Lecture 14 Neuroimaging of Stress Flashcards
Stress response to maintain homeostasis and how it can be bad for you
Baboon experiment
Quasi experimental
Had good ecological validity
Allostatic load and why it is bad for you
It is bad if too much
Repeated stressor activation leads to higher allostatic load
HPA and SNS work in concert
Early exposure to stress leads to decreased negative feedback and hence increased HPA activation
Abused kids show lower HPA (and compensatory high SNS)
Causal direction unknown
Adaptation to stress
Should adapt to long term stress, if you so not (individual variation) you will get increased allostatic load
Primary consequences of allostatic load
Are direct mechanisms of the stress response
Serum DHEA-S
Overnight urinary cortisol
Overnight noradrenaline and adrenaline excretion
Secondary consequences of allostatic load
Are measures of the response to stress responses
Systolic and systolic BP
Waist-hip ratio
And index of the increased glucocorticoid activity
-adipose here is what is linked with heart issues
Sedum HDL and LDL
Linked with cholesterol damage
Blood plasma levels of glycosylated hemoglobin
Why stress is bad for you, the allostatic load hypothesis
Changes in stress lead to changes in physiology which in turn, lead to changes in disease
Is caused by allostatic load just like glucocorticoid cascades are
Why stress is bad for you, the allostatic load hypothesis
Linked systems that contribute
The environment
Individual differences (genes, development, experiences)
Perceived threats (life events, helplessness, vigilance)
Behavioral responses
ALL THESE LEAD TO
Physiological responses
These cause either allostasis and adaptation OR allostatic load and damage
Tertiary consequences of allostatic load
Disease caused by allostatic load
Psychological - Major Depressive Disorder
Physiological - CV disease, abdominal adiposity, bone loss
Co morbidity between MDD and CVD
If allostatic load is causal, there should be a relationship between the two things. There is!
- Onset of MDD predicts worse CVD
- LDL linked to adiposity, linked to CVD (putting on fat in torso)
- MI most common in the morning (at time of peak cortisol)
- CVD linked to decreases in bone density
It is all correlation but looks convincing
Why stress is bad for you
What the HPA and SNS activity to to help/hinder
Stress hormones are initially beneficial but detrimental long term
Chronic activation is a problem
Glucocorticoids (bind at GR)
- conversion of proteion and lipids to carbohydrates for energy
- Increase food seeking and locomotor activity
- gets you energy to cope with stress
SNS activation
- increase HR and BP
- Gets you up/gives you MI
Increased allostatic load = negative physiological effects
Why stress is bad for your brain
Stress can lead to vivid memory
- flashbulbs
- Good stressors make important memories stand out
Increased CRH in various brain regions following stress
Increases HPA
However
Prolonged activation downregulates receptors
Reduced negative feedback
Cell death in hippocampus
Is one of the first things seen in Alz for example
Also amygdala and frontal cortices
This effect can be seen in humans via imaging
In rats (management of proceptive HPA activation)
Inhibitory action on GABA neurons from Ventral Subiculum and PFC
Only inhibitory T2 neurons here
Gets shut off by circulating GC (so more HPA)
More activation of this = less inhibition of PVN = more HPA
Excitatory action on GABA from amygdala
More activation = more gaba
Why stress is bad for the brain (2)
Chronic stress increases the CRH in the amygdala
Contributes to HPA dysregulation and behavior
Experiment with CRH into rats
Inject via cannulation, CRH into amygdala 1x a day for 5 days
G1 injected
G2 not
G1 Trapped (restraint stressor) G2 Not (control)
2x2 design
ACTH and corticosterone measured
Grooming behaviour measured as a surrogate for the rat being stressed
Higher grooming = higher stress
In the non- chronically stressed (no injection) mice, there was no significant difference in those who were restrained or not in time grooming
In the chronically stressed group (injection) the retrained mice are extremely stressed and do significantly more grooming compared to non restrained ones
A BIGGER STRESS RESPONSE
(Chronic stress might enhance the stress response)
Also this group showed less corticosterone at baseline, after 15 mins this was equal between chronically stressed and control then then at 60 mins they had higher levels again
So higher levels at baseline (released from restrain stress)
Same after 15 mins
Higher after 60 mins (after restraint stress)
What effects can we se in human brains (via imaging)
Yes, imaging stress is critical to extend animal findings
Resolution is poor though
These experiments are guided by rat research as this shows them what region to image
Imaging article review (set up and MIST definition)
Review on the connection between cortisol and brain activity
Anticipatory (processive) vs reactive (systemic) stressors were triggered by the
MIST (Montreal imagine stress test) - doing math backwards out loud in such a time limit that you could not get more than 40% right
Cold pressor - put hand in cold water
Assess response and subjective stress with MRI, PET and fMRI
Chose hippocampus, amygdala and PFC due to rat research
Imaging article review (results)
Hippocampus
See inverse relation between hippocampus volume and cortisol response
Stress reduces hippocampus leading to increased HPA? (due to lack of excitation on GABA neurons)
\Amygdala
Blood flow to amygdala correlates with SCTH levels Having more psychological resources = lower cortisol and amygdala blood flow after stress
This finding is not always observed; this might be because there is no fear as we make animals scared in trials but not humans
This is overall, the least certain region
PFC
Cortisol increase = decreased orbitofrontal and increased medial PFC
mPFC is used to monitor the situation - useful in stress
OFC controls cognitive processes, less needed in stress
Imaging article review (brainstem)
Cannot image it effectively due to nearby blood flow of the carotid artery which obscures the brainstem
Imaging article review (responders/non)
Split into responders and non-responders
Early life might make these ppl more resilient
Deactivation of the Limbic System During Acute Psychosocial Stress Study
Set up
Measure salivary cortisol before and after
for responders and non-responders
Brain activation during this stressor measured by
PET
fMRI
Control and experimental group
Experiment get the MIST
Deactivation of the Limbic System During Acute Psychosocial Stress Study
Results - Salivary Cortisol Patterns
(a) Higher cortisol in experimental group
(b) Corticol in saliva spikes before in anticipation of the stressor, during and then declines after (for the whole group)
(c) When seperated by group, non-responders do not show a spike in salivary cortisol in response to the MIST
Responders do
(d) Cortisol response on awakening is lower for non-responders than responders (they have different cortisol responses on wakeing)
Deactivation of the Limbic System During Acute Psychosocial Stress Study
Results - Brain region activation
Responders/non-responders in control had no change in brain activity
With stress there was less activation in hippocampus and OFC
-Sort of like before when the activity of the PVN was disinhibited
0Reduces inhibition
MAIN FINDING
STRESS = LESS ACTIVITY IN OFC AND HIPPOCAMPUS
Increase in cortisol was correlated with a decrease in hippocampal activation
Increase in HPA driving a decrease in Hipp
Imaging the Amygdala showed a decrease but this has to be images THROUGH the hippocampus so probably this was an artifact created by the hippocampus
There might not have been a change in the amygdala cos there was no fear
Hippocampus sensory processing and memory get decreased under stress so that the human may focus on the stressor
Brain activation as a result of mental arithmetic
Subtracted the activity on the control group from that in the stressor group.
