Neurocognitive Deficits in Schizophrenia Colin Hawco, PhD Oct 5 2015 York University.
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Transcript of Neurocognitive Deficits in Schizophrenia Colin Hawco, PhD Oct 5 2015 York University.
NeurocognitiveDeficits in
SchizophreniaColin Hawco, PhD
Oct 5 2015York University
Magnitude of Cognitive Deficits in Schizophrenia
Meta-Analysis: 204 studies, 7420 patients and
5865 controls
Heinrichs & Zakzanis. Neuropsychology. 1998 Jul;12(3):426-45.
SD below mean of controls
Trajectory of Cognitive Deficits
Lewandowski et al. Psychol Med. 2011 Feb;41(2):225-41.
Cognitive Deficits Predict Functional Outcomes
Functional Outcomes
Learning & Memory
Attention
Executive Function
Green. Am J Psychiatry. 1996; 153:321-330Velligan et al. Schizophr Res. 1997 May 3;25(1):21-31.
Cognitive Deficits and Short-Term Clinical Outcome
Controls (n = 31)
Good Outcome (n = 73)
Poor Outcome (n = 78)
Clinical outcome assessed at 6 monthsGood outcome: > 2 on all global SAPS and > 3 on all global SANS (except attention)
Bodnar et al. The British Journal of Psychiatry 2008 193: 297-304
Domain specific vs. generalized deficits?
MATRICS Consensus Battery • based on domain specific hypothesis
• Speed of Processing• Attention/Vigilance• Working Memory• Verbal Learning and Memory• Visual Learning and Memory• Reasoning and Problem Solving
If generalized deficit, why engage in long neuropsych testing?
• Probably a combination• Generalized deficits, with some
domains affected more than others• Variability in specific domains across
individuals?
3 Clu
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2 Clu
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4 Clu
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5 Clu
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6 Clu
ster
s C2p = 17c = 23
C6p = 5
C5p = 20
C4p = 10 c = 1
C1p = 67c = 37
C3n = 71
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
C2 (n = 14) C1 (n = 57) C3 (n = 57) C4 (n = 9) C5 (n = 20)
Perc
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f pati
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mis
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Pat
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Z-s
core
Above average cognition
Severe cognitive impairments
Hierarchical Clustering of Cognition in First Episode Psychosis
Why such a large deficit for Trails B?
Highly multi-factorial test
Scored by time, allowing “unlimited failure”
• Select, via consensus, specific tasks to evaluate different cognitive functions
• Emphasis on imaging• “Domain specific” in approach• Tasks intended to be highly specific to a particular
cognitive domain or function• Avoids “multifactorial” problem of traditional
neuropsychological tests
Verbal Memory and Encoding Strategies
Incidental encoding (supported ‘deep’ encoding) vs.
Intentional encoding (instruction to memorize)
Bonner-Jackson et al., Psychiatry Research: Neuroimaging 164 (2008) 1–15
Controls > patients
Patients > controls
Meta analysis of fMRI studies of Memory Encoding
Ragland et al. Am J Psychiatry 2009; 166:863–874
Memory deficits mainly related to prefrontal cortex
LTM effects (high subsequent memories)
Working and Long-term Memory Interactions
Greater DLPFC activity for rehearse over reorder related to less negative symptoms
Ragland et al., NeuroImage 59 (2012) 1719–1726
Green ControlRed Schizophrenia
Patients with Schizophrenia have a Deficit in Source Monitoring
Keefe et al., Schizophrenia Research 57 (2002) 51 – 67
- Tendency to attribute internally generated stimuli to an external source
- Particularly in patients who hallucinate
Wang et al. Schizophrenia Research 125 (2011) 136–142
fMRI of Source Memory in Schizophrenia
- Encoding session with two tasks- Source memory: identifying the task associated with a word- 13 Patients and 13 controls
Green: ControlsRed: Schizophrenia
Ragland et al. Schizophr Res. 2006 , 87(1-3):160-171.
Recognition:• Person• Place• Object
Source Memory in Schizophrenia: An fMRI VR Study
Lisa Buchy
X = -45
X = -30
X = -15
X = 0
X = 15
X = 30
X = 45
X = -45
X = -30
X = -15
X = 0
X = 15
X = 30
X = 45
Controls Schizophrenia Controls Schizophrenia
Person > objectPlace > objectPerson AND place > object
Object > personObject > placeObject > person AND place
Schizophrenia vs. Controls
A
X = -55
A
X = -55
0
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6
controls schizophrenia
A: -50, 23, 30
person place objec
Control >Schizophrenia,Personvs. Object Control >Schizophrenia, Placevs. Object Schizophrenia>Control, Placevs. Object
X = -35
B
0
1
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controls schizophrenia
B: -36 -70, 40
person place obje
X = 5
C
-1
0
1
2
3
controls schizophrenia
C: 2, -64, 36
person place objec
X = -15 D
0
0.5
1
1.5
controls schizophrenia
D: -8, 14, 34
person place objec
X = 25
E
-1
-0.5
0
0.5
controls schizophrenia
E: 30, 44, 26
person place objec
X = 55
F-1
-0.5
0
0.5
controls schizophrenia
F: 56, -2, -16
person place obje
Cognitive insight in Schizophrenia
Current Project: TMS-fMRI during working memory in Schizophrenia
2 sec 6 sec 2 sec
Single TMS pulse at 500ms into delayHigh TMS vs. Low TMS
500ms TMS to assess Maintenance vs. manipulation4000ms as a control: Manipulation should have completed and now maintaining
Jennifer Steeves
Reorder Reorder
+
TMS-fMRI gives us a measure of temporally specific connectivity
Treating Cognitive Deficits
• Behavioural Interventions: Cognitive remediation– Transfer effects? Efficacy? Duration?
• Pharmaceutical Interventions: Aripiprazole• Neural Modulation: rTMS, TDCS
– Efficacy? Duration of effects?• Combined approaches
– Brain stimulation combined with cognitive remediation
Neurological effects of Cognitive Remediation
Changes from CRTWorking memory (HCL > SCZ)WM and CRTAffective processing
CRT Changes activity in the left prefrontal cortex, thalamus, caudate, and right anterior insula and parietal cortex
Some regions showing changes overlap areas where SCZ shows reduced activity during working memory.
There is some suggestions that CRT normalized brain function as opposed to compensatory patterns.
Ramsay and McDonald. Schiz Bulletin. 20015,
Future of Brain Stimulation: Targeting?
Summary
• Cognitive deficits are present throughout the lifespan and functionally important.
• While generalized deficits may be present, some domain specificity exits (e.g. worse verbal memory)
• Multi-factorial nature of neuropsychological test may affect results and interpretations
• Cognitive neuroscience approach may better detect specific effects (but longer tests limit utility)
• Patients show deficits across a range of brain regions, often reduced activity.
• Particularly in HUB regions (e.g. DLPFC).• Reduced activity related to less supporting cognitive processing?
• Understanding and treating these deficits may lead improved outcome and quality of life for these patients.
Merci!
Martin Lepage
Jeff Daskalakis
Faranak Farzan George Foussias
Aristotle Voineskos Jennifer
Steeves
Yoon et al., Am J Psychiatry 2008; 165:1006–1014
Functional Connectivity and Cognition
AX-BX continuous performance task
Control > SCZBX-AX
Controls showed increased connectivity between DLPFC and these regions while patients did not.