Task-evoked pupil dilation and BOLD variance as indicators of locus coeruleus dysfunction.
Task-evoked pupil dilation and BOLD variance as indicators of locus coeruleus dysfunction.
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DOI：
10.1016/j.cortex.2017.09.025
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Kremen WS
中科院分区：
文献类型：
--
作者：
Elman JA;Panizzon MS;Hagler DJ Jr;Eyler LT;Granholm EL;Fennema-Notestine C;Lyons MJ;McEvoy LK;Franz CE;Dale AM;Kremen WS
认知任务期间的瞳孔反应与蓝斑（LC）的功能有关。LC是异常tau沉积的早期位点，其可能有助于阿尔茨海默病（AD）病理生理学的关键方面。我们先前发现轻度认知功能障碍（MCI）个体的瞳孔反应对认知负荷增加的衰减，表明瞳孔反应可能提供与LC功能障碍相关的AD早期风险的生物标志物。LC通过两种操作模式调节皮质活动：强直性和相位性。早期LC损伤已被预测导致持续高紧张性LC活动的状态，可能会破坏任务相关的阶段性活动。为了进一步研究瞳孔反应是否与早期LC功能障碍相关，我们在358名中年男性中测量了数字跨度任务期间的瞳孔扩张作为阶段性活动的测量，以及静息状态fMRI期间腹侧注意力网络关键节点的低频BOLD方差（LFBV）作为与LC紧张性活动相关的皮质反应性的测量。在腹侧注意网络节点中具有较大LFBV的个体，即，在休息时较高的紧张性脑活动，显示出从低到中等认知负荷瞳孔扩张的较小增加。因此，静息时较高的强直性LFBV活性与减少的任务适当的阶段性扩张增加有关。这些结果支持LC功能的突出模型的预测，其中早期LC功能障碍导致在休息期间持续的高紧张性活动率和在任务执行期间阶段性反应的较低信噪比。结合先前在LC中发现的早期AD病理生理学和MCI个体对认知负荷增加的阶段性扩张反应减少，目前的结果表明瞳孔反应可能是早期LC功能障碍的指标，应作为AD风险的潜在生物标志物接受进一步研究。
Pupillary responses during cognitive tasks are linked to functioning of the locus coeruleus (LC). The LC is an early site of abnormal tau deposition, which may contribute to key aspects of Alzheimer’s disease (AD) pathophysiology. We previously found attenuation of pupillary responses to increases in cognitive load in individuals with mild cognitive impairment (MCI), suggesting pupillary responses may provide a biomarker of early risk for AD associated with LC dysfunction. The LC modulates cortical activity through two modes of operation: tonic and phasic. Early LC damage has been predicted to result in a state of persistent high tonic LC activity that may disrupt task-related phasic activity. To further examine whether pupillary responses are associated with early LC dysfunction, we measured pupil dilation during a digit span task as a measure of phasic activity, and low frequency BOLD variance (LFBV) during resting-state fMRI in key nodes of the ventral attention network as a measure of cortical reactivity related to LC tonic activity in 358 middle-aged men. Individuals with greater LFBV in ventral attention network nodes, i.e., higher tonic brain activity at rest, showed a smaller increase in pupil dilation from low to moderate cognitive loads. Thus, higher tonic LFBV activity at rest was related to reduced task-appropriate phasic dilation increases. The results support predictions from prominent models of LC functioning in which early LC dysfunction leads to persistent high tonic rates of activity during rest and lower signal-to-noise of phasic responses during task performance. Taken together with previous findings of early AD pathophysiology in LC and reduced phasic dilation responses to increased cognitive load in individuals with MCI, the present results suggest that pupillary responses may index early LC dysfunction and should receive further study as a potential biomarker of risk for AD.
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影响因子：
12.7
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
DOI：
10.1523/jneurosci.1457-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Conner CR;Ellmore TM;Pieters TA;DiSano MA;Tandon N
通讯作者：
Tandon N
影响因子：
5.7
作者：
Dale, AM;Fischl, B;Sereno, MI
通讯作者：
Sereno, MI
影响因子：
--
作者：
Aizenstein, Howard Jay;Nebes, Robert D.;Saxton, Judith A.;Price, Julie C.;Mathis, Chester A.;Tsopelas, Nicholas D.;Ziolko, Scott K.;James, Jeffrey A.;Snitz, Beth E.;Houck, Patricia R.;Bi, Wenzhu;Cohen, Ann D.;Lopresti, Brian J.;DeKosky, Steven T.;Halligan, Edythe M.;Klunk, William E.
通讯作者：
Klunk, William E.
影响因子：
10.6
作者：
Clement, Francis;Belleville, Sylvie
通讯作者：
Belleville, Sylvie