Sleep Fosters Odor Recognition in Children with Attention Deficit Hyperactivity Disorder but Not in Typically Developing Children.

Prior experience represents a prerequisite for memory consolidation across various memory systems. In the context of olfaction, sleep was found to enhance the consolidation of odors in adults but not in typically developing children (TDC), likely due to differences in pre-experience. Interestingly, unmedicated children with attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition related to dopamine dysfunction, showed lower perceptive thresholds for odors, potentially allowing for more odor experience compared to TDC. We investigated sleep-associated odor memory consolidation in ADHD. Twenty-eight children with ADHD and thirty age-matched TDC participated in an incidental odor recognition task. For the sleep groups (ADHD: n = 14, TDC: n = 15), the encoding of 10 target odorants took place in the evening, and the retention of odorants was tested with 10 target odorants and 10 distractor odorants the next morning. In the wake groups (ADHD: n = 14, TDC: n = 15), the time schedule was reversed. Odor memory consolidation was superior in the ADHD sleep group compared to the TDC sleep and the ADHD wake groups. Intensity and familiarity ratings during encoding were substantially higher in ADHD compared to TDC. Sleep-associated odor memory consolidation in ADHD is superior to TDC. Abundant pre-experience due to lower perceptive thresholds is suggested as a possible explanation. Olfaction might serve as a biomarker in ADHD.

Transient Destabilization of Declarative Memory-Opposing Impact of Physical Exercise or Rest after Encoding in Typically Developing Children and Children with Attention Deficit Hyperactivity Disorder but No Difference after Subsequent Sleep.

BACKGROUND: Children are especially sensitive to a broad range of influences and show a remarkable capacity for learning. One prominent example is declarative memory, which may be influenced by a variety of factors and is impaired in attention deficit hyperactivity disorder (ADHD). Exercise and sleep, or both combined, might foster declarative memory. METHODS: Here, 12 typically developing children (TDC) and 12 age-matched children with ADHD participated in an exercise and rest condition before a night in the sleep laboratory. Declarative memory was encoded before exercise or rest and retrieved before and after a night of sleep. RESULTS: Exercise in TDC but rest in ADHD lead to a transient destabilization of declarative memory, while there were no more differences after a night of sleep. Rapid eye movement (REM) sleep latency was prolonged after exercise in both groups. CONCLUSIONS: Exercise leads to opposing effects on immediate declarative memory formation. The factors or contexts that promote or hinder declarative memory formation in children ADHD and TDC differ, and further work is needed to determine the recommendations for declarative learning in children with ADHD.

Acoustic closed-loop stimulation during sleep improves consolidation of reward-related memory information in healthy children but not in children with attention-deficit hyperactivity disorder.

STUDY OBJECTIVES: Slow oscillations (SO) during slow-wave sleep foster the consolidation of declarative memory. Children with attention-deficit hyperactivity disorder (ADHD) display deficits in the sleep-associated consolidation of declarative memory, possibly due to an altered function of SO. The present study aimed at enhancing SO activity using closed-looped acoustic stimulation during slow-wave sleep in children with ADHD. METHODS: A total of 29 male children (14 with ADHD; aged 8-12 years) participated in a double-blind, placebo-controlled study trial. Children spent two experimental nights in a sleep lab, one stimulation night and one sham night. A declarative learning task (word-pair learning) with a reward condition was used as a primary outcome. Secondary outcome variables were a procedural memory (serial reaction time) and working memory (WM; n-back) task. Encoding of declarative and procedural memory took place in the evening before sleep. After sleep, the retrieval took place followed by the n-back task. RESULTS: The stimulation successfully induced SO activity during sleep in children with and without ADHD. After stimulation, only healthy children performed better on high-rewarded memory items (primary outcome). In contrast, there were indications that only children with ADHD benefitted from the stimulation with respect to procedural as well as WM performance (secondary outcome). CONCLUSIONS: We were able to show that the acoustic closed-loop stimulation can be applied to enhance SO activity in children with and without ADHD. Our data indicate that SO activity during sleep interacts with subsequent memory performance (primary outcome: rewarded declarative memory; secondary outcome: procedural and WM) in children with and without ADHD.

Associations between cognitive performance and sigma power during sleep in children with attention-deficit/hyperactivity disorder, healthy children, and healthy adults.

