Evelijne M. Bekker

Functional Disconnection of Frontal Cortex and Visual Cortex in Attention-Deficit/Hyperactivity Disorder

BACKGROUND Current pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) suggest that impaired functional connectivity within brain attention networks may contribute to the disorder. In this electroencephalographic (EEG) study, we analyzed cross-frequency amplitude correlations to investigate differences in cue-induced functional connectivity in typically developing children and children with ADHD. METHODS Electroencephalographic activity was recorded in 25 children aged 8 to 12 years (14 with ADHD) while they performed a cross-modal attention task in which cues signaled the most likely (.75 probability) modality of an upcoming target. The power spectra of the EEG in the theta (3-5 Hz) and alpha (8-12 Hz) bands were calculated for the 1-sec interval after the cue and before the target while subjects prepared to discriminate the expected target. RESULTS Both groups showed behavioral benefits of the predictive attentional cues, being faster and more accurate for validly cued targets (e.g., visual target preceded by a cue predicting a visual target) than to invalidly cued targets (e.g., visual target preceded by a cue predicting an auditory target); in addition, independent of cue-target validity, typical children were faster to respond overall. In the typically developing children, the alpha activity was differentially modulated by the two cues and anticorrelated with midfrontal theta activity; these EEG correlates of attentional control were not observed in the children with ADHD. CONCLUSIONS Our findings provide neurophysiological evidence for a specific deficit in top-down attentional control in children with ADHD that is manifested as a functional disconnection between frontal and occipital cortex.

Stopping and changing in adults with ADHD

BACKGROUND A lack of inhibitory control has been suggested to be the core deficit in children with attention deficit hyperactivity disorder (ADHD). This means that a primary deficit in behavioral inhibition mediates a cascade of secondary deficits in other executive functions, such as arousal regulation. Clinical observations have revealed that with increasing age symptoms of hyperactivity and impulsivity decline at a higher rate than those of inattention. This might imply that a deficit in attention rather than a lack of inhibitory control is the major feature in adult ADHD. METHOD To study whether an attentional or inhibitory deficit predominates, the stop-signal task and the stop-change task were presented to 24 adults with ADHD combined subtype and 24 controls. RESULTS Relative to controls, the stop-signal reaction time (SSRT) was significantly more prolonged than the go-stimulus reaction time (RT) in patients with ADHD. This disproportionate elongation of the SSRT was comparable across tasks, even though the stop-change task exerted more complex (or at least different) demands on the inhibitory system than the stop-signal task. ADHD patients had a higher proportion of choice errors, possibly reflecting more premature responses. Specifically in the stop-change task, patients had more variable choice responses and made more inappropriate change responses, which may also reflect enhanced impulsivity. CONCLUSIONS The results support a core deficit in behavioral inhibition in adults with ADHD. We further suggest that there is more evidence for a critical role of deficient inhibitory control in adults than in children with ADHD.

Differences between low and high trait impulsivity are not associated with differences in inhibitory motor control

Objective: The present study investigates whether there is an association between trait impulsivity in the normal population and inhibitory motor control as assessed by the stop task. Method: Low- and high-impulsive participants (as assessed by the I7 questionnaire; both groups n = 31) performed the stop task. Differences in performance were analyzed by an independent samples t-test. Furthermore, a short meta-analysis was performed on this study and three previous studies with a similar aim. Results: The low- and high-impulsive groups did not differ on the speed to stop the response (SSRT). However, the meta-analysis revealed that high-impulsives are marginally slower in stopping than low-impulsives (effect size = -0.26, p = 0.06). Conclusions: There is only minor evidence that impulsivity in the common population is associated with poor inhibitory motor control.

Methylphenidate significantly improves driving performance of adults with attention-deficit hyperactivity disorder: a randomized crossover trial.

Although patients with attention-deficit hyperactivity disorder (ADHD) have reported improved driving performance on methylphenidate, limited evidence exists to support an effect of treatment on driving performance and some regions prohibit driving on methylphenidate. A randomized, crossover trial examining the effects of methylphenidate versus placebo on highway driving in 18 adults with ADHD was carried out. After three days of no treatment, patients received either their usual methylphenidate dose (mean: 14.7 mg; range: 10—30 mg) or placebo and then the opposite treatment after a six to seven days washout period. Patients performed a 100 km driving test during normal traffic, 1.5 h after treatment administration. Standard deviation of lateral position (SDLP), the weaving of the car, was the primary outcome measure. Secondary outcome measurements included the standard deviation of speed and patient reports of driving performance. Driving performance was significantly better in the methylphenidate than in the placebo condition, as reflected by the SDLP difference (2.3 cm, 95% CI = 0.8—3.8, P = 0.004). Variation in speed was similar on treatment and on placebo (-0.05 km/h, 95% CI = -0.4 to 0.2, P = 0.70). Among adults with ADHD, with a history of a positive clinical response to methylphenidate, methylphenidate significantly improves driving performance.

