COGNITIVE TRAINING AND ADHD: Can training each day keep

impairments at bay?

Rosemary Tannock, PhDErskine Visiting Fellow, University of Canterbury(Feb-April, 2015)

Senior Scientist, Neurosciences & Mental Health Research ProgramThe Hospital for Sick Children; &

Professor Emerita (Special Education, Psychiatry), University of Toronto

rosemary.tannock@utoronto.ca

Disclosure: potential conflicts of interest

• Faculty: Rosemary Tannock, PhD• Relationships with commercial interests:

• Research Grants: Federal grants (IES-USA; CIHR)• Research Support: Cogmed; Purdue Pharma• Honoraria: Shire; Janssen-Ortho• Consulting Fees: Biomed Central (publisher) Editors Advisory Group• Other:

• Royalties: Springer, as Co-Editor of book (Behavioral Neuroscience of ADHD and its Treatment, 2011)

• Member DSM-5 Workgroup on ADHD, & liaison member to Neurodevelopmental Disorders workgroup (for Learning Disorders)

• Member International Steering Committee for WHO International Classification of Functioning (ICF)-Core Set for ADHD

• Affiliate member WHO ICD-11 Specific Learning Disorders subcommittee

CFPC CoI Templates: Slide 1

Scope of this talk• Cognitive training has wide range of meaning

• Application of self-monitoring & self-reinforcement techniques to enhance functioning (e.g., Abikoff et al., 1988, J Abnorm Child Psychol, 16:411-432)

• Application of EEG feedback for self-monitoring & sustaining attention – Neurofeedback (e.g., Hurt et al., 2014, Child Adolesc Psychiatric Clin N Am, 23:465-486)

• Intensive, adaptive practice of specific cognitive process (e.g., Klingberg, 2010, Trends Cog Sci 14: 317-324)

• This talk focuses on computerized cognitive training designed to target WM: specifically on a software program called “COGMED”

Neuroplasticity

Scientific dogma until 1970’s…

“In the adult [brain] centres, the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated.”

Santiago Ramon v Cajal (1913). Spanish physician, neuroanatomist & Nobel Laureate

By contrast, scientists now recognize that the human brain (even in adulthood) shows remarkable

neuroplasticity

IS WORKING MEMORY CAPACITY A MALLEABLE FACTOR?

CAN IT BE IMPROVED BY COMPUTERIZED TRAINING?

By improving a person’s WM, beneficial effects should also be expected in various

related abilities utilizing WM, including real-world behavior (beyond the Laboratory)

COMPUTERIZED COGNITIVE TRAINING

Cogmed™ [abbrev. CWMT]

Jungle Memory™

Cognifit™

BrainTrain: Captain’s Log™

Lumosity™

Nintendo: Brain Age

6

Features of Cogmed WM Training• Intensive & adaptive training

• Adaptive: automatically, continuously adjusted in difficulty relative to individual’s WM capacity

• Extensive repetition, practice, feedback – designed to enhance the development & efficiency of underlying neural substrates (for WM)

• Underlying assumption: improvements in WM will generalize or transfer to other tasks or activities that rely on the same neural networks or require WM (Klingberg, 2010)

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Computerized Working Memory Computerized Working Memory Training Training (Cogmed JM/RM/QM)

45 min training/day5 days/week,5 weeksAdaptive algorithm

◦ individually-basedReinforcement

◦ Immediate performance-based feedback;

◦ internal reinforcement activities ◦ external reinforcement for completing

pre-specified # sessionsWeekly monitoring calls from licensed provider, using uploaded tracking data Cogmed/Pearson

http://www.cogmed.com/rm

What does the training entail?• EQUIPMENT

• Software (license per person)$

• Computer (per person) linked to internet$

• [Headphones for group administration] $

• COACHING/Supervision$

• Weekly telephone call from a trained & licensed ‘coach’ to give feedback on performance, give advice about training activities, answer questions

• For youth - Daily supervision of training – parent, school-aide, volunteer, (often by members of research study)

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The beginning…a startling finding suggesting that WM might be mutable – like a muscle!

• In 2002, Torkel Klingberg, a Swedish researcher challenged the prevailing notion that WM capacity is fixed - he reported that 5 weeks of playing specific memory-based computer games (every day for about 30-45 mins), not only boosted WM, of children with ADHD but also intellectual ability!

But a very small sample ( n ~ 7 per group) Double-blind but not randomized

Klingberg et al. (2005) JAACAP

Repeat this letters in the same order they are given....

”2 8 4 7 2 9”

Promising findings from first randomized controlled trial!

(Klingberg et al, 2005)Adaptive training: n=20 ‘ADHD’Non-adaptive training: n=24’ ADHD’

ES:.93/.92

ES:.73/?

