Elsevier

Biological Psychiatry

Volume 58, Issue 10, 15 November 2005, Pages 796-804
Biological Psychiatry

Original article
Brain Regions Associated with the Expression and Contextual Regulation of Anxiety in Primates

https://doi.org/10.1016/j.biopsych.2005.05.021Get rights and content

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.

Section snippets

Subjects

Twenty-five male rhesus monkeys (M. mulatta) ranging in age from 2.2 to 4.6 years (mean age = 3.1 years) and weighing between 3.2 and 7.4 kg (mean weight = 5.0 kg) were the subjects. The monkeys were pair housed and maintained on a 12-hour light/dark cycle at the Wisconsin National Primate Research Center and at the Harlow Primate Laboratory. Animals had water ad libitum and were fed monkey chow every morning. Animal housing and experimental procedures were in accordance with institutional

Brain Activity and Freezing Duration During NEC and ALN Conditions

As can be seen in Figure 1, freezing occurred in both the ALN and NEC conditions with significantly more freezing expressed during NEC (t = 2.594, p = .016). During NEC, freezing duration was correlated with activation in an area of the basal forebrain that predominantly encompassed the bed nucleus of the stria terminalis (BNST), a portion of the substantia innominata and more anteriorly the shell of the nucleus accumbens (NAC) (this region will be referred to as BNST/NAC) (R2 = .511, p < .001)

Discussion

The high-resolution, small-animal, PET scanner allowed us to examine patterns of brain activity in rhesus monkeys that are associated with freezing, as well as brain regions associated with the ability to adaptively regulate this threat-related response. The rhesus monkey is an excellent model because similar to humans, rhesus monkeys have a well-developed prefrontal cortex with bidirectional connections to the amygdala and other key subcortical structures (Amaral et al 1992, Fuster 1997). This

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