)n SCHIZOPHRENIA is. RESEARCH
k:s Schizophrenia Research 13 (1994) 23-34 n:
Event-related and motor responses to probes in a forewarned :e- reaction time task in schizophrenic patients
a a b Brigitte Rockstroh ,*, Matthias Miillef', Michael Wagnef', Rudolf Cohen , Thomas Elbert
ill 'Department ofPsychology, University ofKonstanz, Postfach 5560-D23, D-78434 Konstanz, Germany, bInstitute for ld Experimental Audiology, University of Munster, Munster, Gennany Received 5 Aprill993; revised 27 September 1993; accepted 27 September 1993 d, A )1. Abstract of ld Surface-negative brain potentials indicate increased excitability of the underlying cortical neural networks. Consequently, deviant patterns of event-related potentials in schizophrenic patients reveal an atypical regulation of A cs cortical excitability. Twelve patients with a chronic schizophrenic disorder and 12 matched control subjects were investigated using a probe paradigm: A contingent negative variation (C~'V) was evoked in a forewarned reaction or time paradigm. Clicks were presented before, during and after elicitation of the CNV. Click-evoked responses allow J1. one to 'probe' the current brain state, particularly neuronal excitability, which is also reflected by the slow potentials. During the measurements, subjects pressed one button in response to the offset of the visual warning stimulus and a different button in response to the acoustic probes, the latter button press being a behavioral indication of the brain's excitability. In the forewarned reaction time task, patients developed a CNV with a frontal maximum, while the CNV in control subjects was predominantly centro-parietal. This atypical topographical pattern of the CNV may indicate a different spatio-temporal regulation of cortical preparatory processes in schizophrenics. MotOI' responses were accelerated during negative potential shifts in both patients and controls, with responses being slower overall in patients. In patients, probe-evoked potentials revealed a smaller NIOO, but a larger P300, than in controls. The covariation of these brain waves with slow potentials, however, turned out to be similar for both groups.
Key words: Contingent negative variation; Evoked potential; Probe; NIOO: P300; (Schizophrenia) ..,)
1. Introduction. reported for schizophrenic patients relative to con trol subjects (for summary see Cohen, 1991; Cohen Hypotheses concerning deviancies in infonna- . et al., 1991; Pritchard, 1986; Rockstroh et al., tion processing and response preparation in schizo 1989; Callaway, 1975). A number of attempts have phrenic patients have been substantiated by been made to try to specify the nature of such characteristically deviant patterns of event-related deviancies, these include: impaired processing in potentials (ERP) which \vere displayed by many tasks requiring frontocortical functions, a lack of of the patients. For instance, smaller amplitudes motivation, the inability to concentrate and an ofN100, P300 and C]\;Y, but a prolonged negativ increased trial-to-trial variability of event-related ity following the imperative stimulus, have been responses (Callaway, 1966, 1975; Cohen, 1973). Because such nonspecific factors always lead to * Corresponding author. Te1: (49) 7531-88-2085. Fax: (49) attenuation of ERP amplitudes, it is unlikely that 7531-88-3017. they also account for the enhanced amplitudes
0920-9964/94/$7.00 © 1994 E1sevier Science B.V. All rights reserved ·'''"c.:::"'':':'.:''::'''·.,·",, ·ssbI092o=9964 (9'3' )EO"O 8 F4:::·: ...._. ,. :.', .". :" :""c,:,,- .::":.:·,'.'C".'.'.... ":'.:""""" ..:'."::"""""'::'::"'.:::"'.'::".""'''::::'""",''.',. 