Neuropsychology of Attention Deficit Hyperactivity Disorder (ADHD)

Neuropsychology of Attention Deficit Hyperactivity Disorder (ADHD) Ronna Fried, Ed.D. Director of Neuropsychology Clinical & Research Programs in Pediatric Psychopharmacology and Adult ADHD Massachusetts General Hospital, Instructor in Psychology Harvard Medical School

Disclosures Dr. Fried has served as a consultant, speaker, or has received grant support from the following: NIH Shire

Interest in Executive Functions *5 articles in 1985 *14 articles in 1995 501articles by 2005 -Bernstein & Waber Executive Function, 2007 500 450 400 350 300 250 200 150 100 50 0 1985 1995 2005 3-D Column 1

What are Executive Functions? Orchestration of basic cognitive processes during goal-oriented problem-solving: the CONDUCTOR

Executive Functions Functions of the Orchestra Functions of the Conductor Perception Attention Language processes Visual-spatial processes Memory Sensory Inputs Motor Outputs Knowledge& Skills social Non-social Inhibit Shift Flexibly Modulate Emotions Initiate Working Memory Plan Organize Fried, R. (2010). Impact of Executive Functions in Youth with Bipolar I Disorder: A Controlled Study [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

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

Assessment of EFDs Neuropsychological Testing Checklists

Neuropsychological Testing A large meta-analysis domains of executive functioning deficits in ADHD Domains of Executive Functioning Set shifting 0.50 Working memory (verbal) 0.45 Working memory (spatial) Meta-analytic Effect Size (d) 1.00 Planning 0.55 Inhibition 0.60 Nigg, J.T. (2006). What causes ADHD?: Understanding what goes wrong and why. New York, NY: The Guilford Press.

Neuropsychological Tests Neuropsychological Test Color Word (D-KEFS) Trails Making (D-KEFS), IED (CANTAB), Letter-Number Test (WAIS) Stockings of Cambridge (CANTAB) Symbol Search (WAIS/WISC) Digit Span, Arithmetic, Letter-Number Test (WAIS/WISC) Coding (WAIS) Matrix (WAIS) Executive Function Inhibition Set Shifting Planning/Organizing Task Monitoring, Initiating Working Memory Initiating Inhibition, Spatial Working Memory

Inhibition Ability to control impulses and stop one s own behavior at the appropriate time Test Color Word (D-KEFS) BRIEF examples Interrupts or disrupts group activities Has trouble putting on the brakes Says/does things impulsively without thinking Makes decisions that get them into trouble Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Color Word Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-kaplan executive function system (d-kefs). San Antonio, TX: Pearson Education.

Color Word red blue red green red blue red blue green blue green red Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-kaplan executive function system (d-kefs). San Antonio, TX: Pearson Education.

Color Word red blue red green red blue red blue green blue green red Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-kaplan executive function system (d-kefs). San Antonio, TX: Pearson Education.

Set Shifting Ability to move from one situation, activity, or part of a problem to another as the condition demands Test Trails Making (D-KEFS) Intra-Extra Dimensional Shift Set (CANTAB), BRIEF examples Tries the same approach even when it does not work Has trouble moving from activity to activity Resists accepting a different solution Experiences anxiety, or extreme anger when things change Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Trails Making Switch between connecting the numbers and letters Begin at number 1 and draw a line from 1 to A, A to 2, 2 to B, B to 3 and so on until you reach the end G H I B C 10 2 4 7 8 9 J 1 3 D End Start 6 A F E 5 Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-kaplan executive function system (d-kefs). San Antonio, TX: Pearson Education.

Planning/Organizing Ability to manage current and future oriented task demands within the situational context Test Stockings of Cambridge (CANTAB), TOWER tasks BRIEF examples Starts tasks without the right materials Has trouble prioritizing or organizing activities Starts homework or chores at the last minute Underestimates the time to finish tasks Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Stockings Of Cambridge Use the balls in the bottom to copy the pattern in the top Fried, R. (2006). Executive Functioning/Cognitive Performance Assessment: New Battery, Distinction of EFD, and Pilot CANTAB Results [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Task Monitoring Ability to check work and assess performance during or after finishing a task to ensure a goal is finished Test Symbol Search (WAIS/WISC) BRIEF examples Does not check work for mistakes Makes careless errors Fails to catch one s errors while completing a task Does not problem solve during a task Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Symbol Search One of these shapes is in this group of shapes over here, so draw a line through the shape Neither of these shapes is in this group of shapes over here, so draw a line through the NO box NO NO NO Wechsler, D. (2008). Wechsler adult intelligence scale (wais). San Antonio, TX: Pearson Education.

