Early Developmental Trajectories of Functional Connectivity Along the Visual Pathways in Rhesus Monkeys

Abstract

Early social interactions shape the development of social behavior, although the critical periods or the underlying neurodevelopmental processes are not completely understood. Here, we studied the developmental changes in neural pathways underlying visual social engagement in the translational rhesus monkey model. Changes in functional connectivity (FC) along the ventral object and motion pathways and the dorsal attention/visuo-spatial pathways were studied longitudinally using resting-state functional MRI in infant rhesus monkeys, from birth through early weaning (3 months), given the socioemotional changes experienced during this period. Our results revealed that (1) maturation along the visual pathways proceeds in a caudo-rostral progression with primary visual areas (V1–V3) showing strong FC as early as 2 weeks of age, whereas higher-order visual and attentional areas (e.g., MT–AST, LIP–FEF) show weak FC; (2) functional changes were pathway-specific (e.g., robust FC increases detected in the most anterior aspect of the object pathway (TE–AMY), but FC remained weak in the other pathways (e.g., AST–AMY)); (3) FC matures similarly in both right and left hemispheres. Our findings suggest that visual pathways in infant macaques undergo selective remodeling during the first 3 months of life, likely regulated by early social interactions and supporting the transition to independence from the mother.

Developmental outcomes of early adverse care on amygdala functional connectivity in nonhuman primates

“…Notwithstanding the above defense of GSR, we acknowledge that controversy regarding this method persists (Murphy & Fox, 2017). Because of this, we previously compared infant macaque FC with and without GSR and obtained similar results throughout development (Kovacs-Balint et al, 2018), including the current dataset, in which similar effects of maltreatment were detected on amygdala FC with and without GSR (Morin et al, 2015 ).…”

“…mean ± standard deviation) and intubation, scans were collected under the lowest possible level of isoflurane anesthesia (1.0 ± 0.1%, inhalation; mean ± standard deviation) to minimize its reported dampening effect on blood oxygen level dependent (BOLD signal) (Hutchison, Womelsdorf, Gati, Everling, & Menon, 2013; Li, Patel, Auerbach, & Zhang, 2013; Miranda-Dominguez et al, 2014b; Tang & Ramani, 2016; Vincent et al, 2007). MRI images were acquired and processed following approaches optimized by our group for studies of macaque neurodevelopment (Kovacs-Balint et al, 2018; Mavigner et al, 2018) and protocols developed and widely used for macaques (Grayson et al, 2016; Hutchison et al, 2012; Li et al, 2013; Margulies et al, 2009; Sallet et al, 2011; Vincent et al, 2007). Our isoflurane levels are even lower than previously used in macaque studies of sensory, motor, visual, and cognitive-task related systems that reported patterns of coherent BOLD fluctuations similar to those observed in awake behaving monkeys (Vincent et al, 2007; Hutchison et al, 2013; Li et al, 2013; Miranda-Dominguez et al, 2014b; Tang & Ramani, 2016).…”

“…The first three volumes were removed from each EPI scan to ensure scan environment stabilization, resulting in a total of 794 concatenated volumes per 15-min scan. These protocols and scan sequences have been optimized at the YNPRC for longitudinal infant macaque imaging (Kovacs-Balint et al, 2018; Mavigner et al, 2018; Shi et al, 2017; Zhang et al, 2017).…”

“…Data pre-processing was done using the FMRIB Software Library (FSL, Oxford, UK; Smith et al, 2004; Woolrich et al, 2009), 4dfp, and an in-house pipeline built using Nipype (Gorgolewski et al, 2011), modified based on published functional MRI (fMRI) analysis methods (Fair et al, 2007; Fair et al, 2009; Fair et al, 2012; Iyer et al, 2013; Miranda-Dominguez et al, 2014a), and optimized for macaques (Miranda-Dominguez et al, 2014b), including resting state fMRI (rsfMRI) studies in infant rhesus by our group (Kovacs-Balint et al, 2018; Mavigner et al, 2018). This procedure consisted of (a) quantification and correction of dynamic field map changes, (b) slice-time correction of intensity differences as a result of interleaved slice image acquisition, (c) combined resampling of: within-run rigid-body motion correction, registration of the EPI to the subject's own averaged T1-weighted structural image, and registration of the T1 to age-specific T1-weighted rhesus infant and juvenile brain structural MRI atlases developed by our group (publicly available at: ), using nonlinear registration methods in FSL (FNIRT), (d) BOLD signal normalization to mode of 1000, to scale BOLD values across participants at an acceptable range, (e) BOLD signal detrending, (f) regression of rigid body head motion (six directions), global brain signal, BOLD signal of the ventricles and white matter (derived from manually drawn masks), and first-order derivatives of these signals, and (g) low-pass (f < 0.1 Hz) temporal filter (second order Butterworth filter) (Fair et al, 2007; Fair et al, 2009; Fair et al, 2012; Miranda-Dominguez et al, 2014b).…”

Structural development of cortical lobes during the first 6 months of life in infant macaques

“…Twenty-one infant male rhesus monkeys (Macaca mulatta) were studied longitudinally as part of a larger project that also examined developmental trajectories of resting state functional brain connectivity ( Kovacs-Balint et al, 2019 ), white matter maturation (DTI), and social visual perception of relevance for ASD-deficits using eye-tracking ( Muschinski et al, 2016 ; Parr et al, 2016 ; Wang et al, 2020 ). Only males were studied due to the higher male:female ratio diagnosis of ASD ( Loomes et al, 2017 ; Baio et al, 2018 ) and other neurodevelopmental disorders, and to increase power for our analyses.…”