24 B. Rockstroh el clLjSchl::.oph,.,mia Research 13 (1994, 23-34 observed in schizophrenic patients after response such "';{;'" ine'P3CJO' 'mCrlcate . completion (postimperative negative variation, reduced excirabiliry in cortical neuronal nerworks, a PThv). We suggest to take characteristics of the the processing of probe stimuli presented during t generation of ERPs into consideration, because the development of a P300 should be inhibited.. I linking ERPs to the dynamics of neural mass Facilitation and inhibition of rhe processing of action should add to our understanding of their probe stimuli were evaluared by measuring the significance for cognitive or behavioural processes. evoked potential to the probe stimuli and reaction The present study was designed to examine the time of a motor response required to the probe hypothesis that atypical ERP in schizophrenic stimuli. It was expected that probe-evoked patients may be related to the regulation of excit responses were facilitated parallel to the C~\l but ability in cortical neural networks; this hypothesis inhibited parallel to the P300. should provide a framework for linking (atypical) Within an acoustic oddbalIparadigm, probe ERP amplitudes to (atypical) neuronal processes. stimuli were presented at different time delays We have previously suggested a model which might following standard or target stimuli. In subjects account for certain features observable in extended who developed an 'oddball P300' following target neuronal networks (Elbert and Rockstroh, 1987; stimuli, the amplitude of the vertexpotential Rockstroh et aI., 1989; Elbert, 1993): Infonnation (N1/P2) was attenuated and motor responses to may be coded by an increase or a decrease in the the probe stimuli were delayed during occurences firing rates of neurons, it may equally well be of cortical positivity (Rockstroh et aI., 1992; coded through distinct spatial patterns of activa Woodward et aI., 1991). In a reaction time para tion, or most likely by a combination of both (as digm, the amplitude of the vertexpotential was described by Van der Malsburg and Schneider, enhanced and the speed of motor responses to the 1986), but certainly not through synchronous acti probes increased when probes were presented vation of many or all neuronal elements. during the CNV compared to probe-evoked Therefore, overexcitation must somehow be con responses before and after the CNV (Rockstroh trolled by the brain's intrinsic mechanisms, and et aI., 1993). The latter results, indicating faster or excitability, as represented by the depolarization more efficient responses to probes parallel to the of the dendritic trees, to be regulated by imposing development of a CNV, support our hypothesis limits on the dynamic patterns of neural mass that the CNV represents increased cortical excit action (Elbert, 1993). A depolarization in the ability, thereby facilitating the processing ofstimuli apical dendritic trees results in surface negative presented to a more easily excitable network. Such potentials (such as the CNv) which therefore a tuning mechanism may serve as a basis for reveal enhanced cortical excitability enabling a attentional regulation. preparatory state or 'potentiality' for cerebral pro The present study utilized the above mentioned cessing in the underlying networks (Rockstroh probe-design (Rockstroh et aI., 1993) to test the et aI., 1989). In contrast, slow positive shifts can regulation of slow potentials and to test its covaria be produced by a 'disfacilitation' in cortical neural tion with probe-evoked responses in schizophrenic networks. patients. By this, we intended to examine to what In analyzing this hypothesis, test stimuli were extent an atypical regulation of cortical excitability used to 'probe' the functional brain state during and/or an atypical functional significance would electrically positive and negative potentials, i.e. underlie deviant ERP patterns in schizophrenic P300- and CNV-evocation, respectively (Rock patients. A deviancy from thenonnal response stroh et al. 1992; 1993; Woodward et aI., could be expected for the following reasons: (1) It 1991). Probe stimuli presented during surface can be assumed that cortical excitability is modu negative potentials would be presented to already lated within a feedback loop from the cortex to excited cell assemblies and, hence, ignition of the the basal ganglia and thalamic structures back to corresponding cell assemblies should be faster and the cortex with tuning functions through frontal more widespread: on the other hand, if positive structures (Elbert and Rockstroh, 1987; Elbert, B. Rockstroh et al.iSchizophrenia Research 13 (1994) 23-34 25 lte 1993). There is increasing evidence that functional significance of slow potential shifts. If