The Ability to Voluntarily Regulate Theta Band Activity Affects How Pharmacological Manipulation of the Catecholaminergic System Impacts Cognitive Control.

BACKGROUND: The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical considerations suggest that the voluntary modulability of theta band activity can explain this variance. The study aimed to investigate to what extent interindividual differences in catecholaminergic effects on response inhibition depend on voluntary theta band activity modulation. METHODS: A total of 67 healthy adults were tested in a randomized, double-blind, cross-over study design. At each appointment, they received a single dose of methylphenidate or placebo and performed a Go/Nogo task with stimuli of varying complexity. Before the first appointment, the individual's ability to modulate theta band activity was measured. Recorded EEG data were analyzed using temporal decomposition and multivariate pattern analysis. RESULTS: Methylphenidate effects and voluntary modulability of theta band activity showed an interactive effect on the false alarm rates of the different Nogo conditions. The multivariate pattern analysis revealed that methylphenidate effects interacted with voluntary modulability of theta band activity at a stimulus processing level, whereas during response selection methylphenidate effects interacted with the complexity of the Nogo condition. CONCLUSIONS: The findings reveal that the individual's theta band modulability affects the responsiveness of an individual's catecholaminergic system to pharmacological modulation. Thus, the impact of pharmacological manipulation of the catecholaminergic system on cognitive control most likely depends on the existing ability to self-modulate relevant brain oscillatory patterns underlying the cognitive processes being targeted by pharmacological modulations.

Effects of methylphenidate and physiotherapeutic treatment on graphomotor movements in children with ADHD.

In addition to the core symptoms defining ADHD, affected children often experience motor problems; in particular, graphomotor movements including handwriting are affected. However, in clinical settings, there is little emphasis on standardized and objective diagnosing and treatment of those difficulties. The present study investigated for the first time the effects of methylphenidate as well as physiotherapeutic treatment on objectively assessed graphomotor movements compared to a control condition, i.e. parental psychoeducation, in 58 children (mean age: 9.52 ± 1.91 years) newly diagnosed with ADHD in an outpatient clinic for child and adolescent psychiatry. Families were invited to join one of the treatment groups. Before and after 8 weeks of treatment, children performed six different tasks on a digitizing tablet which allowed the objective analysis of three important kinematic parameters of graphomotor movements (fluency, velocity, and pen pressure) in different levels of visual control and automation. Graphomotor movement fluency and velocity improves over time across the groups, especially in tasks with eyes closed. We did not find clear evidence for beneficial effects of methylphenidate or physiotherapeutic treatment on children's overall graphomotor movements suggesting that treatments need to be better tailored towards specific and individual deficits in graphomotor movements.

Alpha and theta band activity share information relevant to proactive and reactive control during conflict-modulated response inhibition.

Response inhibition is an important instance of cognitive control and can be complicated by perceptual conflict. The neurophysiological mechanisms underlying these processes are still not understood. Especially the relationship between neural processes directly preceding cognitive control (proactive control) and processes underlying cognitive control (reactive control) has not been examined although there should be close links. In the current study, we investigate these aspects in a sample of N = 50 healthy adults. Time-frequency and beamforming approaches were applied to analyze the interrelation of brain states before (pre-trial) and during (within-trial) cognitive control. The behavioral data replicate a perceptual conflict-dependent modulation of response inhibition. During the pre-trial period, insular, inferior frontal, superior temporal, and precentral alpha activity was positively correlated with theta activity in the same regions and the superior frontal gyrus. Additionally, participants with a stronger pre-trial alpha activity in the primary motor cortex showed a stronger (within-trial) conflict effect in the theta band in the primary motor cortex. This theta conflict effect was further related to a stronger theta conflict effect in the midcingulate cortex until the end of the trial. The temporal cascade of these processes suggests that successful proactive preparation (anticipatory information gating) entails a stronger reactive processing of the conflicting stimulus information likely resulting in a realization of the need to adapt the current action plan. The results indicate that theta and alpha band activity share and transfer aspects of information when it comes to the interrelationship between proactive and reactive control during conflict-modulated motor inhibition.

FamilyCoviDD19: results of a cross-sectional study-long-term outcomes of infected and uninfected household members.

