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Transcript of Working Memory & ADHD Prof Maurice Place Prof Maurice Place [email protected].
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Disclosure:Disclosure:
Currently member of the speakers panel of Currently member of the speakers panel of
AstraZenecaAstraZeneca
Eli LillyEli Lilly
Janssen CilagJanssen Cilag
ShireShire
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The executive function
comprises those mental functions involved in
formulating goals, planning how to achieve them,
carrying out the plans,
and revising those plans in the event of failure
(Lezak, 1982)
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The executive function
comprises those mental functions involved in
formulating goals, planning how to achieve them,
carrying out the plans,
and revising those plans in the event of failure
Executive functioning becomes engaged for the more high level tasks
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Working Memory
a dynamic, short-term storage
of information to be actively used or manipulated
and is a localised function (Alloway et al., 2006)
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How Memory WorksHow Memory Works
Sensory inputs are held through transient functional changes in the strength of pre-existing synaptic connections
The basal ganglia and pre-frontal cortex analyze sensory inputs and decide if they're worth remembering
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How Memory WorksHow Memory Works
Sensory inputs are held through transient functional changes in the strength of pre-existing synaptic connections
The basal ganglia and pre-frontal cortex analyze sensory inputs and decide if they're worth remembering
If SO - create stable and permanent changes in neural connections throughout the brain by the synthesis of new protein and the growth of new connections.
(Malenka &Nicoll 1999; Kandel 2000; McNab & Klingberg 2007)
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How Memory WorksHow Memory Works
Sensory inputs are held through transient functional changes in the strength of pre-existing synaptic connections
The basal ganglia and pre-frontal cortex analyze sensory inputs and decide if they're worth remembering
If SO create stable and permanent changes in neural connections throughout the brain by the synthesis of new protein and the growth of new connections.
Especially during sleep (Diekelman & Born 2010)
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Short-term memoryShort-term memory is the term for short-term storage of information with no manipulation or organizational element
Working memoryWorking memory is the structures and processes used for temporarily storing and manipulating informationmanipulating information.
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Professionals use working memory for…
◦ Getting to work on time◦ Meeting deadlines at work◦ Multi-tasking and prioritizing◦ Working effectively in pressure situations◦ Remembering important names and phone
numbers◦ Interaction with co-workers◦ Writing emails, memos, or summaries
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(Baddeley 2000)
Rehearsal
Storage
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Anatomical and imaging studies indicate Working Memory use frontal-parietalcircuitry (Paulesu et al., 1993; Smith & Jonides 1998)
The processes are significantly dependent upon dopamine (Goldman-Rakic 1998).
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Children who have been treated for PKU tend to have a deficit in prefrontal dopamine (Diamond 2007)
These children have Working Memory problems even when the primary symptoms of the disorder are successfully treated (Topakas et al., 2010; Bik-Multanowski et al., 2011)
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Children who have been treated for PKU tend to have a deficit in prefrontal dopamine (Diamond 2007)
These children have Working Memory problems even when the primary symptoms of the disorder are successfully treated (Topakas et al., 2010; Bik-Multanowski et al., 2011)
Similarly patients with Fragile X show specific deficits in Working Memory (Hooper et al., 2008;
Cornish et al., 2009;
Baker et al., 2011)
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Working Memory deficiency plays a central role in schizophrenia (Lewis et al., 2005; Lewis & Gonzalez-Burgos, 2006).
Memory impairment is one of the earliest and most consistent manifestations of the disease
Working Memory impairment is stable over timeand is independent of psychotic symptoms (Zhang & Luck 2008; Gold et al., 2010)
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Working Memory deficiency plays a central role in schizophrenia (Lewis et al., 2005; Lewis & Gonzalez-Burgos, 2006).
