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Semin Neurol 2005; 25(1): 9-18
DOI: 10.1055/s-2005-867070
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Functional Neuroimaging of Sleep

Eric A. Nofzinger1
  • 1Sleep Neuroimaging Research Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Publication History

Publication Date:
29 March 2005 (online)

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ABSTRACT

Sleep and sleep disorders have traditionally been viewed from a polysomnographic perspective. Although these methods provide information on the timing of various stages of sleep and wakefulness, they do not provide information regarding function in brain structures that have been implicated in the generation of sleep and that may be abnormal in different sleep disorders. Functional neuroimaging methods provide information regarding changes in brain function across the sleep-wake cycle that provides information for models of sleep dysregulation in a variety of sleep disorders. Early studies show reliable increases in function in limbic and anterior paralimbic cortex in rapid eye movement (REM) sleep and decreases in function in higher-order cortical regions in known thalamocortical networks during non-REM sleep. Although most of the early work in this area has been devoted to the study of normal sleep mechanisms, a collection of studies in diverse sleep disorders such as sleep deprivation, depression, insomnia, dyssomnias, narcolepsy, and sleep apnea suggest that functional neuroimaging methods have the potential to clarify the pathophysiology of sleep disorders and to guide treatment strategies.

KEYWORDS

Sleep - functional brain imaging

REFERENCES

  • 1 Meyer J S, Hayman L A, Amano T et al.. Mapping local blood flow of human brain by CT scanning during stable xenon inhalation.  Stroke. 1981;  12 426-436
    PubMedSearch in Google Scholar
  • 2 Buchsbaum M S, Gillin J C, Wu J et al.. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography.  Life Sci. 1989;  45 1349-1356
    CrossrefPubMedSearch in Google Scholar
  • 3 Buchsbaum M S, Hazlett E A, Wu J, Bunney W E. Positron emission tomography with deoxyglucose-F18 imaging of sleep.  Neuropsychopharmacology. 2001;  25 S50-S56
    CrossrefPubMedSearch in Google Scholar
  • 4 Maquet P, Dive D, Salmon E et al.. Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose method.  Brain Res. 1990;  513 136-143
    CrossrefPubMedSearch in Google Scholar
  • 5 Madsen P L, Holm S, Vorstrup S, Friberg L, Lassen N A, Wildschiodtz G. Human regional cerebral blood flow during rapid-eye-movement sleep.  J Cereb Blood Flow Metab. 1991;  11 502-507
    PubMedSearch in Google Scholar
  • 6 Maquet P, Peters J, Aerts J et al.. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming.  Nature. 1996;  383 163-166
    CrossrefPubMedSearch in Google Scholar
  • 7 Peigneux P, Laureys S, Fuchs S et al.. Generation of rapid eye movements during paradoxical sleep in humans.  Neuroimage. 2001;  14 701-708
    CrossrefPubMedSearch in Google Scholar
  • 8 Braun A R, Balkin T J, Wesenten N J et al.. Regional cerebral blood flow throughout the sleep-wake cycle: an H2(15)O PET study.  Brain. 1997;  120 1173-1197
    CrossrefPubMedSearch in Google Scholar
  • 9 Braun A R, Balkin T J, Wesensten N J et al.. Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep.  Science. 1998;  279 91-95
    CrossrefPubMedSearch in Google Scholar
  • 10 Nofzinger E A, Mintun M A, Wiseman M B, Kupfer D J, Moore R Y. Forebrain activation in REM sleep: an FDG PET study.  Brain Res. 1997;  770 192-201
    CrossrefPubMedSearch in Google Scholar
  • 11 Heiss W D, Pawlik G, Herholz K, Wagner R, Wienhard K. Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming.  Brain Res. 1985;  327 362-366
    CrossrefPubMedSearch in Google Scholar
  • 12 Maquet P, Dive D, Salmon E et al.. Cerebral glucose utilization during stage 2 sleep in man.  Brain Res. 1992;  571 149-153
    CrossrefPubMedSearch in Google Scholar
  • 13 Hofle N, Paus T, Reutens D et al.. Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans.  J Neurosci. 1997;  17 4800-4808
