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The sleep in our eyes
Clinical Neurophysiology 122 (2011) 1485–1486
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
The sleep in our eyes See Article, pages 1556–1561
The eyes represent the key structure at the basis of two functions that are fundamental for behavioral adaptation and survival. Indeed, they are the entry point of the visual-forming system, and have also the role of light-detectors for the photoentrainment of circadian rhythms. Both these functions rely on ‘photoreceptors’ with inhomogeneous distribution across the retina: the higher density of cones within the fovea centralis accounts for the central vision (Jacobs, 1993), on the other hand the melanopsin-containing retinal ganglion cells (the ‘circadian photoreceptors’) are more abundant and better preserved from ageing processes in the parafoveal sector (La Morgia et al., 2010). For these reasons it becomes evident that, in order to point the foveae toward both visual stimuli and light, the eye movements are of extreme importance for primates like humans. The neural machinery of both saccadic and slow pursuit eye movements, notwithstanding its high complexity, is relatively well understood, together with its involvement in visuo-motor tasks and higher functions (Lisberger, 2010; Yang and Lisberger, 2010). This knowledge is focused on voluntary and automatic ocular motion linked to vision, whereas the function of eye movements occurring while eyes are closed is still scarcely elucidated. The equivalent of saccades performed with eye closed are represented by the rapid eye movements occurring during sleep (REMs), thought to be related to dream imagery (Dement and Wolpert, 1958; Leclair-Visonneau et al., 2010); while slow eye movements (SEMs), with features very similar to smooth pursuit during wakefulness, have been observed to occur during relaxed wakefulness, drowsiness and sleep, but their functions are entirely unexplored. Polygraphic studies have revealed that SEMs are mostly recorded during relaxed wakefulness preceding the onset of sleep and stage 1 of non-REM sleep, but they are abundant also in REM sleep (Jacobs et al., 1971; Hansotia et al., 1990). Interestingly, SEMs appear long before birth, as observed by real-time ultrasonography in human fetuses (Prechtl and Nijhuis, 1983; Horimoto et al., 1990), both during behaviorally defined non-REM and REM sleep periods (Koyanagi, 1991), suggesting that they constitute an hardwired inborn behavior evolved in concert with primate sleep. However, until the study reported in this issue (Pizza et al., 2011) quantitative studies have been performed only at the wake-sleep transition, documenting their potential role in distinguishing drowsiness, or NREM sleep stage 1, from slow-wave sleep (Hori, 1982; De Gennaro et al., 2000, 2005). Evaluation of this phenomenon during the ‘sleep onset’ period acquires additional inter-
est when computer-aided techniques allow a real-time SEM detection that could be used in preventing sleepiness-related accidents (Torsvall and Akerstedt, 1988; Shin et al., 2010). In this issue, Pizza and colleagues, by means of a validated computer-based detector of SEMs (Magosso et al., 2007), provide for the first time a systematic evaluation of SEMs amount in the different sleep stages during nocturnal sleep, remarkably also searching for possible correlations between SEMs occurrence and other fundamental variables such as arousals and slow-wave activity (SWA). They found, consistently in each subject, that SEMs were differently represented in the different sleep stages, being mostly represented during the wake-time after sleep onset, NREM sleep stage 1 and REM sleep. Further partitioning nocturnal sleep in subsequent sleep cycles, a significant progressive reduction in the number of SEMs across the entire nocturnal sleep is found only for stage 2, in a fashion that parallels the homeostatic sleep pressure or Process S (Borbély and Achermann, 2005). Sleep homeostasis probably reflects local synaptic modifications, namely downscaling of synaptic strength, underlying the restorative function of sleep (Tononi and Cirelli, 2006). During sleep membrane potentials of cortical neurons alternate between a depolarized ‘upstate’ and a hyperpolarized ‘downstate’ (Steriade et al., 1993). When this phenomenon is synchronized in large regions of the cortex these oscillations become detectable in the surface EEG as slow waves (Vyazovskiy et al., 2009), so that homeostatic behavior of SWA can be mostly observed in slow sleep stages. On the contrary SEMs could be an easily detectable physiological parameter to study Process S in humans during relaxed wakefulness and light NREM sleep. Furthermore, the stable SEMs amount found across subsequent REM-sleep episodes, either considering phasic or tonic REM sleep is in line with evidences that, although REM sleep deprivation produces an enhancement in the attempts to enter REM sleep and an increased amount of time spent in REM sleep during recovery, REM and NREM sleep are regulated by at least partially distinct homeostatic mechanisms (Wurts and Edgar, 2000). Additionally, the dissimilar behavior during REM sleep of SEMs and REMs, with the latter significantly increasing across cycles, supports the hypothesis that these oculomotor events have different generators and reflect distinct phenomena during sleep. It has been demonstrated that cortical areas implicated in saccadic and pursuit eye movements are not involved or at least differently activated during SEMs in monkeys (Bon and Lucchetti, 1997), while studies on cortical control of SEMs in humans are lacking.
