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Psychosocial stress reversibly disrupts prefrontal processing and attentional control

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Psychosocial stress reversibly disrupts prefrontal processing and attentional control Liston, McEwen & Casey Presented by Justin P. Smith Thank You fMRI Assumption in ... – PowerPoint PPT presentation

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Title: Psychosocial stress reversibly disrupts prefrontal processing and attentional control


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

2
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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!

5
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6
Todays Article
  • Chronic stressrisk 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)

8
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9
Methods
  • N40
  • 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?
  •  ___0never ___1almost never ___2sometimes
    ___3fairly often ___4very often
  • 2.  In the last month, how often have you felt
    confident about your ability to handle your
    personal problems?
  •  ___0never ___1almost never ___2sometimes
    ___3fairly often ___4very often
  • 3.  In the last month, how often have you felt
    that things were going your way?
  •  ___0never ___1almost never ___2sometimes
    ___3fairly often ___4very often
  • 4.  In the last month, how often have you felt
    difficulties were piling up so high that you
    could not overcome them?
  •   ___0never ___1almost never ___2sometimes
    ___3fairly often ___4very 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. 2000 Dec
    4428(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

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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
Its 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
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