Efficient recall of memories associated with previous stressors is crucial
for survival. For instance, if one encounters a dangerous animal, the rapid recall
of the memory of a previous encounter with a dangerous  animal of the same type
may be life saving. Brain regions involved in the recall of memory simultaneously
activate the body’s stress response system, leading to increased release
of stress-related neurotransmitters and neuropeptides. These in turn modulate
the encoding of memory, which results in a type of feedback loop of the body’s
stress response system on memory storage.
Brain regions involved
in memory also play a prominent role in the execution of the stress response.
In the early part of this century the observation was made that, with the removal
of the cerebral cortex, a hyperexcitability of anger developed, which was termed
sham rage. Animals in the sham-rage state were quick to attack, and behaved as
if they were experiencing a profoundly threatening situation. Papez proposed that
the hypothalamus, thalamus, hippocampus, and cingulate are responsible for the
behaviors of the decorticate cat. Kluver and Bucy noted that removal of the temporal
lobe (including hippocampus and amygdala) resulted in “psychic blindness,”
or the absence of anger and fear. These observations led to the development of
the concept of the limbic brain, in which the brain regions listed above (and
others, including the orbitofrontal cortex) mediate the stress response. The circuits
constructed by these authors are no longer valid, based on the current evidence,
although the individual brain regions described above as being part of the limbic
system play an important role in the effects of stress on memory function. There
is considerable literature claiming that stress also results in alterations in
memory function. Therefore, the brain regions that are responsible for memory
function and the stress response are in turn affected by exposure to traumatic
stress. We review below the effects of stress on brain regions involved in memory.
Stress
has effects on the hippocampus, which leads to both changes in its cytoarchitecture
as well as to deficits in explicit recall. Twenty-one days of restraint stress
has been shown to be associated with deficits in spatial memory as measured by
the radial arm maze. A release of glucocorticoids follows exposure to stress,
and the hippocampus is a major target organ for glucocorticoids in the brain.
In addition, the hippocampus appears to play an important role in the pituitary
adrenocortical response to stress. Studies of monkeys who died spontaneously following
exposure to severe stress from improper caging and overcrowding were found on
autopsy to have multiple gastric ulcers, which is consistent with exposure to
chronic stress, and hyperplastic adrenal cortices, which is consistent with sustained
glucocorticoid release. They also suffered damage to the CA2 and CA3 subfields
of the hippocampus. Follow-up studies suggested that hippocampal damage was associated
with direct exposure of glucocorticoids to the hippocampus. Studies in a variety
of animal species have shown that direct glucocorticoid exposure results in a
loss of pyramidal neurons and dendritic branching which are steroid and tissue
specific. Glucocorticoids appear to exert their effect by increasing the vulnerability
of hippocampal neurons to endogenously released excitatory amino acids. The same
paradigm of stress exposure which increases glucocorticoids and causes loss
of apical dendritic branching in the CA3 region of the hippocampus is associated
with deficits in spatial memory. This suggests that the effects of glucocorticoids
on the hippocampus have functional implications.
The hippocampus
also plays an important role in emotional memory of the context of a fear-inducing
situation. In conditioned fear response experiments where a tone (conditioned
stimulus) is paired with an electric footshock (unconditioned stimulus), reexposure
of the animal to the tone will result in conditioned fear responses (increase
in “freezing” responses, which is characteristic of fear), even in the
absence of the shock. In addition, reintroduction to the context of the shock,
or the environment where the shock took place (the testing box), even in the absence
of the shock or the tone, will result in conditioned fear responses. Lesions of
the amygdala before fear conditioning block fear responses to both simple stimuli
(tone) and to the context of the footshock. Lesions of the hippocampus, on the
other hand, do not interfere with acquisition of conditioned emotional responses
to the tone in the absence of the shock, although they do interfere with acquisition
of conditioned emotional responses to the context.9’ Lesions of the hippocampus
1 day after fear conditioning (but not as much as 28 days after fear conditioning)
also abolish context related fear responses, but not the fear response related
to the cue (tone), while lesions of the amygdala block fear responses to both
the cue and the context. These studies suggest that the hippocampus has a time-limited
role in fear responses to complex phenomena with stimuli from multiple sensory
modalities, but not to stimuli from simple sensory stimuli.
Stress
also has effects on amygdala function. The amygdala integrates information
necessary for the proper execution of the stress response, including (internal)
emotion and information from the external environment. Information from the environment
that has emotional significance is transmitted through the dorsal thalamus to
sensory cortical receiving areas, and from there to the amygdala. Emotional responses
to auditory stimuli are also mediated by direct projections from the medial geniculate
in the thalamus to the amygdala, which suggests that the cerebral cortex is not
necessary for emotional responses to stimuli. Evidence suggests that the lateral
nucleus of the amygdala is the site of convergence of stimuli from multiple sensory
modalities, including somatosensory and auditory stimuli. This suggests that
this region may be the site where information from unconditioned stimuli (footshock)
and conditioned stimuli (tone) converge, and are translated into a final common
pathway of the conditioned emotional response. The amygdala then activates the
peripheral sympathetic system, which plays a key role in the stress response,
through the lateral nucleus of the hypothalamus and the central gray, leading
to increased heart rate and blood pressure, as well as activating other aspects
of the body’s stress response system. Projections from the central nucleus
of the amygdala to brainstem regions, including the parabrachial nucleus, dorsal
motor vagal complex, and nucleus of the solitary tract, mediate the cardiovascular
response to stress (increased heart rate and blood pressure). Repeated exposure
to stress can result in an exaggerated startle response, which indicates an increased
sensitivity of amygdala function.
Very little is known about
the effects of stress on dorsolateral prefrontal cortical function. Studies are
currently underway using the Wisconsin Card Sort Test, which is felt to represent
a measure of dorsolateral prefrontal cortical function, in PTSD patients and controls
(R. Yehuda, personal communication, 1994). We have found a differential effect
of yohimbine on dorsolateral prefrontal cortex metabolism in patients with PTSD
in comparison with controls.
Studies have demonstrated that
the anteromedial prefrontal cortex (including the anterior cingulate) plays an
important role in the stress response. Lesions of the anteromedial prefrontal
cortex (including the anterior cingulate) in the rat interfere with conditioned
emotional responses to fear-eliciting stimuli. Specifically, these lesions result
in a decrease in freezing behaviors and conditioned cardiovascular responses (increased
heart rate) with fear-inducing stimuli. Lesions of the cingulate gyms increase
plasma levels of adrenocorticotropin (ACTH) and corticosterone in response to
restraint stress. This suggests that this area is a target site for the negative
feedback effects of glucocorticoids on stress induced hypothalamic—pituitary—adrenal
(HPA) activity. In other words, the cingulate has a braking effect on the HPA
axis system response to stress.
Little is known about the effects of stress on parietal cortex function. Since the parietal cortex is
involved in attention, it is reasonable to predict that the increase in focused
attention which occurs during stressful situations is associated with activation
of the parietal cortex. As reviewed above, studies in normal human subjects have
found differences in recall during stressful as compared with nonstressful situations,
with an increase of focused attention on central details of stressful situations.
- Appelbaum, Paul S., Uyehara, Lisa A., & Elin, Mark R., Trauma and Memory,
Oxford University Press: New York, 1997.
The article above contains foundational information. Articles below contain optional updates.
=================================
Personal
Reflection Exercise #1
The preceding section contained information
about effects of stress on brain regions involved in memory. Write three case
study examples regarding how you might use the content of this section in your
practice.
QUESTION
7
What part of the brain plays an important part in emotional memory
regarding the context of a fear-induced situation? Record the letter of the correct
answer the .
|
