This video was made possible by NIH grant R25MH080794 and is shared under the terms of a Creative Commons license (CC BY-SA 4.0)

What Are ERPs Good For? https://erpinfo.org/erp-core

C E A D A B E D C C B A E Press button 1 for B (target) Press button 2 for A, C, D, E (standard)

10 µV Target The P3 wave is larger for rare targets than for Standard frequent standards. Pz Does this tell us anything interesting −200 200 400 600 800 ms about how the Target works? Minus Standard

−200 200 400 600 800 ms ERP elicited by rare targets P3 Matched Control Subjects

+5µV People with Schizophrenia

-200 200 400 600 -5µV

Many studies have shown that the P3 wave for oddballs is smaller in people with schizophrenia than in healthy control subjects. But what does this tell us about the nature of brain function in people with schizophrenia?

Luck et al (2009, Psychophysiology) ERP elicited by rare targets P3 Matched Control Subjects Mean RT = 576 ms

+5µV People with Schizophrenia -200 200 400 600 Mean RT = 648 ms -5µV

How is the temporal resolution of the ERP technique any different from the temporal resolution of response time?

Luck et al (2009, Psychophysiology) ERPs provide a continuous measure of activity at each Stimulus Onset Task-Dependent Post-Response moment in time. Categorization Evaluation Prestimulus Initial Preparatory Sensory Response Processes Response Selection This allows us to measure Higher Working the brain processes that Perceptual Memory Processes Encoding occur between the stimulus and the response instead of P3 just measuring the P1 P2 behavioral response that +1 µV comes at the end of these N2 processes. -1 µV C1 N1

0 200 400 600 ms ERPs allow us to measure All the the “good stuff” good stuff

Stimulus Onset Task-Dependent Post-Response Prestimulus Initial Categorization Evaluation Preparatory Sensory Response Processes Response Selection Higher Working Emotional Perceptual Memory Response Processes Encoding

P3 Stimulus P1 P2 +1 µV N2

-1 µV C1 N1

0 200 400 600 ms ERPs allow us to measure All the the “good stuff” good stuff

Stimulus Onset Task-Dependent Post-Response Prestimulus Initial Categorization Evaluation Preparatory Sensory Response Processes Response Selection Higher Working Emotional Perceptual Memory Response Processes Encoding

In fMRI, all of these P3 processes are collapsed Stimulus P1 P2 into a single time slice. +1 µV N2

-1 µV C1 N1

0 200 400 600 ms What is the main virtue of the ERP technique?

A Continuous, High Temporal Resolution Signal to Threat Images

+ A common use of this temporal resolution is to track processes that are difficult to see directly in +1µV Contralateral-minus-Ipsilateral behavior. Diference Waveform P7/P8 -200 -100 100 200 300 400 500 ms

–1µV N2pc These data tell us that the threat and neutral images are differentially processed by the

Kappenman et al. (2014, Frontiers in ) brain as early as 100 ms after stimulus onset. ERP elicited by rare targets P3 Matched Control Subjects

+5µV People with Schizophrenia

-200 200 400 600 -5µV

Another common use of the temporal resolution of the ERP technique is to determine the nature of a difference in behavior between experimental conditions or between groups of subjects.

Luck et al (2009, Psychophysiology) This video was made possible by NIH grant R25MH080794 and is shared under the terms of a Creative Commons license (CC BY-SA 4.0) What Are ERPs Good For? ERP Latencies: The P3 Wave Robert Standard William Standard George Standard Michael Standard James Standard Richard Standard Kevin Standard Nancy Oddball David Standard John Standard Brian Standard Charles Standard

Kutas, M., G. McCarthy, & E. Donchin. (1977). Augmenting Sarah Oddball mental chronometry: The as a measure of stimulus evaluation time. Science, 197, 792–795. Paul Standard P3 amplitude is sensitive to the probability of the task-definedRobertcategory,Standard not the probability of the physical stimulusWilliam Standard 80% of the names were typical American male George Standard names. 20% of the names were typical female Michael Standard names. Each individual name only appeared once James Standard for a given subject. Richard Standard Because 80% of the stimuli were male names and Kevin Standard 20% were female names, the male names were Nancy Oddball standards and the female names were oddballs. David Standard John Standard Button 1: Male Names (80%) Brian Standard Button 2: Female Names (20%) Charles Standard

Kutas, M., G. McCarthy, & E. Donchin. (1977). Augmenting Sarah Oddball mental chronometry: The P300 as a measure of stimulus evaluation time. Science, 197, 792–795. Paul Standard P3 amplitude is sensitive to the probability of the task-defined category, not the probability of the physical stimulus

C E A D A B E D C C B A E Press button 1 for B (oddball) Press button 2 for A, C, D, E (standard) P3

10 µV Oddball P3 Pz Standard

−200 200 400 600 800 ms https://erpinfo.org/erp-core P3 amplitude is sensitive to the probability of the task-defined category, not the probability of the physical stimulus Kutas et al. (1977) found that the rare female names generated a larger P3 than the frequent male names even though any individual male or female name was presented only once.

