Behavioral Differences in Effortful Control

Based on the multi-source interference task, all subjects' cognitive functions will be
assessed based on reaction time, reaction variability, and accuracy of performance on the
attention control task.

This study aims to recruit 120 total healthy participants. Overall Safety Plan Subject
Protections and Safety Monitoring

1. Confidentiality of records is assured by assigning the subjects research numbers and
storing computer files without reference to name, except for a single linking file that
links subject's names with their research numbers. Paper records are kept in locked file
drawers in a locked room, to which only authorized research personnel have access. When
the study is completed, the linking file that links subject's names with their research
numbers will be permanently destroyed.

2. Furthermore, upon the event of a subject's participation being terminated, all
information collected prior to the subject being removed from the study, will be
destroyed.

3. Personnel involved in the study are acutely sensitive to people's unease about revealing
personal information. Research personnel also take the required Program for Education
and Evaluation in Responsible Research and Scholarship certification, and take the
utmost precautions about protecting confidentiality. When potential subject voices their
lack of interest in participating, all identifying information is destroyed. During the
study, subjects are reminded that they do not have to answer questions that make them
feel uncomfortable

i. Data Safety and Monitoring Plan

1. No subjects will be recruited or run until the protocol receives full review and
approval by the Medical IRB at the University of Michigan. A clinical research associate
will accompany all subjects throughout the study. Any minor anxiety arising during the
course of the procedures will be immediately assessed, and typically managed with
reassurance and simple relaxation techniques. Assessment will always include an
evaluation of the subject's ability to continue in the protocol.

2. All subjects will be fully informed of all the possible side-effects that could be
encountered during the study. Every measure will be taken to protect subjects against
even the rarest possible side effects. Principal Investigator, Dr. Chandra Sripada, has
extensive prior experience with methylphenidate and the challenges utilized in this
study.

3. Subjects will be encouraged to contact the investigator if they notice any symptoms or
untoward side effects. All subjects will have direct access to the phone numbers and
pagers of the study coordinator and the responsible physician (Dr. Sripada), as well as
a 24-hour contact number (emergency room services). This information is included in the
copy of the consent forms provided to the subjects.

ii. Reporting of adverse events

Adverse events (AEs) will be recorded and tracked for these projects. Adverse events will be
reported per IRBs, FDA, and NIH guidelines. An adverse event is any experience that has taken
place during the course of a research project, which, in the opinion of the investigators,
was harmful to a subject participating in the research, increased the risks of harm in the
research, or had an unfavorable impact on the risk/benefit ratio. Adverse events will be
graded using the mild, moderate, severe terminology as defined:

- Mild - Noticeable to the subject, does not interfere with the subject's daily
activities, usually does not require additional therapy, dose reduction, or
discontinuation of the study.

- Moderate - Interferes with the subject's daily activities, possibly requires additional
therapy, but does not require discontinuation of the study.

- Severe - Severely limits the subject's daily activities and may require discontinuation
of the study. This would include all adverse events defined as "Serious" by the IRBMED.

The PI will assign attribution as definitely associated, probably associated, possibly
associated, or unrelated. Adverse events will also be recorded as expected or unexpected. All
Serious AEs and/or unexpected AEs will be reported to the IRB, NIH, and the FDA, within 7
days of occurrence or recognition. Fatal or life-threatening adverse events will be reported
to the above institutions within 24 hours. Regular annual reviews of protocol activity and
all adverse events will be submitted to the IRBs and NIH. Other less serious and expected AEs
will also be reported to the above institutions with compliance to their requirements.

iii. Persons responsible Chandra Sekhar Sripada and Project Coordinator Christina Bohensky
will be responsible for overseeing data integrity, safety monitoring, and reporting of
adverse events. During the phone conferences and semi -annual meetings adverse events,
recruitment, data quality and integrity and compliance with protocols will be discussed as
well.

VI. Data Analysis Regression analysis will be utilized to assess whether the dependent
measures for the tasks (accuracy, reaction time) are significantly correlated with measures
of trait impulsivity derived from the Barratt Impulsivity Scale-11 questionnaire. Independent
samples t-tests will be used to determine whether task performance differs due to
methylphenidate versus placebo administration.

Inclusion Criteria:

- Age range 18-35

Exclusion Criteria:

- Pregnant or nursing (females)

- Any clinically significant medical condition

- Currently taking any medications (i.e., decongestants)

- Currently taking any psychoactive medications

- Alcohol or substance abuse (current or in the past 2 years)

- Liver or Kidney disease

- Any clinically significant personal or family history of cardiac problems