Influence of Stimulant Medication on Brain Processes for Decision Making in Attention Deficit Hyperactivity Disorder

The goal of this trial is to investigate the cognitive- and brain-mechanisms underlying decision making (DM) and learning in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) as well as the modulation of task-related and task-independent brain activation by methylphenidate. The study aims at using a double-blinded, placebo controlled, cross-over, withdrawal design to study the effects of ADHD and methylphenidate in both a behavioural study investigating cognitive effects on decision making and instrumental learning, and a functional MRI (fMRI) study investigating the effects on brain mechanisms during decision making alone. A secondary objective of the trial is to measure the effect of adult ADHD and methylphenidate on cerebral perfusion. This will be done through applying a novel arterial spin labelling MRI-technique on the participants in the fMRI arm of the study.

The immediate scientific goal of this trial is to investigate the cognitive- and brain-mechanisms underlying Decision Making (DM) and instrumental learning in young adults with ADHD as well as the modulation of task-related and task-independent brain activation by MPH. In a more applied perspective, the investigators hope this trial will contribute to the development of tools for improved diagnosis and treatment monitoring of ADHD. Diagnostic tools should be based on the understanding of cognitive and brain mechanisms contributing to the symptom manifestation of ADHD. The study aims at using a double-blinded, placebo controlled cross-over withdrawal design to study the effects of ADHD and MPH in both a behavioural study investigating cognitive effects on DM and instrumental learning, and an fMRI study investigating the effects on brain mechanisms during DM alone. The results of the behavioural DM task from the fMRI experiment will be pooled with the data from the behavioural study to achieve higher statistical power in the analysis of the behavioural data.

A distinctive characteristic of this proposal is to gain insight into differences between ADHD-patients and healthy controls and the effects of methylphenidate (MPH) medication with an approach termed "computational psychiatry" (Maia and Frank, 2011). In this approach, the investigators apply mathematical models of cognition to observed behaviour in order to derive latent decision variables characterizing the DM- and instrumental learning processes. When combined with neuroimaging methods, computational models allow identification of differences in affective and cognitive processes together with the neurobiological processes that underlie these differences (Frank et al., 2004). Such insights should be the foundation of new tools for diagnosis and therapeutic treatment of ADHD.

Eligibility Criteria:
Inclusion Criteria:

Drug-Naïve Group

* Comply with Diagnostic and Statistical Manual (DSM) -IV criteria for ADHD.
* No history of medication with Methylphenidate.
* Must be between the age of 18 and 40.
* Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to International Conference on Harmonisation (ICH) Good Clinical Practice (GCP), and national/local regulations.
* After stable medication is established, these will be incorporated into the study following the procedures of the "drug group".

Drug group

* Comply with DSM-IV criteria for ADHD.
* On stable treatment with MPH.
* Must be between the age of 18 and 40.
* Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to ICH GCP, and national/local regulations.

Healthy Control Group

* Must be between the age of 18 and 40.
* No current psychiatric diagnosis.
* Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion Criteria:

* Treatment with the following groups of pharmacological agents will be considered as exclusion criteria for participation:
* Antidepressants (MOA-inhibitors, Tricyclic antidepressants, Selective Serotonin Re-uptake Inhibitors)
* Antipsychotics (both first and second generation)
* Anxiolytics/hypnotics (benzodiazepines, barbiturates)
* Opiates
* History of alcohol or drug abuse.
* History of moderate to severe head injury.
* Major psychiatric comorbidity (i.e. psychosis, active suicidal ideation or acute exacerbation of other psychiatric condition in need of immediate treatment).
* Epilepsy
* History of severe memory loss
* Under treatment for metabolic disorders
* Severe primary sensory loss
* Any condition contraindicating treatment with methylphenidate will automatically lead to exclusion, since these patients will not receive methylphenidate from clinician and thus will not meet inclusion criteria (including pregnancy, methylphenidate allergies, incompatible concomitant medication etc.).
* MRI specific criteria: contraindications for MRI (i.e. metallic or circuit-containing implants, severe claustrophobia)