Cortisol predicts increased internal capsule integrity in a large sample of non-human primates

Abstract

Background : Cortisol is critical for survival and reflects a primary mechanism by which emotions can influence immune responses throughout the periphery. Although cortisol release is adaptive in response to stress, chronically increased cortisol is known to have negative effects on both body and brain. Here we use a large sample of rhesus monkeys to examine individual differences in stress-related cortisol, in relation to white matter (WM) structure within a distributed brain network. We correlated individual differences in stress-induced cortisol with diffusion tensor imaging (DTI) measures of WM microstructure in 330 young rhesus monkeys. Methods : 330 young rhesus macaques were scanned. Diffusion-weighted imaging was performed using a GE SIGNA 3T scanner. Scanning parameters were b=1000 s/mm2, TR = 10 s, TE = 77.2 ms, FOV = 14 cm, matrix = 128×128, 2.5 mm slices. Brains were transformed to a standard space using DTI-TK normalization tool (http://www.nitrc.org/projects/dtitk), which iteratively constructs a nonlinear template from the tensor files. Fractional anisotropy maps were computed in standard space. Cortisol was measured from the blood after a No Eye Contact (NEC) challenge, where a human intruder entered the room for 30 minutes without having eye contact with the monkey. We used robust regression to examine the relationship between fractional anisotropy (FA) and cortisol levels while controlling for age and sex. Results : Individual differences in cortisol were correlated with DTI-measured FA in the internal capsule (p<0.001, two-tailed test, uncorrected), among other regions. The internal capsule is widely connected to distributed brain regions. Therefore, we used deterministic tractography to specifically identify the regions that were connected to the internal capsule region that predicted plasma cortisol levels. Results demonstrated connectivity with the dorsal putamen, anterior cingulate, hypothalamus, and brainstem structures. Conclusions : Our data suggest that naturally occurring increased levels of cortisol are associated with structural differences in key WM regions that coordinate long-range connectivity. Because these connections are important for adaptive and maladaptive stress responses, these findings are highly relevant to understanding the development of stress-related psychopathology.

Keywords

• cortisol
• diffusion tensor imaging
• DTI
• primate
• anxiety