1. Liston, McEwen & Casey Presented by Justin P. Smith
Psychosocial stress reversibly disrupts prefrontal processing and attentional control
Liston, McEwen & Casey
Presented by Justin P. Smith

3. fMRI Assumption
in oxygenated blood flow = neuronal activity

4. Breaking fMRI News!
2 macaque monkeys measured both blood flow & neuron firing
Light fixation task
Results indicate that the flow of O2 blood to brain region doesn't just increase in response to neural activity but can anticipate an expected task, even when nearby neurons are relatively quiet!

6. Today’s Article
Chronic stress=risk factor for neuropsychiatric conditions that effect PFC
Depression
Bipolar disorder
Schizophrenia
Anxiety disorders
PTSD?
For healthy individuals
Flexible problem solving
Working memory

7. Chronic Stress Can impair attention set-shifting (PFC dependent task)
Does not effect reversal learning (independent of mPFC)
Effects are reversible, i.e. plastic and resilient pyramidal cells (shown in rats studies)

9. Methods
N=40
20 USMLE takers, 20 control

10. Cohen Perceived Stress Scale
1.  In the last month, how often have you felt that you were unable to control the important things in your life?
 ___0=never ___1=almost never ___2=sometimes ___3=fairly often ___4=very often
2.  In the last month, how often have you felt confident about your ability to handle your personal problems?
3.  In the last month, how often have you felt that things were going your way?
4.  In the last month, how often have you felt difficulties were piling up so high that you could not overcome them?
  ___0=never ___1=almost never ___2=sometimes ___3=fairly often ___4=very often

11. Attention shift task 2 circles: 1 red, 1 green Moved up or down
Cue of M (motion) or C (color)
When “M” then subject clicked side that had upward moving circle
When “C” clicked side with red

12. Fig 1

13. Stroop Effect
RED BLUE

14. Stroop Effect Diagram

15. Chronic PSS disrupted prefrontal functional connectivity
Attention shifts engaged dlPFC (homolog to rodent mPFC)
In rats stress decreased axospinous inputs and dendritic arborization in prefontal layer II/III pyramidal cells
Hypothesis: PSS may disrupt fMRI measures of corticocortical connectivity

16. Connectivity?
corticocortical connections of architectonically defined areas of parietal and temporoparietal cortex, with emphasis on areas in the intraparietal sulcus (IPS) that are implicated in visual and somatosensory integration
Lewis JW, Van Essen DC , J Comp Neurol Dec 4;428(1):112-37

17. Connectivity cont. Coupling between the dlPFC &
Anterior cingulate (ACC)
Ventrolateral prefrontal (VLPFC)
Premotor
Posterior parietal (PPC)
Occipitotemporal visual areas

18. Findings (Fig 2) Attention shifts engaged dlPFC bilaterally (2A)
Functional connectivity analysis (2B)- used A to quantify coupling with other areas
Functional connectivity analysis assesses the degree to which the voxel wise BOLD signal covaries with activity in a particular region of interest, termed the seed volume
Took peak activation in dlPFC coupled with significantly active regions then examined how this coupling varied with stress

20. Fig 3

21. Fig 3

22. Fig 3
Left
Right

23. Rodent data matches human data (Fig 4)

24. Caveats!
There was variability in participants perception of USMLE (aka varying PSS levels)
“Higher order neocortical processing of perceived meaning of stimulus WITH activity in medial & central amygdala are thought to activate HPA axis”

25. Caveat 2 Med students were used pre/post USMLE
Within-subjects design
Assess reversibility
PSS scores and hippocampal volume-finding a reduction in hippocampal gray matter volume w/ high PSS in postmenopausal women
STRESS EFFECTS ON BRAIN STRUCTURE MAY GENERALIZE TO OTHER CONTEXTS

26. Caveat 3 Limitations of PSS for quantifying stress exposure
Subjective (self reported)
Diurnal salivary cortisol levels to assess stress
*only one part in a long cascade
Excitatory A.A.
Neurotrophins
Adhesion molecules
Altered receptor expression
Neuromodulators (5-HT, etc)

27. Still Provocative Results
Ferrari 612 Scaglietti

28. Reasons
Show chronic PSS selectively and reversibly disrupts human PFC function
Demonstrate utility of translating rodent models to humans (rat restraint stress vs. neuroimaging)
Rodent studies show alts in dendritic arborization & axospinous inputs
Interfere with top-down regulation of dlPFC & functional coupling (connectivity?)

29. Reasons cont. Add to literature that stress acutely alters PFC fxn
DA & NE (D1 & a2 receptors) enhance PFC fxn, enhances functional connectivity w/in PFC by inhibiting cAMP-dependent hyperpolarization
In CONTRAST- excessive monoamine release from chronic PSS impairs PFC (working memory & cognitive flexibility)
Pharmacologically preventable w/ pretreatment of neuromodulator antagonists

30. It’s the dendrites
PSS effects on PFC may be caused by changes in monoaminergic tone & longer-term structural changes in dendritic arborization & spine density
More work needed here…

31. Clinically important Stress reduction interventions
A decrease in cognitive control of attention seen in:
PTSD
Depression
Anxiety disorders
Other stress related diseases

32. Stress-induced plasticity
May serve as neuroprotective fxn by decreasing excitatory neurotoxicity in hippocampus (in rodents)
PFC connectivity did NOT decrease uniformly
Stress increased dlPFC coupling w/ temporal lobe areas (visual processing) at expense of areas mediating flexibility & control
Give and Take

33. Take home message Stress effects are adaptive in short term
Bias processing in favor of a single salient stimulus
Reversible after decrease in stress in healthy individuals
Chronic stress impairs mPFC flexibility & contributes to neuropsychiatric diseases

34. Thank You