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George Foussias, MD PhD FRCPC VR & Behavioural Neuroscience Research Lab

Slaight Family Centre, Campbell Research Institute, and Schizophrenia Division, CAMH

Novel Virtual Reality-Based Strategies for Evaluating and Treating Negative Symptoms In Schizophrenia

Disclosures

No relevant disclosures

1. Mason et al. 1996; 2. Schooler 2006.

Cumulative Recovery Rates in First-Episode Schizophrenia2

Symptom remission Social functioning Full recovery

Per

cent

age

of s

ubje

cts

100

0 Year 3 Year 4 Year 5 Year 6

80

60

40

20

50

40

30

20

10

0 Year 0 Year 1 Year 2 Year 13

WHO-ISOS Social adjustment over 13 years1

Poor Fair Good

Functional Outcomes in Schizophrenia

Strauss et al. 2010; Sayers et al. 1996; Kiang et al. 2003; Faerden et al. 2009 & 2010; Fervaha et al. 2014; Foussias et al. 2009 & 2011; Konstantakopoulos

et al. 2011; Nakagami et al. 2008; Gard et al. 2007 & 2009.

Functional Outcomes in Schizophrenia

Motivation

Social Cognition

Neurocognition

Functional Outcomes

Waltz et al. 2007; Gold et al. 2008; Juckel et al. 2006; Gold et al. 2013; Fervaha et al. 2013; Barch et al. 2014; Treadway et al. 2014.

Objective Evaluations of Motivation in Schizophrenia

Animals At Work

Real-World Motivation Deficits in Schizophrenia

Demographics

SZ (n=50) Mean (SD)

HC (n=57) Mean (SD)

p Age 36.9 (10.6) 35.8 (11.6) ns Sex (M:F) 31:19 35:22 ns Duration of Illness (yrs) 13.6 (10.0)

Bivariate Correlations (rho)

Points Earned

Task Completions

Task Completion

Rate Amotivation (n=107) - .26** - .25** .29**

SZ Only (n=50) Amotivation - .29* - .41** .37** Positive symptoms - - - Diminished Expression - - - Depression - - - Anticipatory Pleasure - - - Consummatory Pleasure - - - Neurocognition - - - Motor speed - - - * p

Functional Neuroimaging in a Virtual Environment

• 3T GE scanner 6 x 5 min. runs MR-compatible

joystick

Demographics and Clinical Characteristics

SZ (n=18) Mean (SD)

HC (n=19) Mean (SD) p

Age 36.6 (11.3) 35.6 (12.7) ns Sex (M:F) 10:8 11:8 ns Diagnosis

Schizophrenia 16 Schizoaffective Disorder 2

Duration of Illness (yrs) 14.2 (8.6)

Positive symptoms (SAPS) 13.9 (3.0) Negative symptoms (SANS) 22.8 (8.3) 6.8 (6.4)

Striatal Function During Effortful Behavior

Subcortical ROI

Group Difference

s

Task Completio

ns (ρ) Effort Events

Accumbens - - Caudate - - Putamen - .40*

Reward Events Accumbens pcorr=.033 - Caudate pcorr=.066 - Putamen - .41*

* p

Whole Brain Functional Deficits in Effortful Behavior in SZ

Whole Brain Analysis

Coordinates

Beta-value Correlations (ρ)

Anatomic Region

x

y

z

Cluster size

Max T

SANS-Amotivation

Task Completions

Effort Events (HC>SZ)

E1

R Anterior Cingulate

18

38

32

357

4.12

-.37*

E2

L Medial Superior Frontal Gyrus

-6

30

46

196

4.1

-.56***

.39*

E3

L Inferior Frontal Gyrus

-52

26

16

121

4.05

-.47**

.35*

E4

R Angular Gyrus

40

-72

52

117

4.05

E5

L Middle Temporal Gyrus

-56

-72

16

160

3.97

-.37*

E6

L Angular Gyrus

-32

-56

34

196

3.76

-.34*

E7

R Cerebellum 6

32

-52

-30

181

3.73

-.34*

.38*

E8

R Cerebellum 6

14

-64

-20

121

3.69

-.45**

.40*

E9

R Inferior Frontal Gyrus

40

6

30

488

3.61

-.41*

.38*

E10

R Cerebellum Crus II

22

-78

-44

132

3.42

Reward Events (HC>SZ)

