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Neural correlates of reversal learning in frontotemporal dementia
Cortex ( IF 3.6 ) Pub Date : 2021-07-23 , DOI: 10.1016/j.cortex.2021.06.016
Tamara P Tavares 1 , Derek G V Mitchell 2 , Kristy K L Coleman 3 , Elizabeth Finger 4
Affiliation  

Objective

Frontotemporal Dementia (FTD) is a neurodegenerative disorder that results in disinhibition and difficulty with flexible responding when provided feedback. Inflexible responding is observed early in the course of the illness and contributes to the financial and social morbidities of FTD. Reversal learning is an established cognitive paradigm that indexes flexible responding in the face of feedback signaling a change in reinforcement contingencies, with components of reversal learning associated with specific neurotransmitter systems. The objective of the study was to evaluate the neural mechanisms underlying impaired flexible behavioural responding in FTD using a reversal learning paradigm combined with fMRI.

Methods

Twenty-two patients meeting the diagnostic criteria for FTD and twenty-one healthy controls completed the study. Participants completed an fMRI-adapted reversal learning task that indexes behavioural flexibility when provided positive and negative feedback.

Results

Patients with FTD demonstrated poorer behavioural flexibility relative to controls and abnormal BOLD responses within the left ventrolateral prefrontal cortex to incorrect responses made during the learning phase, and during correct responses when reward contingencies were reversed. As well, patients showed decreased activity within the left dorsal lateral prefrontal cortex to incorrect responses compared to controls.

Conclusions

These findings suggest that reversal learning impairments in patients with FTD, in particular those with frontal predominant atrophy, may be related to impaired flexible motor responding when selecting among several choices and deficient attention to relevant stimuli during instances of conflict (i.e., receiving negative feedback). These results and the associated neurotransmitter systems mediating these regions may provide targets for future pharmacological or behavioural interventions mediating these cognitive deficits.



中文翻译:

额颞叶痴呆逆转学习的神经相关性

客观的

Frontotemporal Dementia (FTD) is a neurodegenerative disorder that results in disinhibition and difficulty with flexible responding when provided feedback. Inflexible responding is observed early in the course of the illness and contributes to the financial and social morbidities of FTD. Reversal learning is an established cognitive paradigm that indexes flexible responding in the face of feedback signaling a change in reinforcement contingencies, with components of reversal learning associated with specific neurotransmitter systems. The objective of the study was to evaluate the neural mechanisms underlying impaired flexible behavioural responding in FTD using a reversal learning paradigm combined with fMRI.

Methods

符合 FTD 诊断标准的 22 名患者和 21 名健康对照完成了研究。参与者完成了一项适应 fMRI 的逆转学习任务,该任务在提供正面和负面反馈时对行为灵活性进行索引。

结果

与对照组相比,FTD 患者表现出较差的行为灵活性,并且左腹外侧前额叶皮层内的异常 BOLD 反应对学习阶段做出的不正确反应以及在奖励意外事件逆转时做出的正确反应期间表现出较差。同样,与对照组相比,患者对不正确反应的左背外侧前额叶皮层内的活动减少。

结论

这些发现表明,FTD 患者的逆转学习障碍,尤其是额叶主要萎缩的患者,可能与在发生冲突时(即接受负面反馈)期间在多种选择中进行选择时的柔性运动反应受损以及对相关刺激的关注不足有关. 这些结果和介导这些区域的相关神经递质系统可能为未来介导这些认知缺陷的药理学或行为干预提供目标。

更新日期:2021-08-15
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