Memory impairment is one of the earliest and most consistent manifestations of the disease
Working Memory impairment is stable over timeand is independent of psychotic symptoms (Zhang & Luck 2008; Gold et al., 2010)
It probably uses GABA pathways (Timofeeva & Levin 2011)
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Working Memory performance is heritable (Ando et al., 2001; Chen et al., 2009)
And although no genetic correlation between gray matter density and Working Memory performance,
inheritance of white matter structure is likely to be one of the mechanisms of genetic transmission (Karlsgodt et al., 2010)
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Indicators that a working memory needs improving
Frequently late to work
Underestimates time required to complete a task
Problems breaking a project down into manageable
steps or dealing with more than one task at a time
Can’t concentrate under pressure; prone to
panicking
Can’t remember clients’ names or numbers after
meeting them or hanging up the phone
Difficulty creating neat and coherent emails,
memos, or summaries
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assessed using simple cognitive tasks
4 aspects of memory
verbal and visuo-spatial storage (simple span)
verbal and visuo-spatial processing and storage (complex span)
Working Memory
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verbal short term memory
– ability to hold verbal information in memory for a short period
…eg new telephone number
…problems mean slow to acquire new vocabulary
verbal working memory
– to hold and manipulate verbal information
…links to academic ability including literacy and numeracy
visuo-spatial short term memory
– holding visuo-spatial information
….problems with mathematics, and word problems.
visuo-spatial working memory
– to hold and manipulate visuo-spatial information
…links to academic ability including literacy and numeracy
and is predictor of poor scholastic attainment.
Working Memory
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assessed using simple cognitive tasks:
WMI of the WAIS or WISC
Automated Working Memory Assessment
(Alloway, 2008)
Working Memory
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839251 839251
DIGIT RECALL
Verbal STM/Verbal simple span tasks
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MAZES MEMORY
Visuo-spatial STM/Visuo-spatial simple span tasks
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MAZES MEMORY
Visuo-spatial STM/Visuo-spatial simple span tasks
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MAZES MEMORY
Visuo-spatial STM/Visuo-spatial simple span tasks
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chairs lay eggs
false
false
bananas have teeth
LISTENING RECALL TASK
Verbal STM/Verbal Complex span tasks
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chairs lay eggs
false
false
bananas have teeth
LISTENING RECALL TASK
Verbal STM/Verbal Complex span tasks
eggs, teeth
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Visuo-spatial WM/Complex visuo-spatial tasks
SPATIAL SPAN TASK
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Visuo-spatial WM/Complex visuo-spatial tasks
SPATIAL SPAN TASK
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Visuo-spatial WM/Complex visuo-spatial tasks
SPATIAL SPAN TASK
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Visuo-spatial WM/Complex visuo-spatial tasks
SPATIAL SPAN TASK
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Visuo-spatial WM/Complex visuo-spatial tasks
SPATIAL SPAN TASK
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Associations with Specific Disorders
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Specific Working Memory problems evident in various disorders:
PKU Schizophrenia
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Specific Working Memory problems evident in various disorders:
PKU Schizophrenia Depression: deficits in working memory for both visual and verbal material even in young adulthood (Castaneda et al., 2008)
Deficits which appear to persist even in the remitted state (Hasselbalch et al., 2010)
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Specific Working Memory problems evident in various disorders:
PKU Schizophrenia Depression PTSD: (Yehuda et al., 1995;Vasterling et al., 2002;
Liberzon & Sripada, 2008).
with structural imaging correlating with predicted deficits (Liberzon & Sripada, 2008;
Woodward et al., 2009).
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Specific Working Memory problems evident in various disorders:
PKU Schizophrenia Depression ODD: substantial deficits in information storage and verbal and spatial domains of Working Memory.
- Verbal WM less damaged in ADHD (Rhodes et al 2012)
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In childhood abuse:
emotional forms of abuse/neglect show visual memory and emotional processing deficits.
sexual abuse most associated with spatial working memory deficits, Not seen in other types of abuse. Not seen in other types of abuse.
physical forms of abuse/neglect most strongly linked to processing speed and emotional processing deficits.
