Neural Circuitry of Salience and Reward Processing in Psychosis

Abstract

The processing of salient and rewarding stimuli is integral to engaging our attention, stimulating anticipation for future events, and driving goal-directed behaviors. Widespread impairments in these processes are observed in psychosis, which may be associated with worse functional outcomes or mechanistically linked to the development of symptoms. Here, we summarize the current knowledge of behavioral and functional neuroimaging in salience, prediction error, and reward. Although each is a specific process, they are situated in multiple feedback and feedforward systems integral to decision making and cognition more generally. We argue that the origin of salience and reward processing dysfunctions may be centered in the subcortex during the earliest stages of psychosis, with cortical abnormalities being initially more spared but becoming more prominent in established psychotic illness/schizophrenia. The neural circuits underpinning salience and reward processing may provide targets for delaying or preventing progressive behavioral and neurobiological decline.

Keywords: Dopamine; Nucleus accumbens; Prediction error; Psychosis; Punishment; Reward; Salience; Schizophrenia.

Figure 1

Conceptual interactions between external events (cyan), salience and prediction error (red), and reward processing (purple) in decision making. An external event (e.g., action outcome) will be perceived and attended to when it overcomes a certain level of salience (referred to as a salience threshold). The input is then integrated into associative learning networks to inform decision-making processes. Computation of potential rewards available (valuation) and the effort required for each (effort-cost trade-off) are then used to identify the optimal choice and whether or not it is acted upon. In this example, the outcome is rewarding (external feedback as action outcome), which is then compared with our prior expectations. Our prior expectation is associated with how accurate our valuation of the outcome is. In cases where the outcome matches the expectation (green tick), the associations are reinforced. In cases where there is a mismatch between the outcome and our expectation, a prediction error signal is generated. The prediction error is used to update our understanding of input-output relationships. Prediction error information (magnitude, precision, and so on) is then used to update our beliefs and goals associated with the initial stimuli (or action required). This updates our salience threshold so that when we encounter this same event in the future (n + 1), it is more likely to be considered salient. Reward processing (purple) affects multiple stages in this process to subsequently increase attention (reward anticipation), drive associative learning (reward learning), and govern our motivation to work toward a future goal. Here, we focus on a rewarding outcome; however, perceptual and attentional processes of sensory stimuli work similarly, causing belief updating and salience threshold updating via prediction errors.

Figure 2

Salience areas and psychosis. Simplified diagram of key regions involved in salience processing and underlying problems observed in psychosis. See text for citations and details. dl, dorsolateral; vm, ventromedial; VTA, ventral tegmental area.

Figure 3

Prediction error areas and psychosis. Simplified diagram of key regions involved in prediction error signaling and underlying problems observed in psychosis. See text for citations and details. VTA, ventral tegmental area.

Figure 4

Reward areas and psychosis. Simplified diagram of key regions involved in reward processing and underlying problems observed in psychosis. Impairments tend to be less obvious in earlier disease stages or, in the case of reward/punishment learning, may actually be in opposition. See text for citations and details.

Figure 5

Neurochemical and functional imaging associations with salience and reward processing in those at risk for and in early psychosis compared with (A) chronic psychosis and (B) schizophrenia. Colored arrows reflect key neurochemical changes, and black arrows indicate functional magnetic resonance imaging changes in those with psychosis and their associated behavior. Evidence of salience and reward impairments in those at risk for and in early psychosis are commonly found in subcortical structures, such as the associative striatum, nucleus accumbens, ventral tegmental area (VTA), and substantia nigra (SN). However, evidence of cortical glutamatergic abnormalities in the anterior cingulate cortex (ACC) have been observed. In contrast, there is evidence of widespread functional impairments in those with chronic psychosis or schizophrenia. This includes reduced functional connectivity in thalamocortical and corticostriatal projections (dashed lines) and reduced functional activity during salience and reward processing in the ACC, ventral prefrontal cortex (vPFC), and dorsolateral PFC (dlPFC). Therefore, it may be that subcortical alterations precede cortical impairments in driving negative symptoms and deficits in salience and reward processing.