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Effects of Alcohol Use on Brain Function: Analysis of ERP Data . Jared James Zach Schmitz. Goals of our summer project. Gain insight into an ongoing laboratory study of alcohol use consequences for the brain Have a greater understanding of ERP methodology

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Presentation Transcript
goals of our summer project
Goals of our summer project

Gain insight into an ongoing laboratory study of alcohol use consequences for the brain

Have a greater understanding of ERP methodology

Receive a hands-on experience in data analysis

background
Background
  • Overall hypothesis: heavy drinking (5+ drinks/occasion) affects neural and cognitive functions
  • More specific: Alcohol exposure can influence:
    • Error Monitoring
    • Response Inhibition
    • Emotion Processing
  • Can measure processing behaviorally or with Event Related Potentials (ERP)
background erp
Background (ERP)
  • Change in voltage  neurons firing  information processing
  • Temporally accurate, spatially inaccurate
  • Amplitude and Latency both important
  • Heritable
problem how to distinguish between causes and consequences
Problem: How to distinguish between causes and consequences?
  • Showing association between alcohol use and cognitive deficits may be insufficient to draw conclusions
  • What about causation?
    • Alcohol exposure leads to decreased cognitive functioning
    • OR
    • Decreased cognitive functioning increases risk for excessive drinking?
approach
Approach
  • Can take steps to disentangle determinants and consequences using Co-Twin Control Approach
    • Controlling for genetic as well as many environmental factors
  • 3 groups (68 pairs total)
    • Twins concordant for low alcohol exposure
    • Twins concordant for high alcohol exposure
    • Twins discordant for alcohol exposure
  • If discordant twins differ, alcohol exposure may serve causal role
outcome of the discordant pairs indicates the causal effects
Outcome of the Discordant pairs indicates the causal effects

General Liability Hypothesis

Exposure Hypothesis

Concordant Discordant

Concordant Discordant

E+ E- E+ E-

E+ E- E+ E-

erp tasks
ERP Tasks
  • CPT
    • Executive Control (Response Inhibition)
    • Frontal Electrodes
  • Flanker
    • Executive Control (Error Monitoring)
    • Frontal Electrodes
  • Affective Faces (AF)
    • Facial Expression Processing
    • Right parietal (P8)
continuous performance test cpt
Continuous Performance Test (CPT)

Go trial

No-Go trial

Go/No Go task measuring response inhibition

G….L….O….X….P….T….Z….O….Y....

4..……..4..….…..1..…..….2..……..4..…..….4..…….4..…..…..1…..…...3…..….

flanker
Flanker

A task designed to cause subject error to analyze error-related ERP response

Response

Left Hand Right Hand

SSSSS HHHHH

HHSHH SSHSS

slide11
Affective FacesERPs evoked by different facial expressions can reveal biases in processing different emotional content
hypothesis
Hypothesis
  • Executive Function and Emotional Processing
  • AF
    • Exposure interferes with emotional processing
    • Expect deviance between groups in peak amplitude, direction unknown
  • FL
    • Exposure interferes with error recognition
    • Reduced amplitudes in error-related peaks
  • CPT
    • Exposed increased N2, Decreased frontal No-Go P3
outline of experiment
Outline of Experiment

Obtain subjects

Administer Survey

Run behavioral tasks (while not intoxicated)

Run ERP tasks (while not intoxicated)

Process data

Analyze Data

Draw Conclusions

what we look at
What We Look At

Latency

N2

amplitude

P3

slide15

Contingent Negative Variation (CNV)Reflects stimulus anticipation and response preparation Slow shifts of cortical potentials with no distinct peaks can be quantified using the area under the curve

data processing
Data Processing

Turning this…

Into this

processing
Processing

Epoch

Baseline Correct

Averaging

Peak Detection

Peak Checking

Sweep Checking

data analysis
Data Analysis

Fun fact: longest code written all summer = 10,064 lines

  • Data Manipulation for within-pair comparisons:
    • Pair of twins is a single observation, two variables
    • Re-arranged according to exposure status
  • Statistical tests:
    • Paired T-test (comparisons within discordant pairs)
    • Repeated Measures ANOVA
    • Independent Samples T-tests (comparisons between concordant pairs)
    • Correlations
categorical alcohol phenotypes
Categorical Alcohol Phenotypes
  • Defined alcohol exposure in a variety of ways
    • Category 1: Regular binge drinking: 1+ day per month with a binge (5+ drinks) or not
    • Category 2: 2+ days per month with a binge or not during heaviest drinking period of life
    • Category 3: 2 days per month with a binge or no drinking during heaviest drinking year of life (stricter version of above)
    • Age of onset
    • Max drinks in one outing
    • Drinks usually had per outing
    • Drinks per year (cut off at 100, 300, and 1000)
    • Binges in past year
slide25
AF
  • No significant difference on any variable tested for either concordant groups or within the discordant pairs
  • Happy
  • Sad
  • Angry
  • Fearful
  • Neutral
  • Happy After Neutral
  • Change Face
  • Target
af within pair category 1 1 binge per month currently
AF Within PairCategory 1: 1 Binge per Month Currently