(Gould et al., 2012)
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Working Memory Capacity & Learning
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Important for successful learning
in individual classroom activities
(Gathercole & Alloway, 2008)
Working Memory Capacity & Learning
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Associated with reading and mathematics ability
(Gathercole & Pickering, 2000; Geary et al., 2004)
Working Memory Capacity & Learning
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One specific function important in readingcomprehension is processing speed. (Willcutt et al. ,2001; Laasonen et al., 2009)
Commonly associated with ADHD
with a correlation of 0.7 between the two disorders. (Shanahan et al., 2006)
Working Memory Capacity & Learning
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“Most of the time when I’m reading assignments
In my textbooks, I’m just licking the words rather
than chewing them. That’s why I have to keep
going back to read it all over again.” (Brown et al., 2011)
Working Memory Capacity & Learning
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IN ADHD can be relatively situation specific:
little impairment in ability when doing tasks which hold strong personal interest or anxiety for them,
though show significant impairment in most other situations.
(Brown 2009; Anmarkrud & Braten 2009)
Working Memory Capacity & Learning
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Age Working memory is crucial for...
Indicators that a working memory needs exercise
Learning the alphabet
Completing a puzzle independently
Understanding textual content (reading comprehension)
Inability to understand what is read
Mental arithmetic Problems memorizing the multiplication table
Completing homework independently
Can’t complete homework without parental supervision and direction
Complex math problems, especially word problems
Inability to grasp/ break down word problems
Studying for an exam
Constantly procrastinates; panics the night before an exam
Participation in group projects
Doesn’t listen or participate during a group project
Keeping focus/ interest during a lecture
Difficulty remaining attentive during lectures
Working Memory and Academic Activity
Pre-school Unwillingness to learn
Difficulty writing neat, coherent essays
College
Infant school
Junior school
Senior school Writing essays
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Message from the research:
low working memory = educational underachievementlow working memory = educational underachievement
Working Memory Capacity & Learning
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Working Memory & ADHD
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What are the Academic and EducationalCharacteristics of Children with ADHD?
Children with ADHD show
significant academic underachievement
poor academic performance
educational problems
(Hinshaw, 1992; Fergusson & Horwood 1995; Rapport et al., 1999; Sayal 2008; Galéra et al., 2009)
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What are the Academic and EducationalCharacteristics of Children with ADHD?
IQ - compared with controls score on average within the normal range (Biederman et al., 1996)
BUT score significantly lower on reading and arithmetic achievement tests than controls. (Biederman et al., 1996)
Children with ADHD are 4 to 5 times more likelyneed special educational services. (LeFever et al., 2002; Jensen et al., 2004)
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Academic difficulties begin early in life. Symptoms are common in children aged 3 to 6 years, (Gadow et al., 2001)
preschool children with ADHD are more likely to be behind in basic academic readiness skills. (Mariani & Barkley 1997; DuPaul, et al., 2001)
have impaired handwriting performance characterized by illegible written material and/or inappropriate speed of execution (Racine et al., 2008)
What are the Academic and EducationalCharacteristics of Children with ADHD?
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In adolescence: achieve lower ratings on all school subjects have lower class rankings perform poorly on standardized academic achievement tests (Gittelman et al., 1985; Barkley et al., 1990; Weiss et al., 1999).
x2 likely to repeat a grade (Currie & Stabile 2006; Beiderman et al., 2006)
x2 - 4 to have lower than expected grades (Todd et al., 2002)
What are the Academic and EducationalCharacteristics of Children with ADHD?
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School histories indicate
persistent problems in social participation
more years to complete high school
lower rates of college attendance
lower rates of college graduation (Mannuza et al., 1993;
Weiss et al., 1999;
Barkley 2002).
What are the Academic and EducationalCharacteristics of Children with ADHD?
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In College relative to other students
have lower GPAs more academic concerns depressive symptoms social concerns emotional instability and substance use.
BUT most said were coping.
(Blase et al., 2009)
What are the Academic and EducationalCharacteristics of Children with ADHD?
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longitudinal studies into young adulthood
Initial symptoms of hyperactivity distractibility impulsivity aggression tend to decrease in severity over time
BUT remain present and increased in comparison to controls
(Weiss et al., 1999).
What are the Academic and EducationalCharacteristics of Children with ADHD?
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For instance….
