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Mismatch negativity: An index of a preattentive processing deficit in schizophrenia
BIOL ~¥cmATRY 1991 ;30:1059- |062
1059
Mismatch Negativity: An Index of a Preattentive Processing Deficit in Schizophrenia A. M. Shelley, P. B. Ward, S. V. Catts, P. T. Michie, S. Andrews, and N. McConaghy
Introduction Although there is little doubt that schizophrenics have attentional problems, the precise nature of the deficit remains obscure. Following the distinction between automatic and controlled processes (Shiffrin and Schneider 1977), some theorists have proposed that schizophrenic attention deficits are confined to controlled, or active attentional processes (Caiiaway and Naghdi 1982; Nuechterlein and Dawson 1984), whereas others have postulated an automatic, or preattentive dysfunction, such as a failure of inhibition (Johnson 1985) or defective filtering (Shagass 1976). Most event-related potential (ERP) studies of schizophrenic attention deficits suggest an impairment in controlled processing indexed by reduced P3 amplitude and an attenuation of processing negativity (PN) (Michie et al 1990; Ward et al 1991). However, it is possible that dysfunctions in controlled processes may be secondary to defects in preattentive mechanisms. Mismatch negativity (MMN) is an ERP component elicited in the auditory "oddball" paradigm by low probability "deviant" stimuli embedded in a sequence of high probability
From the School of Psychology (SA) and Psychiatry (AMS, PBW, SVC, NMcC), University of New South Wales, Kensington, N.S.W., Australia; ~ld the School of Behavioural Sciences, Macquarie University, N.S.W., Australia (PTM). Address reprint requests to A.M. Shelley, Psychiatry Department Prince of Wales Hospital, High Street, Randwick, N.S.W. 2031 Australia. Received May 4, 1991; revised June 24, 1991.
© 1991 Society of Biological Psychiatry
"'standard" stimuli. The MMN is most clearly evident in conditions in which subjects are asked to ignore auditory stimuli or to perform a distracting task, suggesting that it is an index of preattentive processing. N~it~en (1990) has proposed that the MMN is generated automatically whenever there is a mismatch between the neuronal model of the physical features of the standard stimulus and the deviant stimulus. At short interstimulus intervals (ISis), all auditory stimuli elicit an N I and P2, but deviants also elicit the MMN, which overlaps NI and P2 (N~i[it~en and Picton 1987) and peaks 100-300 ms after stimulus onset. M I ~ amplitude is increased for low probability deviant stimuli and for larger differences between deviants and standards. The auditory MMN has been observed when stimulus deviance is defined by changes in pitch, intensity, duration, spatial location, and phoneme change (see N~it~inen 1990). The magnetic counterpart of MMN, the mismatch field, has been observed in response to deviations in stimulus frequency, intensity, and duration (see Kaukoranta et al 1989). The present study investigated whether schizophrenics show deficits in preattentive processes indexed by the MMN.
Subjects and Methods Subjects consisted of 11 medicated schizophrenics (7 men, 4 women, mean age 29 years, range 18--44 years) diagnosed according to
0006-3223/91/$03.50
1060
BIOL PSYCHIATRY 1991;~: 1059-1062
Brief Reports
DSM-III-R (APA 1987) criteria and 11 age- Results and gender-matched controls. Patients mean For this brief report, only data from Fz will be total score on the Brief Psychiatric Rathag Scale considered. Grand average difference wave(BPRS) (Lukoff et al 1986) was 47.0 (SD = forms at Fz for the long deviant and short de9.7). Mean neuroleptic dose, expressed in viant conditions in the patient and control groups chlorpromazine equivalents (Davis 1976), was are shown in Figure 1. There was a significant 469.1 rag/day (SD = 262.9). Tones were difference between groups (F(I,20) = 6.49, presented monaurally via TDH-39 headp < 0.02), with patients showing an attenuation phones. Subjects heard i2 blocks of 290 auof MMN amplitude. The difference between the ditory tones (633 Hz, rise/fall time 10 ms, intwo deviant types approached significance tensity 80 dB SPL) of short (50 ms) and long (F(I,20) = 4.06, p < u.