The Meaning of P50 Suppression : Interaction of Gamma and Alpha Waves

  • Lee, Kyungjun (Department of Neuropsychiatry, Seoul National University Hospital) ;
  • Kang, Ung Gu (Department of Neuropsychiatry, Seoul National University Hospital)
  • Received : 2014.07.21
  • Accepted : 2014.10.04
  • Published : 2014.11.30

Abstract

Objectives Sensory gating dysfunctions in patients with schizophrenia and bipolar disorder have been investigated through two similar methods ; P50 suppression and prepulse inhibition paradigms. However, recent studies have demonstrated that the two measures are not correlated but rather constitute as distinct neural processes. Recent studies adopting spectral frequency analysis suggest that P50 suppression reflects the interaction between gamma and other frequency bands. The aim of the present study is to investigate which frequency component shows more significant interaction with gamma band. Methods A total of 108 mood disorder patients and 36 normal subjects were included in the study. The P50 responses to conditioning and test stimuli with an intra-pair interval of 500 msec were measured in the study population. According to P50 ratio (amplitude to the test stimulus/amplitude to the conditioning stimulus), the subjects with P50 ratio less than 0.2 were defined as suppressed group (SG) ; non-suppressed group (NSG) consisted of P50 ratio more than 0.8. Thirty-five and 25 subjects were included in SG and NSG, respectively. Point-to-point correlation coefficients (PPCCs) of both groups were calculated between two time-windows : the first window (S1) was defined as the time-window of one hundred millisecond after the conditioning auditory stimulus and the second window (S2) was defined as the time-window of 100 msec after the test auditory stimulus. Spectral frequency analysis was performed to investigate which frequency band results in the difference of PPCC between SG and NSG. Results Significant reduction of PPCC between S1 and S2 was observed in the SG (Pearson's r = 0.24), compared to PPCC of the NSG (r = 0.58, p < 0.05). In spectral frequency analysis, gamma band showed "phase-reset" and similar responses after the two auditory stimuli in suppressed and non-suppressed group. However in the case of alpha band, comparison showed significantly low PPCC in SG (r = -0.14) compared to NSG (r = 0.36, p < 0.05). This may be reflecting "phase-out" of alpha band against gamma band at approximately 50 msecs after the test stimulus in the SG. Conclusions Our study suggests that normal P50 suppression is caused by phase-out of alpha band against gamma band after the second auditory stimulus. Thus it is demonstrated that normal sensory gating process is constituted with attenuated alpha power, superimposed on consistent gamma response. Implications of preserved gamma and decreased alpha band in sensory gating function are discussed.

