Patterns of anterior versus posterior white matter fractional anistotropy concordance in adult nonhuman primates: Effects of early life stress

Abstract

Introduction 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. Methods 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. Results 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. Conclusions 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.

Unraveling the mystery of white matter in depression: A translational perspective on recent advances

“…This hypothesis is in line with the fact that macaques exposed to early life stress show decreased myelination in postnatally maturing brain areas, but not in areas where the maturation is already completed prenatally (Coplan et al, 2016). Since frontal areas show postnatal maturation in humans as well (Staudt et al, 2000), this mechanism might also be present in MDD patients having suffered from childhood abuse.…”

Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach

“…This anterior–posterior dichotomy is believed to be the result of reduced rostral input, leading to increased caudal activity. 44 , 45 For example, treatment-resistant depression patients showed significant functional dysconnectivity between PFC and caudal brain structures at baseline. However, ketamine treatment, which increased PFC f -GBCr, led to increased PFC–occipital/parietal connectivity and simultaneous reduction in occipital/parietal f -GBCr.…”

Disentangling the effects of early caregiving experience and heritable factors on brain white matter development in rhesus monkeys

“…Early adversity has been previously related to WM microstructural alterations in these circuits in individuals with histories of adverse caregiving, including institutional rearing and childhood maltreatment (Bick et al, 2015;Dannlowski et al, 2012;De Bellis et al, 1999;Eluvathingal et al, 2006;Govindan et al, 2010;Hackman and Farah, 2009;Hanson et al, 2013;Kumar et al, 2014;McCrory et al, 2012;Teicher et al, 2003Teicher et al, , 2014. These regions are also sensitive to ELS in animal models (Bolton et al, 2018;Coplan et al, 2016; Brittany R. Howell et al, 2017Howell et al, , 2016Howell et al, , 2014McEwen, 2008). Additionally, alterations in these WM regions are implicated in the psychopathologies and several of the affective disorders for which ELS is a risk factor (Dannlowski et al, 2012;Fields, 2008;Pechtel and Pizzagalli, 2011;Thomason and Thompson, 2011).…”