Protocol Number: 09-M-0123

Title:

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

Number:

09-M-0123

Summary:

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 15 subjects under the following three conditions: 1) awake and sleep-sated, 2) awake and sleep-deprived, and 3) during SWS after sleep-deprivation. 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 15 subjects each: 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. 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.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

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:

-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, reported difficulty sleeping away from home or on their backs).

-Consistent with our exclusion criteria (1)-(6), subjects are not expected to be on (chronic) therapy with prescription medications, however, 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.

-We will exclude subjects who have used illicit drugs (marijuana, cocaine, heroin, etc ) within the immediate 2 wks preceding the study. Because the number of medications which may possibly interfere with sleep architecture is large, it is difficult to provide a comprehensive list and most cases will be evaluated on an individual basis.

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

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

Special Instructions:

Currently Not Provided

Keywords:

Sleep

14C-Leucine

Cerebral Protein Synthesis

Memory

Positron Emission Tomography (PET)

Recruitment Keyword(s):

None

Condition(s):

Memory Disorders

Brain Mapping

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Mental Health

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Armitage R. Microarchitectural findings in sleep EEG in depression: diagnostic implications. Biol Psychiatry. 1995 Jan 15;37(2):72-84.

Bishu S, Schmidt KC, Burlin T, Channing M, Conant S, Huang T, Liu ZH, Qin M, Unterman A, Xia Z, Zametkin A, Herscovitch P, Smith CB. Regional rates of cerebral protein synthesis measured with L- 1-11C]leucine and PET in conscious, young adult men: normal values, variability, and reproducibility. J Cereb Blood Flow Metab. 2008 Aug;28(8):1502-13. Epub 2008 May 21.

Boyle PJ, Scott JC, Krentz AJ, Nagy RJ, Comstock E, Hoffman C. Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans. J Clin Invest. 1994 Feb;9 (2):529-35.

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