Overview Computerized Training of Working Memory in Children with ADHD

Transcription

1 Overview Computerized Training of Working Memory in Children with ADHD Torkel Klingberg, MD PhD Stockholm Brain Ititute Karolika Ititute Stockholm, Sweden What is working memory Neural basis Psychological studies Links to ADHD Training of working memory Visuo-spatial working memory Visuo-spatial working memory The ability to retain information on-line for a short period of time (seconds) Associated with sustained prefrontal and parietal brain activity Visuo-spatial working memory Development of working memory WM capacity Age

2 Anatomy of WM Development of working memory Klingberg et al. () Klingberg et al. Klingberg et al., Olesen et al., 3 Olesen et al., 6 Klingberg 6 WM and dopamine Top-down attention and WM Enhanced by dopaminergic agonists Impaired by dopamine antagonists Cortical D-receptors What is WM used for? What is WM used for? Capacity correlated to: Mathematics Problem solving Language =? Reading compreheion Control of attention remember what to focus on Remember an itruction Planning and organizing activities Resisting distraction

3 WM and distractability (I) WM and distractability (II) Ability to attend to only part of a noisy environment. Fails in approx 33% individuals Those with low working memory capacity (Conway, Cowan, Bunting, ) (Kane et al., Psychol Sci, 8(7): 64-6, 7) Impairments in clinical populatio Concurrents with disorders of Prefrontal or parietal cortex Dopamine system Populatio Traumatic head injury Stroke ADHD Schizophrenia MS Experienced as Less focused More distractible Problems in planning Forgetting ADHD Proposed endophenotypes Rewardcircle Temporal processing Inhibitory function Working memory Barkley, R (997) Rapport, MD () Castellanos, FX and Tannock, R () WM and ADHD WM and ADHD Span-board like tasks Dowson -4 CANTAB WM.5 WAIS span-board - Kempton Barnett studies on WM in ADHD Review by Martinussen et al. 5 Westerberg Mean =.6 SD 3

4 ADHD, WM and medication ADHD genetics Stimulant medication (methylphenidate) improves WM Kempton 999 Barnett Bedard 4 Mehta 4 Heritability.76 DRD4 DRD5 DAT DBH 5-HTT HTRB SNAP-5 Faraone et al. 5 DLPFC Inferior parietal Basal ganglia Orbitofrontal Anterior cingulate Cerebellum ADHD anatomy Working memory WM and ADHD ADHD Dopamine Klingberg et al. () Can WM be improved by training? Computerized Training of Working Memory 4 min training / day 5 days/week, 5 weeks Adaptive algorithm Internet based feedback If so, does improved WM: - effect others areas of cognition? - effect symptoms? Later developed with the company Cogmed 4

5 Computerized Training of Working Memory WM capacity index Training curve N = Day of training Attention-deficit/hyperactivity disorder Klingberg, T, Forssberg, H, Westerberg, H () Training of Working Memory in Children with ADHD J Clinical and Experimental Neuropsychology 4(6): Klingberg, T, Fernell, E, Olesen, P, Johon, M, Gustafsson, P, Dahlström, K, Gillberg, CG, Forssberg, H, Westerberg, H. (5) Computerized Training of Working Memory in Children with ADHD a Randomized, Controlled Trial. J Am Acad Child Adolesc Psychiatry 44():77-86 Stroke Westerberg H, Jacobaeus H, Hirvikoski T, Clevberger P, Osteson J, Bartfai A, Forssberg H, Klingberg T (7), Computerized working memory training - a method of cognitive rehabilitation after stroke. Brain Injury. Brain imaging in young adults Olesen, Westerberg, Klingberg (4) Increased prefrontal and parietal activity after training of working memory. Nature Neuroscience. 6: Westerberg H, Klingberg, T (7) Changes in cortical activity after training of working memory a single subject analysis. Physiology and Behavior. Effect of medication Klingberg, T, Andersson, M, Ljungbäck, H. Forssberg, H (submitted) The Effect of Stimulant Medication on Cognitive Training Shool trials Dahlin, Myrberg, Klingberg (submitted) Training of working memory in children with special education needs. Pre-schoolers Thorell, Lindqvist, Bergman, Klingberg (in press) Training and trafer effects of executive function in preschoolers Subjects 53 children (9 girls, 44 boys) 7- years of age (mean 9.9 years) 5 ADHD predominantly inattentive 38 ADHD combined type Without medication Klingberg et al. (5) JAACAP Treatment Verbal and non-verbal working memory trials Adaptation of difficulty level Control Verbal and non-verbal working memory trials Easy trials Intervention Klingberg et al. (5) JAACAP 5

