Cognitive Training and ADHD: Can training each day keep impairments at bay?

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Cognitive Training and ADHD Can training each
day keep impairments at bay?

• Rosemary Tannock, PhD
• Erskine Visiting Fellow, University of
  Canterbury(Feb-April, 2015)
• Senior Scientist, Neurosciences Mental Health
  Research Program
• The Hospital for Sick Children
• Professor Emerita (Special Education,
  Psychiatry), University of Toronto
• rosemary.tannock_at_utoronto.ca

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Disclosure potential conflicts of interest
CFPC CoI Templates Slide 1

• 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

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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, 16411-432)
• Application of EEG feedback for self-monitoring
  sustaining attention Neurofeedback (e.g., Hurt
  et al., 2014, Child Adolesc Psychiatric Clin N
  Am, 23465-486)
• 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

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Neuroplasticity

• Scientific dogma until 1970s
• 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
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IS working memory CAPACITY A MALLEABLE
FACTOR?CAN IT BE IMPROVED BY Computerized
TRAINING?

• By improving a persons WM, beneficial effects
  should also be expected in various related
  abilities utilizing WM, including real-world
  behavior (beyond the Laboratory)

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Computerized Cognitive training

• Cogmed abbrev. CWMT
• Jungle Memory
• Cognifit
• BrainTrain Captains Log
• Lumosity
• Nintendo Brain Age

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Features of Cogmed WM Training

• Intensive adaptive training
• Adaptive automatically, continuously adjusted in
  difficulty relative to individuals 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 Training (Cogmed
JM/RM/QM)

• 45 min training/day
• 5 days/week,5 weeks
• Adaptive algorithm
• individually-based
• Reinforcement
• Immediate performance-based feedback
• internal reinforcement activities
• external reinforcement for completing
  pre-specified sessions
• Weekly monitoring calls from licensed provider,
  using uploaded tracking data

Cogmed/Pearson http//www.cogmed.com/rm
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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 beginninga startling finding suggesting that
WM might be mutable like a muscle!
But a very small sample ( n 7 per group)
Double-blind but not randomized

• 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!
  

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Promising findings from first randomized
controlled trial! (Klingberg et al, 2005)
Klingberg et al. (2005) JAACAP
Repeat this letters in the same order they are
given.... 2 8 4 7 2 9
Adaptive training n20 ADHD Non-adaptive
training n24 ADHD
ES .93/.92
ES .73/?
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Moreover, training effects appeared to transfer
to other cognitive functions!
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Parent rating of ADHD symptoms (Conners) no
evidence of change in teacher ratings
Controlled for whether training done at home or
school
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Strong claims for WM training
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Including those by Cogmed
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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 gt 1000 schools
world-wide ( is available in NZ)
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So, does WM training (cogmed) enhance WM
capacity?
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Cogmed WM Training Reviewing the Reviews
Shinaver, Entwistle, Söderqvist. APPLIED
NEUROPSYCHOLOGY CHILD, 3 163172, 2014
(Pearson Assessment)

• Cogmed has indeed demonstrated reliable
  immediate improvements in WM capacity in samples
  of typically developing children
  adults.children with ADHDwith poor WMcochlear
  implantsvery low birth weightadolescents 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.

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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.
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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.
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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
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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
VERBAL WM SMD 0.57 99CI .29 - .82 VISUAL
WM SMD 0.47 95CI .23 - .70 CORTESE ET
AL.,920150 META ANALYSIS
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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/Hyp
  eractivity 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)

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

• 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 age14.3 yrs (1.2yr)
• All medicated receiving intense academic
  remediation

• 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

• Study 1
• High-school LD/ADHD

• Study 2
• University ADHD/LD

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Intervention treatment arms

• 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

• 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)

• Study 1
• High-school LD/ADHD

• Study 2
• University ADHD/LD

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Measures

• 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

• 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 Scale

• Study 1
• High-school ADHD/LD

• Study 2
• University ADHD/LD

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Training Compliance

• Generally good overall
• Attrition by post-test 10 (n6) 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

• Good overall
• Attrition at post-test16 (n8) 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 1
• High-school LD/ADHD

• Study 2
• University ADHD/LD

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Compliance outcomes

• WM training group 70 obtained WM Improvement
  Index gt 17
• (Mean Improvement score 18.85, SD 6.3)
• AOM group 57 mastered gt10 skills
• Mean skills mastered 19.81, SD14.14.

• WM training Group97 obtained WM Improvement
  Index gt17 (M25.72, SD6.54)
• 92 completed the required 25 sessions

• Study 1
• High-school LD/ADHD

Study 2 University ADHD/LD
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Overview of Results

• 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

• 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 1
• High-school LD/ADHD

• Study 2
• University ADHD/LD

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Training effects on Criterion MeasureDS-Backwards
Intent-to-Treat Analysis Ancova post-test,
covarying pretest score
ES Cohens d .55
Study 1 adolescent severe LD/ADHD
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Training effects on WRAT-PM Math
p .08
Standardized Level Equivalent scores (LE)
Study 1 High school severe LD/ADHD
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Study 2 Maintenance of gains in criterion
measures at 2-month follow-up
Effect size ?2 .08 Exp Group 28 greater
improvement than controls
Analysis As Treated Repeated measures Exp(WM)
n23 Wait-List n16
Effect size ?2 .22 Exp Group 47 greater
improvement than controls
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So our next question was
Revised manuscript resubmitted to PlosOne Jan 2015

• Does WM training improve WM when controlling for
  participants motivation, engagement
  expectancy? (using independent intervention
  research teams)

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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.

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Hypothetical patterns of findings
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Outcome measures

• Criterion
• WAISIV Digit Span F/B/S
• CANTAB Spatial Span F/B
• WRAML FW F/B
• Near Transfer
• CANTAB Spatial WM
• Kahnemans Addition Task
• Far Transfer
• Symptoms ASRS
• Function BDEFS, CFQ

• Current symptom validation
• ASRS self- interview, Q other-Q
• Compliance
• sessions completed weeks to complete
• coach calls completed
• Cogmed Training Index
• Attrition

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Results examples
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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?
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Brinley Plots A visual approach to displaying
data at both group individual levecalculation
of RCI is in progress..
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But perhaps our neural measures will provide
further insight into effects of CWMT on WM
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Neural measure of training effects on WM
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ADHD impaired in encoding stage of WMKim et al.,
(2014) Clin Neurophysiol

• ADHD (n30) 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
  parietaloccipital sites.
• .

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Group differences in maintenance stage
(preliminary findings)

• ADHD (n 136, 50 F) CTL (n41, 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

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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.

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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!
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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

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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.
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Acknowledgements

• Collaborating Organizations

• 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)

• 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 Toronto

Research Team

• Funding

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TIME FOR ME TO STOP!
ANY QUESTIONS?