Brain regions associated with the expression and contextual regulation of anxiety in primates

Abstract

Background: A key to successful adaptation is the ability to regulate emotional responses in relation to changing environmental demands or contexts.

Methods: High-resolution PET 18fluoro-deoxyglucose (FDG) scanning in rhesus monkeys was performed during two contexts (alone, and human intruder with no eye contact) during which the duration of anxiety related freezing behavior was assessed. Correlations between individual differences in freezing duration and brain activity were performed for each of the two conditions, as well as for the contextual regulation between the two conditions.

Results: In both conditions, activity in the basal forebrain, including the bed nucleus of the stria terminalis and the nucleus accumbens were correlated with individual differences in freezing duration. In contrast, individual differences in the ability to regulate freezing behavior between contexts were correlated with activity in the dorsal anterior cingulate cortex, the thalamus and the dorsal raphe nucleus.

Conclusions: These findings demonstrate differences in the neural circuitry mediating the expression compared to the contextual regulation of freezing behavior. These findings are relevant since altered regulatory processes may underlie anxiety disorders.

Figure 1

The duration of freezing behavior (mean log duration of freezing in sec per min + SEM) for the Alone (ALN) compared to the No Eye Contact (NEC) condition. * p < .05

Figure 2

The BNST/NAC regions that are correlated with freezing duration in the NEC (red) and ALN (blue) conditions are displayed. Regions of interest were defined by voxels that were correlated with the log duration of freezing at an uncorrected threshold of p < .005. The correlated regions, overlaid on an MRI template, are depicted in (A) an anterior region and in (B) a more posterior region of the BNST/NAC area. Corresponding anatomical drawings adapted from a rhesus monkey atlas (Figures 40 and 48) (Paxinos et al 2000) display the location of the nucleus accumbens, bed nucleus of the stria terminalis and the substantia innominata. Scatter plots represent the relation between log freezing duration and brain activity in the BNST/NAC ROIs for the NEC (red) and ALN (blue) conditions. Both variables are standardized and residualized for age. ALN, alone group; NEC, no eye contact group; BNST, bed nucleus of the stria terminalis; NAC, nucleus accumbens; MRI, magnetic resonance imaging; ROI, regions of interest.

Figure 3

The regions of motor cortex that are correlated with freezing duration in the NEC (red) and ALN (blue) conditions. Regions of interest were defined by voxels that were correlated with the log duration of freezing at an uncorrected threshold of p <.005. The correlated regions are overlaid on a slice of an MRI template, which corresponds to Figure 67 of the rhesus monkey atlas (Paxinos et al 2000). Scatter plots represent the relation between log freezing duration and brain activity in the motor cortex ROIs for the NEC (red) and ALN (blue) conditions. Both variables are standardized and residualized for age. ALN, alone group; NEC, no eye contact group; MRI, magnetic resonance imaging; ROI, regions of interest.

Figure 4

Brain regions (dorsal anterior cingulate cortex, thalamus, and brain stem) in which the change in brain activity is correlated with the change in freezing duration between the NEC and ALN conditions. Regions of interest (ROIs) were defined by voxels that were correlated with the log duration of freezing at an uncorrected threshold of p < .005. The correlated regions are overlaid on an MRI template, which correspond to Figures 53, 65, and 83 of the rhesus monkey atlas (Paxinos et al 2000). The ROIs used are highlighted with arrows and scatter plots are presented demonstrating the relation between the change in log freezing duration and the change in brain activity. All the variables are standardized and residualized for age. Other correlated areas are displayed in orange (positive) and blue (negative). ALN, alone condition; NEC, no eye contact condition; MRI, magnetic resonance imaging; ROI, regions of interest.