Impaired Functioning in Schizophrenia: Models,

Mechanisms and Measurement

Dr Kathryn Greenwood

Department of Psychology, University of Sussex & Sussex Partnership NHS Foundation Trust

Overview• Personal Accounts• Theories of symptoms, cognition and function in

schizophrenia• Studies

– 1 Executive impairment profiles in Schizophrenia (JINS)– 2 Executive impairments and symptoms models (Schiz

Bull) – (including in materials in preparation)– 3 Cognitive impairments and Awareness (Schiz Bull)– 4 Genes and outcome (Neuroscience letters) – 5 VR as a measurement tool (in preparation)

• Clinical implications and future directions

Personal Accounts

“My concentration is very poor. I jump from one thing to another. If I am talking to someone they only need to cross their legs or scratch their head and I am distracted and forget what I was saying.”

McGhie and Chapman, 1961

“I was looking at A or B for some subjects now I’m looking at C or D if I’m lucky.”

“Memory loss is the new thing that’s bothering me.”

“I have low concentration”

“I’m coming to terms with the fact that I have got a learning difficulty.”

Michael, Aged 16 yearsInside my head - Channel 4, June 2002

Work

“I want to be able to do things that other people do, like have a boyfriend and a job …”

Social Functioning

“I want to have friends”

Community Function

“I want to be able to cook and eat when I want”

“I want to live in my own place not a hostel”

Theoretical Background

Crow 1980Type I schizophrenia Type II schizophrenia

Positive symptoms Negative symptoms

Intact cognition Impaired cognition

Dopamine abnormalities Ventricular and other structural abnormalities

Good treatment response Poor treatment response

Good outcome Poor outcome

Liddle 1987, 1991Reality Distortion Disorganisation Psychomotor

PovertyHallucinations/Delusions

Disorders of thinking and affect

Flat affectPoverty of speech movement, gesture

Impaired figure-ground perception

InitiationOrientation AttentionInhibitionWorking memory

InitiationStrategy use Processing in LTM

Poor self care and occupation fx

Poor poor social and recreational fx

Baddeley’s Working Memory Model

Central Executive Visuospatial Sketchpad

Phonological

LoopStore

Baddeley and Hitch, 1978; Baddeley and Della Sala 1996

Goldman-Rakic 1987

Central Executive

sensory

motor

Articulat - ory loop

Object

Features

Visual-

Spatial

Adjacent modality-specific working memory systems in DLPFC with own control systems: a fundamental impairment in schizophrenia

Shallice’s Supervisory Attentional System

• Automatic contention schedulingUntil• i) novel environment • ii) requirement to inhibit one strong or

several weak competing schema

• New Schema construction• Implementation in working memory• Monitoring and Inhibition

Norman and Shallice 1982; Shallice and Burgess 1992; 1996

Frith’s Cognitive Neuropsychology of Schizophrenia 1992

Three main (theory of mind) disorders:

1) Disorders of willed intentions (action driven by intention)

2) Disorders of self-monitoring 3) Monitoring the Intentions of others

Negative symptoms = absence of initiation of willed intentions, plans and strategies and impaired monitoring of others so missed communication cues

Thought disorder (incoherence of behaviour/affect) = poor inhibition of stimulus driven responses by intentions, as well as impaired self monitoring of communication goal to output and impaired monitoring of listener’s understanding

Do Specific Cognitive deficits predict specific domains of function?

Velligan et al. 2000

Neurocognition and function: Are we measuring the right stuff?

Green 2000

learning potential and skill acquisition as mediators of functional outcome

Card Sort

Immediate verbal memory

Community/daily

activities

Social problem solving/ instrumental skills

Psychosocial skill acquisition

Verbal fluency

Green’s conclusions 2000‘We have learned whether but not HOWneurcognition is related to functional

outcome?’

Need to know what mediates relation between neurocognition and outcome?

• Processes (learning potential) that underlie the ability to acquire and perform life skills

• Social cognition

There is a need for new cognitive models of negative

symptoms and function in order to improve functional outcomes

Lincoln et al. (in press)Negative symptoms associated with Impaired Social

Cognition: difficulties in ToMlower self-esteem less self-serving bias Negative self-concepts related to interpersonal abilitiesDysfunctional acceptance beliefs.

Some social cognitive impairments (ToM) were associated with negative symptoms only in people with low self-esteem.