1388-2457/$36.00 Ó 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2011.01.009
1486
Editorial / Clinical Neurophysiology 122 (2011) 1485–1486
Investigations using intracerebral EEG recordings – as used in studies on saccadic movements (Lachaux et al., 2006) – or EOG-fMRI co-registrations – since now applied to eye blinking (Yoon et al., 2005) – would allow us a better understanding of the cortical and subcortical network underlying the generation of slow eye movements. In conclusion, the work of professor Montagna’s group (Pizza et al., 2011) is of great value because it provides normative data in adult healthy subjects regarding the amount of SEMs throughout the different phases of the entire overnight sleep. This, together with the use of an operator-independent computation, will allow further investigations on human disorders, particularly those accounted for an abnormal homeostatic process. Following the umpteenth intriguing line of research conceived by Pasquale Montagna will be one active way to commemorate him and help us to fill the empty space left in the scientific field by his premature demise. References Bon L, Lucchetti C. Activity of neurons related to eye movements during drowsiness in the frontal cortex of the macaca monkey. Sleep 1997;20:501–4. Borbély AA, Achermann P. Sleep homeostasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia: Elsevier Saunders; 2005. p. 405–17. De Gennaro L, Devoto A, Lucidi F, Violani C. Oculomotor changes are associated to daytime sleepiness in the multiple sleep latency test. J Sleep Res 2005;14: 107–12. De Gennaro L, Ferrara M, Ferlazzo F, Bertini M. Slow eye movements and EEG power spectra during wake-sleep transition. Clin Neurophysiol 2000;111: 2107–15. Dement W, Wolpert E. The relation of eye movements, body motility, and external stimuli to dream content. J Exp Psychol 1958;55:543–53. Hansotia P, Broste S, So E, Ruggles K, Wall R, Friske M. Eye movement patterns in REM sleep. Electroencephalogr Clin Neurophysiol 1990;76:388–99. Hori T. Electrodermal and electro-oculographic activity in hypnagogic state. Psychophysiology 1982;19:668–72. Horimoto N, Koyanagi T, Satoh S, Yoshizato T, Nakano H. Fetal eye movement assessed with real-time ultrasonography: are there rapid and slow eye movements? Am J Obstet Gynecol 1990;163:1480–4. Jacobs GH. The distribution and nature of colour vision among the mammals. Biol Rev 1993;68:413–71. Jacobs L, Feldman M, Bender MB. Eye movements during sleep: I. The pattem in the normal human. Arch Neurol 1971;25:151–9. Koyanagi T. Ontogeny of behavioral patterns in relation to the concurrent development of central nervous system function, focusing on REM sleep, NREM sleep and waking states in the human fetus Nippon. Sanka Fujinka Gakkai Zasshi 1991;43:843–52. La Morgia C, Ross-Cisneros FN, Sadun A, Hannibal J, Munarini A, Mantovani V, et al. Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies. Brain 2010;133:2426–38.