R1

R Mid Cingulate / Middle Frontal Gyrus

12

-6

32

492

5.53

R2

R Inferior Frontal Gyrus

50

36

20

159

4.87

.36*

R3

L Mid Cingulate

-6

0

28

263

4.34

R4

L Precentral Gyrus

-58

4

30

260

4.04

-.45**

R5

L Mid Cingulate

-8

20

38

178

3.87

* p

E2

E3

Functional Deficits in Effortful Behavior in SZ

E7 / E8

Functional Deficits in Effortful Behavior in SZ

E9

R2

Functional Deficits in Effortful Behavior in SZ

Antipsychotics

Antidepressants

CBT

Cognitive Remediation

Glutamatergic Agents

Stimulants

rTMS tDCS

Rummel et al. 2006; Murphy et al. 2006; Tuominen et al. 2006; Buckley et al. 2007; Singh et al. 2010

Treatments for Negative Symptoms

Computerized Brain Training

Game-Based and Virtual Therapy

Merry et al. 2012

PresenterPresentation NotesAnd translation to more engaging video games, with underlying CBT principles that show promise for effective treatment of depression in teens.Distinct modules, and text-based feedback and communication of underlying principles.Along with persistence of benefit (remission) beyond the end of treatment.

VR-based Treatment of Motivation Deficits

0

10

20

30

40

50

60

70

80

1 2 3 4 5

Effo

rt to

Rew

ard

Rat

io

Training Step

VR Rehabilitation for Motivation Deficits

Objective: • Pilot study to evaluate a VR-based treatment for motivation deficits in

early schizophrenia • Evaluate the secondary effects of VR-based motivation treatment on

community functioning

Participants • Schizophrenia or Schizoaffective Disorder • 18 – 35 years of age • Minimum Apathy Evaluation Scale (AES) score of 34 (moderate

motivation deficits)

Intervention • VR-based motivation training – 1hr per week x 8 weeks

VR Rehabilitation for Motivation Deficits

Participant Demographics

Mean (SD) at Baseline (n=15)

Age 25.3 (4.5)

Sex (M:F) 10:5

Positive symptoms (SAPS) 31.5 (16.9)

Negative symptoms (SANS) 41.1 (15.0)

Motivation Deficits (AES) 41.9 (4.8)

Cognition (BACS) -1.5 (0.9)

Depression (CDSS) 2.9 (2.5)

Community Functioning (QLS) 57.1 (14.8)

VR Rehabilitation for Motivation Deficits

* *

*

Significant reduction in motivation deficits F(4,45.7)=2.74, p=.04

Modest 9% improvement in motivation

27% increase in intrinsic motivation • 50% experiencing

>20% improvement

VR Rehabilitation for Motivation Deficits

Baseline Mean (SD)

Post-treatment Mean (SD) t p

Intrinsic Motivation (QLS) 20.1 (6.1) 24.2 (4.0) -2.9 0.014

Community Functioning (QLS) 54.9 (15.8) 64.6 (13.7) -1.94 0.079

Interpersonal Functioning (QLS) 22.3 (9.9) 22.0 (8.4) 0.16 ns

Instrumental Functioning (QLS) 5.8 (5.0) 9.6 (7.0) -2.41 0.035

Positive Symptoms (SAPS) 36.4 (14.8) 30.9 (20.2) 2.61 0.024

Depression (CDSS) 3.1 (2.5) 3.2 (3.4) -0.12 ns

Cognition (BACS) -1.7 (0.9) -1.7 (1.1) 0.19 ns

VR Rehabilitation for Motivation Deficits

* 56% improvement in role

functioning

50% of patients experienced > 20% improvement

VR Rehabilitation for Motivation Deficits

Acknowledgements

Gary Remington Albert Wong Martin Lepage Konstantine Zakzanis Paul Fletcher Ishraq Siddiqui Gagan Fervaha Sarah Saperia Susana Da Silva John Zawadzki Krysta McDonald Areti Apatsidou

Aristotle N. Voineskos Colin Hawco Joseph Viviano Research participants

Thank you

Slide Number 1DisclosuresFunctional Outcomes in SchizophreniaFunctional Outcomes in SchizophreniaObjective Evaluations of Motivation in SchizophreniaAnimals At WorkReal-World Motivation Deficits in SchizophreniaSlide Number 8Functional Neuroimaging in a Virtual EnvironmentSlide Number 10Striatal Function During Effortful BehaviorWhole Brain Functional Deficits in Effortful Behavior in SZSlide Number 13Slide Number 14Slide Number 15Treatments for Negative SymptomsComputerized Brain TrainingGame-Based and Virtual TherapyVR-based Treatment of Motivation DeficitsVR Rehabilitation for Motivation DeficitsVR Rehabilitation for Motivation DeficitsVR Rehabilitation for Motivation DeficitsVR Rehabilitation for Motivation DeficitsVR Rehabilitation for Motivation DeficitsVR Rehabilitation for Motivation DeficitsAcknowledgementsThank you