Implications of Event Related Potentials in Clinical research Dr Arun Sasidharan MBBS, PhD Senior Research Officer & Research Program Manager Axxonet Brain Research Laboratory (ABRL) Axxonet System Technologies Pvt. Ltd., Bengaluru Presentation for: N-CORTEX – 2017 on Jan 5th @ Dept. of Psychology, Mount Carmel College, Bengaluru

Structure of the talk Simplify the concept and technique of ERP Quick overview on different types of ERPs Walk-through the design of simple ERP tasks Structure of the talk

Structure of the talk Simplify the concept and technique of ERP Quick overview on different types of ERPs Walk-through the design of simple ERP tasks Structure of the talk

What is ERP? – simplistic view ERP – Event Related Potential They are tiny fluctuations in a person’s EEG, related to a stimulus presentation or an event occurrence. ERPs are informative about the exact timing of cognitive processes http://erpinfo.org/

Why ERPs? Most assessments in mental health involve subjective component ERPs can provide more objective assessment of brain function ERPs can tap into brain functions at very high temporal resolutions Can be set up in most clinics??

EEG setups – So easy!! 1 2 3

Post-synaptic potentials generate EEG/ERP How are ERPs generated? Post-synaptic potentials generate EEG/ERP Not Action potentials Prof. Gilley; https://www.youtube.com/watch?v=OCpYdSN_kts&t=36s&spfreload=10

How are ERPs derived? - concept Task-relevant brain processes are time-locked to the task events Averaging EEG portions or epochs that are time-locked to events Identify task relevant brain processes in terms of size & latency of the resulting waveforms - ERPs

How are ERPs derived? Stimulus Source: http://www.studyblue.com

How are ERPs derived? Source: https://web.cs.dal.ca/~tt/CSCI690611/eeg_intro_lecture.pdf An Introduction to the Event-Related Potential Technique by Steven J. Luck

How are ERPs derived? Raw EEG

How are ERPs derived? Raw EEG Cleaning

How are ERPs derived? Raw EEG Cleaning Epoching 1500ms 1500ms 1500ms

How are ERPs derived? Raw EEG Cleaning Epoching Trial 1 Trial 2

How are ERPs derived? Raw EEG Cleaning Epoching ERP 1500 ms Trial 1 Event related potential ERP

Exploring the ERP time window Methods… Exploring the ERP time window Check if individual subject data are correctly detected Start with all subject grand average Modify to fit all data

What causes ERPs? + + + Phase-locked evoked potentials Phase-reset spontaneous oscillations Non phase-locked induced potentials + + + Turi et al. NeuroImage 59 (2012) 2607–2624

Structure of the talk Simplify the concept and technique of ERP Quick overview on different types of ERPs Walk-through the design of simple ERP tasks Structure of the talk

Temporal relation in ERP Prof. Gilley; https://www.youtube.com/watch?v=OCpYdSN_kts&t=36s&spfreload=10

P50 sensory gating CNT Standard S1 CNT Standard S2 SCZ Standard S1 P50 suppression N1-P2 suppression Measurement time-window Measurement parameter Electrodes analysed Number of epochs analysed Negative peak in -100ms to 0ms; Positive peak (P50) in 20ms to 90ms Ratio of peak to peak amplitude difference between second of the standard tone-pair and first one. FCz & Cz SCZ: 262.40 ± 31.06 (147.0-285.0) CNT: 271.80 ± 8.27 (259.0-286.0) t statistic = 1.032; p-value = 0.325; CI = -4.3 to 22.6 Negative peak (N1) in 60ms to 170ms; Positive peak (P2) in 140ms to 250ms Ratio of peak to peak amplitude difference between second of the standard tone- pair and first one. FCz & Cz CNT Standard S1 CNT Standard S2 SCZ Standard S1 SCZ Standard S2

Measurement time-window Measurement parameter auditory sensory memory MMN Measurement time-window Measurement parameter Electrodes analysed 150ms to 250ms Mean amplitude difference between first of the standard tone-pair and first of deviant tone-pair. FCz & Cz CNT Standard S1 CNT Deviant S1 SCZ Standard S1 SCZ Deviant S1 Thought to reflect automatic comparison of incoming stimuli to a sensory memory trace of preceding stimuli

structural encoding of faces Negative potential at lateral occipital sites with a peak at approximately 170 ms More for face than non-face stimuli; highly familiar non-face stimuli also show high N170 Image source: Kuefner et al. 2010