Lachaux JP, Hoffmann D, Minotti L, Berthoz A, Kahane P. Intracerebral dynamics of saccade generation in the human frontal eye field and supplementary eye field. Neuroimage 2006;30:1302–12. Leclair-Visonneau L, Oudiette D, Gaymard B, Leu-Semenescu S, Arnulf I. Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model. Brain 2010;133: 1737–46. Lisberger SG. Visual guidance of smooth pursuit eye movements: sensation, action, and what happens in between. Neuron 2010;66:477–91. Magosso E, Ursino M, Provini F, Montagna P. Wavelet analysis of electroencephalographic and electro-oculographic changes during the sleep onset period. Conf Proc IEEE Eng Med Biol Soc 2007:4006–10. Pizza F, Fabbri M, Magosso E, Ursino M, Provini F, Ferri R, et al. Slow Eye Movements distribution during nocturnal sleep. Clin Neurophysiol 2011;122: 1555–60. Prechtl HF, Nijhuis JG. Eye movements in the human fetus and newborn. Behav Brain Res 1983;10:119–24. Shin D, Sakai H, Uchiyama Y. Slow eye movement detection can prevent sleeprelated accidents effectively in a simulated driving task. J Sleep Res 2010, in press. doi:10.1111/j.1365-2869.2010.00891.x. [Epub ahead of print]. Steriade M, McCormick DA, Sejnowski TJ. Thalamocortical oscillations in the sleeping and aroused brain. Science 1993;262:679–85. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Med Rev 2006;10:49–62. Torsvall L, Akerstedt T. Extreme sleepiness: quantification of EOG and spectral EEG parameters. Int J Neurosci 1988;38:435–41. Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, et al. Cortical firing and sleep homeostasis. Neuron 2009;63:865–78. Wurts SW, Edgar DM. Circadian and homeostatic control of rapid eye movement (REM) sleep: promotion of REM tendency by the suprachiasmatic nucleus. J Neurosci 2000;20:4300–10. Yang Y, Lisberger SG. Learning on multiple timescales in smooth pursuit eye movements. J Neurophysiol 2010;104:2850–62. Yoon HW, Chung JY, Song MS, Park H. Neural correlates of eye blinking; improved by simultaneous fMRI and EOG measurement. Neurosci Lett 2005;381:26–30.
Gaetano Cantalupo Child Neuropsychiatry Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy Tel.: +39 0521 702205; fax: +39 0521 704708. E-mail address: [email protected] Carlo Alberto Tassinari Neuroscience Department, University of Parma, Parma, Italy Address: Neuroscience Department, University of Parma, Via Volturno 39, 43125 Parma, Italy. Tel.: +39 0521 903881, fax: +39 0521 903900. E-mail addresses: [email protected] Available online 12 February 2011
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
The sleep in our eyes See Article, pages 1556–1561
The eyes represent the key structure at the basis of two functions that are fundamental for behavioral adaptation and survival. Indeed, they are the entry point of the visual-forming system, and have also the role of light-detectors for the photoentrainment of circadian rhythms. Both these functions rely on ‘photoreceptors’ with inhomogeneous distribution across the retina: the higher density of cones within the fovea centralis accounts for the central vision (Jacobs, 1993), on the other hand the melanopsin-containing retinal ganglion cells (the ‘circadian photoreceptors’) are more abundant and better preserved from ageing processes in the parafoveal sector (La Morgia et al., 2010). For these reasons it becomes evident that, in order to point the foveae toward both visual stimuli and light, the eye movements are of extreme importance for primates like humans. The neural machinery of both saccadic and slow pursuit eye movements, notwithstanding its high complexity, is relatively well understood, together with its involvement in visuo-motor tasks and higher functions (Lisberger, 2010; Yang and Lisberger, 2010). This knowledge is focused on voluntary and automatic ocular motion linked to vision, whereas the function of eye movements occurring while eyes are closed is still scarcely elucidated. The equivalent of saccades performed with eye closed are represented by the rapid eye movements occurring during sleep (REMs), thought to be related to dream imagery (Dement and Wolpert, 1958; Leclair-Visonneau et al., 2010); while slow eye movements (SEMs), with features very similar to smooth pursuit during wakefulness, have been observed to occur during relaxed wakefulness, drowsiness and sleep, but their functions are entirely unexplored. Polygraphic studies have revealed that SEMs are mostly recorded during relaxed wakefulness preceding the onset of sleep and stage 1 of