Skip to main content
Log in

EEG–mapping differences between narcolepsy patients and controls and subsequent double–blind, placebo–controlled studies with modafinil

  • ORIGINAL PAPER
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

The aim of the present study was to investigate the role of EEG mapping as an objective and quantitative measure of vigilance in untreated and modafinil–treated narcoleptics, and compare it with the conventional neurophysiological method of the Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS). In 16 drug–free narcoleptics and 16 normal controls a baseline 3–min vigilance–controlled EEG (V–EEG) and a 4–min resting EEG (R–EEG) were recorded during midmorning hours. Thereafter, in a double–blind, placebo–controlled crossover design, patients were treated with a 3–week fixed titration of modafinil (200, 300, 400 mg) and placebo. EEG–mapping, MSLT and ESS measures were obtained before and at the end of the third week of therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant EEG differences between untreated patients and controls in the resting condition only (R–EEG). Subsequent univariate analysis revealed an increase in absolute and relative theta power, a decrease in alpha–2 and beta power as well as a slowing of the dominant frequency and the centroids of the alpha, beta and total power spectrum and thus objectified a vigilance decrement in narcolepsy. Modafinil 400 mg/d significantly improved vigilance as compared with placebo (p ≤ 0.01), inducing changes opposite to the aforementioned baseline differences (key–lock principle). The MSLT and the ESS also improved under modafinil as compared with placebo, but changes were less consistent. Spearman rank correlations revealed the highest correlations between EEG mapping and the ESS, followed by those between EEG mapping and the MSLT, while the lowest correlation was found between the MSLT and the ESS. In conclusion, EEG mapping is a valuable instrument for measuring vigilance decrements in narcolepsy and their improvement under psychostimulant treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Alloway CE, Ogilvie RD, Shapiro CM (1997) The alpha attenuation test: assessing excessive daytime sleepiness in narcolepsycataplexy. Sleep 20(4):258–266

    CAS  PubMed  Google Scholar 

  2. American Sleep Disorder Association (1997) The International Classification of Sleep Disorders, revised. Diagnostic and Coding Manual, Rochester

  3. Anderer P, Saletu B, Kinsperger K, Semlitsch H (1987) Topographic brain mapping of EEG in neuropsychopharmacology – part I Methodological aspects. Meth Findings in Experimental Clin Pharmacol 9:371–384

    CAS  Google Scholar 

  4. Anderer P, Semlitsch H, Saletu B, Barbanoj M (1992) Artifact processing in topographic mapping of electroencephalic activity in neuropsychopharmacology. Psychiatry Res 45:79–93

    CAS  PubMed  Google Scholar 

  5. Bastuji H, Jouvet M (1988) Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Neuro-Psychopharmacol & Biol Psychiatry 12(5):695–700

    Google Scholar 

  6. Bente D (1977) Vigilanz: psychophysiologische Aspekte. Verh Deutscher Gesellschaft für Innere Medizin 83:945–952

    CAS  Google Scholar 

  7. Besset A, Tafti M, Villemin E, Billiard M (1993) The effects of modafinil (300 mg) on sleep, sleepiness and arousal in narcoleptic patients. Neurophysiologie Clinique/Clin Neurophysiol 23(1):47–60

    Google Scholar 

  8. Billiard M, Besset A, Montplaisir J, Laffont F, Goldenberg F, Weill JS, Lubin S (1994) Modafinil: a double-blind multicentric study. Sleep 17(8 Suppl):S107–S112

    CAS  PubMed  Google Scholar 

  9. Billiard M (1998) The pharmacological treatment of narcolepsy. Eur Neuropsychopharmacol 8(Suppl 2):90–91

    Google Scholar 

  10. Boivin DB, Montplaisir J, Petit D, Lambert C, Lubin S (1993) Effects of modafinil on symptomatology of human narcolepsy. Clin Neuropharmacol 16(1):46–53

    CAS  PubMed  Google Scholar 

  11. Broughton RJ, Fleming JA, George CF, Hill JD, Kryger MH, Moldofsky H, Montplaisir JY, Morehouse RL, Moscovitch A, Murphy WF (1997) Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49(2):444–451