~p. " "~' The~c was also a (100 ms) duration with a constant ISI of 510 significant interaction between group and dems. In half of the blocks, 10% of tones (deviants) were of long duration and 90% (stan- viant type (F(l,20) = 4.79,p < 0.05). Patients showed a significant attenuation of the MMN in dards) were of short duration, whereas in the the long deviant condition (2.0 ttV versus 4.4 other half of the blocks, deviants were short ttV) (F(I,20) = 8.64, p < 0.01) but not in the duration and standards were long duration short deviant condition (2.1 ttV versus 2.8 IxV) tones. Presentation of short and long deviant (F(I,20) = 1.44, NS). There were no signifiblocks was counterbalanced, alternating becant correlations between mean MMN amplitween short and long deviants from one block to the next. ERPs were recorded from 16 scalp tude and total scores on SAPS, SANS, BPRS, or chlorpromazine equivalents. locations: four midline sites (Fpz, Fz, Cz, Pz) and 12 lateral sites (F3, F4, F7, F8, C3, C4, T3, T4, T5, T6, P3, P4). Eye mover, s=at artifact was monitored by vertical anJ ~:~rizon- Discussiea tal electrooculogram (EOG). Electroencepha- The finding that the MMN component is attenlogram (EEG) and EOG were amplified with uated in schizophrenics is consistent with other a bandpass of 0.01-30 Hz and digitized at 200 demonstrations of anomalous preattentive proHz for 760 ms, which included a 250 ms cessing in schizophrenia such as gating abnorprestimulus baseline. All recordings were re- malities as indexed by the P50 (Baker et al 1987) ferred to linked ears. All 12 blocks were per- and the absence of visual perceptual grouping formed under a distraction condition in which effects (Place and Gilmore 1980). The results subjects made a manual response to visual raise the possibility that schizophrenic deficits stimuli presented on a computer screen. Fol- in controlled attention, as indexed by reductions lowing ERP recording, patients were rated on of PN and P3 amplitude (Michie et all !9_00_; the Schedules for Positive and Negative Ward et al 1991), may, at least partly, be due Symptoms (SAPS and SANS) (Andreasen to impairments in preattentive mechanisms. The 1982, 1984~ ERPs were analyzed using the finding that group differences existed for long methods adopted by Niiiitiinen and colleagues but not short deviants is puzzling. It is possible (1987, 1990), that is, difference waveforms that short deviants are more attention capturing were obtained by subtracting standard ERPs and elicit a P3a in control subjects that artififrom deviant ERPs. Mean MMN amplitude cially reduces MMN amplitude. This possibility over the 150--225 ms epoch was calculated for needs to be addressed by future research, pareach subject and analyzed using a repeated ticularly in view of recent controversy regarding measures analysis of variance with factors of the purely preattentive nature of MMN (Wolgroup and deviant type (long versus short). dorff et al 1991; Alho et ai, unpublished data). Correlations between symptom ratings and Both magnetoencephalography (Kaukoranta MMN mean amplitude were examined with et al 1989) and source analysis (Scherg et al Spearman's rho. 1989) have localized the MMN to the superior
BIOL PSYCHIATRY 199|~0: | ~ 9 - I062
Brief Repots
|~ |
v
-2#v
-
0
200
400
r'r~s
2#V
0
200
400
r'~s
Figure I. Grand average difference waveforms at the Fz electrode site for the long deviant (left) and the short deviant (right) conditions in the p.~tient (dotted line) and control (solid line) groups.
Baker N, Adler LE, Franks RD, et al (1987): Neurophysiological assessment of sensory gating in psychiatric inpatients: Comparison between schizophrenia and other diagnoses. Biol Psychiatry 22:603-617. Barta PE, Pearlson GD, Powers RE, Richards S$, Tune LE (1990): Auditory hallucinations ~ d smiler superior temporal gyral v o l ~ e in schizophrenia. Am J Psychiatrs, 147:I457-1462. Callaway E, Naghdi S (1982): An information processing model for schizophrenia. Arch Gen Psychiatry 39:339-347. Davis JM (1976): Comparative doses and costs of antipsychofic medication. Arch Gen Psychiatry 33:858-861. Johnson JD (1985): A mechanism to inhibit input activation and its dysfunction in schizophrenia. This research was supported by the National Health and Br J Psychiatry. i46:429-435. Medical ResearchCouncil and the Rebecca L. Cooper MedKaukoranta E, Sams M, Had R, H~n~l~finen M, ical Research Foundation. N~t~aen R (1989): Reactions of human auditory cortex to a change in tone duration. Hear Res 41:15-21. References Lukoff D, Liberman RP, Nuechterlein KH (1986): Symptom monitoring in the rehabilitation of American Psychiatric Association (1987): DSM-IlIschizophrenic patients. Schizophr Bull 12:578-602. R: Diagnostic and Statistical Manual of Mental Disorders. ed 3, Washington, DC: The Associ- Michie PT, Fox AM, Ward PB, Carts SV, McConaghy N (1990): ERP indices of selective atation. tention and cortical lateralization m schizophreAndreasen NC (1982): Negative syrup:ores in schizonia. Psychophysiology 27:209-227. phrenia: Definition and reliability. Arch Gen PsyN~fftnen R (1990): The role of attention in auditory chiatry 39:784-788. information processing as revealed by event-reAndreasen NC (1984): The Scale for the Assessment lated potentials and other brain measures of cogof Positive Symptoms (SAPS). Iowa City, Iowa: nitive function. Behav Brain Sci 13:201-288. The University of Iowa.
