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Effects of Alcohol Use on Brain Function: Analysis of ERP Data Jared JamesZach Schmitz1Goals of our summer projectGain insight into an ongoing laboratory study of alcohol use consequences for the brainHave a greater understanding of ERP methodologyReceive a hands-on experience in data analysisNeed goals slide? If so, revise through here2BackgroundOverall hypothesis: heavy drinking (5+ drinks/occasion) affects neural and cognitive functionsMore specific: Alcohol exposure can influence:Error Monitoring Response InhibitionEmotion ProcessingCan measure processing behaviorally or with Event Related Potentials (ERP)Background (ERP)

Change in voltage neurons firing information processingTemporally accurate, spatially inaccurateAmplitude and Latency both importantHeritableMaybe see if we can screenshot and crop one of our ERPs here, especially since this one is not the negative up convention.Remember to say something about the epochs being locked to response or stimuli maybe?4Problem: 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 functioningORDecreased cognitive functioning increases risk for excessive drinking?

5ApproachCan take steps to disentangle determinants and consequences using Co-Twin Control ApproachControlling for genetic as well as many environmental factors3 groups (68 pairs total)Twins concordant for low alcohol exposureTwins concordant for high alcohol exposureTwins discordant for alcohol exposureIf discordant twins differ, alcohol exposure may serve causal role6Outcome of the Discordant pairs indicates the causal effectsGeneral Liability HypothesisExposure Hypothesis E+E- E+ E- E+ E- E+ E- Concordant DiscordantConcordant DiscordantCheck over this Zach and feel free to edit it. I just threw it together. I guess Ill present it since it goes with the previous two slides.7ERP TasksCPTExecutive Control (Response Inhibition)Frontal ElectrodesFlanker Executive Control (Error Monitoring)Frontal ElectrodesAffective Faces (AF)Facial Expression ProcessingRight parietal (P8)

Continuous Performance Test (CPT)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...Go trialNo-Go trialFlankerA task designed to cause subject error to analyze error-related ERP response

ResponseLeft HandRight Hand SSSSS HHHHH HHSHH SSHSS10

Affective FacesERPs evoked by different facial expressions can reveal biases in processing different emotional content

For affected faces need to get pics from Stim computer11HypothesisExecutive Function and Emotional ProcessingAFExposure interferes with emotional processingExpect deviance between groups in peak amplitude, direction unknownFLExposure interferes with error recognitionReduced amplitudes in error-related peaksCPTExposed increased N2, Decreased frontal No-Go P3

Children increased N2, Decreased P3

12Outline of ExperimentObtain subjectsAdminister SurveyRun behavioral tasks (while not intoxicated)Run ERP tasks (while not intoxicated)Process dataAnalyze DataDraw ConclusionsWhat We Look At

N2P3LatencyamplitudeCPT/FL N2 and P3AF N2When potentials evoked by images of faces are compared to those elicited by other visual stimuli, the former show increased negativity 130-200 ms after stimulus presentation. This response is maximal over occipito-temporal electrode sites, which is consistent with a source located at the fusiform and inferior-temporal gyri. The N170 generally displays right-hemisphere lateralization and has been linked with the structural encoding of faces[1].

14Contingent 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

The contingent negative variation (CNV) was one of the first event-related potential (ERP) components to be described. The CNV component was first described by Dr. W. Grey Walter and colleagues in an article published in Nature in 1964.[1] The importance of this finding was that it was one of the first studies which showed that consistent patterns of the amplitude of electric responses could be obtained from the large background noise which occurs in electroencephalography (EEG) recordings and that this activity could be related to a cognitive process such as expectancy.

15Data ProcessingTurning thisInto this

Point out eye blink, bad chanel, messyness (importance of filtering)17

Importance of Manual Artifact Rejection18

Then you get thisPoint out EKG, EOGs and why they are importantAlso point out behavioral data and connect with CPT from earlier19ProcessingEpochBaseline CorrectAveragingPeak DetectionPeak CheckingSweep Checking

Italics all done automatically via batch20

Blue for CPT/FL, red for AF21Data AnalysisData Manipulation for within-pair comparisons: Pair of twins is a single observation, two variables Re-arranged according to exposure statusStatistical tests:Paired T-test (comparisons within discordant pairs) Repeated Measures ANOVAIndependent Samples T-tests (comparisons between concordant pairs)Correlations

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

Merging Data SetsArrange by TwinsLagging23Categorical Alcohol PhenotypesDefined alcohol exposure in a variety of waysCategory 1: Regular binge drinking: 1+ day per month with a binge (5+ drinks) or notCategory 2: 2+ days per month with a binge or not during heaviest drinking period of lifeCategory 3: 2 days per month with a binge or no drinking during heaviest drinking year of life (stricter version of above)Age of onsetMax drinks in one outingDrinks usually had per outingDrinks per year (cut off at 100, 300, and 1000)Binges in past yearAFNo significant difference on any variable tested for either concordant groups or within the discordant pairsHappySadAngryFearfulNeutralHappy After NeutralChange FaceTargetAF Within PairCategory 1: 1 Binge per Month Currently

