Multifractal Evidence of Nonlinear Correlations in Golgi/Cox-Stained Slices of Orbitofrontal Cortex Predicts Anxiety Behavior Following Corticosterone Injection

Multifractal geometry has found growing support as the proper framework for mapping, stimulating, and scaffolding growth of neural structures. We predicted that multifractal structure reflecting nonlinear interactions across scales might moderate effects of stimulation on subsequent behavioral response. We reanalyzed Golgi/Cox stained slices of orbitofrontal cortex from rats injected with either saline or with corticosterone, a stress hormone whose effects can depend on reshaping neural morphology at the fine scale of dendritic spines. Following injection, the rats completed the elevated plus maze (EPM) and open field task (OFT), and their general activity and anxiety-related behaviors were observed. We used spatial multifractal analysis to estimate the multifractal spectrum of neurons at two objective magnifications, and we used surrogate comparison to calculate the degree of multifractal nonlinearity reflecting interactions across scales at each magnification. Regression modeling demonstrated that corticosterone and coarse-scale multifractal nonlinearity of neural tissue promoted anxiety-related behaviors. Meanwhile, multifractal nonlinearity at the finer scales was associated with reduced anxiety following corticosterone injection. For older rats, multifractality was itself sensitive to corticosterone but did not mediate its effects. Multifractal nonlinearity of neural tissues may thus provide constraints on the effects that chemical changes have on organism behavior.