Neuroscience of Executive Functions: Implications for Assessment & T reatment

1. Neuroscience of Executive Functions: Implications for Assessment & Treatment Nancy S. Koven, Ph.D. Bates College Robert M. Roth, Ph.D. Geisel School of Medicine at Dartmouth November 3, 2012

2. Disclosure • Robert Roth is a consultant to Shire Pharmaceuticals and co-author of some instruments that will be discussed during this presentation (BRIEF, TEC).

3. Plan • What are Executive Functions? • How do we assess them? • What is the developmental course? • What is the brain basis? • How do they relate to healthy and maladaptive functioning? • How can you improve them?

4. Executive Function: Definitions A Rose by Any Other Name: Executive Function Executive Control Processes Cognition Control Self Regulation Behavior Regulation Higher Order Cognitive Processes Supervisory System Frontal Lobe Function

5. Phineas Gage: 1848 in Cavendish, VT • 3’ tamping iron shot through left cheek and exited left frontal • Destroyed much of left frontal lobe

6. Phineas Gage: A changed man “He is fitful, irreverent, indulging at times in the grossest profanity, impatient of restraint or advice when it conflicts with his desires; at times pertinaciously obstinate yet capricious and vacillating. His friends and acquaintances said he was no longer Gage.” - Harlow, 1868

7. Executive Function Definitions Lezak (1995): Those “capacities that enable a person to engage successfully in independent, purpose, self-serving behavior” Stuss (1984): Higher-order cognitive control functions that are distinguishable from more “basic” cognitive abilities (e.g., language, visuospatial, memory abilities) Gioia (2001), Stuss (2000): An umbrella construct reflecting self-regulatory functions that organize, direct, and manage cognitive activities, emotional responses, and overt behaviors

8. Orchestration of basic cognitive processes during goal-oriented problem-solving - Neisser, 1967

9. Functions of the “Orchestra” • Perception • Attention • Language processes • Visual-spatial processes • Memory • Sensory inputs • Motor outputs • Knowledge and skills • Functions of the “Conductor” • Inhibit • Shift flexibly • Modulate emotions • Initiate • Working memory • Plan • Organize • Monitor

10. Interest in Executive Function in Children • 5 articles in 1985 • 14 articles in 1995 • 501 articles by 2005 • >1000 by 2009 Bernstein & Waber (2007)

11. Interest in Executive Function in Adults • 36 articles in 1996 • 85 articles in 1999 • 169 articles in 2002 • 294 articles in 2005 • 438 articles by 2009 1996 1999 2002 2005 2009

12. Executive Functions: Why care? Tourette’s Syndrome Learning Disability Parkinson’s Disease Huntington’s Disease Progressive Supranuclear Palsy Multiple Sclerosis Alzheimer’s Disease Frontotemporal Dementia Mild Cognitive Impairment Traumatic Brain Injury Epilepsy Stroke Brain Tumors Sleep Apnea Mental Retardation Sleep Apnea Post-Cardiac Surgery Phenylketonuria ADHD Antisocial Personality Disorder Borderline Personality Disorder Schizotypal Personality Disorder Bipolar Disorder Major Depressive Disorder Obsessive Compulsive Disorder Schizophrenia Alcohol Use Disorder Cocaine Use Disorder Methamphetamine Abuse Cannabis Use Disorder Eating Disorders Autism Spectrum Disorders Pyromania

13. Methods of Assessing Executive Function Molar Macro Micro Genetics Structural & Functional Imaging Observations Performance Tests

14. Methods of Assessing Executive Function:Performance-Based tests

15. Simon Task press left for green arrow and right for red arrow Ignore direction arrow pointing !

16. Limitations of Executive Function “Tests” • Tests and tasks require content and EF • Many tests are too structured to observe EF • Examiner as “Executive” • “Extraneous” factors can impact executive functions (e.g., fatigue, pain, mood, medications)

17. Methods of Assessing Executive Function:Rating Scales

18. Advantages of Rating Scales • Assess EF in dynamic contexts • Capture multiple perspectives • Time and cost efficient • Growing literature • Ecological validity

19. Ecological Validity • The “functional and predictive relationship between the patient’s behavior on a set of neuropsychological tests and the patient’s behavior in a variety of real-world settings….” • Sbordone(1996) • Functional = verisimilitude • Predictive = veridicality

20. Limitations of Rating Scales • Less process-specific information, that is, • everyday behavior requires integration of EF • (e.g., inhibit + working memory + planning) • Poor control over environmental demands • (e.g., work vs. home)

21. Limitations of Rating Scales • Rater Bias: • Emotional state and personality of rater • Rater’s context (e.g., school vs. home) • Halo effect (general opinion of person rated) • Awareness of deficits

22. Development of Executive Functions: Plan/Organize/Monitor 3–32 yrs Emotional Modulation 3–?? yrs Verbal Working Memory 2–13 yrs Nonverbal Working Memory 3-24 mo Inhibit 0 - ?