Discordant

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

af between pair category 1 1 binge per month currently
AF Between PairCategory 1: 1 Binge per Month Currently

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

erp comparison
ERP Comparison

Between Pair (N=49)

Within-Pair (n=18)

AE+

AE-

AE+

AE-

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

af analysis
AF Analysis

Alcohol exposure at the level studied here has no effect on ability to perceive facial expression information while the participant is not intoxicated

Comparison to Hypothesis

flanker task erp overview
Error

Correct

Flanker Task ERP: Overview

AE+

AE-

AE+

AE-

Fz

Cz

fl within pair results category 2 time in life with heaviest binge pattern
FL Within-Pair ResultsCategory 2 : Time in Life with Heaviest Binge Pattern*

* ≥ 2 times/month for 12 months with 5 drinks in 2 hours

fl between pair results category 2 time in life with heaviest binge pattern
FL Between-Pair ResultsCategory 2 : Time in Life with Heaviest Binge Pattern*

* ≥ 2 times/month for 12 months with 5 drinks in 2 hours

fl results category 1 1 binge per month
FL ResultsCategory 1: 1 Binge per Month

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

fl results category 1 1 binge per month1
FL ResultsCategory 1: 1 Binge per Month

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

fl analysis
FL Analysis

Only one alcohol phenotype yielded significant results

Evidence of an increase in amplitude in the error-related peaks

Comparison to Hypothesis

Continuation of the study needed to increase sample and statistical power

cpt within pair erp category 1 1 binge per month
CPT Within-Pair ERPCategory 1: 1 Binge per Month

N=19 Pairs

No-go

Go

AE+

AE-

AE+

AE-

Fz

Cz

Pz

cpt between pair erp category 1 1 binge per month
CPT Between-Pair ERPCategory 1: 1 Binge per Month

N=49 Pairs

No-go

Go

AE+

AE-

AE+

AE-

Fz

Cz

Pz

cpt grand averages category 1 1 binge per month
CPT Grand AveragesCategory 1: 1 Binge Per Month

Between-pair (N=49)

Within-pair (N=19)

AE+

AE-

AE+

AE-

cpt results within pair category 1 1 binge per month
CPT Results: Within-PairCategory 1: 1 Binge per Month

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

cpt results between pair category 1 1 binge per month
CPT Results: Between-PairCategory 1: 1 Binge per Month

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

cpt within pair behavioral results category 1 1 binge per month
CPT Within Pair Behavioral ResultsCategory 1: 1 Binge Per Month

≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking

cpt grand averages category 2 time in life with heavy binge pattern
CPT Grand AveragesCategory 2: Time in Life with Heavy Binge Pattern*

Within-pair (N=21)

Between-pair (N=47)

AE+

AE-

AE+

AE-

N2

P3

*Heavy Binging ≥ 2 times/month for 12 months with 5 drinks in 2 hours

cpt results within pair category 2 time in life with heavy binge pattern
CPT Results: Within-PairCategory 2: Time in Life with Heavy Binge Pattern

>= 2 times/month for 12 months with 5 drinks in 2 hours

cpt results between pair category 2 time in life with heavy binge pattern
CPT Results: Between-PairCategory 2: Time in Life with Heavy Binge Pattern

*≥ 2 binges per month or no drinking (nothing in between)

cpt results within pair category 3 binge higher contrast
CPT Results: Within PairCategory 3:Binge (Higher Contrast)*

*≥ 2 binges per month or no drinking (nothing in between)

cpt results between pair category 3 binge higher contrast
CPT Results: Between PairCategory 3: Binge (Higher Contrast)

*≥ 2 binges per month or no drinking (nothing in between)

cpt analysis
CPT Analysis

Flip in between-pair and within-pair

ERP waveforms

Significant differences in all peaks for the within-pair analysis

Also differences for the between-pair analysis, but opposite results

Comparison to our hypothesis

conclusions
Conclusions

No significant differences in terms of emotional processing

Significant differences in terms of executive control and behavior regulation

potential directions for future study
Potential Directions for Future Study

Continue to build size of sample

Increase difficulty of the Flanker test to generate a larger error sample

Number of discordant twin pairs with higher contrast in exposure