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

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fMRI Assumption

• in oxygenated blood flow neuronal
  activity

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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!

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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

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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)

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Methods

• N40
• 20 USMLE takers, 20 control

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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

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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

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Fig 1
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Stroop Effect

• RED
• BLUE

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Stroop Effect Diagram
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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

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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

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Connectivity cont.

• Coupling between the dlPFC
• Anterior cingulate (ACC)
• Ventrolateral prefrontal (VLPFC)
• Premotor
• Posterior parietal (PPC)
• Occipitotemporal visual areas

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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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Fig 3
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Fig 3
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Fig 3
Left
Right
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Rodent data matches human data (Fig 4)
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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

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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

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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)

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Still Provocative Results
Ferrari 612 Scaglietti
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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?)

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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

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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

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Clinically important

• Stress reduction interventions
• A decrease in cognitive control of attention seen
  in
• PTSD
• Depression
• Anxiety disorders
• Other stress related diseases

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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

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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

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Thank You