Discordant1 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinking

26AF Between PairCategory 1: 1 Binge per Month Currently

1 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinkingERP ComparisonBetween 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 drinkingArea Comparison

AE+AE-AF AnalysisAlcohol exposure at the level studied here has no effect on ability to perceive facial expression information while the participant is not intoxicatedComparison to HypothesisErrorCorrectFlanker Task ERP: OverviewFzCz

AE+AE-AE+AE-FL Within-Pair ResultsCategory 2 : Time in Life with Heaviest Binge Pattern* * 2 times/month for 12 months with 5 drinks in 2 hoursRegular Binge FlMean (SD (V)sig. (two-tailed)N twin pairs = 21ExposedNonexposedFz-16(7.6)-14(7.9)0.439ERNerrorCz-18(9.9)-16(11)0.319Pz-12(7)-11(6.8)0.474Fz-7(2.4)-7(3.4)0.990ERNcorrectCz-7(3.5)-7(4)0.731Pz-7(2.5)-8(3)0.952Fz10(7.2)9(8.6)0.708P3errorCz16(10.8)11(10.2)0.036Pz15(9)11(7.5)0.033Fz0.6(3.3)0(5)0.513P3correctCz1(4.8)0.4(5.7)0.588Pz-0.5(4.2)-0.9(4.2)0.633FL Between-Pair ResultsCategory 2 : Time in Life with Heaviest Binge Pattern* * 2 times/month for 12 months with 5 drinks in 2 hoursRegular Binge FlMean (SD (V)sig. (two-tailed)N exposed = 37ExposedNonexposedN non exp = 49Fz-16(9.7)-15(8.7)0.520ERNerrorCz-18(10.4)-16(10)0.566Pz-10(6.5)-12(11.8)0.610Fz-8(3.6)-7(3.1)0.281ERNcorrectCz-7(3.7)-6(4)0.245Pz-8(3.7)-7(5.4)0.761ERPerrorCz14(8.2)14(8.5)0.809Pz14(7.8)15(10.2)0.902Fz-0.3(4.2)-0.1(4.1)0.759ERPcorrectCz0.7(4.1)2(5.1)0.382Pz0.4(4)0.8(5)0.682FL ResultsCategory 1: 1 Binge per Month

1 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinkingFL ResultsCategory 1: 1 Binge per MonthWithin-PairMean (SD (V)sig. (two-tailed)N twin pairs =19ExposedNonexposed0.852Fz-14(6.7)-14(7.6)ERNerrorCz-16(7.1)-15 (7.5)0.516Pz-12(6.9)-11 (6.1)0.346Fz-8(3.1)-7 (3.5)0.222ERNcorrectCz-7(4.2)-6 (3.7)0.281Pz-7(2.6)-7 (3.1)0.940Fz9 (4.9)8(9.0)0.749ERPerrorCz14 (9.5)10 (11.0)0.075Pz14 (8.6)11 (8.3)0.108Fz-1 (3.0)-1 (4.3)0.970ERPcorrectCz-0.4 (3.5)-0.5 (4.9)0.880Pz-0.3 (3.9)-0.8 (4.0)0.661Between-PairMean (SD (V)sig. (two-tailed)N exposed =49ExposedNonexposed0.665N non-exp =41Fz-16(9.1)-15(9.4)ERNerrorCz-18(11.4)-17(10.9)0.475Pz-10(6.5)-12(12.7)0.425Fz-7(3.4)-7(2.8)0.120ERNcorrectCz-7(3.8)-6(3.7)0.147Pz-7(3.3)-8(5.7)0.984ERPerrorCz14(8.3)15(8.8)0.684Pz14(7.5)15(11.0)0.531Fz0.4(4.5)0.4(4.0)0.904ERPcorrectCz2(4.9)2(5.2)0.857Pz0.5(4.3)0.6(5.2)0.9371 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinkingFL AnalysisOnly one alcohol phenotype yielded significant resultsEvidence of an increase in amplitude in the error-related peaksComparison to HypothesisContinuation of the study needed to increase sample and statistical powerIndicates strongly that the exposure is the cause of the difference with assuming similar environment as well as identical genetics in the discordant pairs while assuming differing environments in between pairs it shows the studies success in eliminating interfering factors to see only the exposure effectsHypothesis not supported as the amplitudes both increased and was significantly increased in the ERP36CPT Within-Pair ERPCategory 1: 1 Binge per MonthNo-goGoFzCzPz

N=19 PairsAE+AE-AE+AE-CPT Between-Pair ERPCategory 1: 1 Binge per MonthNo-goGoFzCz

Pz

N=49 PairsAE+AE-AE+AE-CPT Grand AveragesCategory 1: 1 Binge Per MonthBetween-pair (N=49)Within-pair (N=19)

