Abstract

We will use schizophrenia as a case study of computational psychiatry. We first review the basic phenomenology and pathophysiological theories of schizophrenia. These motivate the choice of a formal or computational framework within which to understand the symptoms and signs of schizophrenia. This framework is the Bayesian brain or Bayesian decision theory. We will focus on the encoding of uncertainty or precision within predictive coding implementations of the Bayesian brain to demonstrate how computational approaches can disclose the nature of hallucinations and delusions. The computational anatomy of psychosis Karl Friston

Computational Psychiatry Course - 29th-30th April 2015Venue: Basement Lecture Theatre, 33 Queen Square, London, WC1N 3BG

The symptoms and signs of schizophreniaDelusionsFalse beliefsDelusional systems

Hallucinations False percepts

Thought disorder Listening of associationsDisintegration of the psychePsychomotor propertyCognitive deficits

Soft neurological signsAbnormal eye movementsAbnormal mismatch negativity

Bleuler

Dysmorphophobia

Delusional mood

Depersonalisation

Compulsions

Intrusive thoughts

Obsessional beliefs

Affective symptoms

Dissociation syndromes

Capgras syndrome

Functional medical syndromes

Anxiety

Persecutory beliefs

Aberrant beliefs and false inferencePathophysiological and aetiological theoriesDopamine hypothesisAbnormal plasticityAberrant salience

Glutamate hypothesisNMDA receptor dysfunctionAberrant synchrony

GABAergic hypothesisAberrant gain controlAbnormal E-I balanceGenetic

Neurodevelopmental

Psychotomimetic drugs

Psychosocial

AutoimmuneBleuler

Aberrant neuromodulation and synaptic gain control

Bleuler E. Dementia Praecox oder Gruppe der Schizophrenien, 1911: Disintegration of conscious processing (the psyche) Wernicke C. Grundrisse der Psychiatrie. 1906:Sejunction disruption of associative connectivity

Anatomical disconnectionFunctional dysconnection

Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull. 2009 May;35(3):509-27Klaas E. Stephan, Karl J. Friston and Chris D. Frith

Aberrant neuromodulation and synaptic gain controlWhich computational (formal) framework?Reinforcement learning, optimal control and expected utility theory

Information theory and minimum redundancy

Self-organisation, synergetics and allostasis

Bayesian brain, Bayesian decision theory and predictive coding

PavlovHakenHelmholtz

Barlow

Which computational (formal) framework?Reinforcement learning, optimal control and expected utility theory

Information theory and minimum redundancy

Self-organisation, synergetics and allostasis

Bayesian brain, Bayesian decision theory and predictive coding

PavlovHakenHelmholtz

Barlow

Active inference, predictive coding and precision

Precision and false inference

Simulations of :

Auditory perception (and omission related responses)Smooth pursuit eye movements (under occlusion)Sensory attenuation (and the force matching illusion)

Objects are always imagined as being present in the field of vision as would have to be there in order to produce the same impression on the nervous mechanism - von Helmholtz

Thomas BayesGeoffrey HintonRichard FeynmanFrom the Helmholtz machine to the Bayesian brainRichard Gregory

Hermann von Helmholtz Bayesian filtering and predictive coding

prediction update

prediction error

Making our own sensations

Changing sensationssensations predictionsPrediction errorChanging predictionsActionPerceptionGenerative modelsHidden states

Action

Control states

Continuous statesDiscrete statesBayesian filtering (predictive coding)Variational Bayes(belief updating)

the

DescendingpredictionsAscending prediction errors

whatwhereSensory fluctuations

Hierarchical generative models

frontal eye fieldsgeniculatevisual cortexretinal inputponsoculomotor signals

Prediction error (superficial pyramidal cells)Conditional predictions (deep pyramidal cells)Top-down or backward predictionsBottom-up or forward prediction errorproprioceptive inputreflex arcPerceptionVTA

David MumfordPredictive coding with reflexesAction

Precision

Bayesian belief updating

VTA/SNPrefrontal CortexMotor CortexInferotemporal CortexStriatum

1234050100150200250300350400Simulated (CS & US) responsesPeristimulus time (sec)Rate1234050100150200250300350400Simulated (US) responsesPeristimulus time (sec)Rate

Condition stimulus (CS)Unconditioned stimulus (US)

Perception

Action selection

Incentive salience

Active inference, predictive coding and precision

Precision and false inference

Simulations of :

Auditory perception (and omission related responses)Smooth pursuit eye movements (under occlusion)Sensory attenuation (and the force matching illusion)

+-De-compensation(trait abnormalities)Compensation (to psychotic state)Neuromodulatory failure (of sensory attenuation)Attenuated violation responsesLoss of perceptual GestaltSPEM abnormalitiesPsychomotor povertyResistance to illusionsHallucinationsDelusions

Active inference, predictive coding and precision

Precision and false inference

Simulations of :

Auditory perception (and omission related responses)Smooth pursuit eye movements (under occlusion)Sensory attenuation (and the force matching illusion)

Generative model

SyrinxNeuronal hierarchy Time (sec)Frequency (KHz)sonogram0.511.5

Frequency (Hz)perceptprediction error

Predictive coding500100015002000-6-4-20246810peristimulus time (ms)LFP (micro-volts)

Reduced prior precision

Compensatory attenuation of sensory precision

Omission related responses, MMN and hallucinosis

Active inference, predictive coding and precision

Precision and false inference

Simulations of :