schizophre cs, and structural impairments occur in these struc nic patients exhibit an atypical spatio-temporal rrg tures in schizophrenia (e.g., Andreasen et al., 1990; regulation of excitability, a different scalp distribu :d. Pfefferbaum and Zipursky, 1991). (2) From a tion should appear; however, potential amplitudes of synopsis of neurological, neurophysiological, neu may change in either direction. If negative poten he rochelnical and neuropsychological findings in tial shifts differ in their nature. between schizophre In schizophrenic patients, Cleghorn and Albert nic patients and control subjects, the probe be (1990) concluded an inadequate temporal associa responses should be modulated differently. It is of ~d tion of 'cognitive modules' (defined as functional particular interest whether the PINV represents a. ut entities of cerebral processes), and an inadequate prolonged CI'rV or whether it is an inhibitory area-specific allocation of processing resources to rather than a facilitatory response. Je be at the basis of cognitive, aitentional, perceptual ys and affective symptomatology in schizophrenia. :ts (3) Pfefferbaum and Elbert (unpubL data) fitted 2. Materials and methods et one central dipole which accounted for the major al portion of topographical variance in the event 2.1. Subjects to related potentiaL During an acoustic oddball task, es the Lissajous trajectories of the equivalent dipole Twelve patients (9 men, 3 women) with a chronic ...."),. in schizophrenic patients differed from those of schizophrenic disorder according to DSM~III-R a the control subjects. The P300-vector oriented and twelve matched control subjects were paid for 1S parietally in controls points towards the vertex in participation in the study that lasted approxi le schizophrenics, confirming differences in topo mately one hour. Except for one patient all subjects :d graphical distribution and suggesting that the were right-handed according to a modified version :d reduced P300-amplitudes at parietal locations may of the Oldfield handedness questionnaire. The cur ,h be due to a variant topography. rent status of symptomatology was evaluated by )r As of yet, few studies have been performed using the Brief Psychiatric Rating Scale (BPRS) during le the probe-paradigm to investigate schizophrenia, the week of the investigation (mean sum score IS and conclusions are controversial. Timsit-Berthier 41.8, range 31-52). All patients except one were t et al. (1971) demonstrated a reduced probe-evoked under neuroleptic medication (mean 219.7 mgiday .li potential in schizophrenic patients for probe stim CPZ equivalent). One patient was receiving 400 mg :h uli presented shortly after the imperative signal, carbamazepin in addition, and another anticholin Jr i.e. during the postimperative negative variation. ergics (AJcineton). Control subjects were matched Based on this result, the authors concluded the for sex, age and education (employment status and d postimperative negativity to be of inhibitory educational degree). It was assured that control le nature. Wagner et al. (1993) presented task subjects were not under current medication and L- irrelevant sounds before the warning signal interval had not suffered from any central nervous system IC and/or during the Sl-S2-interval. Sounds presented abnormality. The mean age of the patient group Lt prior to the imperative-stimulus increased reaction was 29.7 years, and that of the control group 29.6 Y time differentially, which was discussed as evidence years (range 22-45). d for 'a heightened susceptibility for the irrelevant ~c events during time estimation and motor prepara 2.2. Design andprocedure ,e tion' (p.168). [t In summary, the present study aims to evaluate Within a reaction time paradigm a scattered l- the hypothesis of an atypical regulation of cortical light of 3 s duration was presented as a warning o excitability in patients suffering from schizophrenia signal (WS). Subjects were asked to press a black o on the bases of (a) the scalp distribution of slow button with the left hand as fast as possible in tl potential shifts and (b) the modulation of probe response to the offset of the WS. Clicks served as r-, evoked responses as indicator of the functional acoustic probe stimuli. Counterbalanced across 26 B Rockstroh er al./Schizophrenia Research 13 (1994) ]3-3-1