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26 ADHD individuals and 31 controls (paired for gender, age, & intelligence)
Using mathematics and language scores
academic underachievement was 2.98 times higher in students with ADHD
(Pastura et al., 2009)
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Ethnically diverse cohort of 823 assessed at 6 years for behavioural problems and IQ
and at 17 years of age for academic achievement in math and reading, and other parameters.
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Ethnically diverse cohort of 823 assessed at 6 years for behavioural problems and IQ
and at 17 years of age for academic achievement in math and reading, and other parameters.
Attention problems predicted poor maths and reading achievement with little benefit from intervention.
Whereas reducing externalizing and internalizing
problems materially reduced academic problems. (Breslau et al., 2009)
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3 main groups of outcome as young adults:
(1) approximately 25% eventually function comparably to matched normal controls
(2) the majority show continuing functional impairment, limitations in learning and applying knowledge restricted social participation, particularly poor progress through school
(3) about 25% develop significant, severe problems, including psychiatric and/or antisocial disturbance (Hechtman 2000)
What are the Academic and EducationalCharacteristics of Children with ADHD?
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Academic difficulties associated with inattention are cross-cultural and not
specific to the Western countries.
(Norvilitis et al., 2010)
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People with ADHD have difficulties with:
planning, organization, reasoning, response inhibition, decision-making, set-shifting working memory (Tranel et al., 1994;
Pennington and Ozonoff 1996;
Barkley 1997;
Geurts et al., 2004)
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ADHD symptom severity is associated with magnitude of impairment in executive functions
BUT this relationship can be obscured by the presence of comorbid disruptive disorders.
(Barnett et al., 2009)
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The Impact of MedicationThe Impact of Medication
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Methylphenidate improves the transmission of signal versus noise by reducing response to the noise.
AND improves concentration by increasing dopamine levels in fronto-striatal pathways
(Williams & Goldman-Rakic, 1995).
The Impact of Medication
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Neuroimaging studies have also shown
methylphenidate blocks up to 70% of transporters in these pathways – improving dopamine availability
(Krause 2008)
Continued use of stimulants tends to normalise deficits (Shaw et al., 2009;
Bledsoe et al., 2009;
Nakao et al., 2011)
The Impact of Medication
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medication improves academic productivity as indicated by
improvements in the quality of note-taking
scores on quizzes and worksheets
the amount of written-language output
homework completion.
(Evans et al., 2001)
methylphenidate increases in dopamine with
improved interest and motivation to do maths tasks
(Volkow et al., 2004)
The Impact of Medication
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However, stimulants are not associated with
normalization of skills in the domain
of learning and applying knowledge.
(Rapport et al., 1994)
The Impact of Medication
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1195 children were tested at 5 points:compared the academic performance of treated with untreated children at each testing node. medicated gained 2.9 points in mathematics performance between the first and final testing reading performance medicated gained 5.4 points above unmedicated
Early Childhood Longitudinal Study
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1195 children were tested at 5 points:compared the academic performance of treated with untreated children at each testing node. medicated gained 2.9 points in mathematics performance between the first and final testing reading performance medicated gained 5.4 points above unmedicated Despite this improvement the performance of the medicated children with ADHD lagged their peers without ADHD. (Scheffler et al., 2009)
Early Childhood Longitudinal Study
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177 ADHD effectively medicated vs 95 untreated ADHD and 101 normal controls.
Neuro Cognitive Index - computed as the average of the z scores of five domains (memory, psychomotor speed, reaction time, complex attention, and shifting attention flexibility)
untreated ADHD patients perform 15% lower than normals.
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177 ADHD effectively medicated vs 95 untreated ADHD and 101 normal controls.
Neuro Cognitive Index - computed as the average of the z scores of five domains (memory, psychomotor speed, reaction time, complex attention, and shifting attention flexibility)
untreated ADHD patients perform 15% lower than normals.
