Predictive Coding and Psychosis/Schizophrenia

Paul Fletcher

pcf22@cam.ac.uk

Workshop on:

The Free Energy PrincipleWTCN July 2012

Bernard Wolfe Health Neuroscience Fund

Overview…

• What is psychosis? how does it related to schizophrenia?

• A disintegration of functions underlain by perturbations in receptor function and consequence oddities of neural responses and of synaptic efficacy and gain

• Using the principles emerging from a predictive coding model, we can understand the array of symptoms, experiences and behaviour that characterise schizophrenia?

• The FEP lays out a model that, in disclosing relationships between perception/inference, learning/memory and attention/salience, equips us with a framework that links the disease to the brain.

“If I have a fight with my sister and I run to my room, then I can still hear her whispering about me, calling me names, telling people lies about me”

Is she outside your room? Is that how you can hear her?

“No. She’s still downstairs and she is just whispering…I don’t know how I can hear her so clearly but I can”

Video slide

PsychosisDelusions - Hallucinations

DisorganisationIn thought/language/behaviour

Negative featuresVolition

BehaviourLanguage

Social

Cognitive impairmentPervasive

Schizophrenia

Associations underlie all knowledge and belief

Most beliefs (including delusions) are instances of abduction

perceive believe

Starting point…

• Perturbed prediction error signal, leading to abnormal associative learning, underlies delusion formation

Brain marker for PE-dependent learning

Fletcher et al Nature Neurosci, 2001

Turner et al Cereb Cortex, 2004

Corlett et al Neuron, 2004

Murray et al, Molecular Psych, 2007; Corlett et al, Arch Gen Psych 2006; Brain 2007

PE+ PE- PE+ PE-

PE+ PE- PE+ PE-

Corlett et al, Brain 2007

Corlett et al Brain 2007

Controlled perturbation of the system

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placebo ketaminePlacebo Ketamine

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PE-Corlett et al Arch Gen Psych, 2006

PE+ PE- PE+ PE-

Ketamine- Target-controlled infusion to 100ng/ml plasma (sub-psychotic dose- Healthy controls- Within-subject, placebo-controlled

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Corlett et al, Arch Gen Psych 2006

But…

PsychosisDelusions - Hallucinations

DisorganisationIn thought/language/behaviour

Negative featuresVolition

BehaviourLanguage

Social

Cognitive impairmentPervasive

Schizophrenia

Perception, learning and attention in early schizophrenia

• Selected verbatim reports from the first two years of the illness…– Chapman/McGhie– Matussek– Norma MacDonald

Perceptual changes in early schizophrenia

• “Colours seem to be brighter now…almost as if they were luminous”

• “Everything’s brighter and louder and noisier”

• “I was sitting listening to another person and suddenly the other person became smaller and then larger and then he seemed to get smaller again.”

Perception-action interactions

• “Everything is all right when I stop. If I move, every thing I see keeps changing, everything I'm looking at gets broken up and I stop to put it together again. Moving is like a motion picture. If you move, the picture in front of you changes. The rate of change in the picture depends on the speed of walking. If you run you receive the signals at a faster rate.”

Perception-action interactions

• “I try to keep moving, and at the same time try to pay attention to what I see, that's when things become difficult…You only see a still picture if you don't move your head and eyes.”

• “When I start walking I get a fast series of pictures in front of me. Everything seems to change and revolve around me. Something goes wrong with my eyes and I've got to stop and stand still.”

Attention and salience

• “The sensitivity”• “At ordinary times I would have taken pleasure in

watching the dog but would never have been so captivated by it”

• “…It was as if parts of my mind “awoke”…I became interested in a wide assortment of people, events, places and ideas which normally would make no impression on me” (source)

• “I can't control my thoughts. I can't keep thoughts out. It comes on automatically.”

Perception-attention interaction

• “At these times, perceptual stability appears to be lost and the patients are unable to reduce, organize, and interpret visual information in a normal fashion. The patient's attention is diverted to inspection of different parts of a whole, instead of being free to interpret and assimilate the whole itself.”– McGhie and Chapman

Are actions altered in schizophrenia?

• Yes

• Stereotypies and mannerisms

• Echopraxia

• Waxy flexibility

• (Agency misattribution)

Video

Video

Video

Video

Echopraxia in schizophrenia

• A consequence of impaired perceptual and attentional functions– Chapman & McGhie, 1964

• “there is a close relationship between the perception and knowledge of the external world, of one’s body and of one’s self. All three are affected in schizophrenia probably by a disturbance of some underlying physiological mechanism”– Weckowicz and Sommer, 1960

The echopractic moment:

• “…my senses withdraw completely, my mind just comes to a stop and then I don’t pay attention to anything…I lose myself and become a mirror of them…I am nothing if I haven’t got contact with the outside world”

• “you look at the object and concentrate on it so that you become the object. There’s nothing else to hold the mind…”

• “somebody moves or crosses his knees. I feel I have to move at the same time…it makes it easier to understand the person’s thoughts” [Frequently at interviews with this patient, verbal communication tended to break down and the patient’s attention was taken up by minor irrelevant actions on the part of the observer]

Video

Flexibilitas Cerea – minimising prediction error by not acting?

• “Everything is all right when I stop. If I move every thing I see keeps changing, everything I'm looking at gets broken up…”

• “You only see a still picture if you don't move your head and eyes.”

• “When I start walking…Everything seems to change and revolve around me…I've got to stop and stand still.”

Video

• Cambridge– BCNI:

• Psychiatry: PR Corlett, GK Murray, G Honey, E Pomarol-Clotet, A Blackwell, E Bullmore, P McKenna, DC Turner PB Jones JA McCabe, FS Arana, HL Morgan, J Everitt, J Piggott, J Gardner, J Moore, C Teufel, A Kingdon

• Psychology: A Dickinson, M Aitken, T Robbins, L Clark– Anaesthetics:

• AR Absalom, DK Menon, M Lee, R Adapa– Engineering: D Wolpert, J Ingram

• London UCL• D Shanks, M Pessiglione

• Acacia- University of Amsterdam• Sanne de Wit

Co-investigators:

Bernard Wolfe Health Neuroscience Fund