temporal plane of the temporal lobe in healthy subjects. These findings suggest that the anatomical locus of the MMN deficit in schizophrenics may be generated in the supratemporal auditory cortex. This suggestion is consistent with recent magnetic resonance imaging (MRI) evidence that in schizophrenics the superior temporal gyrus volume is reduced, particularly in the left hemisphere (Barta et al 1990). The question of whether schizophrenic patients with abnormal MMN components show evidence of structural changes in temporal areas merits careful future scrutiny using MRI.
1062
BIOL PSYCHIATRY 1991;30:1059-1062
N~i/itanen R, Picton TW (1987): The N I wave of the human electric and magnetic response to sound: A review and an analysis of the ¢-omponent structure. Psychophysiology 24:375-425. Nuechterlein KH, Dawson ME (1984): Information processing and attentional functioning in the developmental course of the schizophrenic disorder. Schizophr Bull I 0:160-203. P!.~ce EJS, Gilmore GC (1980): Perceptual organization in schizophrenia. J Abnorm Psycho189:409418. Scherg M, Vajsar J, Picton TW (1989): A source analysis of human auditory-evoked potentials. J Cog Neurosci 1:336-355.
Brief Reports
Shagass C (1976): An electrophysiological view of schizophrenia. Biol Psychiatry I 1:3-29. S h i ~ n RM, Schneider W (1977): Controlled and automatic human information processing. H. Perceptual learning, automatic attending, and a general theory. Psychol Rev 84:127-190. Ward PB, Catts SV, Fox AM, Michie PT, McConaghy N (1991): Auditory selective attention and event-related potentials in schizophrenia. 8r J Psychiatry 158:534-539. Woldorff M, Hackley SA, Hillyatd SA (1991): The effects of channel-selective attention on the mismatch negativity wave elicited by deviant tones. Psychophysiology 28:30--42.
1059
Mismatch Negativity: An Index of a Preattentive Processing Deficit in Schizophrenia A. M. Shelley, P. B. Ward, S. V. Catts, P. T. Michie, S. Andrews, and N. McConaghy
Introduction Although there is little doubt that schizophrenics have attentional problems, the precise nature of the deficit remains obscure. Following the distinction between automatic and controlled processes (Shiffrin and Schneider 1977), some theorists have proposed that schizophrenic attention deficits are confined to controlled, or active attentional processes (Caiiaway and Naghdi 1982; Nuechterlein and Dawson 1984), whereas others have postulated an automatic, or preattentive dysfunction, such as a failure of inhibition (Johnson 1985) or defective filtering (Shagass 1976). Most event-related potential (ERP) studies of schizophrenic attention deficits suggest an impairment in controlled processing indexed by reduced P3 amplitude and an attenuation of processing negativity (PN) (Michie et al 1990; Ward et al 1991). However, it is possible that dysfunctions in controlled processes may be secondary to defects in preattentive mechanisms. Mismatch negativity (MMN) is an ERP component elicited in the auditory "oddball" paradigm by low probability "deviant" stimuli embedded in a sequence of high probability
From the School of Psychology (SA) and Psychiatry (AMS, PBW, SVC, NMcC), University of New South Wales, Kensington, N.S.W., Australia; ~ld the School of Behavioural Sciences, Macquarie University, N.S.W., Australia (PTM). Address reprint requests to A.M. Shelley, Psychiatry Department Prince of Wales Hospital, High Street, Randwick, N.S.W. 2031 Australia. Received May 4, 1991; revised June 24, 1991.
© 1991 Society of Biological Psychiatry
"'standard" stimuli. The MMN is most clearly evident in conditions in which subjects are asked to ignore auditory stimuli or to perform a distracting task, suggesting that it is an index of preattentive processing. N~it~en (1990) has proposed that the MMN is generated automatically whenever there is a mismatch between the neuronal model of the physical features of the standard stimulus and the deviant stimulus. At short interstimulus intervals (ISis), all auditory stimuli elicit an N I and P2, but deviants also elicit the MMN, which overlaps NI and P2 (N~i[it~en and Picton 1987) and peaks 100-300 ms after stimulus onset. M I ~ amplitude is increased for low probability deviant stimuli and for larger differences between deviants and standards. The auditory MMN has been observed when stimulus deviance is defined by changes in pitch, intensity, duration, spatial location, and phoneme change (see N~it~inen 1990). The magnetic counterpart of MMN, the mismatch field, has been observed in response to deviations in stimulus frequency, intensity, and duration (see Kaukoranta et al 1989). The present study investigated whether schizophrenics show deficits in preattentive processes indexed by the MMN.