Working Memory Ability to hold information in one s mind for purpose of generating a response or completing a task Test Digit Span, Letter Number, and Arithmetic (WISC/WAIS) BRIEF examples When given three things, remembers only the first or last Forgets to hand in homework Forgets what they are doing in the middle of things Has trouble remembering things, even for a few minutes ( Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Working Memory

Letter Number I am going to say some numbers and letters and when I m through, I want you to say the numbers first, in order, starting with the lowest number then tell me the letters in alphabetical order 7-N-2-P-6-F-9-A Wechsler, D. (2008). Wechsler adult intelligence scale (wais). San Antonio, TX: Pearson Education.

Arithmetic A post office sorts 20,000 pieces of mail in October. In November, the pieces of mail sorted increased by 10%. In December, the pieces of mail sorted increased by another 5%. How many pieces of mail are sorted in December after both increases? Wechsler, D. (2008). Wechsler adult intelligence scale (wais). San Antonio, TX: Pearson Education.

Initiating Ability to begin a task and independently generate ideas, responses, or problem solving strategies Test Coding, Symbol Search, and Matrix (WAIS/WISC), Color Word and Trails Making (D-KEFS) BRIEF examples Lies around the house a lot (couch potato) Has good ideas but does not get the job done Needs extensive reminders to begin a task Has trouble getting started on tasks Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Self Monitoring Ability to keep track of the effect of one s behavior on others and attend to one s behavior in a social context TEST examples: careless errors (process approach) BRIEF examples Does not notice when behavior causes negative reactions Becomes too wild or silly Does not notice when others get mad until it is too late Makes inappropriate sexual comments Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Emotional Control Ability to modulate one s emotional responses appropriately BRIEF examples Has explosive, angry outbursts Becomes tearful easily Overreacts emotionally to minor events Reacts more emotionally to situations than friends Roth, R.M., Isquith, P.K., & Gioia, G.A. (2005). Behavior rating inventory of executive function-adult version: Professional manual. Lutz, FL: PAR Psychological Assessment Resources, Inc.

Problems with Neuropsychological Testing for Assessment of EFDs Many tests too structured to observe EF Examiner is the Executive One Test Impaired could be random

Total Predictive Value Number of Abnormal Tests 1 No. Abnormal Tests 2 3 4 5 6 7 0 20 40 60 80 100 Total Predictive Value

Impact of EFDs on Children with ADHD Examined psychometrically defined EFDs in children with and without ADHD and EFDs Included male and female (mean age=12.3-13.7 years old) probands from two longitudinal family studies of ADHD Control ADHD N=125 N=159 Male 103 121 Femal e 122 138 Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Children with ADHD 35% 30% 25% 20% 15% 10% 5% 0% Percent of Subjects with >2 tests impaired (EFD)s 33% 12% ADHD Control Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Children with ADHD Special Classes in School 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 45% 24% 2% 0% Control Control + EFDs ADHD ADHD + EFDs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Children with ADHD 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Repeated School Grade 42% 19% 12% 8% Control Control + EDFs ADHD ADHD + EDFs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Children with ADHD Using the psychometrically defined method, significantly more children with ADHD had EFDs than controls Neuropsychological impairments in children with ADHD have implications for functional outcome above and beyond the diagnosis itself Children with ADHD and EFDs had an increased risk for grade retention and a decrease in academic achievement, relative to ADHD alone Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Examined psychometrically defined executive function deficits (EFDs) in adults using traditional neuropsychological tests Control Control + EDF ADHD ADHD +EDF N=122 N=23 N=147 N=66 Age 29.3 ± 8.4 35.4 ± 8.8 34.6 ± 10.4 Gender (% male) 40.0 ± 10.3 55 (45%) 11 (48%) 80 (54%) 33 (50%) Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Prevalence of EFDs in Adults 35% 30% 25% 20% 15% 10% 5% 0% 31% ADHD 16% Control Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Special Classes in School 25% 20% 21% 15% 10% 5% 0% 11% 4% 1% Control Control + EFDs ADHD ADHD + EFDs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Extra Help in School 70% 60% 50% 40% 30% 20% 10% 0% 61% 42% 35% 19% Control Control + EFDs ADHD ADHD + EFDs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Repeated School Grade 35% 30% 25% 20% 15% 10% 5% 0% 32% 22% 17% 2% Control Control + EFDs ADHD ADHD + EFDs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Education Level 7 6 5 4 3 2 1 0 6.2 5.6 5.6 5.1 Control Control + EFDs ADHD ADHD + EFDs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Occupation Level 8 7 6 5 4 3 2 1 0 6.8 6.6 6 5.3 Control Control + EFDs ADHD ADHD + EFDs Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Impact of EFDs on Adults with ADHD Using the psychometrically defined method, significantly more adults with ADHD had EFDs than controls Adults with ADHD and EFDs had significantly lower levels of education, occupation, and overall SES and more impaired interpersonal functioning EFDs in adults were associated with a decrease in academic achievement, irrespective of ADHD status Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

