)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