Sigma power during sleep is associated with cognitive abilities in healthy humans. We examined the relationship between sigma power in sleep EEG and intelligence and alertness in schoolchildren with ADHD (n = 17) in comparison to mentally healthy children (n = 16) and adults (n = 23). We observed a positive correlation between sigma power in sleep stage 2 and IQ in healthy adults but a negative correlation in children with ADHD. Furthermore, children with ADHD showed slower reaction times in alertness testing than both control groups. In contrast, only healthy children displayed a positive correlation between sigma power and reaction times. These data suggest that the associations between sigma power and cognitive performance underlie distinct developmental processes. A negative association between IQ and sigma power indicates a disturbed function of sleep in cognitive functions in ADHD, whereas the function of sleep appears to be matured early in case of motor-related alertness performance.

Negative emotional face perception is diminished on a very early level of processing in autism spectrum disorder.

Deficits in facial affect recognition (FAR) are often reported in autism spectrum disorder (ASD) due to inappropriate visual search strategies. It is unclear, however, whether or not deficits in subliminal FAR are still present in autism when visual focus is controlled. Thirteen persons with ASD and 13 healthy participants took part in this experiment. Supraliminal FAR was assessed using a standardized, computer-aided test. Subliminal FAR was obtained by an emotional face priming paradigm. By using an eye-tracking technique, it was assured that the initial visual focus was on the eyes of the prime. Persons with ASD showed worse FAR in supraliminal face recognition. Although controlled for initial gaze direction, participants also showed reduced negative face priming. These data confirm that FAR is disturbed already on a pre-attentive level in autism.

Reduced microbiome alpha diversity in young patients with ADHD.

ADHD is a psychiatric disorder which is characterized by hyperactivity, impulsivity and attention problems. Due to recent findings of microbial involvement in other psychiatric disorders like autism and depression, a role of the gut microbiota in ADHD pathogenesis is assumed but has not yet been investigated. In this study, the gut microbiota of 14 male ADHD patients (mean age: 11.9 yrs.) and 17 male controls (mean age: 13.1 yrs.) was examined via next generation sequencing of 16S rDNA and analyzed for diversity and biomarkers. We found that the microbial diversity (alpha diversity) was significantly decreased in ADHD patients compared to controls (pShannon = 0.036) and that the composition (beta diversity) differed significantly between patients and controls (pANOSIM = 0.033, pADONIS = 0.006, pbetadisper = 0.002). In detail, the bacterial family Prevotellacae was associated with controls, while patients with ADHD showed elevated levels of Bacteroidaceae, and both Neisseriaceae and Neisseria spec. were found as possible biomarkers for juvenile ADHD. Our results point to a possible link of certain microbiota with ADHD, with Neisseria spec. being a very promising ADHD-associated candidate. This finding provides the basis for a systematic, longitudinal assessment of the role of the gut microbiome in ADHD, yielding promising potential for both prevention and therapeutic intervention.

Does Sleep Help Prevent Forgetting Rewarded Memory Representations in Children and Adults?

Sleep fosters the consolidation of rewarded memory representations in adults. However, sleep and its memory-supporting functions change through healthy development, and it is unclear whether sleep benefits the consolidation of rewarded memory representations in children as it does in adults. Based on previous findings, we expected sleep to benefit the consolidation of rewarded memory representations in children more than it does in adults. For that reason, 16 children (7-11 years) and 20 adults (21-29 years) participated in this experiment. During the encoding session, participants were asked to learn the location of 18 object pairs. Thereafter, one-half of the object locations were allocated to a high-rewarded condition and the other half to a low-rewarded condition. In the sleep condition, the encoding session took place in the evening (for children 7-8 pm, for adults 8-9 pm). After a fixed retention interval of 12 h the retrieval session was conducted the next morning (for children 7-8 am, for adults 8-9 am). In the wake condition, the time schedule was the same but reversed: the encoding session started in the morning (for children 7-8 am, for adults 8-9 am), and retrieval took place in the evening (for children 7-8 pm, for adults 8-9 pm). Sleep/wake had no impact on the memory performance regarding the low-rewarded memory items. In contrast, wakefulness in comparison to sleep reduced the memory performance on high-rewarded memory items. The interaction between sleep/wake and the degree of reward on memory performance was only significant in children. These results show that 12 h of wakefulness can deteriorate the memory performance for high-rewarded representations, whereas sleep can prevent the forgetting of these rewarded representations. It is discussed whether ontogenetic changes in sleep may play a role in conserving relevant but fragile memory representation.

Sleep-Dependent Consolidation of Rewarded Behavior Is Diminished in Children with Attention Deficit Hyperactivity Disorder and a Comorbid Disorder of Social Behavior.

