Elsevier

Cognitive Brain Research

Volume 17, Issue 3, October 2003, Pages 747-758
Cognitive Brain Research

Research report
Altered auditory processing in acutely psychotic never-medicated first-episode patients

https://doi.org/10.1016/S0926-6410(03)00199-XGet rights and content

Abstract

Individuals with psychosis fail to differentiate external impulses and suffer from distortions of reality testing. Schizophrenia group illnesses are also associated with deficits in working memory and perception. We examined the manifestations of a very early phase of psychotic illness to automatic auditory deviance detection to clarify the basic mechanisms underlying misinterpretations of perception. Methods: Twenty-five never-medicated patients admitted for hospital evaluation of acute psychosis were studied. Fifty-eight EEG channels were recorded during an auditory oddball paradigm. Event-related potentials (ERPs) time-locked to non-attended deviant auditory stimuli were studied in patients and compared with healthy controls. Auditory processing was examined both at the level of the measured biosignals (standard and deviant responses) and with subtraction waveforms. Topographical differences were characterized using global field power (GFP) and minimum norm estimates. Results: The maximum GFP amplitudes and mean amplitudes of the 58 channels within the time windows corresponding to the previously known ‘N2b’, ‘P3a’ and ‘P3b’ components were clearly reduced in patients when compared to healthy controls. However, the groups did not differ during attention-independent automatic processing corresponding to the ‘N1’ and ‘MMN’ components, or with respect to the peak latencies of the GFP maxima. Conclusions: Impairment of the processing of a deviance in simple auditory input in acutely ill drug-naive first-episode psychotic patients only appears in attention-dependent processing after about 250 ms. The alterations in auditory processing differed between stimulus types, suggesting at least two mechanisms underlying the auditory discrimination impairments in acute psychosis. After 250 ms there was a linear and gradually increasing difference in magnitude between the groups in their responses to deviant stimuli, probably related to arousal. In addition, however, there was a striking difference between the groups in the processing of standard stimuli. The early processing was similar in patients and controls, but the striking difference appeared in later processing. The sensory memory deficits associated with psychosis may be explained by an abnormality in sensory model formation rather than by impaired deviant detection.

Introduction

The ability to guide behavior by sensory representations is deficient in psychotic illnesses, as has been shown, for example, in working memory deficits associated with schizophrenia [21]. Alterations in selective attention are also recognized findings in schizophrenia. However, the chronological order of the appearance of these defects is still largely unknown. Individuals developing their first psychotic break were selected for the current study in order to clarify whether one or the other type of impairment may be present in the early phase of the disease process.

Attentional mechanisms and emotional coloring of perceptions are modulated by fronto-limbic networks. In everyday life, short-term memory, motor planning, and inhibitory control enable novel behaviors when facing new situations and stimuli from the surroundings [19]. The cingulate cortex is heavily involved in attention shifting from one domain to another as separate large-scale networks are recruited to the perception–action cycle [8]. The normal functioning of these networks creates the necessary conditions for the cycle in which deviance detection plays a part in automatic primary sensory processing, attention and memory functions. These complex phenomena can be investigated by several overlapping but separable event-related potential (ERP) components.

N1 is the most prominent auditory ERP component, which indexes the detection of sound and overlaps with non-specific arousal activity [50]. It is elicited by a change in the acoustic environment and its amplitude is largest to the first stimulus after a period of silence. N1 is known to reflect non-specific orienting and is mainly generated bilaterally in primary auditory cortices [50].

The N2a or mismatch negativity (MMN) is generated by a neuronal mismatch between a deviant auditory input and a sensory memory trace representing standard auditory stimuli [2], [42], [49], [51]. It reflects automatic auditory discrimination and plays an important role in the involuntary switching of attention to a large or salient stimulus change outside the focus of attention [2]. MMN is also mainly generated in the supratemporal auditory cortex [2]. Although the frontal lobes play a role in MMN, the exact cerebral generators depend on the stimulus features [2], [12], [14], [20], [59]. More recently, MMN has been related to bilateral asymmetric dipole sources in the frontal and temporal lobes with right hemispheric dominance [29], [87].

The MMN is succeeded by the N2b component, which indexes attentional deviance detection. It reaches its maximum round 200–300 ms post-stimulus at centroparietal sites posterior to MMN. Thus it is separated from MMN by both latency range and topography [65], [67], [77]. The amplitude of the N2b has been correlated with the outcome of neuropsychological continuous performance tasks in healthy adults [33]. In students at high risk for psychoses, N2b latency prolongation has been reported [53].