+10 µV

-200 200 400 600 800 1000 ms -10 µV Female Names (Rare) Male Names (Frequent) P3 amplitude is sensitive to the probability of the task-defined category, not the probability of the physical stimulus

Brain must have begun Differential processing of to categorize the name rare and frequent names by this time

+10 µV

-200 200 400 600 800 1000 ms -10 µV Female Names (Rare) Male Names (Frequent) Rare minus Frequent If we delay perception, then we delayRobert categorizationStandard If we delay categorization, we delay the onset of theWilliam rare–frequentStandard difference George Standard Imagine that we made the names dimmer. Michael Standard This would increase the amount of time it James Standard takes to perceive each name. Richard Standard Kevin Standard Rare minus Frequent Nancy Oddball +10 µV David Standard Bright Dim John Standard Brian Standard Charles Standard -200 200 400 600 800 ms Sarah Oddball -10 µV Paul Standard If we delay categorization, we delay the onset of the rare–frequentRobert differenceStandard William Standard Imagine that the task was to count the letters in each George Standard name and press one of two buttons to indicate whether John Standard it was an odd number or an even number. If we make Sara Standard odd numbers rare and even numbers frequent, we Lisa Standard could make a rare-minus-frequent difference wave. Carter Standard Rare minus Frequent Kevin Oddball Alison Standard +10 µV Gender Counting Task Task Steven Standard Edward Standard Paul Standard -200 200 400 600 800 ms Susan Oddball -10 µV Gene Standard This video was made possible by NIH grant R25MH080794 and is shared under the terms of a Creative Commons license (CC BY-SA 4.0) What Are ERPs Good For? ERP Latencies: N2pc & LRP Collapsed

+2µV N2pc N2pc Brain must have figured 100 200 out300 the location of the –2µV target by this time Collapsed Contralateral Target Ipsilateral Target +2µV N2pc

100 200 300 –2µV

Contralateral Target Logically, the voltage can’t be more negative over the contralateral hemisphere than over the ipsilateral hemisphere untilIpsilateral the brain Target has determined whether the target is on the left or the right side of the display. If you look at a contra-minus-ipsi difference wave, you can know that the brain has localized the target by the time the difference wave deviates from zero. N2pc The red item immediately popped out from the display, but the green item was a little harder to detect. The response times were about 50 milliseconds slower in the attend-green condition than in the attend-red condition. The N2pc is delayed by ~50 milliseconds in the attend- green condition relative to the attend-red condition.

+0.5 µV Time Poststimulus (ms) -100 100 200 300 400 500

-0.5 µV

Contra minus Ipsi Attend Green Difference Wave Attend Red Luck et al. (2006) N2pc The onset time of the N2pc was essentially identical in the two groups. We concluded that schizophrenia does not slow down the process of finding the target and shifting attention to it.

Time Poststimulus (ms) -100 0 100 200 300 400 500

Contra minus Ipsi Control Difference Wave (collapsed across red and green) Luck et al. (2006) Schizophrenia Lateralized Readiness Potential (LRP)

33

LRP = negative voltage over motor cortex contralateral to the

response hand https://ib.bioninja.com.au/options/option-a-neurobiology-and/a2-the- human-brain/cerebral-hemispheres.html Lateralized Readiness Potential (LRP)

Left Hemisphere (Ipsi)

Right Hemisphere (Contra)

https://ib.bioninja.com.au/options/option-a-neurobiology-and/a2-the- Smulders & Miller (2010) human-brain/cerebral-hemispheres.html Lateralized Readiness Potential (LRP)

Left Hemisphere Right Hemisphere (Ipsi) (Ipsi)

Right Hemisphere Left Hemisphere (Contra) (Contra)

Smulders & Miller (2010) Lateralized Readiness Potential (LRP)

Brain must have figured out which hand should respond by this time

LRP = Contralateral minus ipsilateral, averaged over left & right hands Smulders & Miller (2010) Dehaene, S., Naccache, L., Le Clec’H, G., Koechlin, E., Mueller, M., Dehaene-Lambertz, G., van de Moortele, P. F., & Le Bihan, D. (1998). Imaging unconscious semantic priming. Nature, 395, 597–600. This video was made possible by NIH grant R25MH080794 and is shared under the terms of a Creative Commons license (CC BY-SA 4.0) What Are ERPs Good For? Example: P3 Latency in Schizophrenia Schizophrenia 1-2% lifetime prevalence Characterized by hallucinations, delusions, disorganization

