Objective
Schizophrenia is associated with aberrant event-related potentials (ERPs) such as reductions in P300, processing negativity and mismatch negativity amplitudes. These deficits may be related to the propensity of schizophrenia patients to experience auditory verbal hallucinations (AVH). However, AVH are part of extensive and variable symptomatology in schizophrenia. For this reason non-psychotic individuals with AVH as an isolated symptom provide an excellent opportunity to investigate this relationship.
Methods
P300 waveforms, processing negativity and mismatch negativity were examined with an auditory oddball paradigm in 18 non-psychotic individuals with AVH and 18 controls.
Results
P300 amplitude was increased in the AVH group as compared to controls, reflecting superior effortful attention. A trend in the same direction was found for processing negativity. No significant differences were found for mismatch negativity.
Conclusion
Contrary to our expectations, non-psychotic individuals with AVH show increased rather than decreased psychophysiological measures of effortful attention compared to healthy controls, refuting a pivotal role of decreased effortful attention in the pathophysiology of AVH.
Decreased electrophysiologial measures of attention, such as reduced P300 amplitude, are among the most consistently reported neurobiological abnormalities in schizophrenia (for an overview see Jeon and Polich, 2003). The P300 event-related potential (ERP) is a positive deflection of the electroencephalogram (EEG), occurring approximately 300 ms after the presentation of infrequent (deviant) stimuli. Since the P300 amplitude is largest when subjects are requested to respond to the deviant stimulus, P300 waveforms are usually assessed in an oddball paradigm, in which the participant activily discriminates presented deviant stimuli from standard stimuli (Sutton et al., 1965). The P300 amplitude is thought to reflect aspects of further (conscious) processing of relevant stimuli (Näätänen, 1990), and is proportional to the amount of attentional resources that are allocated to the processing of a stimulus (Grillon et al., 1991, Kramer & Strayer, 1988 and Sutton et al., 1965). The P300 amplitude has been proposed as a potential endophenotype for schizophrenia (Bramon et al., 2004), i.e. a biological marker that is meaningfully associated with the disease.
Another electrophysiological measure of attention associated with schizophrenia is processing negativity (PN). Processing negativity is elicited whenever a participant is requested to selectively attend to a certain stream of information, while having to ignore another (e.g. listen to a male voice, while ignoring a female voice or attend to stimuli to the left ear, while ignoring stimuli to the right ear). This negative deflection is thought to represent a mechanism by which the brain selectively attends to relevant stimuli (Näätänen, 1990). Reduced PN has been reported in medicated (Baribeau-Braun et al., 1983 and Iwanami et al., 1998) as well as unmedicated schizophrenia patients (Michie et al., 1990 and Ward et al., 1991).
In contrast to P300 and PN waveforms, mismatch negativity (MMN) is best elicited by an oddball paradigm in the absence of attention. This negative deflection to deviant stimuli is thought to reflect the automatic, pre-attentive detection of auditory changes (Näätänen et al., 1978 and Näätänen, 1990). Reduced MMN amplitude in schizophrenia patients is a robust finding (Näätanen & Kahkonen, 2009 and Umbricht & Krljes, 2005).
P300, PN and MMN waveform abnormalities may be related to the neuropathology of schizophrenia, or to specific parts of the disorder. Information about associations between attention and specific symptoms of schizophrenia could increase understanding of the role attention may play in the pathophysiology of schizophrenia. However, in schizophrenia patients it is difficult to disentangle specific associations with symptom clusters, as the presence and severity of many symptoms are usually correlated. One of the characteristic symptoms of schizophrenia is auditory verbal hallucinations (AVH), occurring in at least 70% of the patients (Sartorius et al., 1986 and Slade, 1988). Previous studies have found an association between P300 amplitude and AVH in schizophrenia patients. Havermans et al. (1999) reported a reduction in P300 amplitude in schizophrenia patients with chronic auditory hallucinations compared to patients without auditory hallucinations, and Turetsky et al. (1998) found an inverse correlation between the severity of auditory hallucinations and a frontal P300 subcomponent. It could therefore be hypothesized that the liability of schizophrenia patients to experience AVH may be associated to their decreased attentional capacity. However, most schizophrenia patients with AVH also experience delusions, some degree of disorganisation, and negative symptoms. In addition, patients who do not experience AVH may still be predisposed to hallucinate and develop AVH in another stage of their illness. Interestingly, 10–15% of healthy individuals also experience AVH (Tien, 1991). In this population, AVH occur in the absence of delusions and negative or cognitive symptoms, although the tendency for schizotypal behavior and delusional beliefs is higher than in healthy individuals without AVH (Sommer et al., 2008). Moreover, these non-psychotic individuals with AVH are not using antipsychotic medication, nor do they have a history of hospitalization. Therefore, non-psychotic individuals with AVH provide an opportunity to study whether the deficits of attention associated with schizophrenia are specifically related to AVH, or rather to other aspects of the disease such as negative symptoms or cognitive dysfunction.
Because non-psychotic individuals with AVH and schizophrenia patients share a single isolated symptom, we hypothesize that abnormalities in P300, MMN, and PN amplitudes are similar to those found in schizophrenia patients and will be reduced compared to control subjects without AVH.
