Neurobehavioral mechanisms of temporal processing deficits in Parkinson's disease.
Neurobehavioral mechanisms of temporal processing deficits in Parkinson's disease.
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DOI：
10.1371/journal.pone.0017461
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发表时间：
2011-02-25
期刊：
影响因子：
3.7
通讯作者：
Rao SM
中科院分区：
文献类型：
--
作者：
Harrington DL;Castillo GN;Greenberg PA;Song DD;Lessig S;Lee RR;Rao SM
帕金森氏病(PD)扰乱了时间处理，但缺陷的神经元来源及其对多巴胺(DA)治疗的反应尚不清楚。虽然纹状体和多巴胺的传递被认为对计时至关重要，但潜在的工作记忆(WM)和执行问题也可能扰乱计时。目前的研究通过测试对照组和PD志愿者在执行时间感知任务时接受功能磁共振成像时的开启和关闭DA治疗来解决这些问题。为了区分与时间和非时间过程中的异常相关的系统，我们分离了试验编码和决策阶段的大脑活动。虽然这两个阶段都涉及计时，但编码和决策阶段分别强调工作管理和执行过程。这些方法能够探索神经活动的幅度和时间动力学。首先，我们发现时间知觉缺陷与纹状体、皮质和小脑功能障碍有关。与对定时运动的研究不同，我们的结果不能归因于纹状体和小脑在运动中的传统作用。第二，我们首次确定了时间知觉受损的时间来源和非时间来源。在这两个阶段都发现了纹状体功能障碍，这与纹状体在计时中的作用一致。在编码过程中的WM网络(中额叶和顶叶皮质、外侧小脑)和在决策过程中调节执行和记忆功能的网络(副海马体、后扣带回)中，激活也是异常的。第三，帕金森病的典型表现是神经元功能障碍，但有时表现为异常的时间动力学(如滞后、延长)，这不是由于反应时间较长所致。最后，DA疗法并没有缓解计时缺陷。我们的发现表明，帕金森病患者的计时障碍是由黑质纹状体和中皮质功能障碍引起的，这些功能障碍是由调节临时和非临时控制过程的系统引起的。然而，DA治疗并没有改善时间知觉障碍，可能是由于神经元活动的恢复不充分，可能是由于皮质纹状体的有效连接。
Parkinson's disease (PD) disrupts temporal processing, but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping, potential working memory (WM) and executive problems could also disrupt timing. The present study addressed these issues by testing controls and PD volunteers ‘on’ and ‘off’ DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes, we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping, the encoding and decision phases emphasized WM and executive processes, respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction. Unlike studies of timed movement, our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second, for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex, lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus, posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD, but was sometimes characterized by abnormal temporal dynamics (e.g., lagged, prolonged) that were not due to longer response times. Finally, DA therapy did not alleviate timing deficits. Our findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity.
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影响因子：
5.7
作者：
Graham, Steven;Phua, Elaine;Yeh, Ing Berne
通讯作者：
Yeh, Ing Berne
影响因子：
3.2
作者：
Coull, Jennifer T.;Nazarian, Bruno;Vidal, Franck
通讯作者：
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影响因子：
3.7
作者：
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DOI：
10.1111/j.1749-6632.1984.tb23417.x
发表时间：
1984-01-01
影响因子：
5.2
作者：
GIBBON, J;CHURCH, RM;MECK, WH
通讯作者：
MECK, WH
DOI：
10.1196/annals.1440.011
发表时间：
2008-01-01
期刊：
YEAR IN COGNITIVE NEUROSCIENCE 2008
影响因子：
--
作者：
Buckner, Randy L.;Andrews-Hanna, Jessica R.;Schacter, Daniel L.
通讯作者：
Schacter, Daniel L.