A functional anatomic study of emotion in schizophrenia

Abstract

Using salient pictures with aversive (AV) and non-aversive (NA) content, we probed limbic-emotional function in schizophrenia, testing specific hypotheses that the amygdala would exhibit abnormal activity and a relationship with positive symptoms. Fourteen schizophrenic patients and 13 healthy comparison subjects viewed pictures during [¹⁵O] water positron emission tomography (PET). Both groups reported identical subjective experience of the aversive stimuli and both activated right insula (AV–NA). The schizophrenic group showed greater activation of the medial prefrontal cortex (MPFC) for the AV–NA comparison. Control subjects activated bilateral amygdaloid and orbitofrontal regions for NA relative to a blank condition (simple visual fixation, BL), whereas schizophrenic subjects only activated left orbitofrontal cortex. Activity in the left amygdala correlated with positive symptoms in the patients. Both groups activated visual cortex, and the schizophrenic subjects exhibited less modulation throughout visual cortex for NA–BL, as well as more focused deficits in the left fusiform and left mid-occipital gyrus for AV–NA, possibly related to decreased eye movements in the schizophrenic patients. Overall, the data are consistent with a general failure to process salient stimuli in schizophrenia, and the findings support the involvement of the amygdala in the positive symptoms of schizophrenia.

Introduction

Brain regions thought to subserve emotion, often referred to as limbic brain, have long been implicated in the pathophysiology of schizophrenia Chiodo and Bunney, 1983, Stevens, 1973, although surprisingly little work has examined the functional anatomy of abnormal emotion in the illness. Schizophrenia impairs emotional processing in tasks requiring recognition of facial emotion Archer et al., 1992, Kohler et al., 2000, Walker et al., 1984, or in applied aspects of emotion, e.g. social cognition (Penn et al., 1997), although some authors have suggested that these emotional deficits may represent manifestations of broader performance deficits Archer et al., 1992, Kerr and Neale, 1993, Salem et al., 1996. Functional imaging studies have investigated possible links between abnormal emotion and anatomy, finding correlations between affective flattening/psychomotor poverty and reduced activity in the lateral prefrontal cortex during resting conditions Kawasaki et al., 1996, Liddle et al., 1992, Wolkin et al., 1992, although this relationship has not been replicated in other studies Gur et al., 1995, Siegel et al., 1993. However, this earlier work did not employ emotional probes known to activate relevant limbic structures of the brain.

Several authors have suggested that the amygdala should exhibit abnormal activity in schizophrenia, as well as a relationship with positive symptoms Fudge et al., 1998, Grace et al., 1998, Grossberg, 2000. Positive symptoms often represent an inappropriate attribution of relevance to insignificant stimuli, as in a delusion of reference. Since the amygdaloid nuclei respond to affectively relevant stimuli Everitt et al., 1991, Kapp et al., 1992, functional abnormalities of this limbic structure might be predicted. Grace and colleagues Grace et al., 1998, Moore et al., 1999 have hypothesized that schizophrenia involves a disturbance of hippocampal and prefrontal gating of information flow through the nucleus accumbens, leading to inappropriate biasing by amygdaloid projections to the accumbens. Using a mood induction paradigm known to activate the amygdala, as visualized by BOLD fMRI, Schneider and colleagues reported a failure of schizophrenic patients to activate this limbic structure (Schneider et al., 1998). While an intriguing finding, the difficulty of assessing task compliance in the patient group complicates the interpretation of their failure to activate, although the finding that the patients reported similar levels of mood induction is congruent with other studies of emotion in schizophrenia Berenbaum and Oltmanns, 1992, Earnst and Kring, 1999, Kring et al., 1993.

In the study reported here, we employed emotionally salient visual stimuli to probe neural activity in schizophrenia. Using evocative visual stimuli in healthy subjects, several groups have demonstrated activation of basal forebrain, including the extended amygdala Liberzon et al., 2000, Paradiso et al., 1999, Reiman et al., 1997, Taylor et al., 2000, and medial prefrontal cortex (MPFC) Lane et al., 1997b, Simpson et al., 2000, Teasdale et al., 1999. Minimal performance demands are placed on the subjects, thereby reducing the possibility that performance differences might confound our results. We predicted that amygdaloid activity would correlate with positive symptoms, and patients would fail to activate medial prefrontal cortex.