Impact of glutamate levels on neuronal response and cognitive abilities in schizophrenia

Schizophrenia is characterized by impaired cognitive functioning, and brain regions involved in cognitive control processes show marked glutamatergic abnormalities. However, it is presently unclear whether aberrant neuronal response is directly related to the observed deficits at the metabolite level in schizophrenia. Here, 17 medicated schizophrenia patients and 17 matched healthy participants underwent functional magnetic resonance imaging (fMRI) when performing an auditory cognitive control task, as well as proton magnetic resonance spectroscopy (1H-MRS) in order to assess resting-state glutamate in the anterior cingulate cortex. The combined fMRI–1H-MRS analysis revealed that glutamate differentially predicted cortical blood-oxygen level-dependent (BOLD) response in patients and controls. While we found a positive correlation between glutamate and BOLD response bilaterally in the inferior parietal lobes in the patients, the corresponding correlation was negative in the healthy control participants. Further, glutamate levels predicted task performance in patients, such that lower glutamate levels were related to impaired cognitive control functioning. This was not seen for the healthy controls. These findings suggest that schizophrenia patients have a glutamate-related dysregulation of the brain network supporting cognitive control functioning. This could be targeted in future research on glutamatergic treatment of cognitive symptoms in schizophrenia

Auditory verbal hallucinations in schizophrenia as aberrant lateralized speech perception: Evidence from dichotic listening

We report evidence that auditory verbal hallucinations (AVH) in schizophrenia patients are perceptual distortions lateralized to the left hemisphere. We used a dichotic listening task with repeated presentations of consonantvowel syllables, a different syllable in the right and left ear. This task produces more correct reports for the right ear syllable in healthy individuals, indicative of left hemisphere speech processing focus. If AVHs are lateralized to the left hemisphere language receptive areas, then this should interferewith correct right ear reports in the dichotic task, which would result in significant negative correlations with severity of AVHs. We correlated the right and left ear correct reportswith the PANSS hallucination symptom, and a randomly selected negative symptom, in addition to the sum total of the positive and negative symptoms, in 160 patients with schizophrenia. The results confirmed the predictions with significant negative correlations for the right ear scoreswith the PANSS hallucination item, and for the sum total of positive symptoms, while all other correlationswere close to zero. The results are unambiguous evidence for AVHs as aberrant speech perceptions originating in the left hemisphere. (C) 2012 Elsevier B. V. All rights reserved

Hallucinating schizophrenia patients have longer left arcuate fasciculus fiber tracks: a DTI tractography study

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on the constrains for interaction between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer reconstructed tracks along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer tracks in the left compared to the right side. In addition, there were significant positive correlations between PANSS scores and track length, track volume, and number of track streamlines for the posterior AF segment on the left side. It is concluded that the present DTI results may have implications for interpretations of functional imaging results

The role of the primary auditory cortex in the neural mechanism of auditory verbal hallucinations

Auditory verbal hallucinations (AVHs) are a subjective experience of "hearing voices" in the absence of corresponding physical stimulation in the environment. The most remarkable feature of AVHs is their perceptual quality, that is, the experience is subjectively often as vivid as hearing an actual voice, as opposed to mental imagery or auditory memories. This has lead to propositions that dysregulation of the primary auditory cortex (PAC) is a crucial component of the neural mechanism of AVHs. One possible mechanism by which the PAC could give rise to the experience of hallucinations is aberrant patterns of neuronal activity whereby the PAC is overly sensitive to activation arising from internal processing, while being less responsive to external stimulation. In this paper, we review recent research relevant to the role of the PAC in the generation of AVHs. We present new data from a functional magnetic resonance imaging (fMRI) study, examining the responsivity of the left and right PAC to parametrical modulation of the intensity of auditory verbal stimulation, and corresponding attentional top-down control in non-clinical participants with AVHs, and non-clinical participants with no AVHs. Non-clinical hallucinators showed reduced activation to speech sounds but intact attentional modulation in the right PAC. Additionally, we present data from a group of schizophrenia patients with AVHs, who do not show attentional modulation of left or right PAC. The context-appropriate modulation of the PAC may be a protective factor in non-clinical hallucinations