Moreover, training effects appeared to transfer to other cognitive functions!

Parent rating of ADHD symptoms Parent rating of ADHD symptoms (Conners) (Conners) no evidence of change in teacher ratingsno evidence of change in teacher ratings

Controlled for whether training done at home or school

Strong claims for WM training

Including those by Cogmed

The spread of Cogmed~58 published studies; 90+ ongoing studies

• Healthy young adults

• Older/elderly adults• Adults who have had a stroke• Individuals with brain injury• Children with: WM deficits; ADHD; cochlear implants; cancer treated with radiation; Down syndrome, low IQ, born prematurely…

Cogmed is now operating in > 1000 schools world-wide (& is available in NZ)

So, does WM training (cogmed) enhance WM

capacity?

Cogmed WM Training: Reviewing the Reviews

Shinaver*, Entwistle*, Söderqvist*. APPLIED NEUROPSYCHOLOGY: CHILD, 3: 163–172, 2014 (*Pearson Assessment)

• “Cogmed has indeed demonstrated reliable immediate improvements in WM capacity in samples of typically developing children…& adults….children with ADHD…with poor WM…cochlear implants…very low birth weight…adolescents at extremely low birth weight….pediatric cancer survivors…& brain injured adults”

• “In a little more than a decade, there is evidence that suggests that Cogmed has a significant impact upon visual-spatial and verbal WM, and these effects generalize to improved sustained attention up to 6 months”

• “In conclusion, we find that there is a consensus in showing that WM capacity and attention is improved following CWMT.”

Cogmed working memory training is sold as a tool for improving cognitive abilities, such as attention and reasoning. At present, this program is marketed to schools as a means of improving underperforming students’ scholastic performance, and is also available at clinical practices as a treatment for ADHD. We review research conducted with Cogmed software and highlight several concerns regarding methodology and replicability of findings. We conclude that the claims made by Cogmed are largely unsubstantiated, and recommend that future research place greater emphasis on developing theoretically motivated accounts of working memory training.

Conclusions from recent Meta-Analysis

“Collectively, meta-analytic results indicate that claims regarding the academic, behavioral, and cognitive benefits

associated with extant cognitive training programs are unsupported in ADHD.”

“The methodological limitations of the current evidence base,

however, leave open the possibility that cognitive training techniques designed to improve empirically documented

executive function deficits may benefit children with ADHD”.

Optimal research designs for studies of WM training

• Randomized control design• Active control group – to control for

• Test-retest effects & Placebo effects; • Expectations of trainers/testers/participants• Motivation effects; engagement in training

• Measurement• Objective measures (if subjective - blinded informants)• Latent changes (more than one measure/construct)• Transfer of training effects (far transfer)• Duration of changes (sustained effects)• Mechanisms of change

From: Shipstead, Redick, Engle (2012) Psychol Bull [advance online publication]

Published RCTs of WM training in ADHD

Study Cogmed N

Control N

Design/location

Control Total training (min/weeks)

Beck 2010 27 24 RCT/H Waitlist 750/6 weeks

Green et al 2012 12 14 RCT/H Non-Adaptive

615-1000/5 weeks

Klingberg et al 2005 20 24 RCT/ H -S Non-Adaptive

1000/5 weeks

Van Dongan-Boomsma 2014

27 24 RCT/H Non-Adaptive

375/5 weeks

Chacko et al 2014 44 41 RCT/H Non-Adaptive

750-1125/5 wk

Egeland et al., 2014

38 37 RCT/S Waitlist 750-1125/5-7 w

Gropper et al 2014 39 23 RCT/H Waitlist 750/5 weeks

Gray et al., 2012 36 24 RCT/S Adaptive 750/5 weeks

TOTAL 243 211

24

VERBAL WM: SMD = 0.57 [99%CI .29 - .82]

VISUAL WM: SMD = 0.47 [95%CI .23 - .70]CORTESE ET AL.,920150 META ANALYSIS

4 RCTs from Tannock Lab• Study 1: Does WM training enhance WM & other aspects of

cognitive, academic, behavioral functioning in adolescents with severe Learning Disabilities & comorbid ADHD? (Gray et al., 2012, JCPP)

• Study 2. Does WM training enhance WM & other aspects of cognitive, academic, behavioral functioning in college students with ADHD and/or Learning Disabilities? (Gropper et al., 2014., JAD)

• Study 3. Working Memory Training in Post-Secondary Students with Attention-Deficit/Hyperactivity Disorder: Pilot Study of the Effects of Training Session Length (Mawjee et al., in press., JAD)

• Study 4. Does WM training have specific or non-specific effects on WM in college students with ADHD? (Mawjee et al, under review)

Two randomized controlled trialsGray et al 2012; Gropper et al, 2014

Study 1: Study 1:

