems in ADHD may be depended on the handedness of the child. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. 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