Methylphenidate significantly improves declarative memory functioning of adults with ADHD.

BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory functioning of adults with ADHD. METHODS: Eighteen adults with ADHD who were clinical responders to methylphenidate participated in this randomized crossover trial. After 3 days of no treatment, patients received in random order either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo, separated by a 6-7-day washout period. Patients performed an immediate word recall test 1 h after treatment administration. Three hours after intake, patients performed the second part of the memory test (delayed word recall and a recognition test). RESULTS: Delayed recognition and immediate recall was similar on treatment and on placebo. Delayed word recall was significantly better in the methylphenidate than in the placebo condition (F (1, 17) = 7.0, p < 0.017). A significant correlation was found between prestudy CES-D depression scores and difference scores on delayed recall (r = 0.602, p < 0.008). CONCLUSION: Methylphenidate improves declarative memory functioning in patients with ADHD. New studies should further examine whether subclinical depressive symptoms mediate the effect of methylphenidate on declarative memory.

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.

Relation between resting EEG to cognitive performance and clinical symptoms in adults with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) in children is characterized by elevated levels of slow wave activity and reduced fast wave activity in resting-state electroencephalogram (EEG). In adults with ADHD, resting-state EEG findings are scarce and inconsistent. The present study examined whether the disparate findings are due EEG recording conditions (i.e., eyes-open vs. eyes-closed). A second goal of the current study was to assess relations between EEG spectral indices to performance measures obtained using a stop-signal task, and to behavioral ADHD symptoms. The present study included 24 adults with ADHD and 24 control adults. The EEG results showed a greater reduction in alpha power from eyes-closed to eyes-open (i.e., alpha attenuation) in ADHD compared to controls. In addition, theta/beta ratio was negatively correlated to the speed of responding to choice stimuli. These findings were interpreted vis-à-vis a biophysical model assuming that the hypo-arousal in ADHD is due to an overdrive of the nucleus coeruleus resulting in inhibitory activity of the thalamic reticular nucleus.

Methylphenidate restores link between stop-signal sensory impact and successful stopping in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: The ability to revise one's 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.

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.

Reliability, validity, and utility of instruments for self-report and informant report concerning symptoms of ADHD in adult patients.

OBJECTIVE: To study the correlation between symptoms of ADHD in adults, obtained with different methods and from different sources. METHOD: Information was obtained from 120 adults with ADHD, their partners, and their parents, using the ADHD Rating Scale, the Conners' Adult ADHD Rating Scales (CAARS), the Brown Attention-Deficit Disorder Scale (BADDS), and the structured interview Diagnostic Interview Schedule-IV, section L (DIS-L). RESULTS: All self-report rating scales can be used to assess ADHD symptoms in clinical samples of adults. The BADDS and the ADHD Rating Scale proved best in predicting the clinical diagnosis. The DSM-IV factors, originally developed for children, achieve lower patient-informant agreement than the other factors. CONCLUSION: Adults with ADHD appear to be the best informants with regard to their symptoms but tend to underreport the severity of their symptoms. Informant report may be used to get additional information on symptoms and impairment.

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.

Task-dependent exogenous cuing effects depend on cue modality.

Task-dependent exogenous cuing effects on reaction time in detection and discrimination tasks have been ascribed to delayed withdrawal of attention in discrimination tasks. Alternatively, these differences may be due to cue-induced response inhibition in detection tasks. Unimodal and crossmodal versions of the Posner paradigm were examined with short cue-target intervals. Targets above or below fixation required either detection or discrimination responses. Cuing effects were determined for the target-elicited P1 component and for the lateralized readiness potential (LRP). Task-dependent cuing effects on reaction time were found in the unimodal but not in the crossmodal version, but not for the P1 component. The LRP data indicated that inhibition of return in the unimodal detection task had a premotoric locus. These findings suggest that inhibition in the unimodal detection task resulted from speeded motor inhibition triggered by the visual cue.

Disentangling deficits in adults with attention-deficit/hyperactivity disorder.

CONTEXT: A lack of inhibitory control has been suggested to be the core deficit in attention-deficit/hyperactivity disorder (ADHD), especially in adults. This means that a primary deficit in inhibition mediates a cascade of secondary deficits in other executive functions, such as attention. Impaired stopping has been claimed to support the inhibition hypothesis. However, executive functions such as inhibition and attention are hard to disentangle. OBJECTIVE: To use event-related potentials in adult patients with ADHD to show that impaired stopping is associated with abnormalities of attention. DESIGN: The stop signal task was presented to 24 adults with ADHD combined subtype and 24 controls. Stop event-related potentials are distorted by overlap from event-related potentials to other stimuli in close temporal proximity, but we applied a method (Adjar level 2) to effectively remove this overlap. RESULTS: In line with an inhibitory control deficit, the stop signal reaction time was longer in adults with ADHD (F(1,46) = 7.12, P<.01) whereas there was no significant difference for go stimulus reaction time. Overlap-free stop event-related potentials revealed smaller stop P3s in adults with ADHD (F(1,44) = 4.20, P<.05). In children with ADHD, this has been interpreted to reflect deficient inhibitory control. However, controls were also found to have larger early responses in the auditory cortex (N1) when stop signals resulted in successful stops, relative to failed stops, signifying increased attention (F(1,23) = 11.88, P<.01). This difference was completely absent in adults with ADHD. CONCLUSIONS: Disturbed attentional processing of the stop signal contributed to impaired stopping in adults with ADHD. This finding may have implications for treatment.

The pure electrophysiology of stopping.

In the stop-signal task, subjects should withhold their response in a choice reaction time task when a stop-signal, usually a tone, is presented. Successful stops have been associated with event-related potentials (ERPs) featuring a larger frontocentral positivity relative to failed stops. The functional interpretation of this stop-P3 has been disputed, because stop-ERPs are distorted by overlap from ERPs elicited by preceding go-stimuli. We effectively removed confounding potentials with the 'adjacent response filter method (ADJAR)'. Confirming an interpretation in terms of response inhibition, the stop-P3 remained and overlap removal resulted in a more anterior distribution. As a new finding, the N1 was larger on trials with successful stops, which suggests that inhibitory performance at least partly depended on the ability to switch attention to the stop-signal. Finally, the parietal P3 tended to peak earlier for successful than for failed stops. This is in line with the Horse Race Model, which states that faster stop-processes have a higher chance of winning the race against the go-process.

Source analysis of the N2 in a cued Go/NoGo task.

Previous source analyses of event-related potential (ERP) data elicited in Go/NoGo tasks have suggested that the anterior cingulate cortex (ACC) plays an important role in response inhibition. So far, however, source models were derived for the difference wave Go stimulus minus NoGo stimulus. This difference wave is confounded with motor- and attention-related activity. To avoid these confounds, we alternatively derived source models for NoGo stimuli only. The problem of the NoGo-N2 being superimposed on a positive deflection was addressed in two ways. First, a baseline correction was applied using the time points just preceding and succeeding the NoGo-N2. Second, a separate source model was derived at the maximum amplitude of this positive deflection. Subjects were presented with a cued version of the continuous performance task (CPT; ABX). In a second study, the probability of the Go stimulus was gradually increased to heighten subjects' tendency to respond and, as a consequence, to enhance the amplitude of the NoGo-N2. The source models of the NoGo-N2 consistently indicated bilateral dipole pairs in medial frontal regions. This is in accordance with a generator in the anterior cingulate cortex.