High-school LD/ADHDHigh-school LD/ADHD

Treatment-resistant sample of secondary-school students with severe LD with comorbid ADHD,

Attend semi-residential school funded by Ministry of Education (Ontario)

Sample size = 60 Mean age:14.3 yrs (1.2yr)

All medicated & receiving intense academic remediation

Study 2:Study 2:

University ADHD/LDUniversity ADHD/LD

‣ University students with ADHD and/or LD

‣ Registered with student disability services (Most taking reduced course load, poor time management, lower academic grades)

‣ Sample size = 62

‣ Mean age = 27.9 yrs(7.1yr)

‣ None medicated

Intervention: treatment arms

Study 1: Study 1:

High-school LD/ADHDHigh-school LD/ADHD

• Comparison of two active, computerized intervention arms

• Working Memory Training (Cogmed RM)• 20 x 45-min sessions

• Academic Training (Academy of Math)• 20 x 45-min sessions

• During school day

Study 2:Study 2:

University ADHD/LDUniversity ADHD/LD

• Comparison of active vs inactive intervention arm

• Working Memory Training (Cogmed QM)• 25 x 45-min sessions

• Wait-List Control with some phone-calls

• Own schedule (at home/residence)

Measures

Study 1: Study 1:

High-school ADHD/LDHigh-school ADHD/LD

• Criterion• WISC-IV Digit SPAN F/B• CANTAB Spatial Span F

• Near Transfer• CANTAB Spatial WM• D2 Test of Attention

• Far Transfer• Academics

• WRAT-4 Progress Monitoring

• Behavior (Parent/teacher)• SWAN, IOWA• Working Memory Rating

ScaleStudy 2:Study 2:

University ADHD/LDUniversity ADHD/LD

• Criterion• WAIS –IV Digit Span F/B/S• CANTAB Spatial Span F

• Near Transfer• CANTAB Spatial WM• Paced Auditory Serial

Addition• Ruff 2& 7 Selective Attention

• Far Transfer• Academics

• Nelson Denny Reading Test• WJ-III Achievement

• Behavior (self-rating) ASRS, Cognitive Failures

Training Compliance

Study 1: Study 1:

High-school LD/ADHDHigh-school LD/ADHD

Good overall Attrition at post-test:16%

(n=8) of 60 participants, equally distributed across treatment arms 4 unable to cope with academic

load & this study 3 moved & left school mid-

program 1 due to computer problems◦ No difference between completers

& non-completers

ANALYSIS: Intent-to-Treat No Follow-up

Study 2:Study 2:

University ADHD/LDUniversity ADHD/LD

• Generally good overall• Attrition by post-test: 10%

(n=6) of 62 participants, equally distributed across treatment arms

• ANALYSIS: Intent-to-Treat

• But, attrition by follow-up: 30% from WM group; 30% from wait-list group

• primarily conflict with exam schedules

• Thus follow-up analysis based on As-Treated

Compliance outcomes• WM training group: 70% obtained WM Improvement Index > 17 • (Mean Improvement

score = 18.85, SD = 6.3)

• AOM group: 57% mastered >10 skills• Mean # skills mastered =

19.81, SD=14.14.

• WM training Group

97% obtained WM Improvement Index >17 (M=25.72, SD=6.54)

• 92% completed the required 25 sessions

Study 1: Study 1: •High-school LD/ADHDHigh-school LD/ADHD

Study 2:Study 2:

University ADHD/LDUniversity ADHD/LD

Overview of Results

Study 1: Study 1:

High-school LD/ADHDHigh-school LD/ADHD

• Criterion• WISC-IV Digit SPAN F/B• CANTAB Spatial Span F

• Near Transfer• CANTAB Spatial WM• Working Memory Rating Scale• D2 Test of Attention

• Far Transfer• Academics

• WRAT-4 Progress Monitoring• Math – trend for Math Training

• Behavior (Parent/teacher)• SWAN, IOWA

Study 2:Study 2:

University ADHD/LDUniversity ADHD/LD

• Criterion• WAIS –IV Digit Span F/B/S• CANTAB Spatial Span F

• Near Transfer• CANTAB Spatial WM• Paced Auditory Serial Addition• Ruff 2& 7 Selective Attention

• Far Transfer• Academics

• Nelson Denny Reading Test• WJ-III Achievement

• Behavior (self-rating) ASRS, Cognitive Failures

Training effects on Criterion MeasureDS-Backwards

Intent-to-Treat Analysis: Ancova post-test, covarying pretest score

ES: Cohen’s d = .55

Training effects on WRAT-PM Math

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p = .08

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ores

(LE

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Study 2: Maintenance of gains in criterion measures at 2-month follow-up

