Medical Imaging for Understanding Sleep Regulation SESAPS October 2011
Research Team Seong K. Mun Linda Larson-Prior Washington Univ. Zang-Hee Cho Gachon University AlpayÖzcan Kenneth H. Wong
Fundamentals of Sleep • A reversible state of disengagement from the conscious world. • Characterized by specific physiological and neurological changes. • A fundamental rhythm of the brain affected by internal clocks and external signals. • Essential to human life (applies to other animals as well).
Hypnogram a.k.a. Sleep Record http://science.education.nih.gov/supplements/nih3/sleep/guide/info-sleep.htm
1. Sleep-related disorders • Insomnia (~30-35% of USA population) • REM Behavior Disorder (RBD) • Periodic Limb Movement Disorders • Restless Leg Syndrome • Narcolepsy • Obstructive Sleep Apnea • Links to Parkinson’s Disorder and other neurodegenerative diseases
Clinical RBD Example “One vivid example involved a man who held his wife's head in a headlock while moving his legs as if running while both were attempting to sleep in bed, then exclaimed, “I'm gonna make that touchdown!” and then attempted to forcefully throw her head down toward the foot of the bed. When awakened, he recalled a dream in which he was running for a touchdown, and he spiked the “football” in the end zone. His wife knew precisely what he had been dreaming about.” Boeve BF, Silber MH, Ferman TJ, et al. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology 1998;51:363–370.
2. Drug Development Opportunities • Significant world market (~3.4B, 2.5B US) • Some major drugs coming off patent (Ambien in 2007, Lunesta in 2014) • Drugs are more effective and targeted now, but side effects still problematic • Sleep-promoting drugs warn that you must have a full night (8+ hrs) available for sleep, but this is often ignored. • Long term consequences have not been studied.
3. Why do we sleep so much? • "If sleep doesn't serve an absolutely vital function, it is the biggest mistake evolution ever made” • Alan Rechtschaffen, PhD ? ? bestof.longislandpress.com gurumia.com
Principal Tools • Electroencephalography (EEG) • Brain electrical activity; defines sleep state • Magnetic Resonance Imaging (MRI) • Brain Structure • Positron Emission Tomography (PET) • Brain Biochemistry • Functional MRI (fMRI) • Brain “Activation”
“10-20” electrode locations from Wikimedia Commons EEG High density EEG sensor net from Electrical Geodesics, Inc. MindflexDuelTM
MRI contrast based on: • Proton density • Tissue Composition • Pulse Sequence
Courtesy of Z.H. Cho, Gachon University, South Korea 7.0 T 1.5 T High resolution MRI opens new windows for scientific discovery
1.5 T Image 7T Image
fMRI is based on changes in cerebral blood flow Blood Oxygen Level Dependence Oxyhemoglobin (diamagnetic) = BOLD Signal Deoxyhemoglobin (paramagnetic)
fMRI examples Visual Signal Motor Activity
Functional Connectivity Larson-Prior et al, 2011
Summary • Sleep is a compelling scientific and medical area of inquiry. • Numerous technologies (designed and improved using physics) can help us to understand more about neuroscience.
Thanks to… Neuroscience Research Institute, Gachon University, South Korea U.S. Army Cooperative Agreement W81XWH-11-2-0187 Michael P. Brazaitis, MD, U.S. Army Grants Officer’s Representative (GOR)