    CAS  PubMed  Google Scholar 

  12. Buchsbaum MS, Hazlett E, Sicotte N, Stein M, Wu J, Zetin M (1985) Topographic EEG changes with benzodiazepine administration in generalized anxiety disorder. Biol Psychiatry 20(8):832–842

    Google Scholar 

  13. Carskadon MA, Dement WC, Mitler MM, Roth T,Westbrook PR, Keenan S (1986) Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep 9(4):519–524

    CAS  PubMed  Google Scholar 

  14. Chervin RD, Aldrich MS, Pickett R, Guilleminault C (1997) Comparison of the results of the Epworth Sleepiness Scale and the Multiple Sleep Latency Test. J Psychosom Res 42(2):145–155

    Article  CAS  PubMed  Google Scholar 

  15. Chua LWY, Yu NC, Golish JA, Nelson DR, Perry MC, Foldvary N, Dinner DS (1998) Epworth sleepiness scale and the multiple sleep latency test: Dilemma of the elusive link. Sleep 21(Suppl):184

    Google Scholar 

  16. Cluydts R, De Valck E, Verstraeten E, Theys P (2002) Daytime sleepiness and its evaluation. Sleep Med Rev 6(2):83–96

    Article  PubMed  Google Scholar 

  17. Cross EM, Chaffin WW (1982) Use of the binomial theorem in interpreting results of multiple tests of significance. Educ Psychol Measurement 42:25–34

    Google Scholar 

  18. Duffy FH, Bartels PH, Burchfield JL (1981) Significance probability mapping: an aid in the topographic analysis of brain electrical activity. Electroencephalogr Clin Neurophysiol 51:455–462

    Google Scholar 

  19. Gasser T, Bacher P, Mocks J (1982) Transformations towards the normal distribution of broad band spectral parameters of the EEG. Electroencephalogr Clin Neurophysiol 53(1):119–124

    Article  CAS  PubMed  Google Scholar 

  20. Gevins A, Le J, Martin NK, Brickett P, Desmond J, Reutter B (1994) High resolution EEG: 124-channel recording, spatial deblurring and MRI integration methods. Electroencephalogr Clin Neurophysiolog 90(5):337–358

    Google Scholar 

  21. Head H (1923) The conception of nervous and mental energy. II. Vigilance: a physiological state of the nervous system. Br J Psychol 14:125–147

    Google Scholar 

  22. Himanen SL, Hasan J (2000) Limitations of Rechtschaffen and Kales. Sleep Med Rev 4(2):149–167

    Article  PubMed  Google Scholar 

  23. Honda Y (1988) Clinical features of narcolepsy: Japanese experiences. In: Honda T, Juji T (eds) HLA in narcolepsy. Berlin-Springer Verlag, pp 24–57

  24. Hublin C, Partinen M, Kaprio J, Koskenvuo M, Guilleminault C (1994) Epidemiology of narcolepsy. Sleep 17(8 Suppl):S7–S12

    CAS  PubMed  Google Scholar 

  25. Itil TM, Shapiro DM, Eralp E, Akmann A, Itil KZ, Garbizu C (1985) A new brain function diagnostic unit, including the dynamic brain mapping of computer-analyzed EEG, evoked potentials and sleep (a new hardware/software system and its application in psychiatry and psychopharmacology). New Trends in Experimental Clinical Psychiatry 1:107–177

    Google Scholar 

  26. John ER, Prichep LS, Fridman J, Easton P (1988) Neurometrics: computer assisted differential diagnosis of brain dysfunctions. Science 239:162–169

    CAS  PubMed  Google Scholar 

  27. Johns MW (1991) A new method for measuring daytime sleepiness: The Epworth Sleepiness Scale. Sleep 14(6):540–545

    CAS  PubMed  Google Scholar 

  28. Laffont F, Mayer G, Minz M (1994) Modafinil in diurnal sleepiness: a study of 123 patients. Sleep 17(8 Suppl):S113–S115

    CAS  PubMed  Google Scholar 

  29. Maurer K, Dierks T (1991) Atlas of brain mapping. Topographic mapping of EEG and evoked potentials. Springer-Verlag, Berlin-New York-Wien

