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doi: 10.1097/01.HJ.0000434630.46891.98
Pathways

Pathways: Schizophrenia and Auditory Evoked Potentials: An Unfolding Story

Brown, Mallory; Musiek, Frank PhD

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Ms. Brown is an audiology doctoral student at the University of Connecticut in Storrs, where Dr. Musiek is professor and director of auditory research in communication sciences.

The title of this article is perhaps a bit unusual for a hearing healthcare publication. After all, schizophrenia is a psychiatric disorder primarily treated by psychiatrists. However, upon a closer look at some of the emerging clinical and basic research about the condition, auditory phenomena surge to the forefront. A key issue is the auditory hallucinations that often accompany schizophrenia (HJ Sept. 2007 issue, pp. 32-52).

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Figure. Shutterstoc...
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Schizophrenia is a chronic mental illness affecting approximately 1 percent of the population (PsychiatryRes 2012;196[2]:188-193). There are five subtypes, and symptoms are broken down into three broad categories: positive, negative, and cognitive. Auditory hallucinations are an example of positive symptoms and reportedly occur in 50 to 80 percent of patients (Int J Psychophysiol 2008;70[1]:3-15).

Figure. Frank Musiek...
Figure. Frank Musiek...
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Schizophrenia results in abnormal brain lateralization, a decreased right-ear advantage on dichotic listening, increase in non-right handedness, altered language lateralization, and reduced cerebral dominance (Psychiatry Res 2012;196[2]:188-193).

A decrease in the volume of Heschl's gyrus, especially for the left hemisphere, has been noted (Int J Psychophysiol 2012;84[2]:130-139), as well as asymmetric volumes of the inferior colliculus and thalamus (Psychiatry Res 2012;196[2]:188-193). The reductions in auditory cortex volumes seem to be linked with auditory hallucinations (Psychiatry Res: Neuroimaging 2007;156[1]:15-21). Of note, the decrease in neural volume appears to take place mostly in key areas of the central auditory system.

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ABR: MIXED MESSAGES

Though there are several attractive audiological topics related to schizophrenia, this paper will discuss abnormalities that are reflected in auditory evoked potentials and, therefore, along the auditory system pathway.

Figure. Auditory Evo...
Figure. Auditory Evo...
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Evoked potential recordings can offer insight into the biological basis of the illness and aid in the diagnosis and tracking of symptoms (Psychiatry Res 2008;161[3]:259-274). While there is consensus regarding certain potentials, discrepancies between findings also persist because of the different variables, including subtypes, symptoms, medications, and methodologies, that come into play in schizophrenia.

The auditory brainstem response (ABR) is an exogenous response occurring within the first 10 msec of stimuli presentation. It reflects synchronous neural activity from the auditory nerve through the brainstem.

Studies have yielded mixed ABR results in patients with schizophrenia. Abnormal findings have been reported, including the absence of waves, increased latencies, and reduced amplitudes (Psychiatry Res 2012;196[2]:188-193). Although the consensus on ABR and schizophrenia still remains unclear, these abnormalities suggest that there are brainstem deficits and possible impairment in very early auditory processing.

The middle latency response (MLR), which occurs from approximately 15-65 msec and is generated by the thalamo-cortical neural tract, has drawn little attention in schizophrenia research. The few studies that exist have again yielded mixed results. Victoria M. Leavitt, MPhil, and colleagues reported abnormalities as soon as 15 msec post stimuli, suggesting that sensory processing deficits may be occurring early (J Psychiatry Neurosci 2007;32[5]:339-353).

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IMPAIRED SENSORY GATING

Many studies consider sensory gating abilities of patients with schizophrenia. Sensory gating refers to “pre-attentional habituation of responses to repeated exposure to the same stimulus” (Schizophr Bul 2006;32[4]:692-700). A large body of evidence shows that patients with schizophrenia demonstrate impairments in filtering incoming sensory information.

The P50, sometimes referred to as P1, is an evoked potential used to assess sensory gating. This response is often elicited by a paired-click paradigm: a tone (S1) is presented and followed by a short interstimulus interval (typically 200-500 msec), and then a second tone (S2) is presented.

In normal individuals, the amplitude of S2 will be smaller, since it is deemed redundant and is therefore “gated out.” Individuals with schizophrenia consistently demonstrate reduced sensory gating ability (Schizophr Bull 2006;32[4]:692-700; (J Psychiatry Neurosci 2007;32[5]:339-353; Clin Neurophysiol 2010;121[8]:1233-1239; Schizophr Res 2009;113[2]:332-338; Schizophr Res 2012;139[1]:253-259).