The attention-dependent P300 component is obtained with a classical oddball paradigm where two separate stimuli are presented with different probabilities in a random order and subjects are required to discriminate infrequent target stimuli from the standards. The P3a component emerges with a fronto-central scalp distribution when novel stimuli are presented [37], and the more parietally recorded P3b is associated with focusing attention on the target stimulus [62].

The aforementioned ERP components occurring later than N1 (MMN, N2b, P3a and P3b) are commonly tested in a so-called oddball paradigm, wherein low-probability deviant tones (commonly 2–15% of the stimuli) are randomly presented among high-probability standard tones (85–97% of the stimuli). Deviant stimuli are called targets, if the recording session includes an active task (e.g. a button press for target stimuli), and they may differ from the standards by duration, pitch or any other quality. The corresponding measured ERP responses are named accordingly: standard response for standard stimuli and deviant/target response for deviant/target stimuli.

The attenuation of various ERP components has been observed in several studies on schizophrenia [1], [11], [26], [28], [31], [41], [43], [45], [57], [73], [82]. However, all reports have concerned previously medicated and/or chronic patients without specific attention to an acute episode of illness. Kathmann [34] and O’Donnell [54] found no difference in MMN, and Hirayasu observed only a left hemisphere preponderance [22] in the early phase of illness compared to healthy subjects. Recent findings suggest that antipsychotic agents improve attention-dependent information processing, but do not necessarily ameliorate pre-attentive deficits [30], [82], [84]. P3 deficits and failures of selective attention have been the best-confirmed, yet non-specific, signs of schizophrenia in many previous studies [55].

Sussman et al. have recently shown that the deviance detection processes within the auditory system are dynamic, and that the healthy brain updates its model of the sensory input instantly as the changes occur [76], [77]. Clinically, the main complication in psychosis, i.e. grossly impaired reality testing, is that the accuracy of perceptions and thoughts is incorrectly evaluated, and the dynamic adapting the thoughts and behavior according to the demands of the external reality fails. We hypothesized that the capacity of psychotic patients to build up a short-term neuronal model of the input is impaired, and they may have working memory deficits. Simultaneously, a hyperarousal state, described in our previous work [86], may enhance the overall brain activity and alter the responses. The hyperarousal state may function as an additional amplifier for specific processes. Several phenomena may underlie such hyperactivity: the resting state activity may be enhanced, the processing of stimuli in psychosis may activate more brain areas, or the active areas may have increased output when compared to ‘normal activity’. The aim of the present study was to clarify in detail the potential psychosis-induced alterations during the different steps of auditory processing. We examined never-medicated psychotic patients in the early phase of their illness, during an acute episode of psychosis, to eliminate the effects of medication and the long-term effects of the disease. We recorded two sets of oddball paradigms. The time windows were analyzed according to previously known ERP components, but the analyses extended to all measured responses and the subtraction waveform. Our aim was to minimize presumptions, since the overall effects of a psychotic state remain largely unknown.

Section snippets

Subjects

We studied 25 acutely psychotic patients (15 females, 10 males; average age 30 years, range 15–56), all of whom were admitted for hospital evaluation for the first time in their lives. Three of them had consulted a psychiatrist once before admittance because of previous prodromal symptoms, but none had received continued treatment. None of the patients had ever used neuroleptics, antidepressants or anxiolytic drugs according to their interview and hospital records. One subject was left-handed.

GFP maximum values

None of the latencies of the GFP maxima differed between the groups (main effect F(1,38)=0.261, P=0.61). The maximum amplitude values of standard responses did not differ between the groups in earlier processing (the ‘N1’ and ‘MMN’ windows), but within the later time windows (‘N2b’, ‘P3a’ and ‘P3b’) there was a significant difference between patients and controls in maximum amplitudes. In deviant responses, there was again a clear level difference across components due to patients’

Discussion

In an effort to clarify the contradictory auditory processing deficits in psychotic illness, we examined auditory responses within the time windows of previously known ERP components of acutely ill never-medicated first-episode patients. Deficits of sensory systems are well known in schizophrenia, although the exact mechanisms as well as the locations of the sources of pathology remain largely unknown. Thus, we took all scalp-recorded activity into account when assessing the responses. The

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