23. Change in Effect Size Across Childhood on Performance Tests of Executive Function Romine & Reynolds, 2005; Applied Neuropsychology

24. Executive Functions From Childhood through Older Age (n = 1007) Like Trails B Stroop Effect Clark et al., 2006; Arch Clin Neuropsychology

25. Age Effects on Self and Informant Report of Executive Functions in Daily Life Inhibit max score = 24 EC max score = 30 Raw Score Roth, Isquith, & Gioia (2005)

26. Changes in Older Adulthood gets worse inhibition manipulation switching stays same abstraction chunking capacity Goh et al., 2012, Psychology & Aging

27. STRUCTURAL BRAIN CHANGES Lenroot et al. (2006, Neuroscience and BiobehavioralReviews)

28. fMRI Activation during Emotion Regulation in Girls (age 8-10) and Women (age 20-30) Girls Women Levesque et al. (2004; Neuroscience)

29. Emotional Control and the Adolescent Brain fMRI at rest in Girls with High and Low BRIEF Emotional Control Right Anterior Temporal Cortex (including insula) more active in the girls with worse emotional control (warm colors) Dorsolateral and cingulate cortex more active in the girls with better control (cool colors) Baird, unpublished, Dartmouth College

30. Inhibitory Control and the Brain Aaron et al. (Biol. Psychiatry, 2011)

31. Neural Circuits and Executive Functions Arnsten et al. (Biol. Psychiatry, 2011)

32. Wisconsin Card Sorting Test Lie et al., 2006 NeuroImage

33. Executive Dysfunction ≠Localization

34. Neurochemical basis of Executive Functions Dopamine pathway: ventral tegmentumto frontal lobe Norepinephrine pathway: brainstem to cortex, including frontal lobe SCHIZOPHRENIA ADHD

35. Neurochemical basis of Executive Functions Serotonin pathway: brainstem to cortex, including frontal lobe Cholinergic pathway: brainstem to hippo/cortex, including frontal lobe ALZHEIMER’S DEPRESSION

36. Genetic Contribution to Executive Function and Brain Volumes in 139 Male Twin pairs age 69-80 years Carmelli et al, 2002; Biol Psychology

37. COMT Effect on Executive Function in 95 Healthy Adults (controlling for APOE and BDNF) Wishart, Roth, et al, 2010; JINS

38. BRAIN and GENES Adults with APOE ε3/ε4 (relative to ε3/ε3)show Increased Brain Activation during a Working Memory Task Wishart et al, 2006; Am J Psychiatry

39. Associations between teacher ratings on the BRIEF-Preschool at 4 years and performance on WJ3 Math Fluency at 6 years Clark, Pritchard, & Woodward (2010; Developmental Psychology)

40. Correlations between Measures and High-Stakes Test scores Measure MCAS English MCAS Mathematics Coding .47*** .32** Symbol Search .42*** .39*** Letter–Number .44*** .37*** NEPSY Tower .07 .15 D-KEFS Inhibition .39*** .24* D-KEFS Inhibition–Switch .38*** .20 BRIEF BRI –.46*** –.47*** BRIEF MI –.61*** –.61*** BASC Internalizing –.44*** –.43*** BASC Externalizing –.42*** –.41*** BASC School Problems –.55*** –.56*** Waber, Gerber, Turcios, Wagner, & Forbes, 2006

41. Peer Ratings of Social Status and Executive Function From Abigail Baird Psychological & Brain Sciences, Dartmouth College

42. Executive Function and Alcohol-Related Aggression Giancola, Godlaski, & Roth, in press, Psychology of Addictive Behaviors

43. Executive Functions in Academic Procrastination (n=212) β = 0.47 β = - 0.30 Initiation and Organization of Materials remained significant predictors of procrastination even after controlling for demographics, mood and personality Rabin et al (JCEN, 2011) Nutter-Upham et al. (ICP, 2008)

44. Executive Function and Ability to Stay Faithful • Executive Control Tasks: Stroop-Like Task; N-Back task • Study 1 – Questionnaire (72 romantically involved students): • I find it hard to stay faithful to my partner • If a cute guy/girl shows interest in me, I find it hard to resist temptation • I find it very easy to stay faithful to my partner (reverse scored) • Study 2 Task - Relationship to flirting (21 heterosexual male students): • Participant in room for 10 minutes with a female confederate instructed to interact as if they were another subject; and behave in a friendly, but not overly interested or flirtatious manner. Interaction was videotaped. Then rated attractiveness of confederate • Confederate and 4 independent raters (blind to goal of study), rated flirting by participant 1 week after study completed (IRR > .9) Pronk et al., 2011; J Personality & Social Psychology

45. Executive Function and Faithfulness Study 1: Poorer executive control r. with more difficulty staying faithful [r(72) = .30, p .01]; no gender difference Study 2: Poorer executive control associated with more flirting Pronk et al., 2011; J Personality & Social Psychology

46. Disorders of Executive Function • No singular, core disorder • Symptom onset delayed due to prolonged development & environmental demand • Performance on standardized tests often appropriate • Discrepancy between ability and performance • Fluid social domain often most challenging

47. 83 Studies 3734 ADHD vs 2969 Controls Effects .43 - .69 (M = .54) No subtype differences (I vs C) ADHD associated with EF Strongest deficits seen in: Inhibition Vigilance Working Memory Planning BUT < ½ in ADHD showed impairment on any EF tasks EF does not explain ADHD Common Tasks: % Impaired Stop signal response time 82 CPT Commissions CPT Omissions 77 WCST Perseveration Trails B time TOH/TOL 59 Porteus Mazes ROCF Sentence Span Digits Backward Self Ordered Pointing Validity of the EF Theory of ADHD Willcutt, Doyle, Nigg, Faraone, & Pennington, 2005

49. Methylphenidate vs Placebo on BRIEF scales in Children with ADHD Kunin-Batson, 2001

50. Executive Functions in Adult ADHD Self Report Executive Function in Unmedicated (n=27) and Medicated (n=16) Adults with ADHD, and Healthy Controls (n=42) Biederman, Fried, et al., unpublished data