Neural correlates of stopping and self-reported impulsivity

OBJECTIVE To examine the relation between self-reported impulsivity, inhibitory control, and the neural correlates of stopping performance within the normal population. METHODS Healthy individuals scoring high and low on trait impulsivity performed an auditory stop-signal task. Stopping performance and neural correlates of stopping (i.e. N1 and stop P3) were compared between the impulsive groups as well as between participants who were slow and fast in stopping. RESULTS As expected, N1 and stop P3 were larger for successful relative to failed stops (i.e. N1 and stop P3 effects). Participants scoring high relative to low on impulsivity showed equal stopping performance, had larger stop P3, but similar N1 effects. Slow as compared to fast stoppers had reduced stop P3, but similar N1 effects. CONCLUSIONS Participants scoring high relative to low on impulsivity may need more effortful inhibitory control to yield equal stopping performance. Slow relative to fast stoppers may have weaker inhibition processes and abnormal error processing. In contrast to ADHD, both high impulsives as well as slow stoppers had an intact N1 effect. SIGNIFICANCE Subjective impulsivity and slow stopping in healthy individuals cannot be generalized to ADHD.

Methylphenidate Restores Link Between Stop-Signal Sensory Impact and Successful Stopping in Adults with Attention-Deficit/Hyperactivity Disorder

BACKGROUND The ability to revise ones action plans, as reflected in so-called stopping performance, is of fundamental importance to adaptive behavior. Previous studies in children and adults with attention-deficit/hyperactivity disorder (ADHD) have revealed impaired stopping, which improved after the administration of methylphenidate (MPH). Event-related brain potentials revealed that one crucial mechanism in adequate stopping is the link between the cortical areas that process the signal to stop and the motor system (stop N1). This stop N1 was severely compromised in adults with ADHD. The present study investigates whether methylphenidate can restore the stop N1, in addition to improving stopping performance. The acute effect of a serotonergic reuptake inhibition on these parameters was also assessed. METHODS Twelve adult combined-type ADHD patients received either placebo, MPH .4 mg/kg or .6 mg/kg, or 20 mg paroxetine in a double-blind, randomized, within-subjects design. RESULTS The .6 mg/kg dose of methylphenidate improved stopping performance, whereas it did not affect go reaction time (RT). It also restored the stop N1 that was absent under placebo. Methylphenidate reduced a later stop-related potential, the stop P3, which may reflect monitoring of failed stops. Paroxetine had no effect on stopping performance or on stop N1, but it reduced stop P3. CONCLUSIONS A .6 mg/kg dose of methylphenidate improves stopping performance and directly targets a stop-related brain mechanism that has been reported before to be compromised in a group of ADHD patients. This mechanism was not influenced by acute serotonergic reuptake inhibition.

Sleep and Quality of Life in ADHD

Attention-deficit hyperactivity disorder (ADHD) is a highly prevalent neuropsychiatric disorder characterized by symptoms of inattention, impulsivity, and hyperactivity. From early childhood to late adulthood, patients with ADHD (or their parents) complain about poor sleep quality and insufficient sleep quantity. As a result, ADHD patients experience excessive daytime sleepiness (EDS). Because EDS has been found to result in behavioral problems and cognitive impairments that mimic ADHD symptoms, sleep problems (e.g., due to a primary sleep disorder) may be misdiagnosed as ADHD. Alternatively, ADHD may actually cause sleep disturbances, e.g., due to dysfunctions in shared dopaminergic or noradrenergic neural systems. Here, we review studies on sleep and ADHD. Studies using subjective measures, such as questionnaires and diaries, have indicated a wide variety of sleep problems, a high prevalence of sleep disorders, and EDS. Studies using objective measures have only partly been able to confirm these findings. Studies using the Multiple Sleep Latency Test (MSLT) have clearly demonstrated EDS in ADHD. Actigraphic studies have inconsistently suggested an increase in nocturnal activity levels, whereas polysomnographic studies have mostly indicated deviations in REM activity and the presence of periodic limb movement disorder (PLMD). Intervention studies yielded mixed results. Sleep problems have been claimed to reduce, increase, and be unaffected by methylphenidate (MPH), the drug of choice for ADHD treatment. The large inconsistencies across studies are likely due to numerous confounding variables, such as small sample sizes, the heterogeneity of ADHD samples, the presence of comorbid conditions, differences in medication status and treatment regiments, differences in pubertal status, gender and the lack of methodological guidelines (e.g., the use of validated questionnaires and the inclusion of adaptation nights). Implications for future research are discussed.