Self-reported EFDs Executive Function Domains Set Shifting not very flexible in my behavior or approach to a situation; overly rigid in how I like things done slower to react to unexpected events Planning/Organizing have trouble planning ahead or preparing for upcoming events trouble organizing my thoughts or thinking clearly Working Memory when shown something complicated to do, cannot keep the information in mind so as to imitate or do it correctly can t seem to hold in mind things I need to remember to do Inhibition find it difficult to tolerate waiting; impatient make impulsive comments to others

Distributions of Current Behavior Scale Total Score for ADHD and Control Subjects 60 50 40 30 20 10 Controls ADHD 0 1-20 21-40 41-60 61-80 81-100 101-120 121-140 141-160 161-180 181-200 201-220 221-240 241-260 261-280

85 80 75 70 65 60 55 50 45 40 BRIEF Scores in Adult ADHD ADHD Medicated ADHD Unmedicated Control Inhibit Shift Emot Con Self Monitor Initiate Working Memory Plan/Organize Task Monitor Org of Materials Biederman, Fried,, et al unpublished data

Can self-reported behavioral scales assess executive function deficits? A controlled study of adults with ADHD Prevalence of EFDs in 194 Adults with ADHD N=28 N=71 ADHD with neither EFD Biederman, J., Petty, C.R., Fried, R., Black, S., Faneuil, A., Doyle, A.E., Seidman, L.J., & Faraone, S.V. (2007). Discordance between psychometric testing and questionnaire-based definitions of executive function deficits in individuals with adhd. Journal of Attention Disorders, 12(1), 92-102.

Social Adjustment Scale: >65 Significant Problem

Educational Level p<0.001 vs. No EFD p<0.01 vs. No EFD p<0.001 vs. No EFD p<0.05 vs. Psychometric EFD

Lifetime GAF

Comparison of main outcomes between ADHD adults with no EFDs, psychometrically defined EFD, self-reported EFD, or both EFDs No EFD Self-report EFD Psychometric EFD Combined EFD 0.5 0-0.5 Mean Z-score -1-1.5-2 AB ABC Current GAF AB AB Social Adjustment Scale AB AB Current ADHD Symptoms AB Total Comorbidities A A Socioeconomic Status B AC A Full IQ B A AC WRAT Arithmetic AB A A WRAT Reading A = p<0.05 vs. No EFD; B = p<0.05 vs. Psychometric EFD; C = p<0.05 vs. Selfreport EFD

Executive Functioning as a Deficit (EFD) Neuropsychological testing At least two EF measures have scores < 1 standard deviations below the norm Rating scales BRIEF-A (at least 2 area in clinical range >65) CBS-Barkley- 1 SD below Controls Biederman, J., Petty, C.R., Fried, R., et al. (2006). Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder. American Journal of Psychiatry, 163, 1730-1738.

Outcomes of EFDs in ADHD ADHD is understood as both a behavioral and cognitive disorder EFDs are common but not ubiquitous in ADHD 30-50% of individuals with ADHD have EFDs Testing and self-report checklists identify EFDs in different people ADHD can cause significant impairment in areas of academic, work, and social functioning Biederman, J., Petty, C.R., Fried, R., et al. (2006). Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder. American Journal of Psychiatry, 163, 1730-1738.

Research Numerous Different Tests Given between Sites Limited Reliability between Administration Un-normed Tests on Controls (differ between sites)

Cambridge Neuropsychological Test Automated Battery Advantages over standardized clinical tests: Separation of mnemonic and strategic components of working memory Data linking performance deficits to focal brain abnormalities Easier administration methods Less vulnerable to practice effects

It is differentially sensitive to specific brain regions Useful in imaging studies examining the neural underpinnings of EFDs Computerized format makes testing administration highly reliable Allows for more streamlined comparisons across studies examining EFDs in children with ADHD Can be administered by trained psychometricians Can be utilized in places where neuropsychology services are limited

Domain of Executive Functioning CANTAB Tasks Traditional Neuropsychological Test Planning Stockings of Cambridge (SOC) Tower of Hanoi; Tower of London Shifting Intra-Extra Dimensional Set Shift (IED) Spatial Working Memory Spatial Working Memory (SWM) Corsi Blocks Working Memory Rapid Visual Information Processing (RVP) Reaction Time Reaction Time (RTI) CPT (ISI) Wisconsin Card Sort (WCST) Trailmaking Digit Span; Wechsler Arithmetic; Letter-Number Inhibition/Vigilance Affective Go/No-go (AGN) CPT (Commission/Omission) Verbal Memory California Verbal Learning Test (CVLT) Verbal Recognition Memory (VRM)

