Neural Response to Emotional Salience in Schizophrenia

Abstract

Neuroimaging probes of brain regions implicated in emotion represent an important research strategy for understanding emotional dysfunction in schizophrenia. Anterior limbic structures, such as the ventral striatum and the amygdala, have been implicated in the pathophysiology of schizophrenia and the generation of emotional responses, although few studies to date have used emotion probes to target these areas in schizophrenia. With this goal in mind, emotionally salient visual images were used in a simple, nondemanding task. In all, 13 medicated, schizophrenic patients, five unmedicated patients, and 10 healthy volunteers viewed complex visual pictures and a nonsalient, blank screen while regional cerebral blood flow was measured with the [O-15] water technique. Pictures consisted of real world scenes with aversive, positive, and nonaversive content. Eye movements were recorded simultaneous with scan acquisition. Positron emission tomography images were analyzed for baseline, tonic activity, in addition to phasic changes ('activation') to salient stimuli. Lateral eye movement measures and on-line ratings showed good behavioral compliance with the task. Patients with schizophrenia showed impaired neural responses to salient stimuli in the right ventral striatum (VS), and they exhibited elevated tonic activity levels in the right VS and bilateral amygdala, inversely correlated with overall symptom severity. The patients also showed reduced modulation of visual cortex by salient stimuli. The results show that patients with schizophrenia exhibit impaired neural responses to emotionally salient stimuli in the VS, supporting a role for this structure in the pathophysiology of the illness. Reduced modulation of visual cortex by emotionally salient stimuli also suggests a failure to organize cerebral activity at a global level.

The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence

“…Patients have been reported to rate the hedonic value of pleasant odors lower Formation of abnormal associations in schizophrenia J Jensen et al than controls and fail to activate limbic/paralimbic structures invoked by normal controls (Crespo-Facorro et al, 2001). Studies using positive and negative pictures as rewarding stimuli (Paradiso et al, 2003;Taylor et al, 2002Taylor et al, , 2005 also showed that patients failed to recruit parts of reward related circuits. These earlier imaging studies on reward in schizophrenia have focused on the failure to activate structures during reward per se whereas the current study suggest an aberrant activation pattern towards cues predicting neutral stimuli in a reward learning paradigm.…”

“…Another study focusing on the effect generated by the rewarding experience rather than reward anticipation, showed that patients rated the hedonic value of the pleasant odors lower than controls and also failed to activate limbic/paralimbic structures invoked by normal controls (Crespo-Facorro et al, 2001). Studies using positive and negative pictures as rewarding stimuli also showed that patients failed to recruit parts of a rewardrelated circuit (ventral striatum, amygdala and the orbitofrontal cortex), which were recruited in controls (Paradiso et al, 2003;Taylor et al, 2002Taylor et al, , 2005.…”

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…Given the central role played by mesolimbic dopamine in the wanting processes, psychotic symptoms in schizophrenic patients could originate from sporadic or stress-induced dopamine spikes causing attribution of salience to random events and/or to trivial subjective experiences (Taylor and Liberzon, 1999;Floresco et al, 2003;Kapur, 2003;Taylor et al, 2005), that is, aberrant conditioned learning (Schultz, 2001). Deficits of the neural mechanism involved in attribution of emotional salience in schizophrenics (Kohler et Table 2) and electrophysiological (Pfefferbaum et al, 1989) studies, employing various natural probes ranging from odors to facial images and aversive vs neutral scenes (Taylor et al, 2002(Taylor et al, , 2005Gur et al, 2002;Paradiso et al, 2003;Takahashi et al, 2004;Williams et al, 2004).…”

“…Deficits of the neural mechanism involved in attribution of emotional salience in schizophrenics (Kohler et Table 2) and electrophysiological (Pfefferbaum et al, 1989) studies, employing various natural probes ranging from odors to facial images and aversive vs neutral scenes (Taylor et al, 2002(Taylor et al, , 2005Gur et al, 2002;Paradiso et al, 2003;Takahashi et al, 2004;Williams et al, 2004).…”

“…Similarly to SUDs, which is another condition associated with erratic supraphysiological dopamine surges in the limbic system (Volkow et al, 2004a), aberrant salience in schizophrenia creates rigid motivational states fixated on irrelevant and idiosyncratic stimuli with diminution of mesolimbic neurons' 'signal detection capability' for normal salience (Taylor and Liberzon, 1999;Taylor et al, 2005) and with the loss of normal modulation of reinforcers' values by nonpsychotic contexts (eg, caloric need state; Breier, 1989). Thus, palatable food (eg, ice cream) may be salient enough to compete with the psychosis-related reinforcers as a result of its effects on reward circuitry (Hajnal et al, 2004) and owing to aggressive and ubiquitous advertisement (Wansink, 2004), whereas less salient and palatable nutrition (eg, lettuce and broccoli), lacking these characteristics, may fail to elicit incentive motivation towards its consumption even within the context of caloric deficits (Breier, 1989).…”