    PubMedSearch in Google Scholar
  • 14 Maquet P. Positron emission tomography studies of sleep and sleep disorders.  J Neurol. 1997;  244 S23-S28
    PubMedSearch in Google Scholar
  • 15 Maquet P, Phillips C. Functional brain imaging of human sleep.  J Sleep Res. 1998;  7 42-47
    CrossrefPubMedSearch in Google Scholar
  • 16 Maquet P. Brain mechanisms of sleep: contribution of neuroimaging techniques.  J Psychopharmacol. 1999;  13 S25-S28
    PubMedSearch in Google Scholar
  • 17 Maquet P. Functional neuroimaging of normal human sleep by positron emission tomography.  J Sleep Res. 2000;  9 207-231
    CrossrefPubMedSearch in Google Scholar
  • 18 Andersson J L, Onoe H, Hetta J et al.. Brain networks affected by synchronized sleep visualized by positron emission tomography.  J Cereb Blood Flow Metab. 1998;  18 701-715
    PubMedSearch in Google Scholar
  • 19 Nofzinger E A, Mintun M A, Price J et al.. A method for the assessment of the functional neuroanatomy of human sleep using FDG PET.  Brain Res Brain Res Protoc. 1998;  2 191-198
    CrossrefPubMedSearch in Google Scholar
  • 20 Nofzinger E A, Buysse D J, Miewald J M et al.. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.  Brain. 2002;  125 1105-1115
    CrossrefPubMedSearch in Google Scholar
  • 21 Kjaer T W, Law I, Wiltschiotz G, Paulson O B, Madsen P L. Regional cerebral blood flow during light sleep-a H (2) (15) O-PET study.  Sleep Res. 2002;  11 201-207
    PubMedSearch in Google Scholar
  • 22 Balkin T J, Braun A R, Wesensten N J et al.. The process of awakening: a PET study of regional brain activity patterns mediating the re-establishment of alertness and consciousness.  Brain. 2002;  125 2308-2319
    CrossrefPubMedSearch in Google Scholar
  • 23 Born A P, Law I, Lund T E et al.. Cortical deactivation induced by visual stimulation in human slow-wave sleep.  Neuroimage. 2002;  17 1325-1335
    CrossrefPubMedSearch in Google Scholar
  • 24 Wu J C, Gillin J C, Buchsbaum M S et al.. The effect of sleep deprivation on cerebral glucose metabolic rate in normal humans assessed with positron emission tomography.  Sleep. 1991;  14 155-162
    PubMedSearch in Google Scholar
  • 25 Thomas M, Sing H, Belenky G et al.. Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity.  J Sleep Res. 2000;  9 335-352
    CrossrefPubMedSearch in Google Scholar
  • 26 Clark C, Dupont R, Lehr P et al.. Is there a relationship between delta sleep at night and afternoon cerebral blood flow, assessed by HMPAO-SPECT in depressed patients and normal control subjects? Preliminary data.  Psychiatry Res. 1998;  84 89-99
    PubMedSearch in Google Scholar
  • 27 Maquet P, Laureys S, Peigneux P et al.. Experience-dependent changes in cerebral activation during human REM sleep.  Nat Neurosci. 2000;  3 831-836
    CrossrefPubMedSearch in Google Scholar
  • 28 Laureys S, Peigneux P, Phillips C et al.. Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep.  Neuroscience. 2001;  105 521-525
    CrossrefPubMedSearch in Google Scholar
  • 29 Paus T, Jech R, Thompson C J, Comeau R, Peters T, Evans A C. Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex.  J Neurosci. 1997;  17 3178-3184
    PubMedSearch in Google Scholar
  • 30 Paus T, Koski L, Caramanos Z, Westbury C. Regional differences in the effects of task difficulty and motor output on blood flow response in the human anterior cingulate cortex: a review of 107 PET activation studies.  Neuroreport. 1998;  9 R37-R47
    PubMedSearch in Google Scholar
  • 31 Fiset P, Paus T, Daloze T et al.. Brain mechanisms of propofol-induced loss of consciousness in humans: a positron emission tomographic study.  J Neurosci. 1999;  19 5506-5513
    PubMedSearch in Google Scholar
  • 32 Sudo Y, Suhara T, Honda Y et al.. Muscarinic cholinergic receptors in human narcolepsy: a PET study.  Neurology. 1998;  51 1297-1302
    PubMedSearch in Google Scholar
  • 33 Tashiro M, Mochizuki H, Iwabuchi K et al.. Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain.  Life Sci. 2002;  72 409-414
    CrossrefPubMedSearch in Google Scholar
