By means of coincidence parametric maps applied on patients with schizophrenia, we have demonstrated the presence of neuronal clusters located in the left superior temporal and bilateral middle temporal gyri with both functional abnormal activation after an emotional auditory paradigm and gray matter reduction.
Auditory hallucinations bilaterally activate the superior and middle temporal gyri. Bilateral middle temporal gyri have been involved in emotion[20
]. Structures activated during the perception of external voices are also activated during auditory hallucinations with the additional activation found in areas responsible for the processing of emotion[10
]. Data are consistent on a negative correlation between the left superior temporal gyrus volumes and auditory hallucinations[2
]. This finding was expected according to the emotional task that was used in the experiment which was designed to elicit the emotional response that patients with schizophrenia have when facing their auditory verbal hallucinations. It is a task aimed to draw out the key areas involved in the pathogenesis of auditory hallucinations and is therefore concordant with many studies of functional auditory stimulation.
It is not surprising that the superior temporal gyrus and middle temporal gyrus are key elements of all pathological models which have been proposed to explain auditory hallucinations. Most of the activity studies have shown that auditory hallucinations are also associated to regional blood flow increases in the left superior temporal gyrus and other fronto-temporal areas[9
]. A neurophysiological interaction among psychopathology (auditory hallucinations), brain function (increased hemodynamic) and structure (gray matter deficits) has been previously hypothesized[15
]. It is generally accepted that areas of decreased perfusion parallel decreases in gray matter concentration as occurs with age-related brain reduction, which is probably associated with a decrease in blood flow and metabolism in those areas. Nevertheless, our findings suggest the contrary effect, showing that in schizophrenic patients an abnormal hyperactivation is found in specific areas of maximal neural density decrement. These areas of coincidence where the same voxels have hemodynamic functional changes associated with the emotional auditory-triggered response and focal decreased density may express a compensation phenomenon in which regions with decreased volume need a larger hemodynamic response to a well-defined paradigm.
An influential model for the pathogenesis of auditory hallucinations in which the superior temporal and middle temporal gyri are key areas has been postulated[10
]. A “top-down” network, presenting an altered activation in speech production areas (i.e., inferior frontal gyrus) and altered coupling with monitoring areas (anterior cingulate) and language reception areas (Wernicke’s area) was suggested. There would also be a “bottom-up” dysfunction through over-activation of secondary and occasionally primary sensory cortices that lead to the experience of vivid perceptions in the absence of sensory stimuli.
The neurobiological basis for temporal gyrus volume reduction is unknown. Abnormal brain maturation processes influenced by multiple genes interact with other potentially causative factors for psychoses such as substance abuse, stress and dysregulation of the hypothalamic-pituitary-adrenal axis function. Other factors may also interfere including poor diet and exercise, smoking, psychosocial and socioeconomic influences, and associated physical comorbidity as well as neuroleptics and other medications[21
Structural and functional abnormalities in the superior temporal and middle temporal gyrus may also be relevant in the pathogenesis of schizophrenia. Several findings support the idea that decreasing superior temporal gyrus volume is a potential endophenotype for schizophrenia-spectrum disorders. Firstly, an MR imaging study in 29 young, non-psychotic subjects with a schizophrenic parent had reported bilateral superior temporal gyrus volume reduction compared to controls with no psychiatric family history[22
]. Secondly, reduced superior temporal gyrus volume has been consistently reported in patients with schizotypal personality disorder[23
]. The superior temporal gyrus is also particularly affected during the first years of illness through progressive gray matter reductions. This is the case even during the prodromal phase and probably has clinical implications[24
The study presented here contains several limitations. Our relatively small sample size may have hampered the ability to detect significant correlations in other potentially relevant areas, although it has been reported that a sample of 20 or more subjects is sufficient to obtain reliable functional neuroimaging data[25
]. The results obtained from a high homogeneous sample (only schizophrenic patients with persistent auditory hallucinations were included) cannot be generalized to all patients with schizophrenia. We assessed our multimodal approach to be a strategy for determining brain areas that should be further assessed to study the neurobiological basis of one particular symptom or aspect of a disorder. Additionally, hallucinatory experiences during fMRI scanning were answered subjectively according to the patients’ perception, with the subsequent lack of certainty derived from this qualitative approach. Finally, all our study patients were medicated with a wide range of first- and second-generation antipsychotics. Our findings can hardly be attributed to medication. In fact, a recent study in antipsychotic-naïve first-episode schizophrenia with [(18)F] fluoro-deoxyglucose (FDG) positron emission tomography has shown that patients experiencing auditory hallucinations during FDG uptake had significantly higher metabolic rates in the left superior and middle temporal cortices, and other brain areas[26
]. Moreover, a neuroleptic-naïve sample would have been out of the scope of this study, as we have chosen to include a highly homogeneous sample of patients based on their refractory behavior to antipsychotic medications.
In conclusion, we identified the left superior and middle temporal gyri as relevant areas in patients with auditory hallucinations. Our findings provide support for the use of multimodal structural and functional MR approaches in the search for areas specifically linked to the pathogenesis of auditory hallucinations. This core approach appears to be a good strategy for studying the neurobiological basis of clinical dimensions which may be particularly indicated at this stage. Similar multimodal approaches could also be used for studying other features as long as specific paradigms for the functional study of such symptoms are provided.