However, treated ADHD patients perform 10%lower than normals. (Gualtieri & Johnson 2008)
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In longitudinal studiesIn longitudinal studies
subjects consistently demonstrate poor outcomes
compared with controls
whether or not they receive medication. (Gittelman et al., 1985; Barkley et al., 1990; Hechtman & Greenfield 2003; Fischer et al., 2002; Loe & Feldman 2007; Powers et al., 2008)
The Impact of Medication
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and in UK studies:and in UK studies:
Despite medication, ADHD association with poor attainment in GCSE’s (Daley et al.,
2009)
The Impact of Medication
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"Given their well-established benefit for
increasing attention and concentration, it
seems counterintuitive that ADHD
medications are not more effective in
improving academic and occupational
attainment,"
(Advokat 2009)
The Impact of Medication
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Anatomical and imaging studies indicate Working Memory use frontal-parietalcircuitry (Paulesu et al., 1993; Smith & Jonides 1998)
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Anatomical and imaging studies indicate Working Memory use frontal-parietalcircuitry (Paulesu et al., 1993; Smith & Jonides 1998)
there are only few dopamine transporters in the prefrontal cortex
probable that dopamine uptake in this part of the brain is via noradrenaline sites.
(Nutt & Fone 2005)
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BUT consistency-impulsivity managed through noradrenaline pathway (Sweitzer et al., 2006)
methylphenidate has only a modest impact upon noradrenaline (Berridge & Waterhouse, 2003)
IN ANIMALS - greater enhancement of working memory function is achieved
with 2 noradrenaline agonists (Arnsten, 2001).
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SO methylphenidate increases dopamine which improves concentration and some cognitive elements
BUT working memory more dependent upon noradrenaline pathways in prefrontal cortex SO methylphenidate alone will not greatly improve working memory
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How do children with ADHD
compare with children with
low working memory
on testing?
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HMS TrincomaleeHMS Trincomalee, built in Bombay for the Admiralty in 1817 the oldest ship afloat in the UK
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The monkey won on a “free bananas” platform
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Working memory comparisons
(Holmes et al., 2009)
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A computerised training programme developed by Klingberg et al. (2002)
Improving Working Memory
Robo Memo
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Does it work?
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Participants 42 children, aged 8-11 years, with low working memory
◦ Identified via routine screening of 345 children on two verbal wm tasks (Listening Recall and Backward Digit Recall)
◦ Scores <86 on both tasks (bottom 15th centile)
Two groups◦ Adaptive, standard version of training
programme training at maximum span level
◦ Non-adaptive, control condition training at fixed span level of 2
Hartlepool Study (1)
(Holmes et al., 2009)
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Working Memory Training
working on memory tasks on a computer
20 minutes everyday for 20-25 days
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*
Results from non-adaptive
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Results from adaptive
****
****
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Working Memory Training
…and at 6 mth follow-up
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Results from adaptive Follow up
****
** **
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Pre-training Post-training6mth follow-
up
Measure M SD M SD M SD
Verbal IQ 88.73 11.14 90.86 11.52 92.78 9.10
Performance IQ 88.05 13.09 90.68 12.96 87.11 9.07
Reading 83.68 12.35 83.00 15.06 82.83 14.1
Mathematics 84.27 12.28 85.68 12.70
89.94* 9.88
Following inst. 14.45 4.0218.27*
* 4.37 16.5* 3.82
No significant improvements for non-adaptive groupNo significant improvements for non-adaptive group
IQ, Reading & Maths Scores - adaptive
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Impact of Medication & Robo Memo on Working Memory in children with ADHD
Participants:
◦ 25 children (21 boys, 4 girls), clinical diagnosis ◦ of ADHD-C◦ receiving quick release stimulant medication (methylphenidate n=22, dexamfetamine n=3)
◦ aged 8-11 years◦ diagnosis for at least 6 months◦ no co morbid ASD (Holmes et al., 2010)
Hartlepool Study (2)
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Effect of medication on IQ
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Effects of medication on working memory
**
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Research on Working Memory & Medication
Stimulant medication mainly improves
visuo-spatial simple span tasks
(Bedard et al., 2004)
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Does RoboMemo
make a difference?