trials a probe could occur during the baseline (1.5 switched bo[h the light bulb and the tone bursts. fr s prior to WS-onset), during the anticipatory Ordinary microswitches served as response but m interval (0.5 s. 1.0 s, 1.5 s, 2.0 s following tons. EEG was amplified from DC to 30 Hz. The tI WS-onset) and 3.0 s following WS-offset. No more amplifier (NIES, Munich) delivered digitized sig tr than one probe was presented during a trial. Probe nals to a second AT 386 which stored the physio 1'( stimuli presented 3.0 s following WS-offset and 1.5 logical signals together with the trigger events on s preceding vVS-onset served for comparisons with an optical storage device. a probes presented during the slow potential shift. EEG recorded from frontal (Fz), central (Cz) o Subjects were asked to press a red button, which and parietal (pz) leads was referenced to the right ti they held in their right hand, as fast as possible in earlobe. Nonpolarizable silver-silverchloride a response to each probe. electrodes (ZAK) were used for the EEG record A total of 120 trials were presented. 25% (30 ings, Grass EC2 electrolyte served as the conduct r trials) were without a probe, in 25% of the trials, ing agent. The skin under the electrodes was s a probe could occur either at 0.5 or 1.0 s following prepared by cleansing with alcohol and by remov WS-onset (15 trials each), 25% of the trials pre ing the outer layers of the skin with an abrasive sented a probe at either 1.5 or 2.0 s delay from paste (OJ\tfNIPREP). The vertical EOG was WS-onset (15 trials each), and 25% of the trial recorded via silver-silverchloride electrodes presented a probe 3.0 s following WS-offset or 1.5 (BECKlV1AN) centered approximately 1 cm above s prior to WS-onset. Whether or not a probe was and below the left eye. Beckman electrode jelly presented, as well as the points in time for a probe served as the electrolyte. Again, the skin was to occur, was determined by random order. The prepared using alcohol and abrasive paste. intervals between successive trials varied pseudo Electrocortical data were digitized and stored at a randomly between 6 and la s. rate of 100 Hz. Response latency was stored to the After the preparation for the physiological nearest ms. recordings subjects. received written instructions describing the tasks. Subjects were instructed to 2.4. Data reduction and analysis adopt a relaxed position, to fL>:ate on a spot on the wall and to avoid head and eye movements. Only trials in which subjects did not respond The experimental series of 120 trials was preceded before WS-offset or with a delay of more than 1 s by 10 practice trials. During the first five of these following WS-offset were considered for data trials the WS was presented without probes in analyses. This criterion was met by 115.9 (96.6%) order to familiarize the subject with the warned trials on average for the entire sample. reaction time task. The following five trials For the remaining trials EEG epochs of 9 s included probe stimuli in order to allow the sub including a 2-s baseline were controlled for arti jects to practice the dual task. Practice trials were facts and corrected for vertical eye movement supervised by the experimenter. artifacts according to Berg (1986). Using a blink template and templates for drifts (large DC-shifts 2.3. Apparatus andphysiological recordings in anyone EEG or EOG-channel of more than 100 ~V with.in 0.5 s), muscle potentials or complex An ASYST (A Scientific Language) program, signals, each trial'was classified as artifact-free or running on an AT 386 computer, controlled the artifact-contaminated. Trials contaminated by timing of the experimental stimuli and the storage large DC-shifts or drifts or otherwise classified of reaction times. As warning stimulus, a60 Watt artifacts were rejected from further analysis. Eye bulb not observable by the subject indirectly illumi blinks were corrected using a regression analysis; nated the wall 2.5 m in front of the subject. The ocular activity was removed from th.e averaged acoustic probe stimulus was