6 time Span-board Span-board Raven Raven items 5,5 5 4,5 4 3,5 3 A comparison treatment T T T3 Klingberg et al. (5) JAACAP items D comparison treatment T T T3 Klingberg et al. (5) JAACAP Headmovements Head movements ADHD symptoms (DSM-IV) 3 Parent +Teacher Inattention Parent +Teacher Hyp/Imp movements E comparison treatment T T T3 Klingberg et al. (5) JAACAP Change (SD),9,8,7,6,5,4,3,, post-treat follow -up control treatment Effect size (Cohen s delta) inattention =.7 Change (SD),9,8,7,6,5,4,3,, post-treat follow-up control treatment Klingberg et al. (5) JAACAP Working memory baseline Effect of working memory training on brain activity Olesen, Westerberg, Klingberg (4) Nature Neuroscience 6

7 Effect of working memory training on brain activity single subj. 9 Long-term effects 85% effect left 4% 8 index months break 5 4 basic training start basic training max booster training start booster training max Westerberg, Klingberg (7) Physiol. Behav. Long-term effects Change in training effect How is the training effect now compared to directly after training: has is decreased, is it unchanged or has it increased Long-term effects 6 month follow-up using BRIEF, rated by psychologist N = 7 5-month follow-up (5 families) -year follow-up (38 families) BRIEF MCI BRIEF WMI Change in training effect after 5 months Change in training effect after year % % 4% 4% decreased unchanged increased % % 36% 43% decreased unchanged increased t-score significant impairment t-score significant impairment 8% unchanged or increased 79% unchanged or increased 5 pre 4 weeks 6 months 5 pre 6 month Bozyliki, S (7) CHADD WM training and school performance Inclusion: Children with special education needs Age: 9-35% with ADHD diagnosis Treatment: N = 4 Working memory training in school Control: N = 5 Ordinary special education activities Improvements in: Non-trained WM task Raven s progressive matrices 7

8 (PIRLS) Reading compreheion 4 WM training and school performance Math (BNST) Mathematical problem solving. WM training and medication (Klingberg et al. submitted) Parent rated symptom decrease score (adjusted) ctrl treat pre T post T follow-up T3 pre T post T follow-up T3 score (adjusted) ctrl treat effect size att hyp att hyp att hyp att hyp unmedicated (N = 7) medicated (N = 66) Klingberg 5 control group. WM training and medication (Klingberg et al. submitted) Parent rated symptom decrease effect size years 7-6 years 6 years and older att hyp att hyp att hyp att hyp unmedicated (N = 7) medicated (N = 66) Klingberg 5 control group WM and inhibitory training in preschool children 48 typically developing children Age 4-5 Four groups: - WM training - Inhibitory training - Commercial computer game - Passive control 5 min training for 5 days Thorell et al. (in press) 8

