Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Abstract

Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyrus were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range:4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci. Highlights

Investigation of Heschl's gyrus and planum temporale in patients with schizophrenia and bipolar disorder: A proton magnetic resonance spectroscopy study

“…However, lower order sensory areas, such as the auditory cortices have simpler receptive fields with only serial processing capabilities (Homan et al, 2014; Rauschecker and Scott, 2009; Yamada and Wilber, 1990). Given the fact that the pathophysiology of psychiatric disorders is so complicated and these disorders may have different influences on different neural systems and circuits, investigating the primary sensory areas may provide an advantage.…”

“…A 31 P MRS study reported correlation between the hallucination score of the Positive and Negative Syndrome Scale (PANSS) and phosphomonoesters and phosphodiesters (Nenadic et al, 2014). A recent 1 H MRS study comparing hallucinations in the STG reported that NAA/Cr ratio correlated with total and negative subscore of the PANSS in schizophrenia (Homan et al, 2014). Neuronal activation patterns for patients with auditory hallucinations were more prominent for the left hemisphere when compared to non-hallucinating patients as shown by functional neuroimaging studies with auditory tasks (Dierks et al, 1999; Shinn et al, 2013), which may indicate the relevance of the left auditory cortex.…”

Understanding auditory verbal hallucinations: a systematic review of current evidence

“…Auditory verbal hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Homan et al investigated the metabolic changes in auditory hallucinations requiring a functional rather than an anatomical definition of speech production and found significant differences in Broca's and Wernicke's areas associated with voice hearing in patients with schizophrenia.…”

“…In teasing out state vs. trait aspects, Kuhn found the state of experiencing AVHs related to brain regions that have been implicated in speech production, that is, Broca's area, whereas trait proneness to AVHs seems to be related to areas involved in auditory stimuli processing and speech perception, that is, auditory cortex . In terms of brain metabolism, magnetic resonance spectroscopy studies have shown some evidence of association between severity of AVHs and left temporal/Heschl gyrus metabolism .…”

The 4th Schizophrenia International Research Society Conference, 5–9 April 2014, Florence, Italy: A summary of topics and trends

“…Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) were presented as potential and safe methods to relieve the hallucinatory burden in those, who did not respond to conventional approaches. The main study presented (Homan et al, 2014) demonstrated involvement of the language system in the generation of AVH. The superior temporal lobe, including primary auditory cortex and its connections, was identified as a region involved in the generation, modulation and therapy of AVH.…”