OBJECTIVE: In this study, we aimed to compare long-term physical and mental health outcome between SARS-CoV-2 infected and uninfected household members to differentiate between infection-related and pandemic-related outcomes after about two and a half years of the pandemic. Furthermore, possible differences in the outcome of adults and children and young people (CYP) were of interest. DESIGN: In a cross-sectional study design, we compared the long-term physical and mental health outcome of between infected and uninfected as well as between adult and CYP (household members). SETTING: The FamilyCoviDD19 study-a serology study in households-was initially conducted to evaluate virus transmission in a close contact setting focusing on households with children and adolescents in Germany. At least 1 year after initial infection in the respective households, a follow-up took place in which the prevalence and type of possible long-term consequences were surveyed on the basis of self-reported information on physical and mental health. PARTICIPANT: In this study, a total of 533 household members of 146 families participated and responded to our survey, including 296 (55.5%) adults and 237 (44.5%) CYP. RESULT: The difference in frequency of reported symptoms between infected and uninfected individuals was very moderate, suggesting that the vast majority of reported symptoms were not attributable to a previous SARS-CoV-2 infection. However, regardless of age and infection status, this study showed overall high rates of self-reported symptoms with CYP having fewer long-term sequelae than adults one year after infection. Furthermore, over 50% of those reporting symptoms were not affected in their daily life, with CYPs reporting an even lower percentage compared with adults. CONCLUSION: CYP are at reduced risk not only to develop symptomatic infection or severe disease courses (previous analyses) but also to develop infection-associated long-term sequelae (this study). Independent of infection CYP reported high rates of neurocognitive, pain, somatic and mood symptoms, which makes the influence of the pandemic itself-including pandemic control measures-decisive.

Preserved perception-action integration in adolescents after a COVID-19 infection.

Evidence is accumulating that the Coronavirus disease (COVID-19) can bring forth deficits in executive functioning via alterations in the dopaminergic system. Importantly, dopaminergic pathways have been shown to modulate how actions and perceptions are integrated within the brain. Such alterations in event file binding could thus underlie the cognitive deficits developing after a COVID-19 infection. We examined action-perception integration in a group of young people (11-19 years of age) that had been infected with COVID-19 before study participation (n = 34) and compared them to a group of uninfected healthy controls (n = 29) on the behavioral (i.e., task accuracy, reaction time) and neurophysiological (EEG) level using an established event file binding paradigm. Groups did not differ from each other regarding demographic variables or in reporting psychiatric symptoms. Overall, multiple lines of evidence (behavioral and neurophysiological) suggest that action-perception integration is preserved in adolescents who suffered from COVID-19 prior to study participation. Event file binding processes were intact in both groups on all levels. While cognitive impairments can occur following a COVID-19 infection, the study demonstrates that action-perception integration as one of the basic building blocks of cognition seems to be largely unaffected in adolescents with a rather mild course of the disease.

Distinct effects of different neurofeedback protocols on the neural mechanisms of response inhibition in ADHD.

OBJECTIVE: In attention deficit/hyperactivity disorder (ADHD), impaired response inhibition is frequently observed. A promising non-pharmacological treatment is electroencephalography (EEG)-neurofeedback (NF) training. However, the widely used theta-down/beta-up regulation (↓θ↑ß) NF protocol may not be optimal for targeting these deficits. We examined how neurofeedback protocols training the upregulation of theta and/or beta power affect inhibitory control in children and adolescents with ADHD. METHODS: 64 patients with ADHD took part in the three NF trainings. Aside from parent-reported ADHD symptoms and behavioural performance data, neurophysiological parameters collected via a Go/Nogo task and corrected to account for intraindividual variability were compared in a pre-post design and to an ADHD (n = 20) as well as a typically developing control group (n = 24). RESULTS: The examined NF protocols resulted in similar improvements in response inhibition with the neurophysiological mechanisms differing substantially. The upregulation of theta led to a specific Nogo-P3 increase, while training beta upregulation as well as the combined protocol resulted in less specific effects. CONCLUSIONS: This study shows distinct effects of different theta/beta-neurofeedback protocols on the neural mechanisms underlying improvements in response inhibition in patients with ADHD. SIGNIFICANCE: These effects shed further light on the oscillatory dynamics underlying cognitive control in ADHD and how these may be targeted in neurofeedback treatments.

Cognitive and Neural Mechanisms of Behavior Therapy for Tics: A Perception-Action Integration Approach.

