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ADHD – QEEG – ERP: Basic

ADHD – QEEG – ERP: Basic. ADHD: Predicting response to stimulant medication on the basis of event related potentials (ERPs). Geir Ogrim , Neuropsychologist, Østfold Hospital Trust, Neuropsychiatric unit, Norway

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ADHD – QEEG – ERP: Basic

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  1. ADHD – QEEG – ERP:Basic Geir Ogrim IPEG 2012

  2. ADHD: Predicting response to stimulant medication on the basis of event related potentials (ERPs) GeirOgrim, Neuropsychologist, Østfold Hospital Trust, Neuropsychiatric unit, Norway National Resource Center for ADHD, Tourettes’ Syndrome and Narcolepsy, Norway JuriKropotov, Professor, Laboratory of the Institute of the Human Brain (HBI) of Russian Accademy of Science, St. Petersburg, Russia. HBImedAG.Chur, Switzerland The Norwegian University of Science and Technology (NTNU), Trondheim Norway Knut Hestad, Professor, The Norwegian University of Science and Technology (NTNU), Trondheim Norway. InnlandetHospital Trust, Div. of Psychiatry, Ottestad, Norway Jan Brunner, Neuropsychologist, St. Olav Hospital, Trondheim, Norway Geir Ogrim IPEG 2012

  3. Contributors to thestudy Geir Ogrim IPEG 2012

  4. Where we come from? Norway Geir Ogrim IPEG 2012

  5. Disclosures • The contributors have no conflicts of interest or financial ties to disclosure. • The study is financially supported byØstfold Hospital Trust, NorwayandThe Norwegian University of Science and Technology (NTNU), Norway Geir Ogrim IPEG 2012

  6. ”The big picture” • Millions of (young) people diagnosed with ADHD are treated with stimulants worldwide • 75(?)% are considered to be responders • Percent responders depend on criteria, method of measurement, informants • Side effects an issue in 30(?)% • Dilemmas: • Are the effects optimal in this particualar case? • Do we see effects beyond ”strong coffee” that everyone can have? Geir Ogrim IPEG 2012

  7. Optimal effect? Geir Ogrim IPEG 2012

  8. Predicting quality of response • Standard predictors do not seem to be clinically useful: • Symptom severity, subtype of ADHD, neuropsychological test results, comorbidity, sex, age • EEG measures • Excess theta, theta/beta ratio, reduced alpha peak… • Reliable predictors can help us decide: • To medicate or not • Who need extra monitoring • To stop medication if effects are marginal Geir Ogrim IPEG 2012

  9. The aim of the study • The broad scope: • Can quality of medication response be predicted based on information related to: • Sex, age, subtype of ADHD, comorbidity, attention testing, EEG spectra, traditional ERPs (waves) and Independent Component ERPs (IC ERPs) • Logistic regression model • Focus of this presentation: • Can Independent Component ERPs (IC ERPs) help us classify young ADHD patients as responders and non-responders to stimulants? • (IC ERPs defined later on) Geir Ogrim IPEG 2012

  10. Our sampletotal N = 74 (70). Age: 7-16 years Geir Ogrim IPEG 2012

  11. Comorbidities - examples Geir Ogrim IPEG 2012

  12. Method of classification:Responders and Non-responders • Diagnosing ADHD and comorbidities: • DSM IV criteria: Medical and developmental history, medical examination, clinical interview, rating scales parents/teachers, (self reports), testing, school reports, team discussion.. • Medication try-out: • 4 weeks (+) titration from 5mg. methylphenidate/day to maximum 3 x 20mg /day (if needed) • Baseline ratings • Daily ratings from parents and teachers (and self reports) • Weekly ratings of side-effects Geir Ogrim IPEG 2012

  13. Method of classification:Responders and Non-responders, cont. • Attention testing on and off medication in some cases • Telephone with doctor if needed • Sum-up meeting after 4 weeks: • Parent(s), teacher(s), child/adolescent (sometimes), child psychiatry (doctor/psychologist) • Changes these weeks? Positive? Negative? At home? At school? Self? (describe), Effects of dose. Data from rating scales. • Continue medication? Stop? Extended try-out (Dose, type..) • Responders vs. non-responders: • Two psychologists independently evaluating all info regarding effects, not knowing data from QEEG/ERP • 85 % agreement. Unclear cases discussed. Geir Ogrim IPEG 2012

