Neural substrates underpinning intra-individual variability in children with ADHD: A voxel-based morphometry study.

BACKGROUND/PURPOSE: Increased intra-individual variability (IIV) in reaction time (RT) is a key feature of attention-deficit/hyperactivity disorder (ADHD). However, little is known about neurobiology underpinnings of IIV in ADHD. METHODS: We assessed 55 youths with ADHD, and 55 individually-matched typically developing control (TDC) with the MRI and Conners' Continuous Performance Test. The ex-Gaussian distribution of RT was estimated to capture IIV with the parameters σ (sigma) and τ (tau). The regional brain volumes, analyzed by voxel-based morphometry, were correlated with IIV parameters. RESULTS: We found both distinct and shared correlations among ADHD and TDC. For grey matter, there were significant σ-by-group interactions in the cingulate cortex and thalamus and also a τ-by-group interaction in the right inferior frontal gyrus. There was also shared negative associations between σ and regional volumes of the right posterior cerebellum and a positive association between τ and the right anterior insula. For white matter, there was a significant σ-by-group interaction in the genu of the corpus callosum and significant τ-by-group interactions in the right anterior corona radiata, the left splenium of the corpus callosum, and bilateral posterior cerebellum. There were also shared patterns that increased τ was associated with increased regional volumes of the right anterior corona radiata and decreased regional volumes of the right posterior limb of the internal capsule. CONCLUSION: This study highlights that brain regions responsible for the motor, salience processing and multimodal information integration are associated with increased IIV in youths with ADHD.

Symptoms of ADHD Affect Intrasubject Variability in Youths with Autism Spectrum Disorder: An Ex-Gaussian Analysis.

Increased intrasubject variability in reaction times (RT-ISV) is frequently found in individuals with autism spectrum disorder (ASD). However, how dimensional attention deficit/hyperactivity disorder (ADHD) symptoms impact RT-ISV in individuals with ASD remains elusive. We assessed 97 high-functioning youths with co-occurring ASD and ADHD (ASD+ADHD), 124 high-functioning youths with ASD only, 98 youths with ADHD only, and 249 typically developing youths, 8-18 years of age, using the Conners Continuous Performance Test (CCPT). We compared the conventional CCPT parameters (omission errors, commission errors, mean RT and RT standard error (RTSE) as well as the ex-Gaussian parameters of RT (mu, sigma, and tau) across the four groups. We also conducted regression analyses to assess the relationships between RT indices and symptoms of ADHD and ASD in the ASD group (i.e., the ASD+ADHD and ASD-only groups). The ASD+ADHD and ADHD-only groups had higher RT-ISV than the other two groups. RT-ISV, specifically RTSE and tau, was significantly associated with ADHD symptoms rather than autistic traits in the ASD group. Regression models also revealed that sex partly accounted for RT-ISV variance in the ASD group. A post hoc analysis showed girls with ASD had higher tau and RTSE values than their male counterparts. Our results suggest that RT-ISV is primarily associated with co-occurring ADHD symptoms/diagnosis in children and adolescents with ASD. These results do not support the hypothesis of response variability as a transdiagnostic phenotype for ASD and ADHD and warrant further validation at a neural level.

Contextual Factors Impact the Variability in ADHD Symptoms in Preschoolers with Situational Hyperactivity.

Objective: This study examined preschoolers with teacher-reported or parent-reported situational hyperactivity, and whether they differed in terms of behavioral problems, attentional problems, and parenting perceptions. Method: We used the Conners' Kiddie Continuous Performance Test and the Color Flanker Task to assess 99 preschoolers with pervasive high-ADHD-symptoms (42), school-situational high-ADHD-symptoms (30), or home-situational high-ADHD-symptoms (27), plus 111 preschoolers with pervasive low-ADHD-symptoms. Parents and teachers reported externalizing/internalizing behavioral problems. Parenting perceptions were measured with the Parenting Stress Index-Short Form and a parenting perceptions scale. Results: Preschoolers with school-situational high-ADHD-symptoms had deficits in attentional control. Parents of preschoolers with home-situational high-ADHD-symptoms had higher levels of parental stress and perceived their parenting to be harsher. Preschoolers with pervasive high-ADHD-symptoms had deficits in attentional control, increased parental stress, and parents with harsher parenting perceptions. Conclusion: Preschoolers with situational high-ADHD-symptoms may have different contextual risk factors related to ADHD symptoms reported by parents versus teachers.

