Computerized Training of Working Memory in Children with ADHD ...

Anatomy of WMDevelopment of working memoryKlingberg et al. (2002)Klingberg et al. 2002Klingberg et al., 2002Olesen et al., 2003Olesen et al., 2006Klingberg 2006WM and dopamineTop-down attention and WM• Enhanced by dopaminergic agonists• Impaired by dopamine antagonists• Cortical D1-receptorsWhat is WM used for?What is WM used for?Capacity correlated to:MathematicsProblem solvingLanguage73 – 7 + 2 = ?Reading comprehension• Control of attention– ”remember what to focus on”• Remember an instruction• Planning and organizing activities• Resisting distraction2

WM and distractability (I)WM and distractability (II)Ability to attend to only partof a noisy environment.Fails in approx 33% individuals…Those with low working memory capacity(Conway, Cowan, Bunting, 2001)(Kane et al., Psychol Sci, 18(7): 614-621, 2007)Impairments in clinicalpopulations• Concurrents with disorders of– Prefrontal or parietal cortex– Dopamine system• Populations– Traumatic head injury–Stroke– ADHD– Schizophrenia–MSExperienced as•Less focused•More distractible•Problems in planning•”Forgetting”ADHD• Proposed endophenotypes–Rewardcircle– Temporal processing– Inhibitory function– Working memory– Barkley, R (1997)– Rapport, MD (2000)– Castellanos, FX and Tannock, R (2002)WM and ADHDWM and ADHDSpan-board like tasksDowson -04CANTAB WM1.15WAIS span-board-Kempton -991.331.22Barnett -011.451.0646 studies on WM in ADHDReview by Martinussen et al. 2005Westerberg -04-1.34Mean = 1.26 SD3

ADHD, WM and medicationADHD genetics• Stimulant medication (methylphenidate)improves WM– Kempton 1999– Barnett 2001– Bedard 2004– Mehta 2004Heritability 0.76DRD4DRD5DATDBH5-HTTHTR1BSNAP-25Faraone et al. 2005•DLPFC• Inferior parietal• Basal ganglia• Orbitofrontal• Anterior cingulate• CerebellumADHD anatomyWorking memoryWM and ADHDADHDDopamineKlingberg et al. (2002)Can WM be improved by training?Computerized Training ofWorking Memory• 40 min training / day• 5 days/week, 5 weeks• Adaptive algorithm• Internet based feedbackIf so, does improved WM:- effect others areas of cognition?- effect symptoms?Later developed with thecompany Cogmed4

Effect of working memory trainingon brain activity – single subj.10090Long-term effects85% effect left104%80index70605 months break5040basic trainingstartbasic trainingmaxboostertraining startboostertraining maxWesterberg, Klingberg (2007) Physiol. Behav.Long-term effectsChange 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 effects6 month follow-up using BRIEF, rated by psychologistN = 175-month follow-up(50 families)1-year follow-up(38 families)BRIEF MCIBRIEF WMIChange in training effect after 5 monthsChange in training effect after 1 year7575%45403530252015105018%42%40%decreased unchanged increased%5040302010021%36%43%decreased unchanged increasedt-score70656055significantimpairmentt-score70656055significantimpairment82% unchanged or increased 79% unchanged or increased50pre 4 weeks 6 months50pre6 monthBozylinski, S (2007) CHADDWM training and schoolperformance• Inclusion: Children with special education needs• Age: 9-12• 35% with ADHD diagnosis• Treatment:–N = 42– Working memory training in school• Control:–N = 15– Ordinary special education activities• Improvements in:– Non-trained WM task– Raven’s progressive matrices7

(PIRLS)Reading comprehension14WM training and schoolperformanceMath (BNST)Mathematical problem solving201.21WM training and medication(Klingberg et al. submitted)Parent rated symptom decreasescore (adjusted)121086420ctrltreat1110pre T1 post T2 follow-up T3pre T1 post T2 follow-up T3score (adjusted)1918171615141312ctrltreateffect size0.80.60.40.20att hyp att hyp att hyp att hypunmedicated(N = 70)medicated(N = 66)Klingberg 2005control group1.2WM training and medication(Klingberg et al. submitted)Parent rated symptom decrease1effect size0.80.60.40.23-7 years 7-16 years 16 years and older0att hyp att hyp att hyp att hypunmedicated(N = 70)medicated(N = 66)Klingberg 2005control groupWM and inhibitory training inpreschool children• 48 typically developing children• Age 4-5• Four groups:- WM training- Inhibitory training- Commercial computer game- Passive control• 15 min training for 25 daysThorell et al. (in press)8

