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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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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 Receive a hands-on experience in data analysis
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) • 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? • 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 • 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 General Liability Hypothesis Exposure Hypothesis Concordant Discordant Concordant Discordant E+ E- E+ E- E+ E- E+ E-
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) 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 A task designed to cause subject error to analyze error-related ERP response Response Left Hand Right Hand SSSSS HHHHH HHSHH SSHSS
Affective FacesERPs evoked by different facial expressions can reveal biases in processing different emotional content
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 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 Latency N2 amplitude P3
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 Turning this… Into this
Processing Epoch Baseline Correct Averaging Peak Detection Peak Checking Sweep Checking
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 • 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
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 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 PairCategory 1: 1 Binge per Month Currently ≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking
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
Area Comparison AE+ AE-
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
Error Correct Flanker Task ERP: Overview AE+ AE- AE+ AE- Fz Cz
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 ResultsCategory 2 : Time in Life with Heaviest Binge Pattern* * ≥ 2 times/month for 12 months with 5 drinks in 2 hours
FL ResultsCategory 1: 1 Binge per Month ≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking
FL ResultsCategory 1: 1 Binge per Month ≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking
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 ERPCategory 1: 1 Binge per Month N=19 Pairs No-go Go AE+ AE- AE+ AE- Fz Cz Pz
CPT Between-Pair ERPCategory 1: 1 Binge per Month N=49 Pairs No-go Go AE+ AE- AE+ AE- Fz Cz Pz
CPT Grand AveragesCategory 1: 1 Binge Per Month Between-pair (N=49) Within-pair (N=19) AE+ AE- AE+ AE-
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-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 ResultsCategory 1: 1 Binge Per Month ≥1 day/m w/5+ drinks; ≥ 1 drink in past month+ >5 drinks when drinking
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-PairCategory 2: Time in Life with Heavy Binge Pattern >= 2 times/month for 12 months with 5 drinks in 2 hours
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 PairCategory 3:Binge (Higher Contrast)* *≥ 2 binges per month or no drinking (nothing in between)
CPT Results: Between PairCategory 3: Binge (Higher Contrast) *≥ 2 binges per month or no drinking (nothing in between)
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 No significant differences in terms of emotional processing Significant differences in terms of executive control and behavior regulation
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