9 Inhibitory training Inhibition training WM training 9 4,4 8,5 4, Flanker Stop-task Go/no-go Level 8 7,5 7 Level 4 3,8 Working memory training 6, ,6 3, Training occasion Training occasion VS WM VS WM VS WM Thorell et al. (in press) Improvement vs control on non-trained task WM Inhibition Span-board Word span Stroop (errors) Sustained att. Go/no-go (omissio) Block-design Go/no-go (commisio) Auditory CPT (omissio) WM training ** ** * * Inh training Thorell et al. (in press) Cogmed WM training programs 3-7 years 7-6 years 6 years and older WM training after stroke WM training after stroke Stroke -36 months prior to the study Documentation with PET, MR or CT Age 3-7 Daily access to PC Self-reported attention deficits IQ > 7 No depression Age IQ Male/Female Education First ever stroke Time since stroke Stroke description Type Hemisphere Lobe Severity (-3) Control 53.6 (8) (3) 4/5. (.8) n = 8.8 (6.) bleedings, 7 infarctio 3 left, 4 right, medial, bilateral frontal, 3 parietal, 5 sub cortical.9 (.8) Treatment 55. (8) 3 () 8/.4 (.7) n = (6.) 6 bleedings, 3 infarc. 4 left, 4 right medial 4 frontal, temporal 5 sub cortical, (.6) All 54 (7.7) ().3 (.7). (6) (.7) Westerberg et al. (7) Westerberg et al. (7) 9

10 diff % Generalization to non-trained tasks PASAT P=.3 train T T Ctrl pat No effect on long term memory diff no of trials to reach % correct,5,5 -,5 Word list recall T T n.s. n.s. train Control Ctrl pat Westerberg et al. (7) Westerberg et al. (7) Questio on daily cognitive functioning. Do you read something and find you haven t been thinking about it and must read it again?. Do you find you forget why you went from one part of the house to the other? CFQ P =. ES =.75 RCT of training in old and young healthy adults Young= -3 years; n=5 Old = 6-7 years; n=5 Significant between-group improvements in - non-trained WM tasks - WM-related cognitive tasks (PASAT) - daily behaviour (CFQ) 59 PASAT OLD TRAINING OLD COMP YOUNG TRAINING YOUNG COMP 45 Cognitive failure questionnaire (CFQ) OLD TRAINING OLD COMP YOUNG TRAINING YOUNG COMP diff raw score -5 - Control train RAWSCORE RAWSCORE SYM PTOM T T Westerberg et al. in preparation Ongoing scientific studies: Gibson et al. Notre Dame Gibson et al. Notre Dame ADHD Homes, Gathercole et al. York Univ. UK ADHD, low-wm Mezzacappa et al. Harvard ADHD in low SES areas Hardy et al., Duke children post-radiation Castellanos, Lucas et al. NYMU ADHD Brubakk et al. Trondheim premature Clinical use: > children in Sweden 8 clinics in the US and Canada, through Cogmed Medical systems > clinics in Europe and Japan (through healthcare systems in Holland) Standardized Change,5,5,5 Klingberg et al. (5) Control Klingberg et al. (5) Treatment Replication Treatment Digit Span Span Board Rave Gibson et al. (CHADD 6)

11 Gibson et al. Notre Dame Standardized Change,5,5,5 Parent Inattentive Parent Hyperactive Klingberg et al. (5) Control Klingberg et al. (5) Treatment Replication Treatment Teacher Inattentive Teacher Hyperactive Gibson et al. (CHADD 6) Summer camp study (NYMU) Lucas, C, Abikoff, H, Petkova, E, Gan, W, Solomon, S, Bruett,L, Eldridge, B 46 children with ADHD 7- years Group : VS-WM training (Cogmed) Group : verbal WM training Significant differences for: VS-WM Behavioral effects ( points earned ) ES=.5 (no difference for verbal WM tasks) APA (8) Jaeggi et al. 7 Conclusio Working memory impairment is a key deficit in ADHD Working memory can be directly improved by specifically targeted training Reduces symptoms of inattention, and improves related cognitive abilities Training effect involves plasticity of parietal and frontal regio Thanks! Karolika Ititute Pernille Olesen Helena Westerberg Helena Ljungbäck Ha Forssberg Elisabeth Fernell Per Gustafsson Sissela Bergman COGMED Jonas Beckeman David Sjölander Maria Andersson Susanna Bitter Program and technology Cogmed Systems info@cogmed.com torkel.klingberg@ki.se