So self-concepts related to social abilities, dysfunctional beliefs and global self-worth alone and in interaction with skill-deficits are associated with negative symptoms

Rector, Beck and Stolar (2005)

• Low expectancies for pleasure, success, acceptance & perception of limited resources play a major role in the formation of negative symptoms

• Dysfunctional performance beliefs (e.g. If I fail partly, it is as bad as being a complete failure) associated with negative symptoms

• Indirect pathways between functional capacity (cognitive impairment), dysfunctional performance beliefs, and negative symptoms and real-world functioning

Past and current studies

Research AimsTo understand the mechanisms through

which bio-psychosocial factors including

• Gene markers • Phenomenology of schizophrenia • Cognitive function &• Psychological function (thinking, mood

and behaviour)

Affect functional outcome in schizophrenia

Study 1 AimsCategorisation of sub-groups by neuropsychological profile in all cases

confounds the relationship between symptoms and chronicity.

AimsTo explore the severity and profile of executive functioning in relation

to disorganisation and psychomotor poverty and simultaneouslyTo investigate the early and late profiles in first episode and chronic

schizophrenia.

Hypothesis Chronicity will associate with similar but more severe impairment Disorganisation will associate with broad executive deficitPsychomotor poverty with impaired working memory and response

initiation

Study 1 Measures• working memory

– Digit span, word span, executive golf • planning and strategy formation

– Tower of london, hayling and executive golf strategy scores

• response initiation– Verbal fluency

• response inhibition– Hayling test and complex reaction time test

• IQ – WAIS-R and NART-R

Novel measures – the question

• To assess similar processes in cognitive & function task Working memory example

• 3KA27

• Crunchy Green salad 250g £1.09Crunchy Green salad 500g £1.24Mixed Salad 250g £1.15Caesar Salad 120g £ 1.05

Example using Search Strategy

Novel measures – the answer

• Example using Working Memory3KA27 237AK

• Caesar Salad 120g £ 1.05 Crunchy Green salad 250g £1.09Mixed Salad 250g £1.15Crunchy Green salad 500g £1.24

Example using Search Strategy

Study 1 AnalysisGroup differences in executive function

MANCOVA’s controlling for WAIS IQ

Executive profiles • Converted to z-scores and compared

using generalised estimating equations (GEE). Group as between and executive function as within subject factor

Specific islets of strength/deficit• Domain score compared to average of all

others while holding IQ constant

Study 1 Symptom studyControls (n = 28)

Psychomotor Poverty ( n =

29)

Disorganisation(n = 29)

Statistical Test_______________

Test statistic df p

Age (Years) 33.1 (7.34) 33.9 (8.81) 36.2 (8.04) F=1.2 2,83 .31

Sex (%Male) 89 93 86 X2 =.74 2 .69

Parental SES 3/15/10 4/13/9 (n=7) 2/18/8 (n=8) X2 =1.4 4 .48

Education(Yrs) 14.5 (2.81) 12.8 (2.37) 12.1 (2.19) F=7.0 2,83 .00

Premorbid IQ 110.0 (6.54) 97.0 (12.1) 96.8 (11.5) F=14.8. 2,83 .00

Current IQ 113.2 (16.0) 90.0 (17.6) 88.7 (12.7) F=22.2 2,83 .00

Illness Length (Yrs) 7.83 (7.4) 11.9 (8.55) F=3.9 1,56 .05

Study 1 Chronicity studyControls (n = 28)

First Episode(n = 22)

Chronic(n = 35)

Statistical Test______________

Test statistic df p

Age (Years) 33.1 (7.34) 28.6 (9.9) 38.1 (6.9) *

Sex (%Male) 89 82 94 X2 = 2.2 2 .33

Parental SES 3/15/10 1/12/8 (n=21) 4/19/11 (n=5) X2 = .87 4 .93

Education(Yrs) 14.5 (2.81) 13.1 (2.98) 12.6 (2.25) F=4.1 2,82

.02

Premorbid IQ 110.0 (6.54) 93.7 (8.9) 99.5 (12.4) F=17.8 2,82

.001

Current IQ 113.2 (16.0) 92.2 (17.2) 91.1 (14.1) F=18.3 2,82

.001

Reality Distortion 19.2 (9.19) 16.9 (9.17) F=.78 1,55

.38

Disorganisation 4.5 (5.9) 10.6 (7.6) F=10.5 1,55

.002

Psychomotor Poverty 7.8 (7.9) 11.6 (8.7) F=2.9 1,55

.095

General Negative 11.5 (7.5) 18.7 (4.7) F=19.7 1,55

.001

-3

-2.5

-2

-1.5

-1

-0.5

0ds sw e vw m sbe pl vss sss ri vinhib sinhib

executive process

z-sc

ore

control psychomotor poverty disorganisation

Distinct profiles and poorer performance in schizophrenia/and disorganisation than controls/pp