a 400 Hz tone pre EEG traces using the weights determined in the sented for 20 ms duration at 80 dB APL (rise and trials with detected blinks (serving as calibration fall time la ms) binaurally via earphones. Stimuli intervals). These procedures of artifact controlled were presented by Coulbourn Instr. modules which to the rejection of the ERP-data of one patient B. Rockstroh et al./Schizophrenia Research 13 (1994) 23-34 27 rsts. from further analysis. For the remainillg sample, freedom with the Greenhouse-Geisser-Epsilon. but an average 85.7 ± 4.9 (71%) artifact-free trials in Means ± standard errors are presented. The the patient group (n=11) and 90.7±3.9 (76%) sig- trials in the control group (n = 12) were accepted ysio for analysis (no significant group difference). 3. Results s on Slow conical potentials were described by the f-~· average amplitudes during. the time segments 3.1. lvIotor responses and slow corticalpotentials (Cz) 0.5-1.5 s 1..5-2.5 s, and 2.5-3.0 s. Since the first during the reaction time task (primary task) right time segment was still dominated by the later Jride aspects of the visual evoked potential to WS-onset, Reaction times (RT) to WS-offset were de1ayed :ord the second time segment was used to score the in schizophrenic patients (463 ± 13 ms) as com iuct- initial CNV (iCNV), while the third score mea pared to controls (361 ±8 ms, main effect Group was sured the terminal CNv' (tCNV). The average (F( 1,22) = 8.1, p < 0.01). If a probe was presented nov amplitude during 1.5-2.5 s post-WS measured the prior to WS-onset or during the first 1.5 s of the lSlVe postimperative negative variation. WS-interval, RT to WS-offset was reduced was Responses to probe stimuli were determined by (Condition: F(6,132)=3.0,p<0.05). However, for odes evoked potentials and reaction times (RT). It was the simple effects, only the differences in' RT bove assumed that the probe-ERP were superimposed between trials without probes and trials with jelly . onto the CNV. Point-by-point difference curves probes at 1.5 s (t(23)=2.6, p<0.05) reached was between trials without probes (as a 'template') and significance. ·aste. each of the probe conditions (with probes during Examples of the mean potential shifts during at a the baseline, 0.5 s following WS-onset, etc.) were the WS- and post-WS-interval in patients and ) the calculated in a first step. From these differences controls are presented in Fig. 1. The potential the maximum negative deflection and the maxi shifts on trials with probe presentation are illust rated by superimposing the grand averages for mum positive deflection between 80 and 400 ms trials with and without probes. After a pronounced relative to a 100 ms interval prior to the probe positive evoked potential to WS-onset, a distinct were determined as NlOO and P300 to probes, Jond CNV, though small in amplitude, developed in respectively. Amplitude and latency scores were n 1 s both groups. The slow potentials are best charac assessed for the three electrode locations Fz, Cz data terized in trials without probes: The iCNV ampli and Pz. The median reaction time (RT) to every 1.6%) tude following the WS-evoked response reached a probe delay condition was calculated as the score frontal maximum in both groups, while the fronto for the motor response to probes. . 9 parietal gradient was steeper in patients than in Differences between groups, conditions and arti controls (Group x Electrode: F(2,42)=6.6, p< recording sites were evaluated by means ofanalyses ment 0.01, main effect Electrode: F(2,42) = 25.4, blink ofvariance with the between-subjects factor Group p control subjects schizophrenic patients Cz ws "1 ws >LV 0 lllVlil'l'i\\,,/U·,.IPf'!If-i'iW!\. rli\;.1• Jpro~, I. +10.J r"'~~~...-',-'.--j-,-r-.....,...... ,-.-, . 3 5 7 9 sec 3 5 7 9 sec -10 -10 Fig, : (n= 1 ordin whiJ the (Elt 4.5, 3 5 7 9 sec 3 5 7 9 sec p<1 -10 -10 F stra (PI: not Ill} inte p< Sig: j probe +10 ...-,~...,...+:.,=;~.,....,..,.....--.