Transcranial Electrical Stimulation (TES) at Slow Oscillation (SO) Frequency During NREM Sleep

40 subjects will be enrolled and randomized to participate in this study. A 60 minute TES
stimulation sequence consisting of a SO frequency stimulation (TES SO) using the NeuroConn DC
Stimulator PLUS or a sham stimulation will be administered during the second hour of a two
hour nocturnal sleep period. During wake period subjects will be tested using various
cognitive, subjective and objective sleepiness and mood measures. Vital signs measurements
will be taken to monitor general health issues. Up to 4 subjects will be enrolled per study
session. Due to logistical reasons, no more then 2 subjects per session can be assigned to
the TES SO group.

Screening visit = approx. 2 hours At-home component = 7 days In-laboratory study period = 138
hours Total in-laboratory period = approx. 138 hours per subject Total participation time (at
home + in-laboratory components) = 15 days

Inclusion Criteria:

- Healthy men and non-pregnant, non-lactating women 18 to 39 years of age (inclusive)

- Must demonstrate adequate comprehension of the protocol, by achieving a score of at
least 80% correct on a short multiple-choice quiz. Individuals who fail to achieve a
passing score on the initial quiz will be given one opportunity to retest after a
review of protocol information. Individuals who fail the comprehension assessment for
the second time will be disqualified.

Exclusion Criteria:

- Self-reported habitual nightly sleep amounts outside the target range of 6 - 9 hours
(i.e., less than 6 hours per night or more than 9 hours per night, on average)
(Post-consent Checklist)

- Self-reported nighttime lights-out times earlier than 2100 hours on average during
weeknights (Sunday through Thursday) or later than 2300. (Post-consent Checklist)

- Self-reported morning wake-up times later than 0800 on average during weekdays (Monday
through Friday) (Post-consent Checklist)

- Self-reported habitual napping (> 1 time a week in conjunction with normal sleep
habits) (Post-consent Checklist)

- A rating of 6 or below on question 2 or 3 of the Nonrestorative Sleep Scale,
indicating the subject experiences relatively non-refreshing sleep

- An average time to sleep onset of greater than 20 minutes as indicated on the
Post-consent Checklist

- Self-reported caffeine use in excess of 400 mg (e.g., approximately 8 caffeinated
sodas or 4 12-oz cups of coffee) per day on average (Post-consent Checklist; document
provides exclusionary limits for various caffeinated products).

- Score of lower than 31 or higher than 69 on the Morningness-Eveningness Questionnaire
(MEQ form)

- Score of 14 or above on the Beck Inventory Form (BDI form)

- Score of 41 or above on the Self-Evaluation Questionnaire

- History of cardiovascular disease (to include but not limited to arrhythmias, valvular
heart disease, congestive heart failure, history of sudden cardiac death or myocardial
infarction) (Medical History and Examination Form)

- History of neurologic disorder (to include, but not limited to epilepsy or another
seizure disorder, amnesia for any reason, hydrocephalus, MS, narcolepsy or other sleep
disorders) (Medical History and Examination form; sleep items on Post-Consent
Checklist)

- Underlying pulmonary disease requiring daily inhaler use (Medical History and
Examination form)

- Kidney disease or kidney abnormalities (Medical History and Examination form,
laboratory results)

- Liver disease or liver abnormalities (Medical History and Examination form, laboratory
results)

- Self-reported history of psychiatric disorder requiring hospitalization or psychiatric
product within the last 2 years or for more than 3 months at one time. (Medical
History and Examination form)

- Self-reported or suspected regular nicotine use or addiction, defined as more than 1
cigarette or equivalent per week, within the last 1 year (Medical History and
Examination form)

- Self-reported or suspected heavy alcohol use; minimum limit to define heavy alcohol
use is 14 drinks per week or as determined by the examining appropriately licensed
study investigator (Medical History and Examination form)

- Self-reported or suspected use of products or drugs that cannot be safely discontinued
during in-laboratory phases, to be determined on a case-by-case basis by the examining
appropriately licensed study investigator (Medical History and Examination form)

- Self-reported or suspected current use of other illicit drugs, to include but not
limited to benzodiazepines, amphetamines, cocaine, marijuana (Medical History and
Examination form)

- Positive urine pregnancy result

- Resting blood pressure above 140/90 or resting pulse > 110 (Medical History and
Examination form). Note that if a repeat measurement is within range then the
volunteer will not be excluded.

- BMI ≥ 30 (Obese Class I or greater) (Medical History and Examination form)

- Clinically significant values (as determined by the appropriately licensed study
investigator reviewing the study) for any hematology or chemistry parameter. The
appropriately licensed study investigator reviewing the laboratory values may opt to
repeat any clinically significant tests and include volunteers whose repeat test
values are not clinically significant.

- Positive urine nicotine/cotinine result during screening visit (NicCheck™ I test strip
results)

- Positive urine drug result during screening visit

- Any use of sleep aids during the 1 year prior to screening

- Inability to read and sign consent

- Lack of access to a quiet, dark environment conducive to sleep from 2100 until 0700
during a seven night period at the beginning of the study

- Participation in any ongoing clinical trials.

- The preceding exclusionary criteria are known to alter sleep (e.g., epilepsy; some
neurological disorders), substantially increase inter-subject variability, and/or the
disease or condition puts the subject outside the range of what is considered healthy.
The PI also maintains the prerogative to disqualify a volunteer if it is deemed that
the volunteer's participation would be unsafe for the volunteer or staff or would be
disruptive to study conduct or their inclusion could compromise data integrity.

- Volunteers meeting the Beck cut-off (a score of at least 14) and who carry health
insurance will be instructed to call their health insurance Mental Health / Substance
Abuse referral number.

- Volunteers meeting the first cut-off (score of at least 14 who are not insured will be
provided with a community mental health referral contact specific to their county of
residence.

- The review of the medical history with the volunteer and the physical examination
itself will be performed by an appropriately licensed study investigator. Results of
screening urine and blood tests will be reviewed by an appropriately licensed study
investigator. The Post-consent Checklist will be administered by a trained research
technician and reviewed by the study principal investigator or an appropriately
licensed study investigator. If an appropriately licensed study investigator deems it
medically advisable, the investigator will share abnormal results with the volunteer,
who will be referred to his/her personal physician for follow-up.

- A volunteer who has been cleared for participation may participate in a session if the
first day of the session is within 90 days of the screening date. If the first day of
the study session is 91 or more days since the volunteer has been screened, the
volunteer must re-screen to ensure there has not been a change in eligibility status.