Role of Theta Frequency Oscillations in Proactive and Reactive Control Processes in Youth With Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD)

Role of Theta Frequency Oscillations in Proactive and Reactive Control Processes in Youth With Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD)

Background:

Attention deficit hyperactivity disorder (ADHD) is common in children. It can cause problems with attention and the ability to control actions and impulses. Obsessive compulsive disorder (OCD) is less common in children but not rare. It involves ongoing thoughts, urges, impulses, and repeated behaviors. Researchers want to study differences in brain activity between healthy children, those with ADHD, and those with OCD.

Objective:

To learn more about how the brain controls thinking and behavior.

Eligibility:

People aged 10 to 17 years with ADHD, OCD, or neither.

Design:

Participants will have 3 to 10 clinic visits in up to 1 year. Each visit will last 2 to 3 hours.

Three visits are required:

Behavioral. Participants will complete a computer task. Their mood, memory, attention, and thinking skills will be tested.

EEG. Participants will undergo electroencephalography (EEG) to measure signals in their brain. Small electrodes will be placed on the scalp. A cap will be stretched over the head. Signals will be recorded while participants rest or do tasks on a computer.

MRI. Participants will have a magnetic resonance imaging scan (MRI). They will lie on a table that rolls into a tube. The MRI will take pictures of their brain while they do tasks on a computer.

Seven more visits are optional. These include 2 more EEG visits and 2 more MRI visits.

Three will be magnetoencephalography (MEG) visits: MEG measures small magnetic field changes in the brain. A helmet with sensors will be placed on the head. Brain changes will be recorded while participants rest or do tasks on a computer.

Study Description:

This is a pilot feasibility/tolerability study to evaluate the role of theta frequency oscillations in proactive and reactive control processes in youth with Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD). We hypothesize that: 1) Procedures will be tolerable for healthy volunteer (HV) children without a primary DSM-5 diagnosis, youth with ADHD and youth with OCD; 2) Procedures will be feasible for healthy volunteer (HV) children without a primary DSM-5 diagnosis, youth with ADHD and youth with OCD; 3) EEG and fMRI data for the majority of participants will be of sufficient quality for analysis (e.g. without artifact or excessive motion); 4) We will be able to identify cortical sources associated with resting-state and task-evoked theta oscillatory activity. This study will inform a future study where EEG-synchronized repetitive transcranial magnetic stimulation (rTMS) will modulate theta oscillations to improve cognitive control in youth with ADHD and youth with OCD.

Objectives:

Primary Objectives:

1. Evaluate the feasibility of MRI and EEG procedures at rest and during cognitive tasks in youth with ADHD, youth with OCD and HV youth.
2. Evaluate the tolerability of study procedures in youth with ADHD, youth with OCD and HV youth.
3. Evaluate the data quality obtained from the EEG and fMRI in youth with ADHD, youth with OCD and HV youth.
4. Identify cortical sources of resting-state and task-evoked theta oscillations in youth with ADHD, youth with OCD and HV youth.

Secondary Objectives:

1. Evaluate the reliability of task performance on cognitive control tasks across sessions.

Exploratory Objectives:

1. Compare the power of resting and task-evoked theta oscillations in the EEG recording across ADHD, OCD, and HV groups.

2a. Evaluate the relation between power in resting-state theta oscillations and task-evoked theta power in the electroencephalogram (EEG).

2b. Evaluate the relationship between power in resting-state theta oscillations in the EEG and task performance.

3. Evaluate the data quality and compare the power of resting and task-evoked theta oscillations in the MEG recording across ADHD, OCD, and HV groups.

4. Compare the BOLD activity, and connectivity within and across "task-positive" function networks (TPNs) across ADHD, OCD, and HV groups.

5. Compare the power of task-evoked EEG and MEG theta oscillations and cortical sources of task-evoked theta oscillations across standardized cognitive control and working memory tasks in youth with ADHD, youth with OCD and HV youth.

6. Develop latent executive functioning factors based on cognitive control and working memory task outcomes and evaluate the relationship between this latent factor and power of resting and task-evoked theta oscillations.

Endpoints:

Primary Endpoints:

1. Participant Retention for all visits of the study and task performance (Primary Objective 1).
2. Adverse Events reported related to study procedures (Primary Objective 2).
3. Percentage of EEG and fMRI data deemed to be of sufficient quality for analysis (e.g. without artifact or excessive motion) (Primary Objective 3).
4. Structural cortical region source localized from a combination of the EEG (and MEG in a subset of patients) and fMRI data (Primary Objective 4).

Secondary Endpoints:

1. Accuracy and reaction time behavioral responses to cognitive control tasks.

Exploratory Endpoints:

1. EEG Power in the theta frequency band (4-7Hz) (Exploratory Objective 1, 2a and 2b, and 5).
2. Power of MEG oscillations in the theta (4-7Hz) frequency band during rest and during cognitive control tasks (Exploratory Objective 3 and 5).
3. BOLD activation and connectivity in TPN networks (Exploratory Objective 4).
4. Structural cortical region source localized from a combination of the EEG (and MEG in a subset of patients) and fMRI data (Exploratory Objective 5).
5. Latent Inhibitory Control Factor and Latent Working Memory Factor derived by structural equation modeling using performance-based metrics across the three inhibitory control tasks and two working memory tasks (Exploratory Objective 6).

• INCLUSION CRITERIA:

  1. Ability to provide informed assent and parent consent

  2. Age: 10-17 years

  3. ADHD Group: Diagnosis of ADHD based on DSM-5 criteria

     OCD Group: Diagnosis of OCD based on DSM-5 criteria

     HV Group: No Neurological or Psychiatric diagnosis based on DSM-5 criteria

  4. Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). WASI-II will be used as a measure of intellectual function. Children will be included when FSIQ > 70.

  5. Normal or corrected to normal vision

EXCLUSION CRITERIA:

Participants will be screened to exclude participants in whom MRI or EEG might result in increased risk of side effects or complications or whose data would not be scientifically valid.

1. Non-English Speakers
2. Pregnancy
3. Any implant, prosthesis or alteration of the body that, in the opinion of the investigator, would be unsafe with MRI or EEG or that would produce an artifact that would compromise the integrity of data;
4. Active or History of psychosis, bipolar I disorder, Level 2 or 3 autism spectrum disorder, active severe substance use disorders (within the last month), have active suicidal intent or plan as detected on screening instruments;
5. Individuals currently taking stimulant medications who cannot tolerate being off their medication for up to 48 hours prior to the study visit and experience an exacerbation of symptoms that necessitates the resumption of medication prior to completion of the study visit.
6. Past or present medical or neurological condition, disease, disorder, genetic finding, or injury that, in the opinion of the Investigator, may significantly increase the potential risks of study participation, reduce or compromise a subject s ability to fully comply with all study requirements for the duration of the study or may compromise the integrity of the data.
7. For the HV group, any impairing current psychiatric diagnosis.