-, bet 3 5 7 9 sec 3 5 7 9 sec pat cat, -10 ·10 tell (F( for prc the prc wi1 3 5 7 9 sec 3 5 7 9 sec 3.:: sti, Fig. 1. Examples of event-related potentials (in 11 V, negativity up) at the central recording site (Cz) during 2 s prestimulus baseline, 3 s WS-interval and 4 s post-WS, averaged across control subjects (n = 12, left) and schizophrenic patients (n = 11, right). ERPs were lowpass-filtered with 15 Hz. Superimposed are group averages for trials without probe (thin lines) and trials with a probe presented at different time points relative to the WS (examples include probes during baseline, probes I sand 2 s after WS-onset th: and 3 s after WS-offset), The time interval of the WS is marked by the shaded area. B. Rockstroh et aL/Schizophrenia Research 13 (1994) 23-34 29 -- schizophrenic patients -- conlrol subjects iCNV tCNV -8 -8 > > ::L :i- t:: .;;; -4 .S: .... Cl) -4 "0 "0 :~ .~ C. ~ a. E 0 E 0 co '" >z >z 0 S2 '~+4 +4 co cot:: Ql Cl) E E +8 +8 Fz Cz pz Fz Cz pz Fig. 2. Fronto-parietal gradient of the initial CNV (iCNV, left) and the terminal CNV (tCNV, right) for schizophrenic patients (n= 11, solid lines) and control subjects (n= 12, dashed lines). Abscissa: electrode locations (frontal: Fz, central: Cz, parietal: Pz), ordinate: Cl\ while trials with probes presented before and after faster to probes than to WS-offset, while controls the WS-interval produced the larger central CNv responded faster to WS-offset than to probes (see (Electrode x Condition for the iCNV: F( 12.252) = Fig. 3; for the respective ANOVA: Group 4.5, p 23-34 .control subjects !!Elschizophrenic patients T 0 0> ·1.5 sec a,s sec 1,0 sec 1,5 sec 2,0 sec +3.0 sec Baseline during WS-interval Post-WS interval Fig, 3. Median reaction times to probe srimuli (ordinate, in ms) averaged separately for schizophrenic patients (light bars) and control subjects (dark bars) for the different time points of probe presentation (abscissa). The horizontal lines mark the mean reaction times (RT) to the WS-offset in patients (solid) and controls (dashed). Error bars indicate standard errors. Group, F(l,22)=3.2, p N 100 • control subjects level). For the P300, the pattern of results was ~schizophrenic patients reversed: In patients, amplitudes were generally -21 larger and increased significantly when probes > "- were presented at 2 s after WS-onset and 3 s after E -16 - '0" -WS-offset, relative to probes during the baseline ~ Ci -11 (F(5,105) =2.4, p<0.05; p<0.05 for the simple E Fig. 4. Mean amplimdes of probe-evoked potentials (NlOO 4. Discussion ~ency top, P300 bottom) averaged separately for schizophrenic patients (light bars) and control subjects (dark bars) for the Three questions were the focus of the present different conditions of probe presentation. Abscissa: the ,5±1.9 study: (1) Would the CNV differ in amplitude and different points in time of probe presentation. Ordinate: ).6±1.4 scalp distribution between patients and control EP-amplitudes in )J.V (negativIty up for NlOO, positivity up .5±L8 for P300). subjects') (2) Would the relationship between slow potentials and responses to probes ,differ for the 12±20.4 '.)+30.8 two groups? (3) If so, does this indicate a different J.4±4.g both components were considered by means of functional meaning of slow potentials? Answers to peak-to-peak amplitudes (Nl/P3), groups demon these questions would help to prove the hypothesis strated the same modulatory dependence of the that slow potentials, a measure ofcortical excitabil l1e 1 for primary task (Group x Condition: F(5,l05)=1.4, ity, are regulated differently in schizophrenic n.s.). patients than in control subjects. :sponse, Including both components separately in a Differences in the topography of the terminal 'a1uated MANOVA resulted in an interaction CNV in patients and control subjects are pro l:P3 as GroupxCondition (F(5,105)=2.7, p<0.05). In nounced: A posterior predominance of the tCNV '.4). patients, N100-amplitudes were generally smaller in control subjects replicated earlier results 2,42) = and did not vary benveen probe delays, whereas (Rockstroh et aI., 1993). In contrast, patients ere pre NlOO increased significantly in control subjects devc1op~d a pronounced frontal tCNV and no . probes from probes presented 1.5 s before WS-onset negativity over Pz. A similar group difference· 'S-offset to 1 s, l.5 sand 2 s after WS-onset though less pronounced - was observed for the resented (Group x Condition x Component F(5,l05)=2.3, earlier portion of the C~ry. Slow fronto-central on time p < 0.1; t-values on the respective comparisons negative shifts were also reported by Cohen et al. '. \\tilen in control subjects were significant on a 5%- (1991), and, particularly for the tCNv, by Wagner . r'""".