Exploring the Variability in Reaction Times of Preschoolers at Risk of Attention-Deficit/Hyperactivity Disorder: an ex-Gaussian Analysis.

Reaction times (RTs) are typically slower and more variable in individuals with attention-deficit/hyperactivity disorder (ADHD). Analysis of the ex-Gaussian RT distribution, which is described by mu, sigma (mean and standard deviation, respectively, of the normal distribution) and tau (that of exponential distribution), reveals that individuals with ADHD do not display overall slower RTs but have a high proportion of extremely slow RTs, represented by a high tau value. Although this is a vital component for describing ADHD-related RT variability in school-aged children, adolescents, and adults, it has not been thoroughly studied at the preschool age. We assessed 65 preschoolers at risk of ADHD and 98 typically developing preschoolers with the Conners' Kiddie Continuous Performance Test (K-CPT) and parental and teacher reports of ADHD symptoms. We found that preschoolers at risk of ADHD had greater values for RT standard deviation, sigma, and tau than typically developing preschoolers at long inter-stimulus intervals (ISIs) (3 s), but not at short ISIs (1.5 s). This suggests that attention problems in preschool children may only be apparent in the tasks with a relatively slow event rate. Our study demonstrates that the ex-Gaussian tau value is essential for describing the inattentive component of task performance in preschoolers with heightened ADHD symptoms. Furthermore, the fact that the tau effect was modulated by ISI suggests that the longer duration (3 s vs. 1.5 s) is a non-optimal energetic state in preschoolers at risk of ADHD, and that this might account for the subtle attentional flaw in task performance.

Relationship between parenting stress and informant discrepancies on symptoms of ADHD/ODD and internalizing behaviors in preschool children.

Parent and teacher ratings of child behaviors are often discrepant, and these discrepancies may be correlated with parenting stress. The present study explored whether various parenting stress factors are associated with discrepancies between parent and teacher ratings of attention-deficit/hyperactivity disorder and oppositional defiant disorder (ODD) as well as internalizing symptoms in preschool children. We recruited 299 Taiwanese preschool children (aged 4-6 years) from the community or via clinical referrals. A structural equation modeling was used to analyze the relationships among three factors derived from the Parenting Stress Index-Short Form and informant discrepancies on symptoms of inattention, hyperactivity/impulsivity, ODD, and internalizing behaviors. Scores reported by parents were higher for each of the symptoms examined than those reported by teachers, and the degree of agreement between informants ranged from low to moderate. The parental distress factor of parenting stress was associated only with parent ratings, whereas other factors of parenting stress-parent-child dysfunctional interaction and parents' stress resulted from their child's temperament-were correlated with both parent and teacher ratings. Only parental distress factor predicted informant discrepancies for all behavioral symptoms assessed. Our findings suggest that parental distress should be considered when parent rating scores show significant discrepancies from that of teacher rating scores.

Atomoxetine could improve intra-individual variability in drug-naïve adults with attention-deficit/hyperactivity disorder comparably with methylphenidate: A head-to-head randomized clinical trial.

OBJECTIVE: Intra-individual variability in reaction time (IIV-RT) is common in individuals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. METHODS: An 8-10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naïve adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate (n=26) thrice daily (10-20 mg per dose) and atomoxetine once daily (n=26) (0.5-1.2 mg/kg/day). IIV-RT, derived from the Conners' continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4±6.3 days). RESULTS: We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. CONCLUSION: Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naïve adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation.

Interval timing deficits assessed by time reproduction dual tasks as cognitive endophenotypes for attention-deficit/hyperactivity disorder.

The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence tests, verbal estimation and time reproduction tasks (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17-second intervals. We found that youths with ADHD tended to overestimate time in verbal estimation more than their unaffected siblings and TD youths, implying that fast subjective internal clock speed might be a characteristic of ADHD, rather than an endophenotype for ADHD. Youths with ADHD and their unaffected siblings were less precise in time reproduction dual tasks than TD youths. The magnitude of estimated errors in time reproduction was greater in youths with ADHD and their unaffected siblings than in TD youths, with an increased time interval at the 17-second interval and with increased task demands on both simple and difficult dual tasks versus the single task. Increased impaired time reproduction in dual tasks with increased intervals and task demands were shown in youths with ADHD and their unaffected siblings, suggesting that time reproduction deficits explained by limited attention capacity might be a useful endophenotype of ADHD.