  30. Mitler MM, Gujavarty KS, Browman CP (1982) Maintenance of wakefulness test: a polysomnographic technique for evaluation treatment efficacy in patients with excessive somnolence. Electroencephalogr Clin Neurophysiol 53(6):658–661

    CAS  PubMed  Google Scholar 

  31. Mitler MM, Walsleben JA, Sangal RB, Hirshkowitz M (1998) Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs. Electroencephalogr Clin Neurophysiol 107:33–38

    CAS  PubMed  Google Scholar 

  32. Mitler MM, Harsh J, Hirshkowitz M, Guilleminault C (2000) Long-term efficacy and safety of modafinil (PROVIGIL®) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 1(3):231–243

    Article  PubMed  Google Scholar 

  33. Moldofsky H, Broughton RJ, Hill JD (2000) A randomized trial of the long-term,continued efficacy and safety of modafinil in narcolepsy. Sleep Med 1(2):109–116

    Article  PubMed  Google Scholar 

  34. Overeem S, Mignot E, Gert van Dijk J, Lammers GJ (2001) Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives. J Clin Neurophysiol 18:78–105

    Article  CAS  PubMed  Google Scholar 

  35. Pascual-Marqui RD, Esslen M, Kochi K, Lehmann D (2002) Functional imaging with low-resolution brain electromagnetic tomography (LORETA): a review. Methods and Findings in Experimental Clinical Pharmacology 24(Suppl C):91–95

    Google Scholar 

  36. Rechtschaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Brain Information Service, Los Angeles

  37. Richardson GS, Carskadon MA, Flagg W, Van den Hoed J, Dement WC, Mitler MM (1978) Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol 45(5):621–627

    Google Scholar 

  38. Saletu B, Grünberger J (1985) Memory dysfunction and vigilance: Neurophysiological and psychopharmacological aspects. Ann N Y Acad Sci 444:406–427

    CAS  PubMed  Google Scholar 

  39. Saletu B, Grünberger J, Linzmayer L, Stöhr H (1986) Pharmaco- EEG, psychometric and plasma level studies with two novel alpha- adrenergic stimulants CRL 40476 and 40028 (Adrafinil) in elderlies. New Trends in Experimental Clinical Psychiatry 2:5–31

    Google Scholar 

  40. Saletu B, Frey R, Krupka M, Anderer P, Grünberger J, Barbanoj MJ (1989 a) Differential effects of a new central adrenergic agonist – modafinil – and d-amphetamine on sleep and early morning behaviour in young healthy volunteers. Int J Clin Pharmacol Res IX (3):183–195

    Google Scholar 

  41. Saletu B, Frey R, Krupka M, Anderer P, Grünberger J, Barbanoj MJ (1989 b) Differential effects of the new central adrenergic agonist modafinil and d-amphetamine on sleep and early morning behaviour in elderlies. Arzneimittelforschung – Drug Research 39(10):1268–1273

    CAS  Google Scholar 

  42. Saletu B, Küfferle B, Anderer P, Grünberger J, Steinberger K (1990a) EEG-brain mapping in schizophrenics with predominantly positive and negative symptoms. Comparative studies with remoxipride/haloperidol. Eur Neuropsychopharmacol 1:27–36

    Article  CAS  Google Scholar 

  43. Saletu B, Saletu M, Grünberger J, Frey R, Zatschek I, Mader R (1990b) On the treatment of the alcoholic organic brain syndrome with an alpha-adrenergic agonist modafinil: doubleblind placebo-controlled clinical, psychometric and neurophysiological studies. Progr Neuro-Psychopharmacol Biol Psychiatry 14:195–214

    Article  CAS  Google Scholar 

  44. Saletu B,Anderer P, Paulus E, Grünberger J, Wicke L, Neuhold A, Fischhof K, Litschauer G (1991) EEG-brain mapping in diagnostic and therapeutic assessment of dementia. Alzheimer Disease and Associated Disorders 5(suppl 1):57–75

    Google Scholar 

  45. Saletu B, Saletu M, Grünberger J, Frey R, Anderer P, Mader R (1993) Treatment of the alcoholic organic brain syndrome: double- blind, placebo-controlled clinical, psychometric and electroencephalographic mapping studies with modafinil. Neuropsychobiology 27:26–39