AE+AE-AE+AE-CPT Results: Within-PairCategory 1: 1 Binge per Month1 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinkingWithin-PairMean (SD (V)sig. (two-tailed)N twin pairs = 19ExposedNonexposedFz-8(4.8)-7(3.9)0.067N2no-goCz-7(4.5)-5(3.6)0.014Pz-5(3.9)-5(2.5)0.545Fz20(8.6)24(11.3)0.086P3no-goCz26(10.1)28(11.0)0.207Pz24(7.3)24(8.2)0.968Fz12(5.7)16(6.9)0.003P3goCz19(6.4)22(7.3)0.041Pz23(5.9)23(5.6)0.78540CPT Results: Between-PairCategory 1: 1 Binge per Month1 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinkingBetween-PairMean (SD (V)sig. (two-tailed)N exposed= 50ExposedNonexposedN non exp= 46Fz-7(3.8)-8(4.6)0.231N2no-goCz-5(3.8)-7(4.6)0.025Pz-4(2.9)-5(3.7)0.156Fz25(10.1)22(9.4)0.089P3no-goCz31(10.2)28(8.5)0.055Pz27(7.7)23(7.0)0.014Fz16(7.5)14(5.3)0.124P3goCz25(8.6)21(6.5)0.024Pz23(7.7)23(6.8)0.021CPT Within Pair Behavioral ResultsCategory 1: 1 Binge Per Month

1 day/m w/5+ drinks; 1 drink in past month+ >5 drinks when drinkingCPT Grand AveragesCategory 2: Time in Life with Heavy Binge Pattern*Within-pair (N=21)Between-pair (N=47)

*Heavy Binging 2 times/month for 12 months with 5 drinks in 2 hoursAE+AE-AE+AE-N2P343CPT Results: Within-PairCategory 2: Time in Life with Heavy Binge Pattern>= 2 times/month for 12 months with 5 drinks in 2 hoursWithin-PairMean (SD (V)sig. (two-tailed)N twin pairs = 21ExposedNonexposedFz-9(4.5)-7(3.9)0.030N2no-goCz-7(4.4)-5(3.4)0.012Pz-5(2.5)-4(2.1)0.199Fz21(8.2)25(11.4)0.014P3no-goCz27(10.0)31(11.0)0.029Pz24(7.1)26(7.8)0.279Fz13(7.1)17(7.4)0.004P3goCz20(8.2)25(8.0)0.020Pz23(7.1)25(5.3)0.361CPT Results: Between-PairCategory 2: Time in Life with Heavy Binge Pattern* 2 binges per month or no drinking (nothing in between)Between-PairMean (SD (V)sig. (two-tailed)N exposed = 54ExposedNonexposedN non exp = 38Fz-7(3.8)-8(4.4)0.267N2no-goCz-5(3.5)-7(4.5)0.018Pz-5(3.0)-6(3.8)0.103Fz25(11.0)22(9.0)0.171P3no-goCz31(11.0)27(8.1)0.066Pz27(8.2)23(6.9)0.007Fz16(7.0)15(5.4)0.280P3goCz24(8.4)21(6.5)0.038Pz27(8.0)23(6.5)0.010CPT Results: Within PairCategory 3:Binge (Higher Contrast)** 2 binges per month or no drinking (nothing in between)Within-PairMean (SD (V)sig. (two-tailed)N twin pairs =11ExposedNonexposedFz-8(4.3)-7(2.4)0.179N2no-goCz-7(3.9)-5(2.9)0.117Pz-5(2.4)-5(2.3)0.854Fz18(7.5)25(8.0)0.029P3no-goCz24(9.0)30(7.9)0.030Pz24(7.5)26(4.3)0.331Fz12(6.0)16(5.6)0.039P3goCz19(5.4)23(5.5)0.085Pz22(6.1)24(4.7)0.136CPT Results: Between PairCategory 3: Binge (Higher Contrast)Between-PairMean (SD (V)sig. (two-tailed)N exposed = 38ExposedNonexposedN non exp = 38Fz-7(3.8)-8(4.7)0.309N2no-goCz-5(3.5)-7(4.8)0.059Pz-5(3.0)-5(3.7)0.496Fz25(11.0)23(9.9)0.370P3no-goCz31(11.0)29(8.6)0.301Pz27(8.2)24(7.0)0.066Fz16(7.0)15(5.6)0.406P3goCz24(8.4)22(6.7)0.119Pz27(8.0)24(7.0)0.065* 2 binges per month or no drinking (nothing in between)CPT AnalysisFlip in between-pair and within-pair ERP waveformsSignificant differences in all peaks for the within-pair analysisAlso differences for the between-pair analysis, but opposite resultsComparison to our hypothesisConclusionsNo significant differences in terms of emotional processing Significant differences in terms of executive control and behavior regulationPotential Directions for Future StudyContinue to build size of sampleIncrease difficulty of the Flanker test to generate a larger error sampleNumber of discordant twin pairs with higher contrast in exposure 50