Auditory hallucinations in schizophrenia: the role of cognitive, brain structural and genetic disturbances in the left temporal lobe

Abstract

In this article we review research in our laboratory on auditory hallucinations using behavioral and MRI measure. The review consists of both previously published and new data that for the first time is presented together in a cohesive way. Auditory hallucinations are among the most common symptoms in schizophrenia, affecting more than 70% of the patients. We here advance the hypothesis that auditory hallucinations are internally generated speech perceptions that are lateralized to the left temporal lobe, in the peri-Sylvian region. From this we predict that hallucinating patients should have problems identifying a simultaneously presented external speech sound, as measured through performance on the dichotic listening (DL) paradigm with consonant-vowel syllables, since this technique lateralizes the stimulus input. Across a series of behavioral experiments, we have shown that patients with schizophrenia who experience frequent auditory hallucinations fail to demonstrate an expected right ear advantage on the dichotic listening test. Absence of a right ear advantage is indicative of a functional deficit in the left peri-Sylvian region. The results also revealed that patients with ongoing auditory hallucinations were more impaired than patients with previous hallucinations, and that a higher score on the hallucination item in a standard symptom rating scale (BPRS) correlated negatively with number of correct reports for the right ear stimulus. Moreover, we have found that schizophrenia patients fail to shift attention to the left ear stimulus, when explicitly instructed to focus on the right or left ear stimulus only, thus showing a deficit in inhibition of attention and response-inhibition. The behavioral DL data are substantiated in two MR morphometry studies that revealed significant reductions in grey matter density in the left peri-Sylvian region in hallucinating patients, and patients with reduced left temporal lobe grey matter density. Hallucinating patients also failed to show a right ear advantage in the dichotic listening test. Ongoing fMRI studies are focused on the underlying synaptic and molecular mechanisms by investigating the effects of the glutamate antagonist drug memantine on auditory perception and speech lateralization, and examination of temporal cortex-specific gene expression in the left peri-Sylvian region.

Keywords: VBM; auditory hallucinations; dichotic listening; fMRI; hemisphere asymmetry; memantine; schizophrenia.

Figure 1

Functional brain activation data when healthy subjects listen to dichotic presentations of consonant–vowel syllables. Note the marked left hemisphere lateralization in both data sets. The left-hand panel shows PET-data (from Hugdahl et al., 1999), the right-hand panel shows corresponding fMRI-data (unpublished data Bergen fMRI-group). Both data sets were evaluated with a statistical significance threshold at p < 0.001 (uncorrected). Neurological left-right display conventions.

Figure 2

Percent correct reports on the CV-syllables DL paradigm split for right and left ear stimulus presentations, and healthy controls, non-hallucinating and hallucinating patients with schizophrenia.

Figure 3

Percent correct reports on the CV-syllables DL paradigm split for healthy controls, patients with ongoing and patients with previous auditory hallucinations.

Figure 4

Percent correct reports on the CV-syllables DL paradigm split for right and left ear stimulus presentations, and healthy controls, non-hallucinating and frequently hallucinating patients.

Figure 5

Percent correct reports on the CV-syllables DL paradigm split for right and left ear stimulus presentations, and healthy controls and patients, when the subjects were instructed to focus attention on either the right (“forced-right”) or left (“forced-left”) ear stimulus.

Figure 6

Colored areas show significant reductions in grey matter density in the schizophrenia patients compared to healthy control subjects. The upper panel shows the sub-group of hallucinating (left) and non-hallucinating (right) patients compared to controls. The lower panel shows the sub-groups of patients that failed (left) respectively managed (right) to show a REA on a dichotic listening test.

Figure 7

Areas with warm (red, yellow) colors show areas with reduced cortical thickness in patients with schizophrenia compared with healthy controls. Note the marked asymmetry in the peri-Sylvian region inside the circles. Areas in cold colors (blue) show increased thickness in the patients. Significance threshold set to p < 0.001 with a cluster extension of at least 10 voxels. Neurological left-right display conventions.

Figure 8

fMRI BOLD activation in the left and right peri-Sylvian areas when listening to dichotic presentations of CV-syllables. The upper row shows activations for the Drug-naive condition, the lower row shows the corresponding activations for the Memantine condition. From left to right: Axial slices corresponding to 16–20 mm above the AC-PC midline in the standardized Talairach and Tournoux (1988) coordinate system. Neurological left-right display conventions.