  • 34 Okamura N, Yanai K, Higuchi M et al.. Functional neuroimaging of cognition impaired by a classical antihistamine, d-chlorpheniramine.  Br J Pharmacol. 2000;  129 115-123
    CrossrefPubMedSearch in Google Scholar
  • 35 Volkow N D, Wang G J, Hitzemann R et al.. Depression of thalamic metabolism by lorazepam is associated with sleepiness.  Neuropsychopharmacology. 1995;  12 123-132
    CrossrefPubMedSearch in Google Scholar
  • 36 Reinsel R A, Veselis R A, Dnistrian A M, Feshchenko V A, Beattie B J, Duff M R. Midazolam decreases cerebral blood flow in the left prefrontal cortex in a dose-dependent fashion.  Int J Neuropsychopharmacol. 2000;  3 117-127
    PubMedSearch in Google Scholar
  • 37 Gillin J C, Buchsbaum M S, Valladares-Neto D C et al.. Effects of zolpidem on local cerebral glucose metabolism during non-REM sleep in normal volunteers: a positron emission tomography study.  Neuropsychopharmacology. 1996;  15 302-313
    CrossrefPubMedSearch in Google Scholar
  • 38 Finelli L A, Landolt H P, Buck A et al.. Functional neuroanatomy of human sleep states after zolpidem and placebo: a H215O-PET study.  J Sleep Res. 2000;  9 161-173
    CrossrefPubMedSearch in Google Scholar
  • 39 Nofzinger E A, Berman S, Fasiczka A et al.. Effects of bupropion SR on anterior paralimbic function during waking and REM sleep in depression: preliminary findings using [18F]-FDG PET.  Psychiatry Res. 2001;  106 95-111
    PubMedSearch in Google Scholar
  • 40 Ficker J H, Feistel H, Moller C et al.. Changes in regional CNS perfusion in obstructive sleep apnea syndrome: initial SPECT studies with injected nocturnal 99mTc-HMPAO [in German].  Pneumologie. 1997;  51 926-930
    PubMedSearch in Google Scholar
  • 41 Hublin C, Launes J, Nikkinen P, Partinen M. Dopamine D2-receptors in human narcolepsy: a SPECT study with 123I-IBZM.  Acta Neurol Scand. 1994;  90 186-189
    PubMedSearch in Google Scholar
  • 42 Asenbaum S, Zeithofer J, Saletu B et al.. Technetium-99m-HMPAO SPECT imaging of cerebral blood flow during REM sleep in narcoleptics.  J Nucl Med. 1995;  36 1150-1155
    PubMedSearch in Google Scholar
  • 43 Nose I, Ookawa T, Tanaka J et al.. Decreased blood flow of the left thalamus during somnolent episodes in a case of recurrent hypersomnia.  Psychiatry Clin Neurosci. 2002;  56 277-278
    CrossrefPubMedSearch in Google Scholar
  • 44 Smith M T, Perlis M L, Chengazi V U et al.. Neuroimaging of NREM sleep in primary insomnia: a Tc-99-HMPAO single photon emission computed tomography study.  Sleep. 2002;  25 325-335
    PubMedSearch in Google Scholar
  • 45 Nofzinger E A, Price J C, Meltzer C C et al.. Towards a neurobiology of dysfunctional arousal in depression: the relationship between beta EEG power and regional cerebral glucose metabolism during NREM sleep.  Psychiatry Res. 2000;  98 71-91
    PubMedSearch in Google Scholar
  • 46 Nofzinger E A, Buysse D J, Germain A, Price J C, Miewald J M, Kupfer D J. Functional neuroimaging evidence for hyperarousal in insomnie.  Am J Psychiatry. 2004;  161 2126-2128
    Search in Google Scholar
  • 47 Perani D, Cortelli P, Lucignani G et al.. [18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions.  Neurology. 1993;  43 2565-2569
    PubMedSearch in Google Scholar
  • 48 Kloppel S, Pirker W, Brucke T, Kovacs G G, Almer G. Beta-CIT SPECT demonstrates reduced availability of serotonin transporters in patients with Fatal Familial Insomnia.  J Neural Transm. 2002;  109 1105-1110
    CrossrefPubMedSearch in Google Scholar
  • 49 Nofzinger E A, Nichols T E, Meltzer C C et al.. Changes in forebrain function from waking to REM sleep in depression: preliminary analyses of [18F] FDG PET studies.  Psychiatry Res. 1999;  91 59-78
    PubMedSearch in Google Scholar
  • 50 Nofzinger E A, Buysse D J, Germain A et al.. Increased activation of anterior paralimbic and executive cortex from waking to REM sleep in depression.  Arch Gen Psychiatry. 2004;  61 695-702
    PubMedSearch in Google Scholar