$l!ii~tt"tt4'~4\!i!ii!&Z;4Ji$,~:;;.;;e;;tt.AM:um',•••L4i4I!4iiiQt;;i;Wmw;,· ;"J ;~~} .>r~j!.(,::;;;~ltQ:l'~tr';<;:>::'[:.!~i·':>'. Cc . . i .;·· ,c.': .. • ·-;';c'·, ...::.:~: '. ,',_, ...... _i_'.-.·.,.>_,~ 32 B. Rockstroh et et al. (1993) and Van den Bosch (1983, 1984). (N100;'P300) with the development of the slow cc Such a topographical patterning does not support potential in th~ control group confirms our previ assumptions of a global frontal impairment of ous results (Rockstroh et al., 1993). Only with ill s~ schizophrenic patients. The increased frontal acti 0 respect to the N 100 are ur results in accord with b, vation may, however, be interpreted as an attempt those of Timsit-Berthier et al. (1971), who demon dl to compensate for insufficient frontal functioning. strated a reduced evoked potential parallel to a SI It is also possible, that shifts over the frontal PINV. These authors consequently attributed their electrode result from volume conducted activity in result to an inhibitory nature of the PI~Y. b· the temporal lobes. In either instance. the hypothe Considering the pronounced P300 and the faster te sis of a deviant spatial modulation of cortical motor responses we believe that the PINV is Ir excitability is confumed. facilitatory in nature. Groups did not differ sig I r n In the present design, patients developed a nificantly in their modulation of the peak-to-peak tl PINv'. The correlation between the fronto-central NlOO;P300 amplitude with the slower potential I Cl PINV and the fronto-central tCNV-amplitude in changes. This result, as well, points to a similar b patients demonstrates that a PINV existed primar functional meaning of slow negative potentials in P ily in patients who also produced a tCNV. schizophrenic patients and control subjects. ti These results emphasize the necessity of con Attenuation of N100- and P300-amplitudes ti sidering the spatio-temporal regulation of brain primarily to acoustic stimuli - is a common finding e: potentials: Patients as well as control subjects in schizophrenic patients (for a summary, see produced a tCNV, however, the locations differed. Cohen, 1991; Ford et al., 1992). However, the Given the visual task, the lack of parietal tCNV present results suggest that a reduced 5 seems maladaptive. Furthermore, the (fronto P300-amplitude is not a general finding in patients. central) negative shift continues on after task NIOO- but not P300-attenuation was replicated in completion in patients, but disappears in control our results. Patients developed pronounced F subjects (possibly because the negativity has served P200;P300 amplitudes of 10-20 ~V in response to t, its functions). This atypical spatio-temporal regu probe stimuli. The different latencies of the P300 f, lation of brain activity indicating the regulation of (with earlier latency at Fz than at pz) may be the P cortical excitability possibly contributes to the result of an overlap of components in the P3-area, t; discussion of atypical information processing in such as P3a and P3b. Although the present design a schizophrenia. Given the dual task condition schiz was not specifically designed to elicit a P3a (i.e., ophrenic patients may have more difficulties coping probes were not novel stimuli to the subjects), they with the forewarned reaction time task (primary could have elicited an orienting response, accom task), a task which profits from adequate atten panied by a P3a (Grillon et al., 1990). It is possible 6 tional preparation (Niemi and NiiiWinen, 1981; that this orienting response was more pronounced Strayer and Kramer, 1990). Encoding spatio in the patient group. Braff and coworkers (e.g., temporal patterns of brain activities will help us Braff, 1985; Grillon et aI., 1990) reported among to understand· the nuances of theattentional others that schizophrenic patients are more suscep deficits. tible to distractions. This was indicated, for E The observation of