cortisol predicts increased internal capsule...
TRANSCRIPT
CORTISOL PREDICTS INCREASED INTERNAL CAPSULE INTEGRITY IN A LARGE SAMPLE OF NON-HUMAN PRIMATES
v RESULTS
Do P.M. Tromp, Andrew S. Fox, Jonathan A. Oler, Nagesh Adluru, Richard J. Davidson, Andrew L. Alexander, Ned H. Kalin
Waisman Center and Department of Psychiatry, University of Wisconsin, Madison, WI, United States
v DISCUSSION
These results demonstrate alterations in white matter integrity that are associated with trait-like levels of cortisol as well as other components of AT. Because cortisol in!uences brain structure and function, the possibility exists that elevated cortisol, occurring over prolonged periods, affects white matter integrity. Alternatively, alterations in speci#c WM tracts linked to the hypothalamus could in!uence the regulation of the pituitary-adrenal system. Longitudinal studies are planned to further understand potential causal links.
v REFERENCES 1. Oler et al. (2010). Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature 466, 864-868. 2. http://www.nitrc.org/projects/dtitk 3. Lazar et al. (2003). White matter tractography using diffusion tensor de!ection. HBM 18, 306-321. We thank the staff at the Wisconsin Na/onal Primate Center, the Harlow Center for Biological Psychology, the HealthEmo/ons Research Ins/tute, the Waisman Laboratory for Brain Imaging and Behavior, P. Roseboom, H. Van Valkenberg, K. Myer, E. Larson, M. Riedel, J. Storey, I. Monosov, and M. Jesson. This work has been supported by Na/onal Ins/tutes of Health grants MH046729, MH081884, MH084051, MH018931, Wisconsin Na/onal Primate Research Center, P51OD011106 / P51RR000167 and the HealthEmo/ons Research Ins/tute.
v METHODS
30 min
Stress-induced cortisol was measured directly after the no eye contact (NEC) condition. During this condition the animals were placed in a test-cage, after which a human intruder entered the room and stood still at a distance of 2.5 meters presenting his pro#le, while avoiding eye contact. During this period spontaneous behaviors were measured. Following 30-minutes of exposure to the experimental condition, animals were anesthetized and blood samples were taken to assess plasma cortisol levels1. 542 young rhesus macaques (237 females, mean age 1.87 years) were scanned within two weeks of testing. Diffusion-weighted imaging was performed using a GE SIGNA 3T scanner. Scanning parameters were b = 1000 s/mm2, TR = 10s, TE = 77.2ms, FOV = 14cm, matrix = 128x128, 2.5mm slices. Brains were transformed to a standard space using DTI-TK normalization tool2, which iteratively constructs a non-linear template from the tensor #les. Fractional Anisotropy (FA) maps were computed from the tensor shapes in standard space. We used robust regression to examine the relationship between FA and cortisol levels while controlling for age and sex. A tensor de!ection algorithm for deterministic tractography3 was run on the DTI population mean to visualize the tracts running through the region where the robust regression revealed a signi#cant relationship with cortisol levels. An FDR-corrected cluster within the right internal capsule was used as a seed region for #ber tracking.
Tensor de!ection (TEND) algorithm for deterministic tractography
The robust regression analysis revealed that individual differences in cortisol were associated with DTI-measured Fractional Anisotropy (FA) in the internal capsule (q < 0.05, two tailed, FDR corrected), among other regions. We previously de#ned anxious temperament (AT) as a composite of stress related cortisol, threat-induced increases in freezing and reductions in coo vocalizations. To further explore the behaviors that are components of AT, we also ran a robust regression for cooing and freezing with FA. Results are consistent with those for cortisol and are shown on the right. The internal capsule carries #bers that connect distributed brain regions. Therefore, we used deterministic tractography to speci#cally identify the regions that were connected to the internal capsule region that predicted plasma cortisol levels. The images below show the output of the #ber tracking algorithm. The seed region predictive of cortisol is shown in green. Fibers are colored by FA intensity along the tract. Results demonstrated connectivity with the dorsal putamen, anterior cingulate, hypothalamus and brainstem structures.
Cortisol is a critical hormonal component of the stress response. Although cortisol release is adaptive in response to stress, chronically increased cortisol is known to have negative effects on both body and brain. Cortisol is a component of anxious temperament (AT) along with threat-induced increases in freezing and reductions in coo vocalizations. Here we use a large sample of rhesus monkeys to examine individual differences in stress-related cortisol, a stable trait-like measure of pituitary-adrenal activity, in relation to white matter (WM) structure within a distributed brain network. We investigated the relationship between individual differences in stress-induced cortisol with diffusion tensor imaging (DTI) measures of WM microstructure in 542 young rhesus monkeys.