  • 51 Ho A P, Gillin J C, Buchsbaum M S, Wu J C, Abel L, Bunney W E. Brain glucose metabolism during non-rapid eye movement sleep in major depression: a positron emission tomography study.  Arch Gen Psychiatry. 1996;  53 645-652
    PubMedSearch in Google Scholar
  • 52 Ebert D, Feistel H, Barocka A. Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: a study with Tc-99m-HMPAO SPECT.  Psychiatry Res. 1991;  40 247-251
    CrossrefPubMedSearch in Google Scholar
  • 53 Wu J C, Gillin J C, Buchsbaum M S, Hershey T, Johnson J C, Bunney W E. Effect of sleep deprivation on brain metabolism of depressed patients.  Am J Psychiatry. 1992;  149 538-543
    PubMedSearch in Google Scholar
  • 54 Volk S A, Kaendler S H, Weber R et al.. Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photo emission computerized tomography.  Acta Psychiatr Scand. 1992;  86 478-483
    PubMedSearch in Google Scholar
  • 55 Ebert D, Feistel H, Kaschka W, Barocka A, Pirner A. Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation: preliminary results.  Biol Psychiatry. 1994;  35 880-885
    CrossrefPubMedSearch in Google Scholar
  • 56 Ebert D, Feistel H, Barocka A, Kaschka W. Increased limbic blood flow and total sleep deprivation in major depression with melancholia.  Psychiatry Res. 1994;  55 101-109
    CrossrefPubMedSearch in Google Scholar
  • 57 Volk S A, Kaendler S H, Hertel A et al.. Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow?.  Psychiatry Res. 1997;  75 67-74
    PubMedSearch in Google Scholar
  • 58 Smith G S, Reynolds C F, Pollock B et al.. Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression.  Am J Psychiatry. 1999;  156 683-689
    PubMedSearch in Google Scholar
  • 59 Smith G S, Reynolds C F, Houck P R et al.. Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression.  Am J Geriatr Psychiatry. 2002;  10 561-567
    PubMedSearch in Google Scholar
  • 60 Wu J, Buchsbaum M S, Gillin J C et al.. Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.  Am J Psychiatry. 1999;  156 1149-1158
    PubMedSearch in Google Scholar
  • 61 Weiler M A, Buchsbaum M S, Gillin J C, Tafalla R, Bunney W E. Explorations in the relationship of dream sleep to schizophrenia using positron emission tomography.  Neuropsychobiology. 1990;  23 109-118
    PubMedSearch in Google Scholar
  • 62 Staedt J, Stoppe G, Kogler A et al.. Dopamine D2 receptor alteration in patients with periodic movements in sleep (nocturnal myoclonus).  J Neural Transm Gen Sect. 1993;  93 71-74
    CrossrefPubMedSearch in Google Scholar
  • 63 Staedt J, Stoppe G, Kogler A et al.. Nocturnal myoclonus syndrome (periodic movements in sleep) related to central dopamine D2-receptor alteration.  Eur Arch Psychiatry Clin Neurosci. 1995;  245 8-10
    PubMedSearch in Google Scholar
  • 64 Staedt J, Stoppe G, Kogler A et al.. Single photon emission tomography (SPET) imaging of dopamine D2 receptors in the course of dopamine replacement therapy in patients with nocturnal myoclonus syndrome (NMS).  J Neural Transm Gen Sect. 1995;  99 187-193
    CrossrefPubMedSearch in Google Scholar
  • 65 Michaud M, Soucy J P, Chabli A, Lavinge G, Montplaisir J. SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep.  J Neurol. 2002;  249 164-170
    PubMedSearch in Google Scholar
  • 66 Bassetti C, Vella S, Donati F, Wielepp P, Weder B. SPECT during sleepwalking.  Lancet. 2000;  356 484-485
    Search in Google Scholar
  • 67 Shirakawa S, Takeuchi N, Uchimura N et al.. Study of image findings in rapid eye movement sleep behavioural disorder.  Psychiatry Clin Neurosci. 2002;  56 291-292
    CrossrefPubMedSearch in Google Scholar
  • 68 Eisensehr I, Linke R, Noachtar S, Schwarz J, Gildehaus F J, Tatsch K. Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson's disease and controls.  Brain. 2000;  123 1155-1160
    CrossrefPubMedSearch in Google Scholar
  • 69 Albin R L, Koeppe R A, Chervin R D et al.. Decreased striatal dopaminergic innervation in REM sleep behavior disorder.  Neurology. 2000;  55 1410-1412
    CrossrefPubMedSearch in Google Scholar

Eric A NofzingerM.D. 

Sleep Neuroimaging Research Program

University of Pittsburgh School of Medicine

3811 O'Hara Street, Pittsburgh, PA 15213