Attentional shift N2pc It is the relatively greater negative deflection observed at posterior electrode sites contralateral to the location of a target visual stimuli It reflects the focusing of spatial attention onto the target location Image source: http://www.uni-marburg.de/fb04/team-schuboe/research/context_configurations

Measurement time-window Measurement parameter Error monitoring ERN Measurement time-window Measurement parameter Electrodes analysed -60ms to 60ms Mean amplitude difference between correct and incorrect responses Fz & FCz CNT Correct CNT Incorrect SCZ Correct SCZ Incorrect

Measurement time-window Measurement parameter automatic attention and contextual updating of working memory P300 Measurement time-window Measurement parameter Electrodes analysed 250ms to 450ms Difference in area under the curve (only positive side) between frequent and rare images Cz & Pz CNT Frequent Passive CNT Rare Active SCZ Frequent Passive SCZ Rare Active Elicited by unpredictable, infrequent changes in ongoing stimuli Usually tested using “Odd-ball” paradigm; more for rare than frequent stimuli

Readiness Potential (RP) & Lateralized Readiness Potential (LRP) RP: Mean of Negative deflection between -100 & 0 ms LRP (for Rt hand): Lt RP – Rt RP More negative when contralateral hand prepares Reflects movement preparation At FC3, FC4, C3, C4, CP3, and CP4 Rt RP Lt RP Baseline Baseline Image source: Nature Reviews Neuroscience 6, 247-255 (March 2005) doi:10.1038/nrn1630

Clinical implication of ERPs ERP Deficits in Schizophrenia ↓P50 suppression (sensory gating) [Adler et al., 1982; Freedman et al., 1983; Bramon et al., 2004] ↓N100 (auditory discerning) [Rosburg et al., 2008] ↓MMN (auditory sensory memory) [Nȁȁtȁnen at al., 2009] ↓P300 (automatic attention & contextual updating of WM) [Bramon et al., 2004; van der Stelt at al., 2005] ↓P100 (global processing of visual perception) [Foxe at al., 2001; Butler at al., 2007; Yeap et al., 2008] ↓N170 (structural encoding of faces) [Campanella et al., 2006; Caharel et al., 2007; Obayashi et al., 2009; Lee et al., 2010]

Structure of the talk Simplify the concept and technique of ERP Quick overview on different types of ERPs Walk-through the design of simple ERP tasks Structure of the talk

Basic ERP Acquisition setup Stimulus Presentation EEG Acquisition Event Markers Paradigm design software ERP analysis software

Define condition requirements E.g. For P300 ERP: Basic requirement? Unpredictable and rare presentation of stimulus; Or having implicit salience Need to attend to stimulus? Yes Need to respond to stimulus? Preferable; Not necessary Which modality? Any; Mostly auditory or visual

Define condition requirements E.g. For P300 ERP:

Uniformity in subject engagement Adequate breaks Divide into smaller blocks Blink holidays Feedbacks

Balance stimulus parameters Auditory: Loudness, duration, complexity Visual: luminance, size, duration, colour, visual frequency Lower spatial frequency (1 cycle/degree) Higher spatial frequency (2 cycle/degree) Colour image Two-tone image

Balance stimulus parameters Visual: visual angle

Complex designs…yet simple tasks 80% Standard paired tones 1000Hz, 15ms long, 500ms apart 20% Deviant paired tones 1500Hz, 15ms long, 500ms apart 1200ms to 1900ms 240ms Pre stimulus Mask Visual distracters (can be at top or bottom) 240ms OR OR Target stimulus (can be at left or right) OR OR 460ms Response window of 700ms OR OR OR 0-100ms 60ms Triangle present Triangle absent Face present Face absent Auditory distractors 200ms Post stimulus Mask 0-600ms Fixed duration Random duration Nair AK, Sasidharan A, John JP, Mehrotra S, Kutty BM. Assessing neurocognition via gamified experimental logic: A novel approach to simultaneous acquisition of multiple ERPs. Front Neurosci. 2016;10(January):1–14.

Thank you