-3

-2.5

-2

-1.5

-1

-0.5

0ds sw e vw m sbe pl vss sss ri vinhib sinhib

executive process

z-sc

ore

control first episode chronic

Parallel non-flat profiles and poorer performance in chronic schizophrenia (and FE) compared to controls

ds swe vwm sbe dat vss sss spl vfno. vfac vler vher sinhib

-4

-3

-2

-1

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1

2

z-sco

re

Executive Profile: Controls Age Young vs Older Controls

Age less than 30

Age greater than 30

ds swe vwm sbe dat vss sss spl vfno. vfac vler vher sinhib

-4

-3

-2

-1

0

1

2 z-s

core

Executive Profile: Medication dose Low vs High Dose

Less than 50% of maximum dose

Greater than 50% of maximum dose

ds swe vwm sbe dat vss sss spl vfno. vfac vler vher sinhib -4

-3

-2

-1

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1

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z-sco

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Executive Profile: Medication Group Standard vs Clozapine vs Atypicals

Standardd.

Clozapine

Atypical

Study 1 Conclusions• Schizophrenia - characterised by a single executive

profile that reflects the make up of symptoms (psychomotor poverty / disorganisation) but not chronicity

• Parallel but attenuated profile at first episode due to incorporation of those with intact function

• Disorganisation - broad impairment profile incorporating planning and working memory

• Psychomotor poverty - particularly impaired response initiation

• Predictive power of either symptoms or cognition on outcome is short lived but stable symptom-cognition markers should be targets of intervention

Study 2 • Schizophrenia - characterised by a single executive

profile that reflects the make up of symptoms (psychomotor poverty / disorganisation) but not chronicity

• Parallel but attenuated profile at first episode due to incorporation of those with intact function

• Disorganisation - broad impairment profile incorporating planning and working memory

• Psychomotor poverty - particularly impaired response initiation

• Predictive power of either symptoms or cognition on outcome is short lived but stable symptom-cognition markers should be targets of intervention

Negative Symptoms matter in the Leap from Cognition to

Community Function in Schizophrenia:

Dr K Greenwood, Dr S Landau, Professor T Wykes

Department of Psychology, Institute of Psychiatry, London, UK.

e-mail: k.greenwood@iop.kcl.ac.uk

Implications for Intervention

Introduction• People with schizophrenia and negative

symptoms have poor functioning (occupation, community and daily living skills)

• Poor functioning is a source of distress for both people with schizophrenia and their families

Negative Symptoms associated with Community Function

• Negative symptoms (flat affect, poverty of speech, apathy) affect function:

• Only Indirectly through link with Cognition

• Independently

Cognitive Impairments associated with Community

Function• Executive function predicts Community

function, Occupation, Daily living • Working Memory predicts Occupation

• Global cognition predicts Daily living

• Cognition is a stronger predictor than symptoms (Green 2000)

Cognitive Impairments associated with negative

symptomsNegative symptoms:

Linked theoretically with : Executive function and Working memory

Initiation/generation of strategies (Frith) Working memory (Goldman-Rakic)

Linked Empirically with: Response Initiation (Franke et al. 1993)

Immediate/working memory (Pantelis et al 2001) Focused/switching attention (Buchanan et al 1994)

Initiation/working memory/strategy use (Greenwood 2000)

Objective • To investigate specific relationships between

negative symptoms, executive/working memory functions and community function and in particular to investigate the independent effect of negative symptoms

• Reducing confounding of negative symptoms and low IQ

• Using process approach and theoretically driven framework

• Also using a novel measure to directly assess community function

Design• Cross sectional Comparison:

22 Healthy controls 28 Schizophrenia & negative symptoms balanced general22 Schizophrenia & no negative symptoms cognitive impairment

