Working Memory & ADHD Prof Maurice Place Prof Maurice Place [email protected]

Working Memory

&

ADHD

Prof Maurice PlaceProf Maurice Place [email protected]

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Eli LillyEli Lilly

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ShireShire

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)

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

Working Memory

a dynamic, short-term storage

of information to be actively used or manipulated

and is a localised function (Alloway et al., 2006)

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)




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)

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.

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

(Baddeley 2000)

Rehearsal

Storage

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).

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)

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)

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)

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)

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)

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

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

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

assessed using simple cognitive tasks:

WMI of the WAIS or WISC

Automated Working Memory Assessment

(Alloway, 2008)

Working Memory

839251 839251

DIGIT RECALL

Verbal STM/Verbal simple span tasks

MAZES MEMORY

Visuo-spatial STM/Visuo-spatial simple span tasks

MAZES MEMORY


MAZES MEMORY


chairs lay eggs

false

false

bananas have teeth

LISTENING RECALL TASK

Verbal STM/Verbal Complex span tasks

chairs lay eggs

false

false

bananas have teeth

LISTENING RECALL TASK

Verbal STM/Verbal Complex span tasks

eggs, teeth

Visuo-spatial WM/Complex visuo-spatial tasks

SPATIAL SPAN TASK


SPATIAL SPAN TASK


SPATIAL SPAN TASK


SPATIAL SPAN TASK


SPATIAL SPAN TASK

Associations with Specific Disorders

Specific Working Memory problems evident in various disorders:

PKU Schizophrenia


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)


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).


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)

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)

Working Memory Capacity & Learning

Important for successful learning

in individual classroom activities

(Gathercole & Alloway, 2008)


Associated with reading and mathematics ability

(Gathercole & Pickering, 2000; Geary et al., 2004)


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)


“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)


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)


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

Message from the research:

low working memory = educational underachievementlow working memory = educational underachievement


Working Memory & ADHD

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)


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)

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)


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)


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).


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)


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).


For instance….

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)

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.

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)

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)


Academic difficulties associated with inattention are cross-cultural and not

specific to the Western countries.

(Norvilitis et al., 2010)

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)

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)

The Impact of MedicationThe Impact of Medication

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

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)


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)


However, stimulants are not associated with

normalization of skills in the domain

of learning and applying knowledge.

(Rapport et al., 1994)


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

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

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.

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)

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)


and in UK studies:and in UK studies:

Despite medication, ADHD association with poor attainment in GCSE’s (Daley et al.,

2009)


"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)




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)

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).

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

How do children with ADHD

compare with children with

low working memory

on testing?

HMS TrincomaleeHMS Trincomalee, built in Bombay for the Admiralty in 1817 the oldest ship afloat in the UK

The monkey won on a “free bananas” platform

Working memory comparisons

(Holmes et al., 2009)

A computerised training programme developed by Klingberg et al. (2002)

Improving Working Memory

Robo Memo

Does it work?

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)


Working Memory Training

working on memory tasks on a computer

20 minutes everyday for 20-25 days

*

Results from non-adaptive

Results from adaptive

****

****

Working Memory Training

…and at 6 mth follow-up

Results from adaptive Follow up

****

** **

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

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)

Effect of medication on IQ

Effects of medication on working memory

**

Research on Working Memory & Medication

Stimulant medication mainly improves

visuo-spatial simple span tasks

(Bedard et al., 2004)

Does RoboMemo

make a difference?

Effects of medication and training on working memory

** **

**

**

**

**

*

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

Sustainability of training effects – 6 mth follow-up

**

**

****

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

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


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)

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)

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

Working Memory

&

ADHD

Prof Maurice PlaceProf Maurice Place [email protected]

General classroom advice

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)

children with ADHD




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

children with ADHD




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

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)

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).

Documents

Working Memory & ADHD Prof Maurice Place Prof Maurice Place [email protected]