Keywords

References

  1. Adler LE, Pachtman E, Franks RD, Pecevich M, Waldo MC, Freedman R. Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 1982;17:639-654.
  2. Judd LL, McAdams L, Budnick B, Braff DL. Sensory gating deficits in schizophrenia: new results. Am J Psychiatry 1992;149:488-493. https://doi.org/10.1176/ajp.149.4.488
  3. Ward PB, Hoffer LD, Liebert BJ, Catts SV, O'Donnell M, Adler LE. Replication of a P50 auditory gating deficit in Australian patients with schizophrenia. Psychiatry Res 1996;64:121-135. https://doi.org/10.1016/0165-1781(96)02876-4
  4. Clementz BA, Geyer MA, Braff DL. Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Am J Psychiatry 1998;155:1691-1694. https://doi.org/10.1176/ajp.155.12.1691
  5. Franks RD, Adler LE, Waldo MC, Alpert J, Freedman R. Neurophysiological studies of sensory gating in mania: comparison with schizophrenia. Biol Psychiatry 1983;18:989-1005.
  6. Adler LE, Gerhardt GA, Franks R, Baker N, Nagamoto H, Drebing C, et al. Sensory physiology and catecholamines in schizophrenia and mania. Psychiatry Res 1990;31:297-309. https://doi.org/10.1016/0165-1781(90)90099-Q
  7. Freedman R, Adler LE, Gerhardt GA, Waldo M, Baker N, Rose GM, et al. Neurobiological studies of sensory gating in schizophrenia. Schizophr Bull 1987;13:669-678. https://doi.org/10.1093/schbul/13.4.669
  8. Graham FK. Presidential Address, 1974. The more or less startling effects of weak prestimulation. Psychophysiology 1975;12:238-248. https://doi.org/10.1111/j.1469-8986.1975.tb01284.x
  9. Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L. Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 1978;15:339-343. https://doi.org/10.1111/j.1469-8986.1978.tb01390.x
  10. Braff DL, Grillon C, Geyer MA. Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 1992;49:206-215. https://doi.org/10.1001/archpsyc.1992.01820030038005
  11. Bolino F, Di Michele V, Di Cicco L, Manna V, Daneluzzo E, Casacchia M. Sensorimotor gating and habituation evoked by electro-cutaneous stimulation in schizophrenia. Biol Psychiatry 1994;36:670-679. https://doi.org/10.1016/0006-3223(94)91176-2
  12. Parwani A, Duncan EJ, Bartlett E, Madonick SH, Efferen TR, Rajan R, et al. Impaired prepulse inhibition of acoustic startle in schizophrenia. Biol Psychiatry 2000;47:662-669. https://doi.org/10.1016/S0006-3223(99)00148-1
  13. Perry W, Minassian A, Feifel D, Braff DL. Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania. Biol Psychiatry 2001;50:418-424. https://doi.org/10.1016/S0006-3223(01)01184-2
  14. Brenner CA, Edwards CR, Carroll CA, Kieffaber PD, Hetrick WP. P50 and acoustic startle gating are not related in healthy participants. Psychophysiology 2004;41:702-708. https://doi.org/10.1111/j.1469-8986.2004.00206.x
  15. Braff DL, Light GA, Swerdlow NR. Prepulse inhibition and P50 suppression are both deficient but not correlated in schizophrenia patients. Biol Psychiatry 2007;61:1204-1207. https://doi.org/10.1016/j.biopsych.2006.08.015
  16. de Wilde OM, Bour LJ, Dingemans PM, Koelman JH, Linszen DH. Failure to find P50 suppression deficits in young first-episode patients with schizophrenia and clinically unaffected siblings. Schizophr Bull 2007;33:1319-1323.
  17. Arnfred SM, Chen AC, Glenthoj BY, Hemmingsen RP. Normal p50 gating in unmedicated schizophrenia outpatients. Am J Psychiatry 2003;160:2236-2238. https://doi.org/10.1176/appi.ajp.160.12.2236
  18. Olincy A, Martin L. Diminished suppression of the P50 auditory evoked potential in bipolar disorder subjects with a history of psychosis. Am J Psychiatry 2005;162:43-49. https://doi.org/10.1176/appi.ajp.162.1.43
  19. de Wilde OM, Bour LJ, Dingemans PM, Koelman JH, Linszen DH. A meta-analysis of P50 studies in patients with schizophrenia and relatives: differences in methodology between research groups. Schizophr Res 2007;97:137-151. https://doi.org/10.1016/j.schres.2007.04.028
  20. Karakas S, Basar E. Early gamma response is sensory in origin: a conclusion based on cross-comparison of results from multiple experimental paradigms. Int J Psychophysiol 1998;31:13-31. https://doi.org/10.1016/S0167-8760(98)00030-0
  21. Carroll CA, Kieffaber PD, Vohs JL, O'Donnell BF, Shekhar A, Hetrick WP. Contributions of spectral frequency analyses to the study of P50 ERP amplitude and suppression in bipolar disorder with or without a history of psychosis. Bipolar Disord 2008;10:776-787. https://doi.org/10.1111/j.1399-5618.2008.00622.x
  22. Kim KJ, Lee NY, Ahn YM, Kang UK. Study on the P50 auditory evoked potential in mood disorder subjects. J Korean Neuropsychiatr Assoc 2010;49:516-522.
  23. Fries P, Nikolic D, Singer W. The gamma cycle. Trends Neurosci 2007; 30:309-316. https://doi.org/10.1016/j.tins.2007.05.005
  24. Kwon JS, O'Donnell BF, Wallenstein GV, Greene RW, Hirayasu Y, Nestor PG, et al. Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. Arch Gen Psychiatry 1999;56:1001-1005. https://doi.org/10.1001/archpsyc.56.11.1001
  25. Brenner CA, Sporns O, Lysaker PH, O'Donnell BF. EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder. Am J Psychiatry 2003; 160:2238-2240. https://doi.org/10.1176/appi.ajp.160.12.2238
  26. Worden MS, Foxe JJ, Wang N, Simpson GV. Anticipatory biasing of visuospatial attention indexed by retinotopically specific alpha-band electroencephalography increases over occipital cortex. J Neurosci 2000;20:RC63.
  27. Klimesch W, Sauseng P, Hanslmayr S. EEG alpha oscillations: the inhibition-timing hypothesis. Brain Res Rev 2007;53:63-88. https://doi.org/10.1016/j.brainresrev.2006.06.003
  28. Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev 1999;29:169-195. https://doi.org/10.1016/S0165-0173(98)00056-3