• Balancing: Age, Sex, Premorbid IQ,

• Predictors: working memory, initation, inhibition, strategy, symptoms

• Analysis: Identify individual associations to function, interactions, and final regression model

The measure A test of supermarket shopping Skills

Participants had to select 10 items from ashopping list. Measures were taken of:

– accuracy (items correct)– Efficiency (time/route length) – Redundancy (no. aisles entered above minimum)– Strategy

(adapted from Test of Grocery Shopping Skills, Hamera and Brown 2000)

Research Questions• Is directly assessed community function more impaired in

people with schizophrenia and negative symptoms (when directly assessed and without IQ confound)

• Do specific executive processes predict specific community functions (working memory-accuracy; strategy-strategy)

• Do the associations differ in different symptom groups (use of theoretical rationale to investigate moderator effect of negative symptoms)

Subject Characteristics

Controls Non-negative

Negative

Age (Years)  

36.23 35.28 35.07

Sex (M/F) 16/6 19/6 20.8

Premorbid IQ

89.77 91.12 91.36

RBMT Score 15.242-23

13.52 7 – 23

WCST Score 2.88 0 - 6

2.07 0 - 6

Total PANSS 50.88 35 - 76

62.11*42 - 88

Statistical Analyses • Association Analyses (GLR – with binomial, Poisson, normal

distribution)*

Stage 1: Identify individual associations (cognition x function)

Stage 2: Identify individual interactions (cognition x symptom group x

function)

Stage 3: Conduct final regression model

Premorbid IQ controlled

Poorer strategy, working memory, initiation

in negative group

0

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control non-neg neg

Spatial Strategy Score

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12

control non-neg neg

Verbal working memory score

05

10152025303540

control non-neg neg

Verbal fluency initiation

Community function: Poorer accuracy, efficiency and strategy in

negative groupCorrect lowest price

012345678

control non-neg neg

Time Taken

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30

40

50

60

control non-neg neg

Tim

e ta

ken

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2

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6

8

10

12

1416

control non-neg neg

Aisles above Minimum

The results

• Some cross group predicted associations between cognition and function (e.g. accuracy and strategy, efficiency and working memory)

• Some executive-function associations only with negative symptoms (working memory and accuracy, IQ and efficiency)

• Not just because of poor general cognition and Not a threshold effect but a true interaction

Executive & premorbid factors associated with community function• Working memory associated with all

function measures (p = .01- < .001)• Strategy associated with strategy measures

and route length (p = .04- < .001)• Initiation associated with correct items,

efficiency and strategy (p = .02 - <.001)

• Premorbid IQ associated with most measures (p = 0.04-<0.001)

Independent cognition to community function associations are present only

for specific groups• In Negative group

Working memory associated with size accuracy price accuracy

Verbal fluency associated with aisles above minimumPremorbid IQ associated with correct items

time• In Controls

Working memory associated with aisle strategyVerbal fluency associated with aisles above minimum

Conclusion so far…

• Community functions are more impaired in schizophrenia with negative symptoms even compared to a group with equivalent general cognitive function

• Executive functions associated with community function only in negative not non-negative schizophrenia

Negative symptoms moderate the association between impaired

executive and community functions• No significant interaction of working

memory severity factor within negative group

• Moderating effect is not a cognitive threshold effect

A synergistic cognition-symptom interaction predicts community

function: A working memory model

Core Working Memory

Negative Symptoms

Community

FunctionAbility

Dom

ain

Spec

ific

WMCF

exp.

Research Question - 2

• Do cognition or symptoms predict changes in community function when investigated longitudinally?

Design - 2• Longitudinal follow-up of shopping

function (n=43) :

• Comparing baseline (t1) to 6 months (t3)

• Broader range Demographics, Cognition, Symptoms and function

Influences on recovery Differences in baseline measures between

improvers (n=21) and non-improvers (n=22)– initial community function (p <.001) – self-esteem (p = 0.026)– working memory (p=0.047)

Independent predictors of improvement on– Initial community function (p = 0.004)– Self esteem (p <0.001)– Working memory (p = 0.088)

A synergistic cognition-symptom interaction predicts community

function: A working memory model

Core Working Memory

Negative Symptoms

Community

FunctionAbility

Dom

ain

Spec

ific

WMCF

Level

Self esteem

The design III: the relationship of SST to other functions

• Cross sectional comparison of standardised shopping function to other function measures(n=53) :

• Accuracy correlated with social behaviour (SBS) (r = -0.4 p = 0.001) but not level of independence in day care, number of activities or self-reported shopping activities

• Efficiency correlated with level of independence in day care and independence in handling money (Spearman’s rho = -0.4 p = 0.005 and -0.3 p = 0.047) but not with social behaviour, number of activities or other self-reported shopping activities

• The ability to shop accurately seems linked to the appropriateness of other social behaviours and the ability to shop efficiently seems linked to other measures of independence in function. Shopping function is unrelated to activity levels in shopping or other behaviours.

