title: Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia.
abstract: Alpha-delta sleep is the abnormal intrusion of alpha activity (8- to 13-Hz oscillations) into the delta activity (1- to 4-Hz oscillations) that defines slow-wave sleep. Alpha-delta sleep is especially prevalent in fibromyalgia patients, and there is evidence suggesting that the irregularities in the sleep of these patients may cause the muscle and tissue pain that characterizes the disorder. We constructed a biophysically realistic mathematical model of alpha-delta sleep. Imaging studies in fibromyalgia patients suggesting altered levels of activity in the thalamus motivated a thalamic model as the source of alpha activity. Since sodium oxybate helps to alleviate the symptoms of fibromyalgia and reduces the amount of alpha-delta sleep in fibromyalgia patients, we examined how changes in the molecular targets of sodium oxybate affected alpha-delta activity in our circuit. Our model shows how alterations in GABAB currents and two thalamic currents, Ih (a hyperpolarization-activated current) and a potassium leak current, transform a circuit that normally produces delta oscillations into one that produces alpha-delta activity. Our findings suggest that drugs that reduce Ih conductances and/or increase potassium conductances, without necessarily increasing GABAB conductances, might be sufficient to restore delta sleep. Furthermore, they suggest that delta sleep might be restored by drugs that preferentially target these currents in the thalamus; such drugs might have fewer side effects than drugs that act systemically.
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, Massachusetts; svijayan9@gmail.com.
authors.forename: Sujith
authors.initials: S
authors.lastname: Vijayan
authors.affiliation: Harvard Medical School, Boston, Massachusetts; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts; and.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Klerman
authors.affiliation: Harvard Medical School, Boston, Massachusetts; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, Massachusetts;
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Kopell
mesh_terms: D000200:Action Potentials; D000513:Alpha Rhythm; D003700:Delta Rhythm; D005260:Female; D005356:Fibromyalgia / Q000503:physiopathology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D011188:Potassium / Q000378:metabolism; D012894:Sleep Stages; D012978:Sodium Oxybate / Q000494:pharmacology; D013788:Thalamus / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate; D011188:Potassium
keywords: fibromyalgia; modeling; oscillations; sleep; thalamus