    CAS  PubMed  Google Scholar 

  46. Saletu B (1997) Visualizing the living human brain. The techniques and promise of EEG and event-related potentials mapping. In: Judd L, Saletu B, Filip V (eds) Basic and Clinical Science of Mental and Addictive Disorders. Bibliotheca Psychiatrica (167). Karger, Basel, pp 54–62

  47. Saletu B, Anderer P, Pascual-Marqui RD (2000) Pharmacodynamics and EEG II. From EEG mapping to EEG tomography. In: Saletu B, Krijzer F, Ferber G, Anderer P (eds) Electrophysiological Brain Research in Preclinical and Clinical Pharmacology and Related Fields – An Update. Facultas Universitätsverlag, Wien, pp 157–163

  48. Saletu B, Anderer P, Saletu-Zyhlarz GM, Arnold O, Pascual-Marqui RD (2002a) Classification and evaluation of the pharmacodynamics of psychotropic drugs by single-lead pharmaco-EEG, EEG mapping and tomography (LORETA). Methods and Findings in Experim Clin Pharmacol 24(Suppl C):97–120

    CAS  Google Scholar 

  49. Saletu B, Anderer P, Saletu-Zyhlarz GM, Pascual-Marqui RD (2002b) EEG topography and tomography in diagnosis and treatment of mental disorders: evidence for a key-lock principle. Methods and Findings in Experim Clin Pharmacol 24(Suppl D):97–106

    CAS  Google Scholar 

  50. Saletu M, Hauer C, Anderer P, Gruber G, Oberndorfer S, Mandl M, Popovic R, Saletu B (2000) Tagesmüdigkeit korreliert mit nächtlichen Atmungs- und Arousal-Variablen bei Schlafapnoepatienten: Polysomnographische und EEG-Mapping Untersuchungen. Wiener Klinische Wochenschrift 112(6):281–289

    CAS  PubMed  Google Scholar 

  51. Saletu M, Anderer P, Saletu B, Lindeck-Pozza L,Hauer C, Saletu- Zyhlarz GM (2002) EEG mapping in patients with restless legs syndrome as compared with normal controls. Psychiatry Res Neuroimaging 115:49–61

    Google Scholar 

  52. Saletu-Zyhlarz GM, Anderer P, Linzmayer L, Semlitsch HV, Assandri A, Prause W, Hassan Abu-Bakr M, Lindeck-Pozza E, Saletu B (2002) Visualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mapping. Int J Neuropsychopharmacol 5(3):199–215

    Article  CAS  PubMed  Google Scholar 

  53. Sangal RB, Sangal JM, Belisle C (1999) Longer auditory and visual P300 latencies in patients with narcolepsy. Clin Electroencephalogr 30(1):28–32

    CAS  PubMed  Google Scholar 

  54. Schmidt-Nowara WW, Wiggings CL, Walsh CK, Bauer C (1989) Prevalence of sleepiness in adult population. Sleep Res 18:302

    Google Scholar 

  55. Stampi C, Stone P, Michimori A (1995) A new quantification method for assessing sleepiness: the alpha attenuation test. Work & Stress 9:368–376

    Google Scholar 

  56. Thorpy M (2001) Current concepts in the etiology, diagnosis and treatment of narcolepsy. Sleep Med 2(1):5–17

    Article  PubMed  Google Scholar 

  57. US Modafinil in Narcolepsy Multicenter Study Group (1998) Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 43(1):88–97

    PubMed  Google Scholar 

  58. US Modafinil in Narcolepsy Multicenter Study Group (2000) Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 54(5):1166–1175

    PubMed  Google Scholar 

  59. Van Ert PM, Gapinski JP, Fuller MJ (1999) The predictive value of the Epworth Sleepiness scale: patients’ versus significant other assessments of patients sleepiness. Sleep 22:48

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. Saletu MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saletu, M.T., Anderer, P., Saletu-Zyhlarz, G.M. et al. EEG–mapping differences between narcolepsy patients and controls and subsequent double–blind, placebo–controlled studies with modafinil. Eur Arch Psychiatry Clin Neurosci 255, 20–32 (2005). https://doi.org/10.1007/s00406-004-0530-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-004-0530-1

Key words

Navigation