1. All slides © S. J. Luck, except as indicated in the notes sections of individual slides Slides may be used for nonprofit educational purposes if this copyright notice is included, except as noted Permission must be obtained from the copyright holder(s) for any other use The ERP Boot Camp What Are ERPs and What Are They Good For?

2. Overview A bit of history A bit of history Review: Basic neurophysiology & electricity Review: Basic neurophysiology & electricity Neural origins of ERPs Neural origins of ERPs Comparison of ERPs with other techniques Comparison of ERPs with other techniques

3. Walter, W. G., Cooper, R., Aldridge, V. J., McCallum, W. C., & Winter, A. L. (1964). Contingent negative variation: An electric sign of sensorimotor association and expectancy in the human brain. Nature, 203, 380-384. The Dawn of History 1964: Gray Walter and the CNV 1964: Gray Walter and the CNV No Task: Click Only No Task: Flashes Only No Task: Click followed by flashes Task: Press button when flashes start CNV

4. Which Way is Up? René Descartes

5. Sutton, S., Braren, M., Zubin, J., & John, E. R. (1965). Evoked potential correlates of stimulus uncertainty. Science, 150, 1187-1188. Scenario: Cue stimulus indicating whether click or flash was likely Delay of 3-5 seconds: Subject guesses whether stimulus will be click or flash Click or flash occurs The Birth of the P300 1965: Sutton, Braren, Zubin, & John 1965: Sutton, Braren, Zubin, & John P300 Sound-Elicited ERPs Light-Elicited ERPs P300

6. The Oddball Paradigm = Standard = Deviant/Oddball/Target Typical Task Alternatives: Count oddballs Press only for oddballs Different buttons for standard, oddball

7. Some Terminology Duration Interstimulus Interval (ISI) Stimulus Onset Asynchrony (SOA) Intertrial Interval (ITI) SOA ISI

8. The Next 4 Decades 1970s 1970s -Development and standardization of methods -Characterization of P3 and application to psychopathology -Selective attention (Hillyard, Näätänen, Harter) The 1980s The 1980s -Kutas & Hillyard (1980) discover N400 -ERPology transitions into cognitive neuroscience -Multichannel recordings (16+ electrodes) and BESA The 1990s The 1990s -More components: LRP, N2pc, ERN, N170, etc. -fMRI takes off, leading to predictions of the demise of ERPs

10. The Next 4 Decades 1970s 1970s -Development and standardization of methods -Characterization of P3 and application to psychopathology -Selective attention (Hillyard, Näätänen, Harter) The 1980s The 1980s -Kutas & Hillyard (1980) discover N400 -ERPology transitions into cognitive neuroscience -Multichannel recordings (16+ electrodes) and BESA The 1990s The 1990s -More components: LRP, N2pc, ERN, N170, etc. -fMRI takes off, leading to predictions of the demise of ERPs The 2000s The 2000s -Time-frequency analyses become mainstream -The ERP Boot Camp!

11. Some Basics of Neuroscience Resting membrane potential Resting membrane potential --70 mV on inside of cell Action potentials Action potentials -Triggered when membrane potential goes sufficiently positive -Starts at axon hillock and travels down axon -Rarely contributes to scalp ERPs Postsynaptic potentials (PSPs) Postsynaptic potentials (PSPs) -Neurotransmitter binds with receptor, opens ion channels -Excitatory: Positive charges move into cell -Inhibitory: Negative charges move into cell -The origin of most ERPs

12. Some Basics of Electricity Current (I for Intensity; Amperes) Current (I for Intensity; Amperes) -Movement of charges across space (coulombs per second) -Like rate of water coming out of a hose (liters per second) Voltage (E for Electromotive Force; Volts) Voltage (E for Electromotive Force; Volts) -Potential for charges to move -Like water pressure Resistance (R; Ohms [Ω]) Resistance (R; Ohms [Ω]) -Resistance to movement of charges -Like having a skinny or blocked hose segment Impedance (Z) Impedance (Z) -Resistance to the flow of alternating current (AC) -Combines resistance, capacitance, and inductance

13. Some Basics of Electricity Power (Watts) = EI (typically proportional to E 2 ) Power (Watts) = EI (typically proportional to E 2 ) Ohm’s Law: E = IR Ohm’s Law: E = IR -If resistance increases and current is constant, voltage increases! -If you keep total water flow constant but constrict part of the hose, the pressure increases

14. Some Basics of Electricity Electricity follows the path of least resistance Electricity follows the path of least resistance Overall R < lowest individual R Overall R = sum of individual Rs

15. Some Basics of Electricity Measuring Electrode Impedances Measuring Electrode Impedances Measuring between E1 and E8 gives you the sum of E1 and E8; which impedance is high? Measuring between E1–E7 (in parallel) and E8 gives you the sum of E8 and less than the lowest of E1–E7 Outside of Skin Inside of Skin

16. Some Basics of Electricity Induction Induction -If you pass an electrical current through a conductor, a magnetic field will run around it (right-hand rule) -If you pass a magnetic field across a conductor, an electrical current is induced in the conductor

17. Some Basics of Electricity AC is “Alternating Current” AC is “Alternating Current” -Changes fairly rapidly over time -Line current (50 or 60 Hz) -EEG DC is “Direct Current” DC is “Direct Current” -Fairly constant “offset” in voltage -Batteries -Skin potentials -In discussions of amplifiers, DC can also mean “Direct Coupled” (as opposed to capacitively coupled) Conveniently, this means that the amplifier can amplify DC (direct current) signals Conveniently, this means that the amplifier can amplify DC (direct current) signals