European clinical guidelines recommend the use of Exposure and Response Prevention (ERP) and Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatments for tic disorders. Although ongoing efforts in research are being made to understand the mechanisms underlying these behavioral approaches, as of yet, the neurophysiological mechanisms behind behavioral interventions are poorly understood. However, this is essential to tailor interventions to individual patients in order to increase compliance and efficacy. The Theory of Event Coding (TEC) and its derivative BRAC (Binding and Retrieval in Action Control) provide a theoretical framework to investigate cognitive and neural processes in the context of tic disorders. In this context, tics are conceptualized as a phenomenon of enhanced perception-action binding, with premonitory urges constituting the perceptual and the motor or vocal expression constituting the action part of an event file. Based on this, CBIT is assumed to strongly affect stimulus-response binding in the context of response selection, whereas the effects of ERP presumably unfold during stimulus-response binding in the response inhibition context. Further studies are needed to clarify the neurophysiological processes underlying behavioral interventions to enable the individualization and further development of therapeutic approaches for tic disorders.

Theta Activity Dynamics during Embedded Response Plan Processing in Tourette Syndrome.

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder. Because motor signs are the defining feature of GTS, addressing the neurophysiology of motor processes is central to understanding GTS. The integration of voluntary motor processes is subject to so-called "binding problems", i.e., how different aspects of an action are integrated. This was conceptualized in the theory of event coding, in which 'action files' accomplish the integration of motor features. We examined the functional neuroanatomical architecture of EEG theta band activity related to action file processing in GTS patients and healthy controls. Whereas, in keeping with previous data, behavioral performance during action file processing did not differ between GTS and controls, underlying patterns of neural activity were profoundly different. Superior parietal regions (BA7) were predominantly engaged in healthy controls, but superior frontal regions (BA9, BA10) in GTS indicated that the processing of different motor feature codes was central for action file processing in healthy controls, whereas episodic processing was more relevant in GTS. The data suggests a cascade of cognitive branching in fronto-polar areas followed by episodic processing in superior frontal regions in GTS. Patients with GTS accomplish the integration of motor plans via qualitatively different neurophysiological processes.

Extra Movements in Healthy People: Challenging the Definition and Diagnostic Practice of Tic Disorders.

The occurrence of motor/vocal tics, that is, "extra movements" and/or "extra vocalizations," is the leading diagnostic criterion for tic disorders. We show that extra movements are common also in healthy controls, so that a surplus of movements per se is not indicative of the presence of a tic disorder. This questions the usefulness of Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for tic disorders in clinical practice. Apparently, it is not solely a surplus of movements that defines tic disorders. Instead, movement characteristics and patterns seem to play a crucial role. ANN NEUROL 2023;93:472-478.

The neural stability of perception-motor representations affects action outcomes and behavioral adaptation.

Actions can fail - even though this is well known, little is known about what distinguishes neurophysiological processes preceding errors and correct actions. In this study, relying on the Theory of Event Coding, we test the assumption that only specific aspects of information coded in EEG activity are relevant for understanding processes leading to response errors. We examined N = 69 healthy participants who performed a mental rotation task and combined temporal EEG signal decomposition with multivariate pattern analysis (MVPA) and source localization analyses. We show that fractions of the EEG signal, primarily representing stimulus-response translation (event file) processes and motor response representations, are essential. Stimulus representations were less critical. The source localization results revealed widespread activity modulations in structures including the frontopolar, the middle and superior frontal, the anterior cingulate cortex, the cuneus, the inferior parietal cortex, and the ventral stream regions. These are associated with differential effects of the neural dynamics preceding correct/erroneous responses. The temporal-generalization MVPA showed that event file representations and representations of the motor response were already distinct 200 ms after stimulus presentation and this lasted till around 700 ms. The stability of this representational content was predictive for the magnitude of posterror slowing, which was particularly strong when there was no clear distinction between the neural activity profile of event file representations associated with a correct or an erroneous response. The study provides a detailed analysis of the dynamics leading to an error/correct response in connection to an overarching framework on action control.

The Effects of Different Theta and Beta Neurofeedback Training Protocols on Cognitive Control in ADHD.