The degree of cognitive impairment is a better predictor of long-term outcome than the degree of hallucinations, delusions, and disorganized thought

http://anndeef.deviantart.com/art/Schizophrenia-269518412 Creative Commons Attribution-Share Alike 3.0 License P3 Matched Control Subjects ERP elicited by oddballs Mean RT = 576 ms

+5µV People with Schizophrenia -200 200 400 600 Mean RT = 648 ms -5µV

Most studies find a reduced amplitude in people with schizophrenia compared to matched control subjects. RTs are slowed, but the P3 is not. Luck et al (2009, Psychophysiology) Nuechterlein, K. H. (1977). Reaction time and attention in schizophrenia: A critical evaluation of the data and theories. Schizophrenia Bulletin, 3(3), 373–428. Stimulus Duration = 200 ms

Time -> Stimulus Onset Asynchrony = 1500±150 ms

= Letters, 80%, Press Left Counter- balanced = Digits, 20%, Press Right

33

Luck, S. J., Kappenman, E. S., Fuller, R. L., Robinson, B., Summerfelt, A., & Gold, J. M. (2009). Impaired response selection in schizophrenia: Evidence from the P3 wave and the lateralized readiness potential. Psychophysiology, 46, 776–786. Luck et al (2009, Psychophysiology) P3 Control Schizophrenia +5µV RT RT Frequent 486 557 -200 200 400 600 P3 amplitude was smaller in people -5µV with schizophrenia than in control P3 subjects for both rare and frequent. Response times were delayed by about +5µV 70 ms in the schizophrenia group. Rare 576 648 -200 200 400 600 The P3 was almost identical for the -5µV two groups in the rare-minus- Rare Minus +5µV P3 frequent difference waves. The Frequent control subjects show an N2 that’s largely missing in the schizophrenia -200 200 400 600 group, but there was no group N2 -5µV difference in the P3 wave. People with Schizophrenia Matched Control Subjects Luck et al (2009, Psychophysiology) P3 +5µV The finding of equivalent timing Frequent of the rare-minus-frequent difference in people with -200 200 400 600 -5µV schizophrenia and control P3 subjects indicates that the two groups perceived and +5µV categorized the stimuli equally Rare quickly.

-200 200 400 600 -5µV The difference in response time Rare Minus +5µV P3 must therefore reflect some kind Frequent of post-categorization slowing, perhaps in response -200 200 400 600 N2 preparation or execution. -5µV People with Schizophrenia Matched Control Subjects Lateralized Readiness Potential A major disruption of the lateralized readiness potential was observed in the schizophrenia +5 µV group. We’ve now replicated this LRP Contra Minus Ipsi difference in several additional experiments.

-5 µV People with Schizophrenia Matched Control Subjects Kappenman, E. S., Kaiser, S. T., Robinson, B. M., Morris, S. E., Hahn, B., Beck, V. M., Leonard, C. J., Gold, J. M., & Luck, S. J. (2012). Response activation impairments in schizophrenia: Evidence from the lateralized readiness potential. Psychophysiology, 49, 73–84. Kappenman, E. S., Luck, S. J., Kring, A. M., Lesh, T. A., Mangun, G. R., Niendam, T., Ragland, J. D., Ranganath, C., Solomon, M., Swaab, T. Y., & Carter, C. S. (2016). Electrophysiological evidence for impaired control of motor output in schizophrenia. Cerebral Cortex, 26, 1891–1899.

Luck et al (2009, Psychophysiology) N2pc to Threat Images ERPs provide a continuous, high temporal resolution measure of the processes that occur between a stimulus and + a response. This makes it possible to see neural processes that are not directly visible in behavior, such as +1µV Contralateral-minus-Ipsilateral shifts of covert attention. Diference Waveform P7/P8 -200 -100 100 200 300 400 500 ms

–1µV N2pc

Kappenman et al. (2014, Frontiers in Psychology) Luck et al (2009, Psychophysiology) P3 +5µV Frequent

-200 200 400 600 -5µV P3

+5µV Rare ERPs also allow us to ask which processes are -200 200 400 600 responsible for differences in -5µV behavior between conditions Rare Minus +5µV P3 Frequent or between groups.

-200 200 400 600 N2 -5µV People with Schizophrenia Matched Control Subjects Mismatch Negativity (MMN) ERP components like the mismatch negativity allow us Time -> 4 µV to monitor processing in FCz Standard 24 µV subjects who can’t do −200FCz -100 100 200Standard300 400 ms behavioral tasks, such as 2 −200 -100 100 200 300 400 ms infants and people in comas. −2 Deviant https://erpinfo.org/erp-core −2 Deviant

https://vector.childrenshospital.org/2018/05/predicting-autism-eegs/