non-REM sleep, but they are abundant also in REM sleep (Jacobs et al., 1971; Hansotia et al., 1990). Interestingly, SEMs appear long before birth, as observed by real-time ultrasonography in human fetuses (Prechtl and Nijhuis, 1983; Horimoto et al., 1990), both during behaviorally defined non-REM and REM sleep periods (Koyanagi, 1991), suggesting that they constitute an hardwired inborn behavior evolved in concert with primate sleep. However, until the study reported in this issue (Pizza et al., 2011) quantitative studies have been performed only at the wake-sleep transition, documenting their potential role in distinguishing drowsiness, or NREM sleep stage 1, from slow-wave sleep (Hori, 1982; De Gennaro et al., 2000, 2005). Evaluation of this phenomenon during the ‘sleep onset’ period acquires additional inter-
est when computer-aided techniques allow a real-time SEM detection that could be used in preventing sleepiness-related accidents (Torsvall and Akerstedt, 1988; Shin et al., 2010). In this issue, Pizza and colleagues, by means of a validated computer-based detector of SEMs (Magosso et al., 2007), provide for the first time a systematic evaluation of SEMs amount in the different sleep stages during nocturnal sleep, remarkably also searching for possible correlations between SEMs occurrence and other fundamental variables such as arousals and slow-wave activity (SWA). They found, consistently in each subject, that SEMs were differently represented in the different sleep stages, being mostly represented during the wake-time after sleep onset, NREM sleep stage 1 and REM sleep. Further partitioning nocturnal sleep in subsequent sleep cycles, a significant progressive reduction in the number of SEMs across the entire nocturnal sleep is found only for stage 2, in a fashion that parallels the homeostatic sleep pressure or Process S (Borbély and Achermann, 2005). Sleep homeostasis probably reflects local synaptic modifications, namely downscaling of synaptic strength, underlying the restorative function of sleep (Tononi and Cirelli, 2006). During sleep membrane potentials of cortical neurons alternate between a depolarized ‘upstate’ and a hyperpolarized ‘downstate’ (Steriade et al., 1993). When this phenomenon is synchronized in large regions of the cortex these oscillations become detectable in the surface EEG as slow waves (Vyazovskiy et al., 2009), so that homeostatic behavior of SWA can be mostly observed in slow sleep stages. On the contrary SEMs could be an easily detectable physiological parameter to study Process S in humans during relaxed wakefulness and light NREM sleep. Furthermore, the stable SEMs amount found across subsequent REM-sleep episodes, either considering phasic or tonic REM sleep is in line with evidences that, although REM sleep deprivation produces an enhancement in the attempts to enter REM sleep and an increased amount of time spent in REM sleep during recovery, REM and NREM sleep are regulated by at least partially distinct homeostatic mechanisms (Wurts and Edgar, 2000). Additionally, the dissimilar behavior during REM sleep of SEMs and REMs, with the latter significantly increasing across cycles, supports the hypothesis that these oculomotor events have different generators and reflect distinct phenomena during sleep. It has been demonstrated that cortical areas implicated in saccadic and pursuit eye movements are not involved or at least differently activated during SEMs in monkeys (Bon and Lucchetti, 1997), while studies on cortical control of SEMs in humans are lacking.
1388-2457/$36.00 Ó 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2011.01.009
1486
Editorial / Clinical Neurophysiology 122 (2011) 1485–1486
Investigations using intracerebral EEG recordings – as used in studies on saccadic movements (Lachaux et al., 2006) – or EOG-fMRI co-registrations – since now applied to eye blinking (Yoon et al., 2005) – would allow us a better understanding of the cortical and subcortical network underlying the generation of slow eye movements. In conclusion, the work of professor Montagna’s group (Pizza et al., 2011) is of great value because it provides normative data in adult healthy subjects regarding the amount of SEMs throughout the different phases of the entire overnight sleep. This, together with the use of an operator-independent computation, will allow further investigations on human disorders, particularly those accounted for an abnormal homeostatic process. Following the umpteenth intriguing line of