  14. Method of ERP registration Geir Ogrim IPEG 2012

  15. EEG registration and ERP task Geir Ogrim IPEG 2012

  16. Event Related Potentials (ERPs) and Independent Component ERPs (IC ERPs) • In contrast to spontaneous EEG activity, event-related • potentials (ERPs) reflect phasic activity of cortical neurons. • They are electrophysiological responses to an internal or external stimulus and are obtained by averaging the brain’s electrical response to the stimuli over a number of trials • Independent component analysis (ICA) separates a set of mixed event-related potentials into a corresponding set of statistically independent source signals, which are likely to represent different functional processes Geir Ogrim IPEG 2012

  17. Results:Comparing IC ERPs in 53 responders, 17 non-responders and 40 matched controls IC P3NoGo early IC P3NoGo late IC cue P3 (after stim. 1) IC CNV early (contingent negative variation) IC CNV late Geir Ogrim IPEG 2012

  18. IC P3 NoGo early Geir Ogrim IPEG 2012

  19. Map and generator of IC P3 NoGo early Over: P3NOGO early: Brodman 6: Superior frontal gyrus, frontal lobe Geir Ogrim IPEG 2012

  20. IC P3NoGo peak amplitude in SPSS T = 2.55 df = 68 Sig(2tailed) = 0.01 Effect size Eta2 = 0.09 (moderate) Eta2 :.01 = Small effect.06 = Moderate effect.14 = large effect Cohen´s d: 0.7 Geir Ogrim IPEG 2012

  21. Problems with IC P3NoGo early? Geir Ogrim IPEG 2012

  22. IC P3 NoGo late • Left: IC ”P3NoGo late”: 53 responders (black) vs. 40 controls (red): NSRight: IC ”P3NoGo late”: 17 nonresponders (black) vs. 40 controls (red): NS Psychologically: A more conscious part of the withholding of action? Responders as well as non-responders are close to normals. Geir Ogrim IPEG 2012

  23. Map and generator of IC P3 NoGo late P3NOGO late: Brodman 25: Anterior singulate, limbic lobe Geir Ogrim IPEG 2012

  24. IC cue P3 (after stim. 1) • Left:17 nonresponders (black) vs. 40 normal controls. IC “cue P3” (after stim. 1). Latency = 320ms, P = 0.0005Middle: 53 responder (black) vs. 40 normal controls: NSRight: 53 responders (black) vs. 17 nonresponders (red), P = 0.0008 Psychologically. “Watch out, animal picture. Create a template to compare with next stimulus” (?) The non-responders have problems with this parietal function. The responders are normal Geir Ogrim IPEG 2012

  25. Map and generator of IC cue P3 Cue P3: Brodman 4: Paracentral lobule, frontal lobe (?) Geir Ogrim IPEG 2012

  26. IC cue P3 peak amplitude in SPSS T = -4.5 df = 48.4 Sig(2tailed) = 0.000 Effect size Eta2 = 0.23 (large) Eta2 :.01 = Small effect.06 = Moderate effect.14 = large effect Cohen´s d: 1.1 Geir Ogrim IPEG 2012

  27. IC CNV late (after 1. stim.) • Left: IC “CNV early”: 53 responders (black) vs. 40 controls (red). At 608ms, P = 0.0015Middle: IC “CNV late”: 53 responders (black) vs. 40 controls (red). From 960ms: P = 0.0001Right: 53 responders (black) and 17 nonresponders (red) were not sign. different in early or late IC CNV. However, nonresponders were closer to the control group Psychologically: Stim 1 was animal: “Keep up your vigilance, stim2 may be an animal too” Both ADHD groups are significantly different from norm, responders a little more Geir Ogrim IPEG 2012

  28. Map and generator of IC CNV late “CNV late”: Brodman 6 Superior frontal gyrus, frontal lobe Geir Ogrim IPEG 2012

  29. Conclusions • Good predictors of response to stimulants in ADHD can have implications for clinic • Two types of independent brain dysfunction in ADHD (frontal and temporal-parietal) were found. • ADHD patients with frontal lobe dysfunction responded best to psychostimulants. • This finding corresponds to mechanisms of psychostimulant medication known to affect the dopaminergic system of the brain with higher densities of receptors in the prefrontal cortical areas. Geir Ogrim IPEG 2012

  30. Predictingacute side-effects • In general side-effectsaresmall. • 30% (?) have side-effects (lasting more than a fewdays) like: • Insomnia • Reducedappetite • Anxiety • Irritability Geir Ogrim IPEG 2012

  31. Article under review: Highlights IC ERP component CNV-late: Reflecting ability to keep up vigilance when 1.st stim was an animal is normal in ADHD patients with side-effects and significantly reduced in patients without side-effects. P: 0.000 Effect size: Large: eta2: 0.21, Cohen´s d: 1.1 AND: Patients with side-effects have sign. shorter reaction time in VCPT test Abstracts – figures - tables Geir Ogrim IPEG 2012

  32. Thank you for your attention

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