Children & Adolescents: 6-16 years With ADHD: n=107 Without ADHD: n=45 Both sexes ADHD status determined by structured diagnostic interview: Schedule for Affective Disorders and Schizophrenia for School Aged Children- Epidemiological Version (KSADS-E)

ADHD and Control Subjects did not significantly differ on age or sex ADHD (N=107) Control (N=45) Test Statistic p-value N (%) Male 84 (79) 31 (69) χ 2 (1) =1.59 0.21 Mean ± SD Mean ± SD Age 11.9 ± 3.0 12.2 ± 3.4 t (150) =-0.72 0.47 Socioeconomi c Status 2.0 ± 1.0 2.0 ± 1.0 z=0.35 0.73

Subjects were administered 7 subtests from the CANTAB. 1. Verbal Recognition Memory (VRM) 2. Intra-Extra Dimension Set Shift (IED) 3. Spatial Working Memory (SWM) 4. Stockings of Cambridge (SOC) 5. Reaction Time (RTI) 6. Rapid Visual Information Processing (RVP) 7. Affective Go/No-go (AGN) Each domain was compared to traditional neuropsychological test

ADHD subjects significantly more impaired on all measures of the CANTAB when compared to Controls. *exception: AGN total omissions Effect sizes for individual CANTAB test: medium range Largest effect sizes seen in Spatial Working Memory total and between errors (f=0.33)

Percent EFD with CANTAB Percent of Subjects with EFDs 60% 50% 49% 40% 30% 20% 22% 10% 0% ADHD Control Fried, R. (2010). Deconstructing Attention and Cognition in ADHD: New Understandings for Improved Management [PowerPoint Slides]. Retrieved from Dr. Ronna Fried, Ed.D.

CANTAB Scores: ADHD vs. Controls 1.5 ADHD Controls 1 0.5 0 p<.01 p<.01 p<.01 p<.01 p<.05 p<.01 0.5 1 1.5 SWM Total Errors SWM Between Errors SWM Within Errors SOC Problems Solved in Minimum Moves IED Set Shift Total Errors RVI Information Processing A'

Domain of Executive Functioning CANTAB Tasks (Present Study) Effect Size Planning.41.62 Shifting.36.46 Spatial Working Memory.58.63 Working Memory.63.75 Reaction Time.39.61 Inhibition/Vigilance.54.60 Traditional Neuropsychological Tests (Wilcutt Meta- Analysis) (Wilcutt et al., 2005) Effect Size

Medication Effect on CANTAB Statistically significant improvements in multiple cognitive domains were observed in a sample of adolescents with ADHD over the course of 12 months of robust treatment with extended release methylphenidate

Figure 1. CANTAB z-scores (rising scores indicate improvement) A. Spatial Working Memory (SWM) Total Errors Controls B. Spatial Working Memory (SWM) Within Errors 2 2 z-score 1.5 1 0.5 0-0.5 A A A 0.89 1 0.93 0.67 0.29 0.02 Baseline 6 weeks 4 months 7 months 10 months 1 year z-score 1.5 1 0.5 0-0.5 0.36 0.36 0.5 0.51 0.54 0.49 Baseline 6 weeks 4 months 7 months 10 months 1 year 2 C. Spatial Working Memory (SWM) Between Errors D. Stockings of Cambridge (SOC) Problems Solved in Minimum Moves (Domain: Planning) z-score 1.5 1 0.5 0-0.5 A 0.68 0.26 0.05 A,B A A 1.01 0.88 0.92 Baseline 6 weeks 4 months 7 months 10 months 1 year z-score 2 1.5 1 0.5 0-0.5-0.01 0.4 0.66 0.96 1.04 1.07 Baseline 6 weeks 4 months 7 months 10 months 1 year A z-score 2 1.5 1 0.5 0-0.5 E. Intra-Extra Dimensional Set Shift (IED) Total Errors F. Rapid Visual Information Processing (RVP) A' (Domain: Working Memory) A A A,B 0.89 1 0.93 0.69 0.3 0.03 Baseline 6 weeks 4 months 7 months 10 months 1 year z-score 2 1.5 1 1.36 1.23 0.5 0.68 0-0.5-0.18 A: p<0.05 vs. 6 weeks, B: p<0.05 vs. 4 months, C: p<0.05 vs. 7 months A A A,B,C 2 1.65 Baseline 6 weeks 4 months 7 months 10 months 1 year A