Neurofeedback (NF) is an important treatment for attention deficit/hyperactivity disorder (ADHD). In ADHD, cognitive control deficits pose considerable problems to patients. However, NF protocols are not yet optimized to enhance cognitive control alongside with clinical symptoms, partly because they are not driven by basic cognitive neuroscience. In this study, we evaluated different EEG theta and/or beta frequency band NF protocols designed to enhance cognitive control. Participants were n = 157 children and adolescents, n = 129 of them were patients with ADHD (n = 28 typically developing (TD) controls). Patients with ADHD were divided into five groups in the order of referral, with four of them taking part in different NF protocols systematically varying theta and beta power. The fifth ADHD group and the TD group did not undergo NF. All NF protocols resulted in reductions of ADHD symptoms. Importantly, only when beta frequencies were enhanced during NF (without any theta regulation or in combination with theta upregulation), consistent enhancing effects in both response inhibition and conflict control were achieved. The theta/beta NF protocol most widely used in clinical settings revealed comparatively limited effects. Enhancements in beta band activity are key when aiming to improve cognitive control functions in ADHD. This calls for a change in the use of theta/beta NF protocols and shows that protocols differing from the current clinical standard are effective in enhancing important facets of cognitive control in ADHD. Further studies need to examine regulation data within the neurofeedback sessions to provide more information about the mechanisms underlying the observed effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s41465-022-00255-6.

Urge-tic associations in children and adolescents with Tourette syndrome.

Premonitory urges preceding tics are a cardinal feature of Gilles de la Tourette syndrome (GTS), a developmental disorder usually starting during middle childhood. However, the temporal relation between urges and tics has only been investigated in adults. In 25 children and adolescents with GTS (8-18 years), we assess urge-tic associations, including inter-individual differences, correlation to clinical measures, and in comparison to a previously reported sample of adult GTS patients. Group-level analyses confirmed positive associations between urges and tics. However, at the individual level, less than half of participants showed positive associations, a similar proportion did not, and in two participants, the association was reversed. Tic expression and subjective urge levels correlated with corresponding clinical scores and participants with more severe tics during the urge monitor exhibited stronger urge-tic associations. Associations between reported urge levels and instantaneous tic intensity tended to be less pronounced in children and adolescents than in adult GTS patients. The observed heterogeneity of urge-tic associations cast doubt on the notion that tics are directly caused by urges. More severe tics may facilitate anticipation of tics and thereby lead to more pronounced urge-tic associations, consistent with a hypothesis of urges as a byproduct of tics.

Training a machine learning classifier to identify ADHD based on real-world clinical data from medical records.

The diagnostic process of attention deficit hyperactivity disorder (ADHD) is complex and relies on criteria sensitive to subjective biases. This may cause significant delays in appropriate treatment initiation. An automated analysis relying on subjective and objective measures might not only simplify the diagnostic process and reduce the time to diagnosis, but also improve reproducibility. While recent machine learning studies have succeeded at distinguishing ADHD from healthy controls, the clinical process requires differentiating among other or multiple psychiatric conditions. We trained a linear support vector machine (SVM) classifier to detect participants with ADHD in a population showing a broad spectrum of psychiatric conditions using anonymized data from clinical records (N = 299 participants). We differentiated children and adolescents with ADHD from those not having the condition with an accuracy of 66.1%. SVM using single features showed slight differences between features and overlapping standard deviations of the achieved accuracies. An automated feature selection achieved the best performance using a combination 19 features. Real-world clinical data from medical records can be used to automatically identify individuals with ADHD among help-seeking individuals using machine learning. The relevant diagnostic information can be reduced using an automated feature selection without loss of performance. A broad combination of symptoms across different domains, rather than specific domains, seems to indicate an ADHD diagnosis.

Resting-state theta activity is linked to information content-specific coding levels during response inhibition.

The neurophysiological processes underlying the inhibition of impulsive responses have been studied extensively. While also the role of theta oscillations during response inhibition is well examined, the relevance of resting-state theta activity for inhibitory control processes is largely unknown. We test the hypothesis that there are specific relationships between resting-state theta activity and sensory/motor coding levels during response inhibition using EEG methods. We show that resting theta activity is specifically linked to the stimulus-related fraction of neurophysiological activity in specific time windows during motor inhibition. In contrast, concomitantly coded processes related to decision-making or response selection as well as the behavioral inhibition performance were not associated with resting theta activity. Even at the peak of task-related theta power, where task-related theta activity and resting theta activity differed the most, there was still predominantly a significant correlation between both types of theta activity. This suggests that aspects similar to resting dynamics are evident in the proportion of inhibition-related neurophysiological activity that reflects an "alarm" signal, whose function is to process and indicate the need for cognitive control. Thus, specific aspects of task-related theta power may build upon resting theta activity when cognitive control is necessary.

