Coplan Jeremy D, Kolavennu Venu, Abdallah Chadi G, Mathew Sanjay J, Perera Tarique D, Pantol Gustavo, Carpenter David, Tang Cheuk
Department of Psychiatry & Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
J Affect Disord. 2016 Mar 1;192:167-75. doi: 10.1016/j.jad.2015.11.049. Epub 2015 Dec 9.
Functional neuroimaging studies report global prefrontal dysconnectivity in mood disorders, supporting the notion of widespread disruptions in brain networks. Microscopic alterations in white matter (WM) tracts - which possess neuroplastic properties and play a central role in brain connectivity - are interrogated herein in the context of brain dysconnectivity. Early life stress (ELS), an antecedent to human mood disorders, induces WM alterations in volumetrics and integrity. We hypothesized that nonhuman primate infants exposed to ELS would exhibit persistent impairments in both frontal and posterior concordance of WM integrity, therefore contributing to global brain dysconnectivity.
Using a 3T MRI, diffusion tensor imaging (DTI) was performed on 21 adult male Bonnet macaques, 12 of whom had been raised under variable foraging demand (VFD) conditions and nine of whom had been raised under normative conditions (Non-VFD). As representative of anterior regions, fractional anisotropy (FA) concordance between anterior corpus callosum (ACorpusC) and anterior limb of the internal capsule (ALIC) was examined. For posterior regions, FA concordance between posterior corpus callosum (PCorpusC) and posterior limb of the internal capsule (PLICA) and between PCorpusC and occipital WM was examined. Examination of posterior FA was explored in the context of frontal markers of neuroplasticity.
A concordant relationship for FA between left ALIC and ACorpusC was evident in Non-VFD-reared subjects, but significantly absent in VFD-reared subjects. For left posterior regions, FA concordance between PLICA and PCorpusC and occipital WM and PCorpusC was evident in VFD-reared and not Non-VFD-reared subjects. The posterior concordance in VFD was significantly distinguishable from the deficit in anterior concordance FA in VFD.
The findings support the view that disrupted emotional integrity of the maternal-infant attachment process affects normative synchronous development of frontal white matter tracts but creates errant posterior concordance and also disrupts an inverse relationship between posterior white matter tracts and markers of neuroplasticity. We provide preliminary evidence that a concordant relationship between capsular-callosal FA may become discordant, providing a putative mechanism for prefrontal functional brain dysconnectivity.
功能神经影像学研究报告了情绪障碍中前额叶整体失连接，支持了脑网络广泛破坏的观点。白质（WM）束的微观改变——其具有神经可塑性并在脑连接中起核心作用——在此文中在脑失连接的背景下进行探讨。早期生活应激（ELS）是人类情绪障碍的一个前驱因素，可导致WM在体积和完整性方面的改变。我们假设，暴露于ELS的非人灵长类动物幼崽在WM完整性的额叶和后部一致性方面均会表现出持续性损伤，从而导致全脑失连接。
使用3T磁共振成像，对21只成年雄性邦内猕猴进行扩散张量成像（DTI），其中12只在可变觅食需求（VFD）条件下饲养，9只在正常条件下（非VFD）饲养。作为前部区域的代表，检查胼胝体前部（ACorpusC）和内囊前肢（ALIC）之间的分数各向异性（FA）一致性。对于后部区域，检查胼胝体后部（PCorpusC）与内囊后肢（PLICA）之间以及PCorpusC与枕叶WM之间的FA一致性。在神经可塑性的额叶标志物背景下探索后部FA的检查。
在非VFD饲养的受试者中，左ALIC和ACorpusC之间FA的一致性关系明显，但在VFD饲养的受试者中显著缺乏。对于左侧后部区域，PLICA与PCorpusC以及枕叶WM与PCorpusC之间的FA一致性在VFD饲养的受试者中明显，而在非VFD饲养的受试者中不明显。VFD中的后部一致性与VFD中前部一致性FA的缺陷有显著差异。
这些发现支持这样一种观点，即母婴依恋过程中情感完整性的破坏会影响额叶白质束的正常同步发育，但会产生错误的后部一致性，并且还会破坏后部白质束与神经可塑性标志物之间的反向关系。我们提供了初步证据表明，囊 - 胼胝体FA之间的一致性关系可能会变得不一致，为前额叶功能性脑失连接提供了一种可能的机制。