research conceived by Pasquale Montagna will be one active way to commemorate him and help us to fill the empty space left in the scientific field by his premature demise. References Bon L, Lucchetti C. Activity of neurons related to eye movements during drowsiness in the frontal cortex of the macaca monkey. Sleep 1997;20:501–4. Borbély AA, Achermann P. Sleep homeostasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia: Elsevier Saunders; 2005. p. 405–17. De Gennaro L, Devoto A, Lucidi F, Violani C. Oculomotor changes are associated to daytime sleepiness in the multiple sleep latency test. J Sleep Res 2005;14: 107–12. De Gennaro L, Ferrara M, Ferlazzo F, Bertini M. Slow eye movements and EEG power spectra during wake-sleep transition. Clin Neurophysiol 2000;111: 2107–15. Dement W, Wolpert E. The relation of eye movements, body motility, and external stimuli to dream content. J Exp Psychol 1958;55:543–53. Hansotia P, Broste S, So E, Ruggles K, Wall R, Friske M. Eye movement patterns in REM sleep. Electroencephalogr Clin Neurophysiol 1990;76:388–99. Hori T. Electrodermal and electro-oculographic activity in hypnagogic state. Psychophysiology 1982;19:668–72. Horimoto N, Koyanagi T, Satoh S, Yoshizato T, Nakano H. Fetal eye movement assessed with real-time ultrasonography: are there rapid and slow eye movements? Am J Obstet Gynecol 1990;163:1480–4. Jacobs GH. The distribution and nature of colour vision among the mammals. Biol Rev 1993;68:413–71. Jacobs L, Feldman M, Bender MB. Eye movements during sleep: I. The pattem in the normal human. Arch Neurol 1971;25:151–9. Koyanagi T. Ontogeny of behavioral patterns in relation to the concurrent development of central nervous system function, focusing on REM sleep, NREM sleep and waking states in the human fetus Nippon. Sanka Fujinka Gakkai Zasshi 1991;43:843–52. La Morgia C, Ross-Cisneros FN, Sadun A, Hannibal J, Munarini A, Mantovani V, et al. Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies. Brain 2010;133:2426–38.
Lachaux JP, Hoffmann D, Minotti L, Berthoz A, Kahane P. Intracerebral dynamics of saccade generation in the human frontal eye field and supplementary eye field. Neuroimage 2006;30:1302–12. Leclair-Visonneau L, Oudiette D, Gaymard B, Leu-Semenescu S, Arnulf I. Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model. Brain 2010;133: 1737–46. Lisberger SG. Visual guidance of smooth pursuit eye movements: sensation, action, and what happens in between. Neuron 2010;66:477–91. Magosso E, Ursino M, Provini F, Montagna P. Wavelet analysis of electroencephalographic and electro-oculographic changes during the sleep onset period. Conf Proc IEEE Eng Med Biol Soc 2007:4006–10. Pizza F, Fabbri M, Magosso E, Ursino M, Provini F, Ferri R, et al. Slow Eye Movements distribution during nocturnal sleep. Clin Neurophysiol 2011;122: 1555–60. Prechtl HF, Nijhuis JG. Eye movements in the human fetus and newborn. Behav Brain Res 1983;10:119–24. Shin D, Sakai H, Uchiyama Y. Slow eye movement detection can prevent sleeprelated accidents effectively in a simulated driving task. J Sleep Res 2010, in press. doi:10.1111/j.1365-2869.2010.00891.x. [Epub ahead of print]. Steriade M, McCormick DA, Sejnowski TJ. Thalamocortical oscillations in the sleeping and aroused brain. Science 1993;262:679–85. Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Med Rev 2006;10:49–62. Torsvall L, Akerstedt T. Extreme sleepiness: quantification of EOG and spectral EEG parameters. Int J Neurosci 1988;38:435–41. Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, et al. Cortical firing and sleep homeostasis. Neuron 2009;63:865–78. Wurts SW, Edgar DM. Circadian and homeostatic control of rapid eye movement (REM) sleep: promotion of REM tendency by the suprachiasmatic nucleus. J Neurosci 2000;20:4300–10. Yang Y, Lisberger SG. Learning on multiple timescales in smooth pursuit eye movements. J Neurophysiol 2010;104:2850–62. Yoon HW, Chung JY, Song MS, Park H. Neural correlates of eye blinking; improved by simultaneous fMRI and EOG measurement. Neurosci Lett 2005;381:26–30.
Gaetano Cantalupo Child Neuropsychiatry Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy Tel.: +39 0521 702205; fax: +39 0521 704708. E-mail address: [email protected] Carlo Alberto Tassinari Neuroscience Department, University of Parma, Parma, Italy Address: Neuroscience Department, University of Parma, Via Volturno 39, 43125 Parma, Italy. Tel.: +39 0521 903881, fax: +39 0521 903900. E-mail addresses: [email protected] Available online 12 February 2011