Imaging Emotion in Schizophrenia: Not Finding Feelings in All the Right Places

Many patients with schizophrenia have difficulties initiating and sustaining goal-directed behavior. Perhaps the simplest way to explain this problem is to invoke the concept of anhedonia: patients do not pursue goals because goal attainment is just not that rewarding. That is, there is a real reduction in the capacity to experience pleasure, and this undermines motivation. This tight coupling of the experience of pleasure and volition informs most approaches to negative symptom rating scales, with which interviewers typically ask about the frequency of social contacts and recreational activities and how much enjoyment a person derives from these experiences. Patients who do not evidence any pursuit of these types of activities receive the most severe ratings for anhedonia. Thus, lack of pleasure-seeking behavior is interpreted as reflecting a lack of capacity for pleasurable emotional experience.

While this clinical inference is straightforward, there is a great deal of evidence to suggest that it is only partially correct, if not actually wrong. The critical evidence comes from a large body of experimental data from situations where people with schizophrenia are presented with a wide array of evocative stimuli (foods, video clips, visual images, words, etc.) and are asked to rate how these stimuli make them feel. More often than not, patients' self-reports of emotional responses closely resemble those of healthy volunteers (1, 2). This is a simple and direct test of hedonic capacity, and the evidence for normative experience is robust. How then to reconcile this body of work on evoked experience with the fact that people with schizophrenia typically report less subjective pleasure on the Chapman anhedonia scales (3) and are routinely rated as being anhedonic on the basis of a clinical interview? In both of these cases, the person is asked to recall past experiences of emotion or make judgments about his or her emotional responses to different situations. In both cases, it is necessary to respond on the basis of a representation of an experience rather than the presentation of an emotionally evocative stimulus. So might the problem be in forming, maintaining, and retrieving affective representations rather than “in the moment” experiences of pleasure? And further, might people with schizophrenia therefore have difficulty initiating and sustaining goal-directed behavior because of a problem in representing the anticipated value of stimuli? If so, they might have difficulty selecting responses that are closely correlated with the value of the desired outcome (4, 5).

A test of the plausibility of this type of account at the level of neural activity would need to provide evidence that people with schizophrenia demonstrate normative neural responses when presented with an evocative stimulus and that they then lose those normative neural responses after a delay when asked to report on their experience of that stimulus. That is precisely what Ursu and colleagues have shown in a study comparing the blood-oxygen-level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) in response to emotional stimuli in a group of 20 people with schizophrenia and 20 healthy comparison subjects (6). As seen in their Figure 3, both groups showed robust and widespread activation in response to the presentation of emotionally evocative stimuli when the scan data were obtained while the stimuli were in view. This stimulus presentation was followed by a 12.5-second delay, during which additional scans were obtained. Then the subjects provided ratings of how positive, negative, and energizing they thought the stimuli were. As seen in Figure 4, the healthy subjects demonstrated a robust, distributed pattern of brain activity during the delay period, whereas the participants with schizophrenia showed very little sustained activity. Thus, in the absence of the stimulus, the evoked neural activity in the schizophrenia group appeared to dissipate, with between-group differences in several prefrontal regions. This pattern of fMRI data is consistent with the proposed distinction between evoked emotional experiences and responses mediated by internal representations. Further, Ursu and colleagues found that reduction in prefrontal delay activity was correlated with severity of clinically rated anhedonia. Thus, clinical anhedonia is related to the loss of ability of prefrontal systems to maintain activity related to representing the value of a stimulus that is no longer in view.

What is curious is that the stimulus ratings of the patient and healthy volunteer groups for the positivity of positive stimuli and negativity of negative stimuli are nearly identical despite the large differences in brain activity during the delay interval. Two rating differences were observed. The ratings given by the patients for neutral stimuli tended to be both more positive and more negative than those given by the comparison subjects, and the two groups had similar ratings for positive and negative stimuli. That is, their positive ratings of positive stimuli were accompanied by slightly increased ratings for the negative value of the same stimuli. Both these types of rating anomalies have been reported previously (1). Whether this reflects heightened ambivalence, difficulties in resolving conflict (the authors' view), or an unusual response to the demand characteristics of the task is uncertain. Indeed, it is somewhat unusual to ask someone how negatively they feel about something that is clearly positive. Perhaps the more intriguing question is, What is the significance of the dissociation between self-report and physiology? That is, the patients reported subjective valuations that were very similar to those of the comparison subjects but on the basis of very different physiology. This has also been observed by others (7) and raises an interesting question: Should we “believe” the brain response or the self-report rating as the more reliable indicator of the motivational salience of a stimulus?

How might the results from this highly constrained laboratory experiment illuminate everyday clinical observation of patients with schizophrenia? It is not uncommon for patients with schizophrenia to articulate sensible short- and long-term goals. It is also not uncommon for patients to fail to persist in the pursuit of such goals. It is as if the representation and motivational salience of goals are insufficient to drive and sustain behavior. The work of Ursu and colleagues is highly relevant for this common clinical problem: The prefrontal systems that are needed to mediate this type of behavior, using mental representations to plan actions, appear to be compromised. Thus, patients may say one thing about an experience, but their brain says something different. Does the finding of impaired brain physiology inevitably lead to clinical nihilism? Is there room for optimism that the motivational deficits of patients are malleable if the neural systems that mediate this function are compromised?

It is too early to answer these questions. Research on emotion and motivation using methods and models of contemporary cognitive and affective neuroscience is still in its infancy in schizophrenia. There is every reason to hope this work will provide new insights that can be the basis of novel therapeutic approaches. Much more basic behavioral and imaging research is needed of the type presented by Ursu et al. So what do we do for our patients in the meantime? Perhaps we can understand them better and find better ways to support them given this understanding. The emotional experience of patients is richer than many of us thought on the basis of their lack of goal-directed behavior (8). However, the critical clinical issue is that the experience of those emotions does not lead to the type of motivational states and behavioral adaptations that we would expect in a healthy person. In essence, patients have less of a problem in experiencing feelings than in remembering and using those feelings as a guide to planning action and making decisions. If it is difficult for patients to call on higher-order prefrontal systems to guide behavior, then compensatory strategies, therapeutic interventions, and environmental supports may be needed to help guide behavioral activation and persistence. The work of Ursu and colleagues helps illuminate the neural basis of this clinical challenge.