其他摘要 | Amotivation and anhedonia are core features of negative symptoms in schizophrenia patients. These deficits can also be found in people at risk of developing psychosis, such as individuals with high level of social anhedonia, and are believed to result in poor social functioning. However, the underlying neural mechanisms of amotivation and anhedonia remain unclear, constituting a major barrier to the development of effective treatments.
Motivation and pleasure experience rely heavily on the representation of expected value and outcome value. Both of these value representations are the results of complex interactive processes between the prior belief which is built upon one's previous experience, and the current value input. These processes generated range adaptive coding .Range adaptation refers to representing a given value based on its relative position in the range of pre-experienced values to enhance value discriminability, and it plays a key role in motivation and pleasure experience. The extant literature is limited, and shows inconsistent findings regarding the relationship of attenuated range adaptation with negative symptoms in clinical and subclinical populations along the schizophrenia spectrum. This dissertation presents findings gathered from four interrelated studies which aimed to examine range-adaptive value representation performance and its relationship with amotivation and anhedonia in clinical schizophrenia patients and people with high level of social anhedonia.
Study 1 examined the behavioural performance of range-adaptive value representation performance in the individuals with schizophrenia spectrum disorder. We administered an Effort-based Pleasure Experience Task to 30 pairs of chronic schizophrenia patients and healthy controls, and 30 pairs of first-episode schizophrenia patients and healthy controls. Our results showed that chronic schizophrenia patients exhibited over-adaptation, and the range adaptation performances tended to be negatively correlated with self-reported anhedonia. On the other hand, first-episode schizophrenia patients exhibited reduced adaptation and showed a significant negative correlation with amotivation symptoms. Moreover, we further examined the range adaptation to expected value in 50 schizophrenia patients and 56 controls, and 132 participants with high level of social anhedonia and 149 participants with low level of social anhedonia. Findings showed that schizophrenia patients exhibited reduced adaptation to expected value, which was positively correlated with amotivation symptoms. On the other hand, participants with high level of social anhedonia only exhibited reduced adaptation to expected value, and such deficits was positively correlated with amotivation and anhedonia symptoms.
Study 2 examined the range adaptation related resting-state functional connectivity and brain excitation-inhibition balance in schizophrenia patients and participants with high level of social anhedonia. We first recruited 60 healthy participants to undertake magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) scanning. The behavioural Effort-based Pleasure Experience Task was administered to assess range adaptive behaviour. Results showed that range adaptive behaviour was determined by the excitation-inhibition balance and the "ventral prefrontal cortex-based" functional connectivity. We then recruited an independent sample of 46 schizophrenia patients and 37 healthy controls as well as 26 pairs of participants with high and low levels of social anhedonia to undertake the same neuroimaging scanning for excitation-inhibition balance and the resting-state functional connectivity described above. Results showed that reduced excitation-inhibition balance in schizophrenia patients, however, did not find any significant difference between participants with high and low levels of social anhedonia. Moreover, "ventral prefrontal cortex-based" functional connectivity was correlated with amotivation and anhedonia symptoms in schizophrenia patients, whilst excitation-inhibition balance and "ventral prefrontal cortex-based" functional connectivity were both correlated with amotivation and anhedonia in participants with high level of social anhedonia. Similar findings were replicated in an independent sample of 40 pairs of participants with high and low levels of social anhedonia.
Study 3 utilized fMRI technique to compare the brain activation pattern for range adaptation between 46 schizophrenia patients and 37 controls, and between 52 participants with high level of social anhedonia versus 51 participants with low level of social anhedonia. Regarding range adaptation to expected value, schizophrenia patients exhibited hypo-activation in the putamen and the insula when expecting gain as well as hyper-activation in the caudate when expecting loss. Regarding range adaptation to outcome value, schizophrenia patients exhibited hypo-activation in the inferior frontal gyros during reception of gainful reward. However, regarding range adaption to expected value, participants with high level of social anhedonia only showed hyper-activation in the insula. These alterations of brain activation patterns were correlated with amotivation and anhedonia symptoms in schizophrenia patients and participants with high level of social anhedonia. No such significant correlation was observed in healthy controls and individuals with low level of social anhedonia.
Study 4 adopted a longitudinal design to track the possible changes of range adaptation in 56 participants with high level of social anhedonia and 48 controls at 3-month intervals for up to 9 months. Results indicated that range adaptation to expected value measured at baseline could predict the progression of anhedonia symptoms in participants with high level of social anhedonia.
Taken together, the present study provided evidence that schizophrenia patients and people with high level of social anhedonia both showed altered range-adaptive value representation performances, albeit in distinct patterns. Moreover, the behavioural performances, resting-state and task-based fMRI brain activity during range-adaptive value representation would be significantly correlated with amotivation and anhedonia symptoms in schizophrenia patients and people with high level of social anhedonia. Furthermore, range adaptation behaviour predicted future progression of anhedonia symptoms in people with high level of social anhedonia. These important empirical findings implicate the important role of range-adaptive value representation in the formation of amotivation and anhedonia symptoms along the schizophrenia spectrum, as putative neurobiological mechanisms as well as potential intervention targets for these symptoms. |
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