Lack of insula reactivity to aversive stimuli in schizophrenia

Patients with schizophrenia may have altered pain perception, as suggested by clinical reports of pain insensitivity, and recent neuroimaging findings. Here, we examined neural responses to an aversive electrical stimulus and the immediate anticipation of such a stimulus using fMRI and a classical conditioning paradigm, which involved pairing an electrical shock with a neutral photograph. Fifteen men with schizophrenia and 13 healthy men, matched for demographic characteristics, electrical stimulation level and scan movement, were studied. The shock induced robust responses in midbrain, thalamus, cingulate gyrus, insula and somatosensory cortex in both groups. However, compared to controls, the schizophrenic patients displayed significantly lower activation of the middle insula (p(FWE)=0.002, T=5.72, cluster size=24 voxels). Moreover, the lack of insula reactivity in the schizophrenia group was predicted by the magnitude of positive symptoms (r=-0.46, p=0.04). In contrast, there were no significant differences between the two groups in the magnitude of neural responses during anticipation of the shock. These findings provide support for the existence of a basic deficit in interoceptive perception in schizophrenia, which could play a role in the generation and/or maintenance of psychotic states.