Acute and chronic alcohol consumption causes sleep disturbances, which may never resolve and may be a key factor in alcoholism relapse. Alcohol-related sleep deficits also become more pronounced with advancing age. The most consistently reported finding of altered sleep in alcoholics is a reduction in spontaneously occurring slow wave sleep (SWS), defined by the presence of delta EEG activity. Further, alcoholics with reduced baseline SWS have an increased likelihood of relapse. External stimulation during sleep can elicit K-complexes, which when averaged produce a large N550 component thought to have the same generator as SWS delta activity. Given the potential value of sleep markers in predicting relapse, it would be advantageous to employ a probe of the sleeping nervous system that can be under experimenter control rather than one that relies on the traditional observation of spontaneous sleep physiological indices. We have demonstrated that sleep-evoked N550 component amplitudes are smaller and K-complexes are produced on a smaller number of trials in elderly than young controls. Our preliminary study indicates that alcoholics have even smaller N550 than would be expected for their age. A candidate generator of the K-complex and N550 is frontal cortical gray matter, which is especially reduced in older alcoholics. Sex differences in brain structure and electrophysiological indices of sleep also occur in alcoholism and aging, and objective study of them may further contribute to our understanding of relevant mechanisms of alcoholism-related sleep disturbance. We propose to test the following hypotheses: Hypothesis 1: Recently detoxified, chronic alcoholics will have smaller N550 amplitudes, lower evoked K-complex proportions, lower SWS levels and delta EEG power compared to sex- and age-matched controls. Hypothesis 2: Low evoked K-complex production rates, small N550 amplitude, low SWS levels and delta EEG power will be associated with small prefrontal gray matter volume. Hypothesis 3: Alcoholic men will have greater sleep abnormalities than alcoholic women. Hypothesis 4: Small amplitude, production rate and power of sleep electrophysiological variables in recently detoxified alcoholics will predict early relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA014211-05
Application #
7234832
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Matochik, John A
Project Start
2003-06-01
Project End
2009-11-30
Budget Start
2007-06-01
Budget End
2009-11-30
Support Year
5
Fiscal Year
2007
Total Cost
$557,721
Indirect Cost
Name
Sri International
Department
Type
DUNS #
009232752
City
Menlo Park
State
CA
Country
United States
Zip Code
94025
Franzen, Peter L; Woodward, Steven H; Bootzin, Richard R et al. (2012) K-complexes are not preferentially evoked to combat sounds in combat-exposed Vietnam veterans with and without post-traumatic stress disorder. Int J Psychophysiol 83:393-8
Padilla, Mayra L; Colrain, Ian M; Sullivan, Edith V et al. (2011) Electrophysiological evidence of enhanced performance monitoring in recently abstinent alcoholic men. Psychopharmacology (Berl) 213:81-91
Colrain, Ian M; Sullivan, Edith V; Ford, Judith M et al. (2011) Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects. Psychopharmacology (Berl) 213:669-79
Colrain, Ian M; Sullivan, Edith V; Rohlfing, Torsten et al. (2011) Independent contributions of cortical gray matter, aging, sex and alcoholism to K-complex amplitude evoked during sleep. Sleep 34:787-95
Colrain, Ian M; Crowley, Kate E; Nicholas, Christian L et al. (2010) Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan. Neurobiol Aging 31:874-83
Colrain, Ian M; Turlington, Sharon; Baker, Fiona C (2009) Impact of alcoholism on sleep architecture and EEG power spectra in men and women. Sleep 32:1341-52
Colrain, Ian M; Crowley, Kate E; Nicholas, Christian L et al. (2009) The impact of alcoholism on sleep evoked Delta frequency responses. Biol Psychiatry 66:177-84
Colrain, Ian M; Campbell, Kenneth B (2007) The use of evoked potentials in sleep research. Sleep Med Rev 11:277-93
Crowley, Kate; Sullivan, Edith V; Adalsteinsson, Elfar et al. (2005) Differentiating pathologic delta from healthy physiologic delta in patients with Alzheimer disease. Sleep 28:865-70