Computational Modeling of Electroencephalography and Functional Magnetic Resonance Imaging Paradigms Indicates a Consistent Loss of Pyramidal Cell Synaptic Gain in Schizophrenia.
Computational Modeling of Electroencephalography and Functional Magnetic Resonance Imaging Paradigms Indicates a Consistent Loss of Pyramidal Cell Synaptic Gain in Schizophrenia.
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DOI：
10.1016/j.biopsych.2021.07.024
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发表时间：
2022-01-15
影响因子：
10.6
通讯作者：
Anticevic A
中科院分区：
文献类型：
--
作者：
Adams RA;Pinotsis D;Tsirlis K;Unruh L;Mahajan A;Horas AM;Convertino L;Summerfelt A;Sampath H;Du XM;Kochunov P;Ji JL;Repovs G;Murray JD;Friston KJ;Hong LE;Anticevic A
突触增益减少（突触后反应对神经输入的敏感性）可能是精神分裂症的基本突触病理。然而，这方面的证据是间接的。此外，尚不清楚锥体细胞或中间神经元（或两者）是否受到影响，或者这些缺陷与症状有何关系。精神分裂症诊断患者 (PScz) (n = 108)、其亲属 (n = 57) 和对照受试者 (n = 107) 接受了 3 种脑电图 (EEG) 范式——静息、失配负性和 40 Hz 听觉稳态反应——以及静息功能磁共振成像。动态因果模型用于量化皮质微电路中的突触连接。 PScz 和对照受试者之间脑电图特征的经典群体差异得到了复制，包括 θ 和其他频谱变化（静息脑电图）增加、失配负性减少和 40 Hz 功率减少。在所有 4 个范式中，特征性 PScz 数据特征都可以通过锥体细胞中具有更大自我抑制（突触增益减少）的模型得到最好的解释。此外，听觉区域的去抑制在 3 种范式中预测 PScz 的听觉异常（和阳性症状）。首先，3种经典范式中PScz的特征性脑电图变化都可归因于相同的潜在参数变化：锥体细胞更大的自我抑制。其次，PScz 的精神病症状与神经回路的去抑制有关。这些发现与以下假设更相符：在 PScz 中，锥体细胞突触增益的主要损失随后通过中间神经元下调（而不是相反）得到补偿。他们进一步表明精神病症状与这种继发性下调有关。
Diminished synaptic gain—the sensitivity of postsynaptic responses to neural inputs—may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms. People with schizophrenia diagnoses (PScz) (n = 108), their relatives (n = 57), and control subjects (n = 107) underwent 3 electroencephalography (EEG) paradigms—resting, mismatch negativity, and 40-Hz auditory steady-state response—and resting functional magnetic resonance imaging. Dynamic causal modeling was used to quantify synaptic connectivity in cortical microcircuits. Classic group differences in EEG features between PScz and control subjects were replicated, including increased theta and other spectral changes (resting EEG), reduced mismatch negativity, and reduced 40-Hz power. Across all 4 paradigms, characteristic PScz data features were all best explained by models with greater self-inhibition (decreased synaptic gain) in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in PScz in 3 paradigms. First, characteristic EEG changes in PScz in 3 classic paradigms are all attributable to the same underlying parameter change: greater self-inhibition in pyramidal cells. Second, psychotic symptoms in PScz relate to disinhibition in neural circuits. These findings are more commensurate with the hypothesis that in PScz, a primary loss of synaptic gain on pyramidal cells is then compensated by interneuron downregulation (rather than the converse). They further suggest that psychotic symptoms relate to this secondary downregulation.
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影响因子：
10.6
作者：
Erickson MA;Ruffle A;Gold JM
通讯作者：
Gold JM
影响因子：
4.5
作者：
Fogelson, Noa;Litvak, Vladimir;Peled, Avi;Fernandez-del-Olmo, Miguel;Friston, Karl
通讯作者：
Friston, Karl
DOI：
10.1176/appi.ajp.2015.14091200
发表时间：
2016-04-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Clementz BA;Sweeney JA;Hamm JP;Ivleva EI;Ethridge LE;Pearlson GD;Keshavan MS;Tamminga CA
通讯作者：
Tamminga CA
DOI：
10.1093/schizbullopen/sgaa072
发表时间：
2021-01
期刊：
Schizophrenia bulletin open
影响因子：
--
作者：
Jeon P;Limongi R;Ford SD;Mackinley M;Dempster K;Théberge J;Palaniyappan L
通讯作者：
Palaniyappan L
影响因子：
6.6
作者：
Bastos-Leite AJ;Ridgway GR;Silveira C;Norton A;Reis S;Friston KJ
通讯作者：
Friston KJ