Analysis: As TreatedRepeated measures:Exp(WM): n=23Wait-List : n=16

Effect size ŋ2 = .08Exp Group 28% greater improvement than controls

Effect size ŋ2 = .22Exp Group 47% greater improvement than controls

So our next question was…

Does WM training improve WM when controlling for participant’s motivation,

engagement & expectancy? (using independent intervention &

research teams)

Revised manuscript resubmitted to PlosOne Jan 2015

Methods: an RCT• Participants: 97 post-secondary students with ADHD• Treatment arms:

• standard-length adaptive Cogmed WM training: 45-min/session 5 days /week, 5 weeks,

• shortened-length adaptive version: 15 min/session, 5 days/week, 5 weeks

• waitlist control group provided with weekly telephone advice about ADHD, WM, Disability Services etc

• All three groups received weekly telephone calls from trained, CMWT coaches independent from research team

• Procedures.• Measures taken before, 3 weeks after training period; those in the two

CWMT groups were also assessed 3 months post-training.

Hypothetical patterns of findings

Outcome measures

• Criterion• WAIS–IV Digit Span F/B/S• CANTAB Spatial Span F/B• WRAML FW F/B

• Near Transfer• CANTAB Spatial WM• Kahneman’s Addition Task

• Far Transfer• Symptoms: ASRS• Function: BDEFS, CFQ

• Current symptom validationASRS: self- interview, Q

other-Q

• Compliance# sessions completed &

# weeks to complete# coach calls completedCogmed Training IndexAttrition

Results: examples

An unexpected pattern of findings (ceiling effects?

Non-specific training effects?…)

These findings are based on analysis

at the group level..what about at the individual level?

Brinley Plots: A visual approach to displaying data at both group & individual leve

calculation of RCI is in progress..

But perhaps our neural measures will provide further insight into effects of CWMT on WM

Neural measure of training effects on WM

ADHD impaired in encoding stage of WM

Kim et al., (2014) Clin Neurophysiol• ADHD (n=30) lower scores on behavioural working memory tasks

compared to CTL (n-25), suggesting impaired behavioural WM performance

• Smaller P3 amplitude in ADHD group compared to CTL group: both load conditions, at parietal–occipital sites.

.

Group differences in maintenance stage (preliminary findings)

• ADHD (n= 136, ~50% F); CTL (n=41, ~50% F)• ADHD poorer WM on standardized tests of WM

• ADHD vs CTL• Behavioral results: delayed match-to-sample task

• ADHD tended to perform more poorly (more errors) than CTL

• Neural results: • ADHD lower alpha power, particularly for high load,

compared to CTL

Preliminary data: training effects on WM during maintenance

phase• Neural pathways associated with working memory do seem to

show treatment changes for the high intensity standard-length training. These effects were only present during the high load condition at parietal sites.

• No evidence for behavioral task differences were found.

PrePost

Waitlist Shortened-length Standard-length

Alpha power

Interpretation & Discussion of results• “Half-empty”

• No robust evidence of transfer of treatment gains to untrained WM activities or daily functioning

• “Half-full”

• Robust evidence that computerized cognitive training enhances WM – as measured on standardized neuropsychological tests-& perhaps neurally

Or does the program simply result in learning how to do the tests better!

Caveat• Not yet an evidence-based intervention for ADHD - But premature to discard cognitive training• Most of the published research studies have methodological weaknesses (including ours)

• Need for better studies & more sensitive measures (e.g., measure concurrent behavior & WM)

• Advances in the training paradigm may yield better outcomes

Spencer-Smith M, Klingberg T (2015)Benefits of a Working Memory Training Program for Inattention in Daily Life: A Systematic Review and Meta-Analysis. PLoS ONE 10(3): e0119522.

AcknowledgementsCollaborating OrganizationsCollaborating Organizations

Cogmed America Inc ◦ provision of research licenses

JVS-Toronto ◦ licensed Cogmed providers

Ontario Provincial Demonstration Schools

University Disability Services◦ York University, University of

Toronto

The Hospital for Sick Children Ontario Institute for Studies in

Education/University of TorontoResearch TeamResearch Team

Drs. H Gottlieb & R Kronitz (JVS) Desiree Smith, Denise

Murnaghan (OPDS) Peter Chaban, Min-Na

Hockenberry, Marisa Catapang (HSC)

Dr Marc Lewis (OISE) Graduate Students (OISE)

Rachel Gropper, Steven Woltering, Zhongxu Liu, Sarah Gray, Christine Popovich

Dr Torkel Klingberg (consultant)

• Canada Research Chairs Program (RT)

• Provincial Centre of Excellence for Child & Youth Mental Health at CHEO (RT)

• Canadian Institutes of Health Research Banting & Best Award (RG)

FundingFunding

TIME FOR ME TO STOP!

ANY QUESTIONS?