Implications• Synergistic interaction between negative

symptoms and working memory impairments may contribute to progressively poorer community function

• Remediation programmes that employ CBT/ CRT to target negative symptoms/ low self esteem AND domain specific cognition/working memory may break the reciprocal link, enhance generalisation and improve functional outcome

Why consider a VR assessment of function?

• Most commonly used measures are the GAF and employment status (recent review Greenwood et al. unpublished data)

• Rehabilitation may be maximised by identifying cognitive targets for intervention through refined assessment (Greenwood et al. 2005)

• But few brief direct standardised assessments (McKibbin et al. 2004)

• Need for brief, easily administered community function assessments in schizophrenia, validated against real life functions and underlying cognitive processes

The Use of Virtual Reality in Assessment and Intervention

• VR apartment for medication management and adherence • VR functional skills assessment for social competence• VR avatar for assessment of social approach and anxiety • VR street, tube train and library for understanding thinking

patterns underpinning to psychosis• VR Park and Maze for real world navigation (allocentric and

egocentric memory)• VR maze for real world sensory integration in working memory• VR supermarket to assess executive function in different clinical

groups BUT no studies in schizophrenia have compared RL and VR

performance on same task and some suggest differential performance in VR dependent on environment and associated cognitive processes

Freeman et al. 2003;2005; Jang et al. 2005; Baker et al 2006; Sorkin et al. 2006; 2008; Kurtz et al. 2007; Ku et al. 2007; Weniger et al 2008; Kim et al. 2008; Park et al. 2009; Zanyi et al. 2009; Josman et al. 2009; Landgraf et al. 2010

The research questions1. Does performance in VR relate to

the same in RL? 2. Do they share common or distinct

cognitive processes?3. Do these processes differ in different

symptom groups?

Community Function Measure • Supermarket Shopping Task

(adapted from TOGSS: Hamera and Brown, 2000)

• Virtual Reality Shopping Taskpresented on flat screen computer with joystick(RG Morris et al.)

In each task participants had to select 10 items from a shopping list. Measures were taken of:

– accuracy (items correct)– time – redundancy (no. aisles entered above minimum)

Cognitive measures

• Memory and Working Memory – Visual Reproduction and Letter-Number Span

• Executive function – BADS- key search & Verbal fluency

• Social Cognition– Intention Inference Test (Sarfarti et al. 1997)

(IQ NART-R and WASI also assessed)

Participant Demographics

Participants (n=43)Mean (n) s.d. range

Age (Years)   39.5 11.9 21-63 Sex (M/F) 23/21 - -

PANNS positive 14.6 6.5 7 – 28PANSS negative 13.4 5.5 8-27

PANSS total 57.8 18.6 32-103

Participant Cognition

Participants (n=43)Mean (n) s.d. range

Premorbid IQ 103.6 11.9 74-129mean scaled score

(WASI) 9.2 3.3 3-16

Verbal Fluency 33.2 12.2 8-62Strategy (BADS KS) 2.0 1.1 0-4

Working Memory (L-N) 8.3 3.3 2-16Spatial Memory (Vis

Rep)6.3 4.7 0-17

Social Cognition(comic strip

20.2 5.8 5-27

Does performance in VR relate to the same in RL?

RL accuracy RL time RL aisles VR accuracy VR time VR aisles

RL accuracy \ -.21 p=.20 -.18 p=.27 .30 p=.05 -.18 p=.25 -.08 p=.61

RL time \ .69 p<.001 -.58 p<.001 .35 p=.02 .45 p= .003

RL aisles \ -.42 p=.006 .65 p<.001 .75 p<.001

VR accuracy \ -.26 p=.087 -.21 p=.19

VR time \ .81 p<.001

VR aisles \

*Significance remained (except trend for RL/VR accuracy) when IQ controlled **No correlations with symptom measures

Does performance in VR relate to the same in RL?

