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Team RITALIN:Research in Testing ADHD's Link to Impulsivity in
Neuroscience
13 June 2013
Impact of prenatal nicotine exposure on impulsivity and neural activity in medial
prefrontal cortex
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Prenatal Nicotine Exposure (PNE) PNE is linked to many psychiatric disorders
Women who smoke during pregnancy are three times as likely to have children diagnosed with ADHD
1 in 5 women still smoke during pregnancy Nicotine causes changes in the development that alters
dopaminergic & noradrenergic pathways in the brain
Several studies show behavioral, neuroanatomical, & neurochemical disturbances after PNE
Benefits of methylphenidate, a common ADHD drug, point to PNE as a valuable animal model of impulsivity
IntroductionIntroduction
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Attention Deficit Hyperactivity Disorder (ADHD) Symptoms: impulsivity, hyperactivity, & inattention
Affects 5-10% of all school age children
Twentyfold increase in prescription of ADHD drugs in the past 30 years
Diagnoses based on qualitative observations
Limited research on the neurobiology of the disorder
ADHD drugs are addictive stimulants
Fetal nicotine rats and humans with ADHD have similar deficits on behavioral tasks for hyperactivity & impulsivity
Introduction
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Modeling Impulsivity Animal model validity
Face validity
Conduct validity
Predictive validity
What areas or circuits are involved?
How can we uncover more about the neurobiology?
Introduction
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Medial Prefrontal Cortex (mPFC)
Introduction
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Stop Signal Task (SST)
Introduction
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Research Questions
I. Is there a correlation between neural firing in the mPFC cortex and impulsivity in control rats?
II. Is neural firing in the mPFC cortex disrupted and impulsivity increased in fetal nicotine rats?
III. Is there a correlation between this disrupted firing and increased impulsivity?
Introduction
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Phase 1: Rat Breeding & Selection
Methodology
Significant differences in water consumption & mother weights
No significant differences in pregnancy duration, pups per litter, pup birth weight, or locomotion*
Randomly selected 8 males each from 37 PNE pups (from 3 dams) and 39 control pups (from 3 dams)
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Phase 2: SST Training & Surgery
Methodology
Compare movement times and percent correct on stop and go trials
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Results
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Results
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Results
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Results
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Results
Post-Surgery Behavior
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Phase 3: Neural Recording & Analysis
Methodology
12 rats from the control and PNE groups performed 157 sessions, over which we collected neural firing from 346 cells
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Methodology
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ResultsHistograms for Above/Below Baseline Firing
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ResultsHistograms for Preferred/Nonpreferred Stop/Go Trials
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ResultsDistributions for Preferred/Nonpreferred for Go Direction
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Results
legend:go ipsi - bluego contra - greenstop ipsi - redstop contra - yellow
legend:go ipsi - bluego contra - greenstop ipsi - redstop contra - yellow
Histograms for Contra/Ipsi Stop/Go Trials
*
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ResultsSubtraction Plots for Preferred/Nonpreferred Stop/Go Trials
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Preliminary Conclusions
Discussion
Behavior
PNE rats were more impulsive (as measured by SCRT)
However, they were better at basic task procedures (eg responding to spatial cue lights)
Neural recordings
Signals from neurons which encode stopping an already initiated movement were attenuated in PNE rats as compared to controls
Signals from neurons which encode direction towards the correct behavioral response were also attenuated as compared to controls
This points to a neurophysiological pathway disruption in inhibiting impulsivity caused by PNE
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Future Directions For my team:
Finish collecting data for additional controls
Complete data analysis
Present data at Society for Neuroscience Conference
Write & present our thesis at the Senior Thesis Conference
For someone else:
Try a different task (or SST with different parameters)
Give nicotine postnatally
Administer ADHD drugs to PNE rats and controls
Discussion
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My Team
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Questions?Questions?