Ventral Tegmental Area (VTA) Self-Activation in Attention Deficit Hyperactivity Disorder (ADHD)

The study involves a screening visit and 4 experimental task sessions.During the screening
visit subjects will undergo psychiatric screening to determine if they meet criteria for a
diagnosis of ADHD. Participants who meet criteria for a diagnosis of ADHD will also have the
following tests done at screening: breath alcohol test, urine drug screen and urine cotinine
(by product of tobacco) screening and intelligence quotient (IQ) assessment. Eligible
participants will complete a battery of cognitive assessments.

Participants meeting study inclusion will then be scheduled for 4 fMRI sessions to assess and
manipulate the ability to self-stimulate VTA activation. Each session will contain the same
tasks and instructions. The experimental imaging task sessions will be done within a one
month window and will consist of two types of runs: Test Runs (one pre-test and post-test
each) and three Training Runs.

The purpose of the Pre-Test is to establish a baseline level of self-generated VTA activation
prior to receiving RTFF.

The Post-Test is designed to assess whether participants are better able to self-induce VTA
BOLD signal in the absence of feedback (after receiving RTFF).

Participants will begin and end each scanning session with a 2-minute resting state scan.
Participants will rest and fixate at a cross hair.

The purpose of the first run is to acquire data in functional space to facilitate
registration of the VTA probabilistic atlas (MNI space) to functional space.

The Pre-Test and Post-Test runs will be identical and will have two trial types: Activate and
Count.

During the Activate trials participants will be instructed to try to increase activity (BOLD
signal) within their VTA. Specifically, we will instruct participants to try to get
themselves into a heightened state of motivation using personally relevant thoughts and
imagery. Importantly, they will be encouraged to optimize strategies for themselves.

During the Count trials, participants will be instructed to count backwards. The purpose of
these trials is to: standardize the baseline period and to provide a distractor task to
prevent engagement in activation strategies. There will be 5 repetitions of both trial types,
separated by a jittered inter-trial-interval (ITI; total duration 4 minutes, 5 seconds).

The purpose of the subsequent training runs (n=3/day on each of the 4 days) is to provide
participants with RTFF to assist them in increasing their VTA BOLD signal.

The training runs will consist of three trial types: Activate, Count, and Rest. For both
Activate and Count Trials, participants will be given the same instructions as during the
test runs. During the Rest trials participants will be instructed to rest and not think of
anything in particular. The Activate and Rest trials will include a thermometer display, as
described below. Each trial type will be repeated 5 times per run, separated by a jittered
ITI (total duration 6 minutes, 18 seconds).

Following the Post-Test each day, the Cognitive Battery assessments will be repeated with the
subject out of the scanner.

Inclusion Criteria:

- 18-45 years of age

- Male or Female

- Confirmed diagnosis, any subtype as determined by the clinician administered Conner's
Adult ADHD Diagnostic Interview for DSM-IV (CAADID) and clinical interview using the
Mini International Neuropsychiatric Interview (MINI)

- T-Score > 65 on one of the DSM-IV relevant scales (Inattentive Symptoms,
Hyperactive-Impulsive Symptoms, Total Symptoms or ADHD Index) on both the Self-Report
and Observer versions of the Conner's Adult ADHD Rating Scales (CAARS)

- Cognitive functioning eaqual or greater than 80 as assessed by the Kaufman Brief
Intelligence test, Second Edition (KBIT-II)

Exclusion Criteria:

- History of chronic/significant medical condition

- Current or past 6 month use of prescription medications for ADHD or other psychiatric
condition

- Meets criteria for any other Axis I Disorder (determined the Mini International
Neuropsychiatric Interview (MINI) other than nicotine dependence that is significantly
impairing and would contraindicate participation in the present study

- Meets criteria for any Axis II Disorder

- Current substance abuse or dependence or history within the last 12 months; expired
breath alcohol level > 0.0; Positive urine drug screen for any of the following:
cannabis, amphetamines, opioids, benzodiazepines, barbiturates, cocaine

- Inability to understand written and/or spoken English language

- Claustrophobia or other contraindications to MRI scanning

- If female, pregnancy as determined by urine pregnancy test on each day of MRI scanning

- Presence of any metal in the body (e.g., implant, non-removable piercing, IUD)

- Head injury resulting in loss of consciousness

- Worked with metal (e.g., welding) or had an injury to the eye involving metal

- Weigh more than 250 pounds