Subjects and Methods Subjects consisted of 11 medicated schizophrenics (7 men, 4 women, mean age 29 years, range 18--44 years) diagnosed according to
0006-3223/91/$03.50
1060
BIOL PSYCHIATRY 1991;~: 1059-1062
Brief Reports
DSM-III-R (APA 1987) criteria and 11 age- Results and gender-matched controls. Patients mean For this brief report, only data from Fz will be total score on the Brief Psychiatric Rathag Scale considered. Grand average difference wave(BPRS) (Lukoff et al 1986) was 47.0 (SD = forms at Fz for the long deviant and short de9.7). Mean neuroleptic dose, expressed in viant conditions in the patient and control groups chlorpromazine equivalents (Davis 1976), was are shown in Figure 1. There was a significant 469.1 rag/day (SD = 262.9). Tones were difference between groups (F(I,20) = 6.49, presented monaurally via TDH-39 headp < 0.02), with patients showing an attenuation phones. Subjects heard i2 blocks of 290 auof MMN amplitude. The difference between the ditory tones (633 Hz, rise/fall time 10 ms, intwo deviant types approached significance tensity 80 dB SPL) of short (50 ms) and long (F(I,20) = 4.06, p < u.~p. " "~' The~c was also a (100 ms) duration with a constant ISI of 510 significant interaction between group and dems. In half of the blocks, 10% of tones (deviants) were of long duration and 90% (stan- viant type (F(l,20) = 4.79,p < 0.05). Patients showed a significant attenuation of the MMN in dards) were of short duration, whereas in the the long deviant condition (2.0 ttV versus 4.4 other half of the blocks, deviants were short ttV) (F(I,20) = 8.64, p < 0.01) but not in the duration and standards were long duration short deviant condition (2.1 ttV versus 2.8 IxV) tones. Presentation of short and long deviant (F(I,20) = 1.44, NS). There were no signifiblocks was counterbalanced, alternating becant correlations between mean MMN amplitween short and long deviants from one block to the next. ERPs were recorded from 16 scalp tude and total scores on SAPS, SANS, BPRS, or chlorpromazine equivalents. locations: four midline sites (Fpz, Fz, Cz, Pz) and 12 lateral sites (F3, F4, F7, F8, C3, C4, T3, T4, T5, T6, P3, P4). Eye mover, s=at artifact was monitored by vertical anJ ~:~rizon- Discussiea tal electrooculogram (EOG). Electroencepha- The finding that the MMN component is attenlogram (EEG) and EOG were amplified with uated in schizophrenics is consistent with other a bandpass of 0.01-30 Hz and digitized at 200 demonstrations of anomalous preattentive proHz for 760 ms, which included a 250 ms cessing in schizophrenia such as gating abnorprestimulus baseline. All recordings were re- malities as indexed by the P50 (Baker et al 1987) ferred to linked ears. All 12 blocks were per- and the absence of visual perceptual grouping formed under a distraction condition in which effects (Place and Gilmore 1980). The results subjects made a manual response to visual raise the possibility that schizophrenic deficits stimuli presented on a computer screen. Fol- in controlled attention, as indexed by reductions lowing ERP recording, patients were rated on of PN and P3 amplitude (Michie et all !9_00_; the Schedules for Positive and Negative Ward et al 1991), may, at least partly, be due Symptoms (SAPS and SANS) (Andreasen to impairments in preattentive mechanisms. The 1982, 1984~ ERPs were analyzed using the finding that group differences existed for long methods adopted by Niiiitiinen and colleagues but not short deviants is puzzling. It is possible (1987, 1990), that is, difference waveforms that short deviants are more attention capturing were obtained by subtracting standard ERPs and elicit a P3a in control subjects that artififrom deviant ERPs. Mean MMN amplitude cially reduces MMN amplitude. This possibility over the 150--225 ms epoch was calculated for needs to be addressed by future research, pareach subject and analyzed using a repeated ticularly in view of recent controversy regarding measures analysis of variance with factors of the purely preattentive nature of MMN (Wolgroup and deviant type (long versus short). dorff et al 1991; Alho et ai, unpublished data). Correlations between symptom ratings and Both magnetoencephalography (Kaukoranta MMN mean amplitude were examined with et al 1989) and source analysis (Scherg et al Spearman's rho. 1989) have localized the MMN to the superior
BIOL PSYCHIATRY 199|~0: | ~ 9 - I062
Brief Repots
|~ |
v
-2#v
-
0
200
400
r'r~s
2#V
0
200
400
r'~s
Figure I. Grand average difference waveforms at the Fz electrode site for the long deviant (left) and the short deviant (right) conditions in the p.~tient (dotted line) and control (solid line) groups.
