健康与遗传心理学研究室知识库

动机与愉快体验缺损是精神分裂症患者和社会快感缺失个体阴性症状的核心表现，对社会功能有着负性的影响，但其治疗效果却有限。针对动机和愉快体验的机制研究对于开发阴性症状的治疗至关重要。

动机和愉快体验依赖于期待和结果价值的表征。价值表征是范围适应性，即个体根据以往经验所建立的先验信念和当前刺激整合后的结果。价值范围适应性表征指个体会采用某一价值在以往所经历的价值范围内的相对位置来对其进行表征，以确保表征区分度。因此，价值范围适应性表征在动机和愉快体验中起着核心的作用。少数研究考察了精神分裂症临床与亚临床群体的价值范围适应性及其与阴性症状的关系，但结果并不一致。本论文将通过四个研究来探讨精神分裂症患者和社会快感缺失个体的期待以及结果价值范围适应性表征在行为、静息态以及任务态脑功能的表现，及其与动机和愉快体验缺损的联系。

研究一采用基于努力付出的情绪体验任务考察精神分裂症患者和社会快感缺失人群的价值范围适应性表征行为。针对结果价值，研究招募了30对首发精神分裂症患者与对照和30对慢性精神分裂症患者与对照。结果表明，慢性精神分裂症患者的结果价值范围适应性异常增大，且与愉快体验缺损呈负相关趋势。首发精神分裂症患者的结果范围适应性异常减小，且与动机和愉快体验缺损呈显著负相关。针对期待价值，本研究纳入50名精神分裂症患者和56名对照。结果发现，精神分裂症患者的期待价值范围适应性异常减小，且与动机和愉快体验缺损显著正相关。研究也招募了132名社会快感缺失个体与149名对照，发现社会快感缺失个体仅表现出减小的期待价值范围适应性及其与愉快体验缺损的显著正相关。

研究二探究精神分裂症患者和社会快感缺失个体在价值范围适应性相关的 静息态脑功能的表现。为明确范围适应性相关的静息态脑功能，60名健康被试完成价值范围适应性的行为任务、磁共振波谱与静息态磁共振成像扫描，结果发现，范围适应性的行为依赖于腹侧前额叶功能连接以及神经递质的兴奋一抑制平衡。本研究招募了46名精神分裂症患者和37名对照和26对社会快感缺失个体与对照并完成相同的腹侧前额叶功能连接和兴奋一抑制平衡的测量，并且另外招募了40对社会快感缺失个体与对照来验证社会快感缺失个体的结果。结果显示精神分裂症患者的兴奋一抑制平衡显著降低，但社会快感缺失个体和对照不存在任何显著差异。精神分裂症患者腹侧前额叶功能连接和动机与愉快体验缺损相关，而社会快感缺失个体的兴奋一抑制平衡与腹侧前额叶功能连接也都与动机和愉快体验缺损相关。

研究三考察精神分裂症患者与社会快感缺失个体价值范围适应性表征的任务态脑功能。被试包括46名精神分裂症患者和37名对照与52名社会快感缺失个体和51名对照。结果发现在期待价值范围适应性中，精神分裂症患者对奖赏条件的壳核和脑岛激活异常减弱，而对损失条件的尾状核激活异常增强。在结果价值中，精神分裂症患者对奖赏条件的额下回激活异常减弱。社会快感缺失个体则只在期待价值范围适应性对损失表现出和患者类似的脑岛激活异常增强。精神分裂症患者与社会快感缺失个体范围适应性的异常激活都与动机和愉快体验缺损相关

研究四对56名社会快感缺失个体和48名对照进行9个月，共4次的线上追踪。结果发现，社会快感缺失个体在前一个时间点的期待价值范围适应性表现，能预测其后一个时间点的愉快体验缺损的变化。

总结而言，本论文支持精神分裂症患者和社会快感缺失个体存在特异的价值范围适应性表征缺损。精神分裂症患者和社会快感缺失个体价值范围适应性的行为、静息态以及任务态脑功能都和动机与愉快体验缺损一致相关。社会快感缺失个体的期待价值范围适应性能预测其愉快体验缺损的纵向变化。因此，价值范围适应性表征可能是精神分裂症谱系的动机和愉快体验缺损潜在的神经机制与干预靶点。

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.