Children suffering from attention-deficit hyperactivity disorder (ADHD) often also display impaired learning and memory. Previous research has documented aberrant reward processing in ADHD as well as impaired sleep-dependent consolidation of declarative memory. We investigated whether sleep also fosters the consolidation of behavior learned by probabilistic reward and whether ADHD patients with a comorbid disorder of social behavior show deficits in this memory domain, too. A group of 17 ADHD patients with comorbid disorders of social behavior aged 8-12 years and healthy controls matched for age, IQ, and handedness took part in the experiment. During the encoding task, children worked on a probabilistic learning task acquiring behavioral preferences for stimuli rewarded most often. After a 12-hr retention interval of either sleep at night or wakefulness during the day, a reversal task was presented where the contingencies were reversed. Consolidation of rewarded behavior is indicated by greater resistance to reversal learning. We found that healthy children consolidate rewarded behavior better during a night of sleep than during a day awake and that the sleep-dependent consolidation of rewarded behavior by trend correlates with non-REM sleep but not with REM sleep. In contrast, children with ADHD and comorbid disorders of social behavior do not show sleep-dependent consolidation of rewarded behavior. Moreover, their consolidation of rewarded behavior does not correlate with sleep. The results indicate that dysfunctional sleep in children suffering from ADHD and disorders of social behavior might be a crucial factor in the consolidation of behavior learned by reward.

Memory consolidation of socially relevant stimuli during sleep in healthy children and children with attention-deficit/hyperactivity disorder and oppositional defiant disorder: What you can see in their eyes.

Children with attention-deficit/hyperactivity disorder (ADHD) display deficits in sleep-dependent memory consolidation, and being comorbid with oppositional defiant disorder (ODD), results in deficits in face processing. The aim of the present study was to investigate the role of sleep in recognizing faces in children with ADHD+ODD. Sixteen healthy children and 16 children diagnosed with ADHD+ODD participated in a sleep and a wake condition. During encoding (sleep condition at 8p.m.; wake condition at 8a.m.) pictures of faces were rated according to their emotional content; the retrieval session (12h after encoding session) contained a recognition task including pupillometry. Pupillometry and behavioral data revealed that healthy children benefited from sleep compared to wake with respect to face picture recognition; in contrast recognition performance in patients with ADHD+ODD was not improved after sleep compared to wake. It is discussed whether in patients with ADHD+ODD social stimuli are preferentially consolidated during daytime.

Melatonin Secretion during a Short Nap Fosters Subsequent Feedback Learning.

Sleep helps to protect and renew hippocampus-dependent declarative learning. Less is known about forms of learning that mainly engage the dopaminergic reward system. Animal studies showed that exogenous melatonin modulates the responses of the dopaminergic reward system and acts as a neuroprotectant promoting memory. In humans, melatonin is mainly secreted in darkness during evening hours supporting sleep. In this study, we investigate the effects of a short period of daytime sleep (nap) and endogenous melatonin on reward learning. Twenty-seven healthy, adult students took part in an experiment, either taking a 90-min afternoon nap or watching videos (within-subject design). Before and after the sleep vs. wake interval, saliva melatonin levels and reward learning were measured, and in the nap condition, a polysomnogram was obtained. Reward learning was assessed using a two-alternative probabilistic reinforcement-learning task. Sleep itself and subjective arousal or valence had no significant effects on reward learning. However, this study showed for the first time that an afternoon nap can elicit a small but significant melatonin response in about 41% of the participants and that the magnitude of the melatonin response predicts subsequent reward learning. Only in melatonin responders did a short nap improve reward learning. The difference between melatonin-responders and non-responders occurred very early during learning indicating that melatonin might have improved working memory rather than reward learning. Future studies should use paradigms differentiating working memory and reward learning to clarify which aspect of human feedback learning might profit from melatonin.

Chemosensory processing in children with attention-deficit/hyperactivity disorder.