Baker N, Adler LE, Franks RD, et al (1987): Neurophysiological assessment of sensory gating in psychiatric inpatients: Comparison between schizophrenia and other diagnoses. Biol Psychiatry 22:603-617. Barta PE, Pearlson GD, Powers RE, Richards S$, Tune LE (1990): Auditory hallucinations ~ d smiler superior temporal gyral v o l ~ e in schizophrenia. Am J Psychiatrs, 147:I457-1462. Callaway E, Naghdi S (1982): An information processing model for schizophrenia. Arch Gen Psychiatry 39:339-347. Davis JM (1976): Comparative doses and costs of antipsychofic medication. Arch Gen Psychiatry 33:858-861. Johnson JD (1985): A mechanism to inhibit input activation and its dysfunction in schizophrenia. This research was supported by the National Health and Br J Psychiatry. i46:429-435. Medical ResearchCouncil and the Rebecca L. Cooper MedKaukoranta E, Sams M, Had R, H~n~l~finen M, ical Research Foundation. N~t~aen R (1989): Reactions of human auditory cortex to a change in tone duration. Hear Res 41:15-21. References Lukoff D, Liberman RP, Nuechterlein KH (1986): Symptom monitoring in the rehabilitation of American Psychiatric Association (1987): DSM-IlIschizophrenic patients. Schizophr Bull 12:578-602. R: Diagnostic and Statistical Manual of Mental Disorders. ed 3, Washington, DC: The Associ- Michie PT, Fox AM, Ward PB, Carts SV, McConaghy N (1990): ERP indices of selective atation. tention and cortical lateralization m schizophreAndreasen NC (1982): Negative syrup:ores in schizonia. Psychophysiology 27:209-227. phrenia: Definition and reliability. Arch Gen PsyN~fftnen R (1990): The role of attention in auditory chiatry 39:784-788. information processing as revealed by event-reAndreasen NC (1984): The Scale for the Assessment lated potentials and other brain measures of cogof Positive Symptoms (SAPS). Iowa City, Iowa: nitive function. Behav Brain Sci 13:201-288. The University of Iowa.
temporal plane of the temporal lobe in healthy subjects. These findings suggest that the anatomical locus of the MMN deficit in schizophrenics may be generated in the supratemporal auditory cortex. This suggestion is consistent with recent magnetic resonance imaging (MRI) evidence that in schizophrenics the superior temporal gyrus volume is reduced, particularly in the left hemisphere (Barta et al 1990). The question of whether schizophrenic patients with abnormal MMN components show evidence of structural changes in temporal areas merits careful future scrutiny using MRI.
1062
BIOL PSYCHIATRY 1991;30:1059-1062
N~i/itanen R, Picton TW (1987): The N I wave of the human electric and magnetic response to sound: A review and an analysis of the ¢-omponent structure. Psychophysiology 24:375-425. Nuechterlein KH, Dawson ME (1984): Information processing and attentional functioning in the developmental course of the schizophrenic disorder. Schizophr Bull I 0:160-203. P!.~ce EJS, Gilmore GC (1980): Perceptual organization in schizophrenia. J Abnorm Psycho189:409418. Scherg M, Vajsar J, Picton TW (1989): A source analysis of human auditory-evoked potentials. J Cog Neurosci 1:336-355.
Brief Reports
Shagass C (1976): An electrophysiological view of schizophrenia. Biol Psychiatry I 1:3-29. S h i ~ n RM, Schneider W (1977): Controlled and automatic human information processing. H. Perceptual learning, automatic attending, and a general theory. Psychol Rev 84:127-190. Ward PB, Catts SV, Fox AM, Michie PT, McConaghy N (1991): Auditory selective attention and event-related potentials in schizophrenia. 8r J Psychiatry 158:534-539. Woldorff M, Hackley SA, Hillyatd SA (1991): The effects of channel-selective attention on the mismatch negativity wave elicited by deviant tones. Psychophysiology 28:30--42.