0

5

10

15

20

25

RL VR

Accuracy

0

1

2

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4

5

6

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9

10

RL VR

Aisles

**

Do RL and VR shopping share the same cognitive

underpinnings?Accuracy

Time

EfficiencyVerbal Fluency

Verbal Fluency

Verbal Fluency

Verbal Fluency

Working Memory

Strategy

Spatial Memory

Social Cognition

R=0.35 p=0.02

R=0.29 p=0.06

R=-0.26 p=0.09

R=0.29 p=0.058

R=-0.27 p=0.08

R=-0.32 p=0.05

Do Cognitive underpinnings of RL and VR differ in Negative

symptom groupAccuracy

Time

EfficiencyVerbal Fluency

Verbal Fluency

Verbal Fluency

Verbal Fluency

Working Memory

Strategy

Spatial Memory

Social Cognition

R=0.47 p=0.04*

R=0.57 p=0.013

R=-0.52 p=0.02

R=0.47 p=0.05*

Do Cognitive underpinnings of RL and VR differ in Negative

symptom groupAccuracy

Time

EfficiencyVerbal Fluency

Verbal Fluency

Verbal Fluency

Verbal Fluency

Working Memory

Strategy

Spatial Memory

Social Cognition

R=0.47 p=0.04*

R=0.57 p=0.013

R=-0.52 p=0.02

R=0.47 p=0.05*

Conclusions 1. Does performance in VR relate to the same in RL? Yes

2. Do they share common or distinct cognitive processes?

Some shared (WM and strategy) but some distinct underlying cognitive processes

3. Do these processes differ in different symptom groups?

Some different and some similar cognitive underpinnings, greater overlap of VR and RL and stronger correlations in Negative symptom sub-group

Particular role for Social Cognition in RL where the social environment is

more important (and in VR with negative symptoms where avatars treated as real) and for spatial memory in VR

Conclusions and Limitations VR may be seen as an intermediate assessment between cognition

and RL but care should be taken in considering the nature of the VR environment, the underlying cognitive processes, and the clinical presentation of the client group

• Risk of type 1 errors with current comparatively small sample

• Participants had a wide range of cognitive performance with mean cognitive function largely in the average range and with mild-moderate negative symptoms.

• A greater contribution of cognition to community function may

occur when cognition is impaired and symptoms greater (Greenwood, Landau & Wykes 2005)

• Future study will consider the validity of VR assessments of community function within a cognitively impaired sample for whom interventions are developed

Executive functionA variety of fractionated cognitive processes concerned with the control, organisation and sequencing of higher cognition.

27-46% of people with schizophrenia have selective ‘executive’ profiles and 54-90% have at least one executive impairment (Johnson-Selfridge and Zalewski, 2001; Kremen et al. 2004; Chan et al. 2006a & b). Executive dysfunction is associated with poor social outcome (Kopelowicz et al. 2005, Laes and Sponheim 2006) . In studies of single symptoms, both syndromes have been associated with impaired verbal initiation and working memory and disorganisation also with attention, inhibition, discourse planning and monitoring (Liddle and Morris 1991; Hoffman et al. 1986; Pantelis et al 2001). First episode schizophrenia shows executive dysfunction at this early stage, with some degree of clinical heterogeneity (Joyce et al. 2005; 2007; Chan et al 2006b), but less impairment than is found in chronic schizophrenia (Saykin et al. 1994; Chan et al 2006b). Profiles have varied between studies, with parallel flat profiles of diffuse general impairment, parallel non-flat profiles with selective impairments, and selective impairments specific to chronic schizophrenia (Saykin et al. 1994, Blanchard and Neale 1994; Albus et al. 1996; Chan et al. 2006 a & b). These variations might result from studies that collapse test scores across broad domains.

Frith Disorganisation symptoms arise from impaired inhibition of habitual responses when plans must be constructed and implemented using working memory, whilst psychomotor poverty results from deficits in the initiation of activities due to impaired initiation of plans.

Conclusions

• Theoretical understanding of function can provide target cognitive processes for remediation

• Individual approach is important because of complex relationship between symptoms, cognition and function

• Remediation should link to day-to-day function ti improve outcome