BACKGROUND: In attention-deficit/hyperactivity disorder (ADHD) not only deficits in dopamine-related cognitive functioning have been found but also a lower dopamine-sensitive olfactory threshold. The aim of the present study was to proof that only olfactory but not trigeminal sensitivity is increased in ADHD. Structural magnetic resonance imaging (MRI) was used to show increased olfactory bulb (OB) volume- a structure which is strongly shaped by olfactory performance through the mechanism of neuroplasticity (e.g. synaptogenesis). To elucidate whether cortical mechanisms are involved in altered olfaction in ADHD, functional MRI (fMRI) was introduced. METHODS: A total of 18 boys with ADHD and 17 healthy controls (aged 7-12) were included in the study. Olfactory as well as trigeminal detection thresholds were examined. OB sizes were measured by means of structural MRI and an analysis of effective functional (fMRI) coupling of primary olfactory cortex was conducted. The frontal piriform cortex (fPIR) was chosen as seed region because of its importance in processing both trigeminal and olfactory stimuli as well as having profound influence on inner OB-signaling. RESULTS: Increased olfactory sensitivity as well as an increase in OB volume was found in ADHD. There were no group differences in sensitivity towards a trigeminal stimulus. Compared to healthy controls, the fPIR in ADHD was more positively coupled with structures belonging to the salience network during olfactory and, to a lesser extent, during trigeminal stimulation. CONCLUSIONS: Olfactory functioning is superior in subjects with ADHD. The observed increase in OB volume may relate to higher olfactory sensitivity in terms of neuroplasticity. During the processing of chemosensory stimuli, the primary olfactory cortex in ADHD is differently coupled to higher cortical structures which might indicate an altered top-down influence on OB structure and function.

Slow oscillating transcranial direct current stimulation during non-rapid eye movement sleep improves behavioral inhibition in attention-deficit/hyperactivity disorder.

BACKGROUND: Behavioral inhibition, which is a later-developing executive function (EF) and anatomically located in prefrontal areas, is impaired in attention-deficit and hyperactivity disorder (ADHD). While optimal EFs have been shown to depend on efficient sleep in healthy subjects, the impact of sleep problems, frequently reported in ADHD, remains elusive. Findings of macroscopic sleep changes in ADHD are inconsistent, but there is emerging evidence for distinct microscopic changes with a focus on prefrontal cortical regions and non-rapid eye movement (non-REM) slow-wave sleep. Recently, slow oscillations (SO) during non-REM sleep were found to be less functional and, as such, may be involved in sleep-dependent memory impairments in ADHD. OBJECTIVE: By augmenting slow-wave power through bilateral, slow oscillating transcranial direct current stimulation (so-tDCS, frequency = 0.75 Hz) during non-REM sleep, we aimed to improve daytime behavioral inhibition in children with ADHD. METHODS: Fourteen boys (10-14 years) diagnosed with ADHD were included. In a randomized, double-blind, cross-over design, patients received so-tDCS either in the first or in the second experimental sleep night. Inhibition control was assessed with a visuomotor go/no-go task. Intrinsic alertness was assessed with a simple stimulus response task. To control for visuomotor performance, motor memory was assessed with a finger sequence tapping task. RESULTS: SO-power was enhanced during early non-REM sleep, accompanied by slowed reaction times and decreased standard deviations of reaction times, in the go/no-go task after so-tDCS. In contrast, intrinsic alertness, and motor memory performance were not improved by so-tDCS. CONCLUSION: Since behavioral inhibition but not intrinsic alertness or motor memory was improved by so-tDCS, our results suggest that lateral prefrontal slow oscillations during sleep might play a specific role for executive functioning in ADHD.

Sleep Supports Memory of Odors in Adults but Not in Children.

Sleep supports the consolidation of declarative memory in children and adults. However, it is unclear whether sleep improves odor memory in children as well as adults. Thirty healthy children (mean age of 10.6, ranging from 8-12 yrs.) and 30 healthy adults (mean age of 25.4, ranging from 20-30 yrs.) participated in an incidental odor recognition paradigm. While learning of 10 target odorants took place in the evening and retrieval (10 target and 10 distractor odorants) the next morning in the sleep groups (adults: n = 15, children: n = 15), the time schedule was vice versa in the wake groups (n = 15 each). During encoding, adults rated odors as being more familiar. After the retention interval, adult participants of the sleep group recognized odors better than adults in the wake group. While children in the wake group showed memory performance comparable to the adult wake group, the children sleep group performed worse than adult and children wake groups. Correlations between memory performance and familiarity ratings during encoding indicate that pre-experiences might be critical in determining whether sleep improves or worsens memory consolidation.

The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories.

Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents.

Early Gamma-Band Activity During Interference Predicts Working Memory Distractibility in ADHD.

OBJECTIVES: Patients with attention-deficit/hyperactivity disorder (ADHD) display deficits in working memory (WM) and enhanced distractibility. METHODS: Evoked gamma-band response (GBR) occurs already 50 ms after stimulus onset and is modulated by attention. 16 boys with ADHD and 20 healthy controls (10-14 years) completed a WM task with distraction. RESULTS: Occipitally evoked 40 Hz-GBR was higher during distraction in ADHD than controls. GBR correlated negatively with interference control. CONCLUSION: These data suggest that ADHD patients are disturbed by interference on an early level of perception.