Feedback-Based Learning of Timing in Attention-Deficit/Hyperactivity Disorder and Neurofibromatosis Type 1.

OBJECTIVE: Patients with Neurofibromatosis Type 1 (NF1) frequently display symptoms resembling those of Attention Deficit/Hyperactivity Disorder (ADHD). Importantly, these disorders are characterised by distinct changes in the dopaminergic system, which plays an important role in timing performance and feedback-based adjustments in timing performance. In a transdiagnostic approach, we examine how far NF1 and ADHD show distinct or comparable profiles of timing performance and feedback-based adjustments in timing. METHOD: We examined time estimation and learning processes in healthy control children (HC), children with ADHD with predominantly inattentive symptoms and those with NF1 using a feedback-based time estimation paradigm. RESULTS: Healthy controls consistently responded closer to the correct time window than both patient groups, were less variable in their reaction times and displayed intact learning-based adjustments across time. The patient groups did not differ from each other regarding the number of in-time responses. In ADHD patients, the performance was rather unstable across time. No performance changes could be observed in patients with NF1 across the entire task. CONCLUSIONS: Children with ADHD and NF1 differ in feedback learning-based adjustments of time estimation processes. ADHD is characterised by behavioural fluctuations during the learning process. These are likely to be associated with inefficiencies in the dopaminergic system. NF1 is characterised by impairments of feedback learning which could be due to various neurotransmitter alterations occurring in addition to deficits in dopamine synthesis. Results show that despite the strong overlap in clinical phenotype and neuropsychological deficits between NF1 and ADHD, the underlying cognitive mechanisms are different.

Increased scale-free and aperiodic neural activity during sensorimotor integration-a novel facet in Tourette syndrome.

Tourette syndrome is a common neurodevelopmental disorder defined by multiple motor and phonic tics. Tics in Tourette syndrome resemble spontaneously occurring movements in healthy controls and are therefore sometimes difficult to distinguish from these. Tics may in fact be mis-interpreted as a meaningful action, i.e. a signal with social content, whereas they lack such information and could be conceived a surplus of action or 'motor noise'. These and other considerations have led to a 'neural noise account' of Tourette syndrome suggesting that the processing of neural noise and adaptation of the signal-to-noise ratio during information processing is relevant for the understanding of Tourette syndrome. So far, there is no direct evidence for this. Here, we tested the 'neural noise account' examining 1/f noise, also called scale-free neural activity as well as aperiodic activity, in n = 74 children, adolescents and adults with Tourette syndrome and n = 74 healthy controls during task performance using EEG data recorded during a sensorimotor integration task. In keeping with results of a previous study in adults with Tourette syndrome, behavioural data confirmed that sensorimotor integration was also stronger in this larger Tourette syndrome cohort underscoring the relevance of perceptual-action processes in this disorder. More importantly, we show that 1/f noise and aperiodic activity during sensorimotor processing is increased in patients with Tourette syndrome supporting the 'neural noise account'. This implies that asynchronous/aperiodic neural activity during sensorimotor integration is stronger in patients with Tourette syndrome compared to healthy controls, which is probably related to abnormalities of GABAergic and dopaminergic transmission in these patients. Differences in 1/f noise and aperiodic activity between patients with Tourette syndrome and healthy controls were driven by high-frequency oscillations and not lower-frequency activity currently discussed to be important in the pathophysiology of tics. This and the fact that Bayesian statistics showed that there is evidence for the absence of a correlation between neural noise and clinical measures of tics, suggest that increased 1/f noise and aperiodic activity are not directly related to tics but rather represents a novel facet of Tourette syndrome.

Neural dynamics of stimulus-response representations during inhibitory control.

