认知与发展心理学研究室知识库

快感缺失是精神分裂症阴性症状的一个核心症状，主要表现为期待性愉快体验方面的缺损。最近对快感缺失机制的研究表明，这种对情绪信息及其效价表征的激活和监控，与工作记忆对记忆表征保持和加工能力密切相关。对愉快体验和工作记忆加工的脑影像研究也表明，二者在神经机制上有共同的脑区参与，比如背外侧前额叶、前扣带和纹状体等。以此为依据，探索通过工作记忆训练对于改善快感缺失的效果，有助于推进改善快感缺失干预研究的进展。考虑到谱系研究能够帮助更好地理解精神分裂症的病理学，并且为这一疾病的早期识别和干预提供依据，本研究将对工作记忆训练改善精神分裂症谱系快感缺失的行为表现和脑
机制进行探讨。
    本论文通过四个研究来探讨工作记忆训练在精神分裂症谱系中的行为与神经机制。研究一通过对工作记忆训练脑影像研究进行定量元分析，结果表明，在正常个体中表现出功能活动水平变化的脑区有背外侧前额叶、顶叶、梭状回、脑岛和纹状体等。在精神分裂症患者进行的元分析表明，有训练效应的脑区包括右侧额上回、额下回、右侧楔前叶，左侧角回和右侧梭状回，和正常人中的研究发现基本重合，表明精神分裂症患者也存在神经可塑性，为在精神分裂症患者中开展工作记忆训练提供支持。研究二考察了工作记忆训练对于改善高快感缺失个体愉快体验加工的作用，进行了为期20 次，每次半个小时的双n-back 训练，结果显示，在训练中工作记忆任务成绩有些显著提升，在愉快体验加工方面，相比较未参加训练的高快感缺失对照组，训练组对积极情绪刺激的趋向动机提高。研究三进一步在15 个高社会快感缺失个体中对工作记忆训练改善快感缺失的脑机制进行了研究，结果发现在期待愉快情绪刺激阶段，前扣带、背侧纹状体和楔前叶激活水平提高；在期待金钱奖励（或惩罚）阶段，在背外侧前额叶和缘上回激活水平提高。研究四在精神分裂症患者中进行工作记忆训练，共招募到训练组患者15 人，对照组患者7 人。研究结果发现，训练后在完成工作记忆脑影像任务时额中回激活水平下降，在期待愉快情绪刺激阶段，颞上回（靠近颞顶联合区）激活水平增加。
    总体来看，本研究结果显示，精神分裂症谱系工作记忆能力和愉快感受具有可塑性，在行为层面表现为工作记忆成绩的提高和对积极情绪刺激的趋向动机提高，在大脑活动上表现为期待阶段激活水平增加。本研究强调了非药物的干预方式在减轻临床与亚临床个体的快感缺失的重要价值，为在高危人群中进行早期预防与早期干预以及在精神分裂症患者中开展康复训练提供重要参考。

  Anhedonia is the core feature of negative symptoms of schizophrenia, and mainly manifests as the deficits of anticipatory pleasure, i.e., reduced pleasurable experiences when anticipating future events. The reduced ability to activate and maintain the representation of value and emotion is associated with working memory (WM) deficit. On the other hand, empirical findings suggest the neural mechanisms of hedonic processing and WM share recruitment of the dorsolateral prefrontal cortex, the anterior cingulate cortex and the striatum.The present dissertation aimed specifically to examine whether WM training would improve anhedonia observed in patients with schizophrenia and individuals with social anhedonia.
     Study 1 adopted the activation likelihood estimation (ALE) meta-analysis to examine whether there would be neuroplastic effect of WM training in healthy volunteers and patients with schizophrenia.The results showed that there was a widespread distribution of activation changes with WM training in the prefrontal, the parietal, the temporal regions, as well as the insula and the putamen in healthy individuals. WM was also accompanied with brain activation changes in patients with schizophrenia, mainly in the dorsolateral prefrontal cortex, the precuneus and the fusiform gyrus. The analysis of neural effects of WM training in healthy volunteers at the dorsolateral prefrontal and the sub-cortical regions provides the basis for the understanding of neuroplastic changes in patients with schizophrenia and sheds light on the possible neural transfer effects to hedonic processing.
     Study 2 aimed to examine whether WM training would improve anhedonia observed in individuals with social anhedonia. We recruited 17 individuals with high social anhedonia to undertake a 20-sessions training on the dual n-back task. Another 17 individuals with high socialanhedonia who did not undertake the dual n-back raining were recruited as control group. The results showed that individuals who received the WM training not only showed significant improvement in WM performance compared to controls, but also showed significant improvement in approach sensitivity to rewards.
     Study 3 recruited an independent sample of high social anhedonia group to examine whether the observed behavioural improvement shown in study 2 could be extended to the underlying mechanisms. Fifteen individuals with high social anhedonia were recruited to undertake the said dual n- back training described in study 2. Moreover, they were required to undertake two functional imaging tasks on the Monetary Incentive Delay (MID) task and the Affective Incentive Delay (AID) task both before and after the training. The results indicated that WM training could improve the behavioural performance of WM tasks and reduce the severity of self-reported anhedonia. Enhanced brain activations related to pleasure anticipation were observed at the anterior cingulate cortex, the left dorsal striatum and the left precuneus on the AID task, and at the dorsolateral prefrontal cortex and the supramarginal gyrus on the MID task. Reduced brain activations were observed in the consummation of both affective and monetary incentives across several frontal and parietal regions, as well as some subcortical regions.
     In study 4, we examined whether the observed neural improvement shown in study 3 could be extended to schizophrenia patients with prominent negative symptoms. We recruited 15 patients with schizophrenia to undertake the 20-sessions of the dual n-back task for 4 weeks. Moreover, we also recruited seven patients with schizophrenia who did not take part the training as the clinical controls. The results showed that there was reduced brain activation at the middle frontal gyurs when performing the WM task, and the reduction of activation correlated significantly with behavorial improvement on the dual n-back task. Moreover, increased brain activation at the superior temporal gyrus in the anticipating of affective rewards was observed, and the increased brain activation at the superior temporal gyrus negatively correlated with reduction of negative symptoms on affective flattening and avolition-apathy in the training group.
     Taken together, the present findings indicated the neuroplasticity of WM training in both individuals with social anhedonia and patients with schizophrenia. The results demonstrated positive transfers to hedonic processing abilities with WM training, manifesting as enhanced motivation towards affective rewards and increased brain activations in the anticipating of rewards. These findings highlight the importance of a non-pharmacological intervention on alleviating anhedonia in both clinical and subclincal samples. It is hoped that these findings can shed light onto the early intervention and rehabilitation of patients with schizophrenia and individuals at-risk for psychosis in mainland China.