faster motor responses to instance, by a larger P3a elicited by distracting probes during the PI~'V-interval in patients sug stimuli relative to the (reduced) P3b to target E gests that this negative shift and the CNV are of stimuli. The present dual task relates to the work the same make. Patients responded faster to acous of Braff and Grillon with respect to challenging tic probes than to the visual signal. Cohen, 1991, distractability in schizophrenic patients. The larger suggested that such findings can be rationalized positive aspect of the probe-evoked potential is in ( because acoustic stimuli require less cooperation line with the findings of Grillon et al. (1990) and ( and conscious effort in order to be perceived may point to this susceptibility. (Posner, 1978). One may assume that reaction time, evoked ( The modulation of the probe-evoked potential responses as well as their modulation in patients B. Rockstroh et al./Schizophrenia Research 13 (1994) 23-34 33 t f: : slow ology. In: A. Kales, e. Stefanis and J. Talbott (Eds.) Recent I could be influenced by the current psychiatric and I preVl medication status. However, for the present Advances in Schizophrenia. Springer, New York, pp. 59-80. .,, Cohen, R. (1973) The influence of task-irrelevant stimulus 1 with sample, we did not find any significant correlation { i with variations on the reliability of auditory evoked responses in between BPRS score, mediaction and the depen schizophrenia. In: A. Fessard and G. Lelord (Eds.l Activites ~mon dent variables. This, however, may be due to the Evoquees et leur Conditionnement. Colloque INSERM. 1 to a small sample size, and thus requires further testing. Editions INSERM, Paris, pp 373-387. i their In sum, event-related potentials dq not seem to Cohen, R. (1991) Event-related potentials and cognitive :lINV. be generally altered in psychotic subjects but rather dysfunctions in schizophrenia. In: H. Hafner and W.F. Gattaz (Eds.) Search for the Causes of Schizophrenia. faster to reflect specific deviancies in functional process 'JV is Springer, Berlin, Heidelberg, New York, pp. 342-360. ing. Although the present results may be prelimi Cohen, R .. Berg, P. and Hopmann, G. (1991) Slow response ~r Slg nary because of a still small sample, they indicate related negativities in chronic schizophrenics. In: G. Racagni, I-peak that the functional meaning of slow potentials is N. Brunello and T. Fukuda (Eds.) Biological Psychiatry. tential comparable in schizophrenic patients and controls Excerpta Medica, Amsterdam, pp. 550-552. imilar but Ihat the spatio-temporal generation of these Elbert, T. (1993) Slow cortical potentials reflect the regulation of cortical excitability. In: W.e. McCallum and S.H. Curry ials i potentials, as represented in their scalp distribu (Eds.) Slow Potential Changes in the Human Brain. Plenum. tion, may be atypical; this asks for closer examina New York, pp. 235-252. ides tion of this spatio-temporal regulation of cortical Elbert,T. and Rockstroh, B. (1987). Threshold regulation - a nding excitability in further studies. key to the understanding of the combined dynamics of EEG {, see and event-related potentials. J. Psychophysiol. 4. 317-333. r, the Ford, J., Pfefferbaum, A., Roth, W. (1992) P3 and schizophre duced nia. In: S. Sutton (Ed.) Annals of the New York Academy 5. Acknowledgement tients. of Science, New York, pp. 146-162. Grillon, e., Courchesne, E., Ameli, R., Geyer, M., Braff, D. ted in Research was supported by the Deutsche (1990) Increased distractability in schizophrenic patients. unced Forschungsgemeinschaft (Ro 805). We would like Arch. Gen. Psychiatry 47, 171-179. Ilse to Niemi, P. and Naatanen, R. (1981) Foreperiod and simple to thank Drs. Watzl, Haslacher and Niedermeier P300 reaction time. Psycho!. Bull. I, 133-162. for accomplishing the BPRS and H.J. Hautkappe, )e the Pfefferbaum, A. and Zipursky, R.P. (1991) Neuroimaging A. Heinz and A. Sterr for assisting in data collec -area, studies of schizophrenia. Schizophr. Res. 48, 563-568. tion and analysis and Ch. Robert for manuscript Posner, M. (1978) Chronometric Explorations of Mind. iesign assistance. Erlbaum, Hillsdale. 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