Regional Rates of Cerebral Protein Synthesis: Effects of Sleep and Memory Consolidation

The importance of sleep is widely appreciated, but the actual function of sleep remains
unknown. Sleep occurs in much of the animal kingdom, in all mammals and birds and even in
some lower forms. Sleep deprivation impairs brain function, and in rats, total sleep
deprivation for 2-3 weeks results in death. One hypothesized role of sleep is for restoration
and reorganization of neuronal circuits. There is some indirect evidence that during sleep,
when cerebral energy requirements are reduced, cell resources are diverted to protein
synthesis for the restoration of structure and function. The objectives of the present study
are: 1) to further define the relationship between regional rates of cerebral protein
synthesis (rCPS) and sleep and 2) to ascertain whether sleep-dependent visual learning during
slow wave sleep (SWS) results in increases in rCPS in the primary visual cortex. We propose
to use a novel positron emission tomography (PET)-based technique to quantify regional rates
of cerebral protein synthesis (rCPS) in young, adult, healthy volunteers. The first objective
will be addressed in Part I in which we will study each subject under the following three
conditions: 1) awake and sleep-sated, 2) awake and sleep-deprived, and 3) during SWS after
sleep-deprivation. Our aim is to complete fully successful studies in 15 subjects. The second
objective will be addressed in Part II in which we will assess the relationship between rCPS
and sleep-dependent visual learning on a retinotopically specific task. Each participant will
serve as his own control by comparing the trained primary visual cortex hemisphere with the
untrained hemisphere to which comparable visual information is presented but without
learning. In Part II we will study two groups of subjects: 1) One group will be studied
during SWS following the training session; 2) The second group will be studied at the same
interval following the training session but awake. Subjects will be monitored with
polysomnography to identify the stages of sleep. Our aim in part II is to complete fully
successful studies in 15 subjects in each of the two groups. We anticipate that the results
of Part I will identify changes in rCPS in specific brain regions which are characteristic of
SWS and results of Part II may reveal relationships between rCPS and memory consolidation
during SWS.

- INCLUSION CRITERIA:

Healthy male and female volunteers who have no present or past diagnosis of neurologic,
medical or psychiatric conditions which may confound either learning trails, normal sleep
patterns or the ability to undergo sleep deprivation.

Healthy male and female subjects, 18-28 years of age, who do not meet any exclusion
criteria, with self-reported normal sleep patterns (i.e., 6-9 h per night) and no major
sleep disruptions during the four weeks prior to evaluation will be considered for
inclusion in the study.

EXCLUSION CRITERIA INCLUDE A HISTORY OF, OR CURRENT:

1. chronic medical condition which is a contraindication for PET or MRI scanning,

2. past or present diagnosis of psychiatric conditions (DSM-IV criteria) (many conditions
(e.g. depression), may confound performance on learning trails or be associated with
baseline sleep abnormalities),

3. chronic/degenerative/acquired neurologic disorder, (4) family history of genetically
transmissible neurologic disorder,

(5) sleep disorders or medical conditions associated with chronically disordered sleep
which may confound performance on learning trails or interfere with the sleep requirements
of this study,

(6) visual impairments which may confound performance on learning trails,

(7) claustrophobic subjects,

(8) subjects who meet the above inclusion criteria, but are unable to cooperate with the
requirements of the study (e.g. refusal to wear actigraphs or maintain 10 hours time in
bed, reported difficulty sleeping away from home or on their backs).

(9) Subjects with chronic indicated or non-indicated use of any medications which interfere
with sleep architecture and/or learning trails will be excluded. Generally, we will
prohibit the use of medications/agents (e.g. anti-histamines, benadryl, melatonin,
cigarettes, chocolate, coffee, tea, caffeine drinks etc.), which have significant CNS
penetration, are alerting, and/or disrupt physiologic sleep-wake cycles or sleep
architecture, for the 72 hrs immediately preceding presentation for the study. To
acclimatize subjects, we will encourage patients to discontinue or minimize the use of
these agents/medications (e.g. less than or equal to 1 cup of coffee/day) at the time of
initial screening (at the same time as actigraphy application, approximately 2 wks prior to
the study).

Similarly, we ask subjects to minimize alcohol use for the 2 wks prior to the study and
will discontinue alcohol use for the 72 hrs immediately preceding the study.

(10) Subjects who have used illicit drugs (marijuana, cocaine, heroin, etc.) within the
immediate 2 wks preceding the study.

(11) Female subjects will be excluded if either clinical history is suspicious for, or
laboratory evaluation is consistent with pregnancy.

(12) Subjects unwilling to undergo HIV testing, unless enrolling in Part IIa of the study.

(13) Subjects who test HIV positive.

(14) Patients with para- and/or ferro-magnetic prosthesis/implants/fragments in their body
will be excluded from the study.