Neurophysiologically-informed markers of individual variability and pharmacological manipulation of human cortical gamma.
Neurophysiologically-informed markers of individual variability and pharmacological manipulation of human cortical gamma.
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DOI：
10.1016/j.neuroimage.2017.08.034
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发表时间：
2017-11-01
期刊：
影响因子：
5.7
通讯作者：
Singh KD
中科院分区：
文献类型：
--
作者：
Shaw AD;Moran RJ;Muthukumaraswamy SD;Brealy J;Linden DE;Friston KJ;Singh KD
从非侵入性数据在皮层微电路水平上量化突触功能的能力将在人类神经元加工和参与许多神经精神疾病的病理生理学的研究中非常有用。在这里，我们提供的原则证明，人们可以估计特定的神经元群体之间的层间和层内的相互作用，在人类受试者的视觉皮层诱导的伽马响应-使用动态因果模型的基础上的典型的微电路（CMC;一个简单的模型的皮质柱）。在一个大的正常受试者队列诱导（光谱）反应的变异性，我们发现，γ反应的主要决定因素依赖于浅表锥体细胞和抑制性中间神经元之间的经常性和内在联系。此外，β反应的变化是由深锥体细胞和抑制性中间神经元之间内在联系的受试者间差异介导的。有趣的是，我们还表明，增加表面锥体细胞的自我抑制的γ活动的幅度，同时增加其峰值频率。这种系统性和非线性关系只有通过模拟诱发反应的原因才能揭示出来。至关重要的是，我们能够通过显示GABA再摄取抑制剂噻加宾对抑制性中间神经元的速率常数的选择性作用来验证这种形式的神经生理学表型。值得注意的是，我们能够在每个受试者的基础上在几个小时内恢复这种作用的药效学。这些发现说明了测量群体特异性突触功能及其对药理学干预的反应的可能性，以使用非侵入性数据提供介观神经元过程的受试者特异性生物标志物。最后，我们的研究结果表明，使用CMC作为代理，突触机制的基础上的增益控制的神经元信息传递内和不同层次的皮质层次之间，现在可以进行定量研究，使用非侵入性（MEG）程序。
The ability to quantify synaptic function at the level of cortical microcircuits from non-invasive data would be enormously useful in the study of neuronal processing in humans and the pathophysiology that attends many neuropsychiatric disorders. Here, we provide proof of principle that one can estimate inter-and intra-laminar interactions among specific neuronal populations using induced gamma responses in the visual cortex of human subjects – using dynamic causal modelling based upon the canonical microcircuit (CMC; a simplistic model of a cortical column). Using variability in induced (spectral) responses over a large cohort of normal subjects, we find that the predominant determinants of gamma responses rest on recurrent and intrinsic connections between superficial pyramidal cells and inhibitory interneurons. Furthermore, variations in beta responses were mediated by inter-subject differences in the intrinsic connections between deep pyramidal cells and inhibitory interneurons. Interestingly, we also show that increasing the self-inhibition of superficial pyramidal cells suppresses the amplitude of gamma activity, while increasing its peak frequency. This systematic and nonlinear relationship was only disclosed by modelling the causes of induced responses. Crucially, we were able to validate this form of neurophysiological phenotyping by showing a selective effect of the GABA re-uptake inhibitor tiagabine on the rate constants of inhibitory interneurons. Remarkably, we were able to recover the pharmacodynamics of this effect over the course of several hours on a per subject basis. These findings speak to the possibility of measuring population specific synaptic function – and its response to pharmacological intervention – to provide subject-specific biomarkers of mesoscopic neuronal processes using non-invasive data. Finally, our results demonstrate that, using the CMC as a proxy, the synaptic mechanisms that underlie the gain control of neuronal message passing within and between different levels of cortical hierarchies may now be amenable to quantitative study using non-invasive (MEG) procedures.
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影响因子：
16.2
作者：
Bastos AM;Usrey WM;Adams RA;Mangun GR;Fries P;Friston KJ
通讯作者：
Friston KJ
DOI：
10.1073/pnas.1011284108
发表时间：
2011-07-05
影响因子：
11.1
作者：
Buffalo, Elizabeth A.;Fries, Pascal;Desimone, Robert
通讯作者：
Desimone, Robert
DOI：
10.1073/pnas.120162397
发表时间：
2000-06-20
影响因子：
11.1
作者：
Haenschel, C;Baldeweg, T;Gruzelier, J
通讯作者：
Gruzelier, J
影响因子：
13.9
作者：
Buzsáki G;Wang XJ
通讯作者：
Wang XJ
DOI：
10.1073/pnas.86.5.1698
发表时间：
1989-03-01
影响因子：
11.1
作者：
GRAY, CM;SINGER, W
通讯作者：
SINGER, W