The investigation of action control processes is one major field in cognitive neuroscience and several theoretical frameworks have been proposed. One established framework is the "Theory of Event Coding" (TEC). However, only rarely, this framework has been used in the context of response inhibition and how stimulus-response association or binding processes modulate response inhibition performance. Particularly the neural dynamics of stimulus-response representations during inhibitory control are elusive. To address this, we examined n = 40 healthy controls and combined temporal EEG signal decomposition with source localization and temporal generalization multivariate pattern analysis (MVPA). We show that overlaps in features of stimuli used to trigger either response execution or inhibition compromised task performance. According to TEC, this indicates that binding processes in event file representations impact response inhibition through partial repetition costs. In the EEG data, reconfiguration of event files modulated processes in time windows well-known to reflect distinct response inhibition mechanisms. Crucially, event file coding processes were only evident in a specific fraction of neurophysiological activity associated with the inferior parietal cortex (BA40). Within that specific fraction of neurophysiological activity, the decoding of the dynamics of event file representations using temporal generalization MVPA suggested that event file representations are stable across several hundred milliseconds, and that event file coding during inhibitory control is reflected by a sustained activation pattern of neural dynamics.NEW & NOTEWORTHY The "mental representation" of how stimulus input translate into the appropriate response is central for goal-directed behavior. However, little is known about the dynamics of such representations on the neurophysiological level when it comes to the inhibition of motor processes. This dynamic is shown in the current study.

Perception-action integration in young age-A cross-sectional EEG study.

Humans differ in their capacity for integrating perceived events and related actions. The "Theory of event coding" (TEC) conceptualizes how stimuli and actions are cognitively bound into a common functional representation (or "code"), known as the "event file". To date, however, the neural processes underlying the development of event file coding mechanisms across age are largely unclear. We investigated age-related neural changes of event file coding from late childhood to early adulthood, using EEG signal decompositions methods. We included a group of healthy participants (n = 91) between 10 and 30 years, performing an event file paradigm. Results of this study revealed age-related effects on event file coding processes both at the behavioural and the neurophysiological level. Performance accuracy data showed that event file unbinding und rebinding processes become more efficient from late childhood to early adulthood. These behavioural effects are reflected by age-related effects in two neurophysiological subprocesses associated with the superior parietal cortex (BA7) as revealed in the analyses using EEG signal decomposition. The first process entails mapping and association processes between stimulus and response; whereas, the second comprises inhibitory control subprocesses subserving the selection of the relevant motor programme amongst competing response options.

The interplay of resting and inhibitory control-related theta-band activity depends on age.

Resting-state neural activity plays an important role for cognitive control processes. Regarding response inhibition processes, an important facet of cognitive control, especially theta-band activity has been the focus of research. Theoretical considerations suggest that the interrelation of resting and task-related theta activity is subject to maturational effects. To investigate whether the relationship between resting theta activity and task-related theta activity during a response inhibition task changes even in young age, we tested N = 166 healthy participants between 8 and 30 years of age. We found significant correlations between resting and inhibitory control-related theta activity as well as behavioral inhibition performance. Importantly, these correlations were moderated by age. The moderation analysis revealed that higher resting theta activity was associated with stronger inhibition-related theta activity in individuals above the age of ~10.7 years. The EEG beamforming analysis showed that this activity is associated with superior frontal region function (BA6). The correlation between resting and superior frontal response inhibition-related theta activity became stronger with increasing age. A similar pattern was found for response inhibition performance, albeit only evident from the age of ~19.5 years. The results suggest that with increasing age, resting theta activity becomes increasingly important for processing the alarm/surprise signals in superior frontal brain regions during inhibitory control. Possible causes for these developmental changes are discussed.

Perception-Action Integration Is Modulated by the Catecholaminergic System Depending on Learning Experience.

BACKGROUND: The process underlying the integration of perception and action is a focal topic in neuroscientific research and cognitive frameworks such as the theory of event coding have been developed to explain the mechanisms of perception-action integration. The neurobiological underpinnings are poorly understood. While it has been suggested that the catecholaminergic system may play a role, there are opposing predictions regarding the effects of catecholamines on perception-action integration. METHODS: Methylphenidate (MPH) is a compound commonly used to modulate the catecholaminergic system. In a double-blind, randomized crossover study design, we examined the effect of MPH (0.25 mg/kg) on perception-action integration using an established "event file coding" paradigm in a group of n = 45 healthy young adults. RESULTS: The data reveal that, compared with the placebo, MPH attenuates binding effects based on the established associations between stimuli and responses, provided participants are already familiar with the task. However, without prior task experience, MPH did not modulate performance compared with the placebo. CONCLUSIONS: Catecholamines and learning experience interactively modulate perception-action integration, especially when perception-action associations have to be reconfigured. The data suggest there is a gain control-based mechanism underlying the interactive effects of learning/task experience and catecholaminergic activity during perception-action integration.