While many studies demonstrate this decreased attenuation, the review by David Potter et al stressed the need for more research on the clinical correlates (Schizophr Bull 2006;32[4]:692-700).

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N1 & P2: AGREE TO DISAGREE

The N1 potential, a negative wave occurring at approximately 100 msec post stimulus and originating within the auditory cortex, has also been evaluated extensively in patients.

Studies have consistently demonstrated a reduction in N1 amplitude (Psychiatry Res 2008;161[3]259-274; Eur Arch Psychiatry Clin Neurosci, 2011;261[5]:331-339; Int J Psychophysiol 2004;53[1]:45-55; Int J Psychophysiol 2012;84[2]:130-139). These findings have also been demonstrated in first-degree relatives of patients with schizophrenia.

John J. Foxe, PhD, and colleagues discussed the possibility of using N1 as an endophenotypic marker for schizophrenia, since the abnormal N1 response may be linked to the genetic risk of developing the disorder rather than to the disorder itself (Eur Arch Psychiatry Clin Neurosci 2011;261[5]:331-339).

In another study, the N1 potential was used to evaluate interhemispheric transfer time (IHTT) for tonal and speech stimuli, comparing schizophrenia patients who experienced auditory hallucinations, schizophrenia patients who did not have auditory hallucinations, and a normal group (Int J Psychophysiol 2012;84[2]:130-139). IHTTs were longer in the auditory hallucination group, but only for speech stimuli.

The P2 response—a positive voltage deflection occurring at approximately 200 msec—is another auditory evoked potential showing conflicting results in schizophrenia research. While abnormalities of reduced P2 amplitude have been demonstrated in schizophrenia, other studies indicate no difference between schizophrenic and normal groups, and still others show an increase in P2 amplitude among patients with schizophrenia (Clin Neurophysiol 2012;123[7]:1300-1308).

This discrepancy across results was evaluated in a meta-analysis, which concluded that many studies failed to account for the stimulus effect, highlighting the importance of looking at event-related potentials of both standard and target stimuli (Clin Neurophysiol 2012;123[7]:1300-1308). The need for more research, with larger sample sizes and better-controlled and structured designs, was stressed.

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LOWER MMN AMPLITUDE

The mismatch negativity (MMN) is a potential that reflects auditory discrimination ability (Actas Esp Psiquiatr 2011;39[6]:363-373). It does not require attention and, therefore, is used as an indicator of pre-attentive processes.

The MMN, which is elicited using the so-called oddball paradigm, is a negative deflection occurring around 200-250 msec after the presentation of the deviant stimuli. In the oddball paradigm, the patient is presented with a series of repetitive sounds, the standards, with random interruptions by deviant, or oddball, sounds that have different physical features.

The most frequently reported finding in schizophrenia is a decrease in MMN amplitude (Actas Esp Psiquiatr 2011;39[6]:363-373;Int J Psychophysiol 2008;70[1]:3-15). While the mismatch negativity has been discussed as an endophenotypic marker, further research is needed.

The P300 event-related response is also elicited using the oddball paradigm. However, unlike the mismatch negativity, this potential requires attention and decision making. A meta-analysis of studies demonstrated a consistent reduction in P300 amplitude and a consistent increase in latency in schizophrenia (Psychophysiology 2003;40[5]:684-701).

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MORE RESEARCH NEEDED

While the understanding of schizophrenia is still incomplete, research appears to suggest that auditory processing impairments occur well before and including the auditory cortex. There is clearly a need for larger, more controlled studies looking at earlier auditory evoked potentials.

More emphasis on the careful analysis of auditory symptoms and their course is needed. Further research should attempt to pinpoint an endophenotype, which would help identify the disorder.

Because schizophrenia encompasses such a wide variety of symptoms and subtypes, drawing conclusions about the patient population as a whole is difficult. New research strategies should continue to group patients by symptoms, an approach that may offer a more thorough understanding of the underlying physiology of symptoms, such as auditory hallucinations.

The reduced amplitude and increased latency of auditory evoked potentials shown by the studies reported here could be secondary to reduced neural volume of the auditory cortex and even subcortical areas of the brain. This reduction could well lead to poor connectivity in the brain, a concept already introduced as a factor in auditory hallucinations and schizophrenia (HJ Sept. 2007 issue, pp. 32-52).

© 2013 by Lippincott Williams & Wilkins, Inc.

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