18. Where Do ERPs Come From? Cortical pyramidal cell (basic input-output cell of cerebral cortex) Excitatory transmitter released on apical dendrites causes positive charges to flow into dendrites Net negative on outside of cell Current flows through cell, completing the circuit Polarity reverses with inhibitory transmitter Polarity reverses with PSP on cell body and basal dendrites Polarity at scalp also depends on orientation of the cortical surface and position of reference electrode

19. Where Do ERPs Come From? To be recorded at a distance, large numbers of neurons must have similar voltage fields Equivalent Current Dipole

20. Where Do ERPs Come From? Scalp-recorded potentials are possible only for layered structures with consistent orientations Primarily cerebral cortex What about: Cerebellum? Brainstem nuclei? Superior colliculus? Possible role of radial glia Local Field Potentials Open FieldClosed Field

21. Where Do ERPs Come From? Voltages spread through the brain by “volume conduction” Nearly speed of light Voltage everywhere except at positive-negative transition Skull causes lateral spread (like spraying hose on cardboard)

22. Magnetoencephalography (MEG) Magnetic fields travel around electrical dipoles The skull is transparent to magnetism -- less blurring Deep and radial dipoles are invisible from outside the head

23. w 1,1 w 2,1 w 3,1 w 1,2 w 2,2 w 3,2 w 1,3 w 2,3 w 3,3 C1 C2 C3 E1 The Superposition Problem C1C2 C3 E2 E1 E3 Voltage at an electrode at time t is a weighted sum of all components that are active at time t There is no foolproof way to recover the underlying components from the observed waveforms E2 E3

24. What are ERPs Good For? Temporal resolution Temporal resolution -Continuous measure of processing between S and R -Many processes occur in a given region at different times Determine whether an experimental manipulation influenced Process A or Process B Determine whether an experimental manipulation influenced Process A or Process B -Which ERP component was affected? Identifying multiple neurocognitive processes Identifying multiple neurocognitive processes -A given behavioral effect is often accompanied by multiple ERP effects (different components) -Easy to identify multiple processes contributing to behavior Covert monitoring of processing Covert monitoring of processing -Processing can be measured without a behavioral response (or from subjects who cannot easily respond) -Did the brain do something that was not evident in behavior?

25. What are ERPs Good For? Link to the brain Link to the brain -Under some conditions, neural systems can be identified -But people often draw unwarranted conclusions about underlying neural processes from ERPs -Many researchers desperately want ERPs to be like fMRI or single-unit recordings, but they are not -“Those English boys want to play the blues so bad—and they DO play it so bad” — Sonny Boy Williamson -“Those ERPers want to study the brain so bad—and they DO study it so bad” — Sonny Boy Luck Sonny Boy Williamson

26. ERPs as Biomarkers ERPs are tightly tied to neurotransmission ERPs are tightly tied to neurotransmission -MMN may reflect current flow through NMDA receptors -A change in ERPs reflects a change in PSPs (not mediated through hemodynamic response) Rodent/primate models available for some components Rodent/primate models available for some components -Potentially useful as an assay in drug discovery Easily tolerated by patients Easily tolerated by patients Some paradigms have excellent stability, reliability Some paradigms have excellent stability, reliability Relatively inexpensive, feasible for large-N studies Relatively inexpensive, feasible for large-N studies May be able to predict which patients will respond to a given treatment May be able to predict which patients will respond to a given treatment Potential roadblocks Potential roadblocks -Individual differences, lack of quality assurance standards See Luck et al. (2011, Biological Psychiatry)

27. ERPs Are Bad When… You desire certainty about the neuroanatomical locus of an effect You desire certainty about the neuroanatomical locus of an effect You are interested in activity that is slow (>~2 s) or not time-locked to a sudden, observable event You are interested in activity that is slow (>~2 s) or not time-locked to a sudden, observable event You cannot collect large numbers of trials in each critical condition You cannot collect large numbers of trials in each critical condition -Long period of time between trials -Severe adaptation of response over trials -Huge number of different control conditions -Need to surprise subjects Subjects make frequent head or mouth movements during the time period of interest Subjects make frequent head or mouth movements during the time period of interest -Speech is particularly bad (tongue has strong dipole)

28. Comparison of Techniques

29. ERPs and fMRI Spatial and temporal resolution Spatial and temporal resolution -If you want to study the sequence of events from 0-500 ms poststimulus, use ERPs -If you want to differentiate V2 from V4, use fMRI Cost Cost -$10/hour versus $500/hour Tolerability Tolerability -Infants and children, obese people, anxious people Specificity for postsynaptic potentials Specificity for postsynaptic potentials -Except in rare instances, ERPs reflect PSPs and not action potentials -fMRI reflects PSPs and APs, plus coupling with hemodynamic response

30. ERPs and fMRI Sustained versus transient responses Sustained versus transient responses -Hard to look at slow, sustained activity with ERPs (no block designs with ERPs) -Low power for infrequent, brief effects with fMRI (hard to pick up a 50- ms effect that occurs every 6 seconds) Components versus anatomical regions Components versus anatomical regions -Who really cares about N170, P300, N400, per se? Flexibility Flexibility -Scalp ERPs are generated by a small fraction of brain processes -fMRI can pick up anything that changes overall activity level

31. Some Terminology Pet Peeves ERPs are not “evoked response potentials” ERPs are not “evoked response potentials” -This is like “irregardless” -These are fine: Evoked Responses; Evoked Potentials; VEPs; AEPs; VERs; AERs; Must put an “s” on the end of “ERP” if and only if you would say “event-related potentials” Must put an “s” on the end of “ERP” if and only if you would say “event-related potentials” -“We recorded event-related potentials…” -“We recorded ERPs…” -Not “We recorded ERP…” -“We conducted an event-related potential experiment...” -“We conducted an ERP experiment…” -Not “We conducted an ERPs experiment…”