Inhibitory trainingInhibition trainingWM training94,48,54,2Flanker Stop-task Go/no-goLevel87,57Level43,8Working memory training6,561 3 5 7 9 11 13 153,63,41 2 3 4 5 6 7 8 9 10 11 12 13Training occasionTraining occasionVS WM VS WM VS WMThorell et al. (in press)Improvement vs control on non-trained taskWMInhibitionSpan-boardWord spanStroop(errors)Sustained att.Go/no-go(omissions)Block-designGo/no-go(commisions)Auditory CPT(omissions)WM training****nsns**nsInh trainingnsnsnsnsnsnsnsThorell et al. (in press)Cogmed WM training programs3-7 years 7-16 years 16 years and olderWM training after strokeWM training after stroke• Stroke 12-36 months prior to the study• Documentation with PET, MR or CT• Age 30-70• Daily access to PC• Self-reported attention deficits• IQ > 70• No depressionAgeIQMale/FemaleEducationFirst ever strokeTime since strokeStroke descriptionTypeHemisphereLobeSeverity (1-3)Control53.6 (8)101 (13)4/512.1 (1.8)n = 820.8 (6.2)2 bleedings, 7 infarctions3 left, 4 right,1 medial, 1 bilateral1 frontal, 3 parietal,5 sub cortical1.9 (0.8)Treatment55.0 (8)103 (11)8/112.4 (1.7)n = 819.3 (6.2)6 bleedings, 3 infarc.4 left, 4 right1 medial4 frontal, 1temporal5 sub cortical2,1 (0.6)All54 (7.7)102 (12)12.3 (1.7)20.1 (6)2 (0.7)Westerberg et al. (2007)Westerberg et al. (2007)9

diff %1383-2Generalization to non-trained tasksPASATP=0.03trainT1T2Ctrl patNo effect on long term memorydiff no of trials to reach100% correct21,510,50-0,5Word list recallT1T2n.s.n.s.trainControlCtrl patWesterberg et al. (2007)Westerberg et al. (2007)Questions on daily cognitive functioning1. Do you read something and find you haven´t been thinking about it and must read itagain?2. Do you find you forget why you went from one part of the house to the other?..25.5CFQP = 0.002ES = 0.75RCT of training in old and younghealthy adultsYoung= 20-30 years; n=50Old = 60-70 years; n=50Significant between-group improvements in- non-trained WM tasks- WM-related cognitive tasks (PASAT)- daily behaviour (CFQ)59PASATOLD TRAININGOLD COMPYOUNG TRAININGYOUNG COMP45Cognitive failure questionnaire (CFQ)OLD TRAININGOLD COMPYOUNG TRAININGYOUNG COMPdiff raw score0-5-10ControltrainRAWSCORE575553514947RAWSCORE SYM PTOM40353025T1T2451 2 3201 2 3Westerberg et al. in preparationOngoing 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 prematureClinical use:> 2000 children in Sweden‣80 clinics in the US and Canada, through Cogmed Medical systems‣www.cogmed.com> 10 clinics in Europe and Japan (through healthcare systems in Holland)Standardized Change2,521,510,50Klingberg et al. (2005) ControlKlingberg et al. (2005) TreatmentReplication TreatmentDigit Span Span Board RavensGibson et al. (CHADD 2006)10

Gibson et al. Notre DameStandardized Change2,521,510,50ParentInattentiveParentHyperactiveKlingberg et al. (2005) ControlKlingberg et al. (2005) TreatmentReplication TreatmentTeacherInattentiveTeacherHyperactiveGibson et al. (CHADD 2006)Summer camp study (NYMU)Lucas, C, Abikoff, H, Petkova, E, Gan, W, Solomon, S,Bruett,L, Eldridge, B• 46 children with ADHD• 7-12 years• Group 1: VS-WM training (Cogmed)• Group 2: verbal WM trainingSignificant differences for:• VS-WM• Behavioral effects (”points earned”) ES=0.5(no difference for verbal WM tasks)APA (2008)Jaeggi et al. 2007Conclusions• Working memory impairment is a keydeficit in ADHD• Working memory can be directly improvedby specifically targeted training• Reduces symptoms of inattention, andimproves related cognitive abilities• Training effect involves plasticity ofparietal and frontal regionsThanks!Karolinska InstitutePernille OlesenHelena WesterbergHelena LjungbäckHans ForssbergElisabeth FernellPer GustafssonSissela BergmanCOGMEDJonas BeckemanDavid SjölanderMaria AnderssonSusanna BitterProgram and technologyCogmed Systemswww.cogmed.cominfo@cogmed.comtorkel.klingberg@ki.sewww.klingberglab.se11