Transcranial oscillatory direct current stimulation during sleep improves declarative memory consolidation in children with attention-deficit/hyperactivity disorder to a level comparable to healthy controls.

BACKGROUND: Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. OBJECTIVE: Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. METHODS: 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. RESULTS: Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. CONCLUSION: These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD.

Sleep promotes consolidation of emotional memory in healthy children but not in children with attention-deficit hyperactivity disorder.

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Sleep restores daytime deficits in procedural memory in children with attention-deficit/hyperactivity disorder.

Sleep supports the consolidation of declarative and procedural memory. While prefrontal cortex (PFC) activity supports the consolidation of declarative memory during sleep, opposite effects of PFC activity are reported with respect to the consolidation of procedural memory during sleep. Patients with attention-deficit/hyperactivity disorder (ADHD) are characterised by a prefrontal hypoactivity. Therefore, we hypothesised that children with ADHD benefit from sleep with respect to procedural memory more than healthy children. Sixteen children with ADHD and 16 healthy controls (aged 9-12) participated in this study. A modification of the serial-reaction-time task was conducted. In the sleep condition, learning took place in the evening and retrieval after a night of sleep, whereas in the wake condition learning took place in the morning and retrieval in the evening without sleep. Children with ADHD showed an improvement in motor skills after sleep compared to the wake condition. Sleep-associated gain in reaction times was positively correlated with the amount of sleep stage 4 and REM-density in ADHD. As expected, sleep did not benefit motor performance in the group of healthy children. These data suggest that sleep in ADHD normalizes deficits in procedural memory observed during daytime. It is discussed whether in patients with ADHD attenuated prefrontal control enables sleep-dependent gains in motor skills by reducing the competitive interference between explicit and implicit components within a motor task.

Reduced sleep-associated consolidation of declarative memory in attention-deficit/hyperactivity disorder.

OBJECTIVE: Sleep supports the consolidation of declarative memory. Patients with attention-deficit/hyperactivity disorder (ADHD) are not only characterized by sleep problems but also by declarative memory deficits. Given that the consolidation of declarative memory during sleep is supported by slow oscillations, which are predominantly generated by the prefrontal cortex, and that ADHD patients display low prefrontal brain activity, we assumed that ADHD patients show reduced sleep-associated consolidation of declarative memory. METHODS: The impact of sleep on the consolidation of declarative memory was examined with a picture recognition task. Twelve ADHD patients (10-16 years) and 12 healthy controls participated in two experimental conditions: in the sleep condition, learning was performed in the evening and picture recognition was tested after nocturnal sleep; in the wake condition, learning was conducted in the morning while retrieval took place after a day of wakefulness. RESULTS: Analyses of recognition accuracy revealed reduced sleep-associated enhancement of recognition accuracy in ADHD. While sleep-associated enhancement of recognition accuracy was correlated with slow oscillation power during non-REM sleep in healthy controls, no such correlations were observed in ADHD. CONCLUSIONS: These data indicate a deficit in sleep-associated consolidation of declarative memory in ADHD. Moreover, our results suggest reduced functionality of slow oscillations in sleep-associated consolidation of declarative memory in ADHD.

Methylphenidate does not improve interference control during a working memory task in young patients with attention-deficit hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) show deficits in working memory (WM) which may be related to prefrontal dysfunction. Methylphenidate (MPH) can restore WM deficits in ADHD by enhancing prefrontal activity. At the same time, changes in striatal activation could cause ADHD patients to be more interference-sensitive during working memory tasks. However, it is unclear whether MPH reduces WM distractibility in ADHD. In this fMRI study, 12 ADHD patients and 12 healthy controls participated on two separate days in a delayed-match-to-sample test. During the delay interval, a distractor stimulus was presented in half of the trials. Children and adolescents with ADHD received MPH only on one of the two sessions. Behavioral data analyses revealed that MPH normalized WM in ADHD. However, MPH did not improve WM performance when a distractor was presented during the delay interval. Functional images showed that MPH enhanced prefrontal activity during the delay in ADHD patients when no distractor was present. If the delay was interrupted by a distractor, only healthy controls showed activation of the caudate. In patients with ADHD, however, in line with behavioral data, MPH did not enhance caudate activity. In healthy youth, caudate activity is involved in interference control allowing the successful maintenance of information in working memory even in the presence of distraction. Our findings suggest that interference control, linked to caudate activity, is not adequately enhanced by MPH in ADHD.