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Effects of medication and training on working memory
** **
**
**
**
**
*
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On MedsPost training (+ on meds)
Inattentivity (teacher) 69.84 (23.33) 58.21 (20.27)**
Hyperactivity (teacher) 81.15 (21.69) 70.31 (23.87)*
Working memory problems (child) 17.60 (5.72) 13.25 (6.00)**
Effects of training on behaviour ratings
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Sustainability of training effects – 6 mth follow-up
**
**
****
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Working Memory Intervention
◦ Significant gains in non-trained working memory tasks, which extended across all four aspects of working memory. Substantial increases in scores
(low-average to average range).◦ Significant reduction in ratings of problem behaviours◦ No effect on IQ
Unlikely to result from practice effect◦ Comparison group showed no test re-test effect ◦ Consistent gains in both the repeated and non- repeated AWMA tasks in the ADHD group
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SO:
Working memory deficits associated with ADHD can be overcome by two different interventions
RoboMemo intervention led to more generalized gains in WM, and reductions in problem behaviours
Medication led to specific gains in visuo-spatial WM, and improves concentration
and improves academic productivity
(Holmes et al., 2010)
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How is training enhancing working memory?
there are only few dopamine transporters in the prefrontal cortex
probable that dopamine uptake in this part of the brain is via noradrenaline sites.
(Nutt & Fone 2005)
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How is training enhancing working memory?
SO not a high density of dopamine receptors in prefrontal cortex
Training changes the density of prefrontal & parietal cortical dopamine D1 receptors. (McNab et al., 2009)
may stimulate the development of WM strategies that compensate for weaknesses in basic processes (Holmes et al., 2010)
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The Research Team
Joni Holmes Senior Lecturer in Experimental Psychology
Maurice Place Professor of Child & Family Psychiatry
Torkel Klingberg Professor in Cognitive Neuroscience
Joe Elliott Professor of Education
Sue Gathercole Unit Director, Professor of Cognition & Neuropsychology
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General classroom advice
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children with ADHD
are more likely to complete more problems
and complete them accurately
when high levels of engaging stimuli
are included within the task.
(Jitendra et al 2008)
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children with ADHD
are more likely to complete more problems
and complete them accurately
when high levels of engaging stimuli
are included within the task. (Jitendra et al 2008)
Pacing of tasks with periods to release energy
Clarity of goals
Instant feedback
Novel & rapidly changing rewards
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children with ADHD
are more likely to complete more problems
and complete them accurately
when high levels of engaging stimuli
are included within the task. (Jitendra et al 2008)
Pacing of tasks with periods to release energy
Clarity of goals
Instant feedback
Novel & rapidly changing rewards
Time out DOES NOT work
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1. Draw or create vivid pictures depicting information that needs to be memorized. Since memory is enhanced by exaggeration, emotion, action, and color, the more ridiculous and detailed the image, the better.
2. Teach memory strategies. Such as mnemonics e.g. Dead Monsters Smell Bad (steps for long division: divide, multiply, subtract, bring down).
3. Create acrostics or whole sentences. “Every Good Boy Does Fine” is an excellent way to help recall the sequence of lines in the treble clef (EGBDF).
4. Try melody and rhythm to teach a series or sequence. There are raps, rhymes, and songs to help attention deficit students memorize multiplication tables, days of the week, etc.
5. Use songs specially created to teach content. Musically Aligned (musicallyaligned.com) creates music and lyrics geared to teach a science curriculum. For physical science, there are songs like “Electromagnets” and “Heat, Light, and Motion.” For teaching concepts in life science, there are “Food Chain Gang” and “Decomposers.”
6. After the lesson, have ADHD students list the things they remember. Ask them to do so as fast as they can, to increase memory recall. (Sandra Rief 2009)
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Improved by reading interventions focused on basic skills
e.g., decoding – such as activities to promote phonological awareness and alphabetic understanding
(Blachman et al 2000).
and maths strategies e.g. problem solving using schema-based instruction
(Jitendra et al 2007).
And strengthened by Peer mediated interventions
Computer assisted instruction (Jitendra et al 2008)
Task modification and varying classroom function
(Daley & Birchwood 2010)
Teaching parents homework strategies
(Raggi & Chronis 2006).