Auditory perception (and omission related responses)Smooth pursuit eye movements (under occlusion)Sensory attenuation (and the force matching illusion)

Generative processGenerative model

retinal inputponsproprioceptive input

Angular position of target in intrinsic coordinatesAngular direction of gaze in extrinsic coordinatesAngular direction of target

timevisual channels

Smooth pursuit eye movements eye (reduced precision)50010001500200025003000-2-1012Angular positiondisplacement (degrees) 50010001500200025003000-20-1001020304050time (ms)velocity (degrees per second)Angular velocity eye target

Eye movements under occlusion and reduced prior precision1002003004005006007008009001000-2-1012target and oculomotor anglestime (ms)displacement (degrees) 1002003004005006007008009001000-30-20-100102030target and oculomotor velocitiestime (ms)velocity (degrees per second) eye (reduced precision) eye target

Paradoxical responses to violations

Active inference, predictive coding and precision

Precision and false inference

Simulations of :

Auditory perception (and omission related responses)Smooth pursuit eye movements (under occlusion)Sensory attenuation (and the force matching illusion)

Generative processGenerative modelMaking your own sensations

25

motor reflex arcthalamussensorimotor cortexprefrontal cortex

ascending prediction errorsdescending modulationdescending predictionsdescending motor predictionsdescending sensory predictions26Sensory attenuation

51015202530-0.500.511.52prediction and errorTime (bins)51015202530-0.500.511.52hidden statesTime (bins)51015202530-0.500.51hidden causesTime (bins)51015202530-0.8-0.6-0.4-0.200.20.40.60.81Time (bins)perturbation and action

Self-made actsFailure of sensory attenuation51015202530-0.500.511.52prediction and errortime51015202530-0.500.511.52hidden statestime51015202530-0.500.51hidden causestime51015202530-0.8-0.6-0.4-0.200.20.40.60.81timeperturbation and actionand psychomotor poverty102030405060-0.500.511.52prediction and errorTime (bins)102030405060-0.500.511.52hidden statesTime (bins)102030405060-0.500.511.52hidden causesTime (bins)102030405060-0.500.511.52Time (bins)perturbation and action102030405060-0.500.511.52hidden statesForce matching illusion102030405060-0.500.511.52prediction and errorTime (bins)Time (bins)Sensory attenuation102030405060-0.500.511.5hidden causesTime (bins)102030405060-0.500.511.5Time (bins)perturbation and actionPerceived as lessReproduced as moreIntrinsic and extrinsic

00.511.522.5300.511.522.53 External (target) forceSelf-generated(matched) forceExternal (target) forceSelf-generated(matched) forceSimulatedEmpirical (Shergill et al)

Compensated failures of sensory attenuationNormal subjectsSchizophrenic subjectsFailure of sensory attenuation and delusions of control102030405060-0.500.511.522.533.5prediction and errorTime (bins)102030405060-0.500.511.522.533.5hidden statesTime (bins)102030405060-1-0.500.511.522.533.5hidden causesTime (bins)102030405060-0.500.511.522.533.5Time (bins)perturbation and action We act by predicting our action to create (attenuated) prediction errors that are suppressed reflexively

A failure of sensory attenuation subverts our predictions and precludes action (psychomotor poverty)

Compensatory increases in prior precision reinstate (unattenuated) prediction errors

Unattenuated prediction errors can only be explained by (antagonistic) external forces (delusions of control and made acts)

A computational account of delusions of agencySigns (of trait abnormalities)Attenuated violation responsesLoss of perceptual GestaltSPEM abnormalitiesPsychomotor povertyResistance to illusions

Symptoms (of psychotic state)HallucinationsDelusions

+-Neuromodulatory failure(of sensory attenuation)Summary

What is the functional deficit?

What is the pathophysiology?

How can we measure it?

What is the aetiology?

What is the intervention?Summary False inference due to aberrant encoding of precisionA neuromodulatory failure of postsynaptic excitability:Aberrant DA/NMDA subunit interactionsAberrant synchronous gain and fast (gamma) dynamicsAberrant cortical gain control and E-I (GABAergic) balanceAberrant dendritic integration (neuro-morphology)Modelling of behaviour and noninvasive brain responsesComputational modelling of choice behaviourComputational fMRIDynamic casual modelling of intrinsic (precision) gain controlAnd thanks to collaborators:

Rick AdamsRyszard AuksztulewiczAndre BastosSven BestmannHarriet BrownJean DaunizeauMark EdwardsChris FrithThomas FitzGeraldXiaosi GuStefan KiebelJames KilnerChristoph MathysJrmie MattoutRosalyn MoranDimitri OgnibeneSasha Ondobaka Will PennyGiovanni PezzuloLisa Quattrocki KnightFrancesco Rigoli Klaas StephanPhilipp Schwartenbeck

And colleagues:

Micah AllenFelix BlankenburgAndy ClarkPeter DayanRay DolanAllan HobsonPaul FletcherPascal FriesGeoffrey HintonJames HopkinsJakob HohwyMateus JoffilyHenry KennedySimon McGregorRead MontagueTobias NolteAnil SethMark SolmsPaul Verschure

And many othersThank you

V5V5V1ITITPCPCVisual inputPrefrontal inputcontrol subjects - predictablecontrol subjects - unpredictableschizophrenia - predictableschizophrenia - unpredictable

V1R V5L V5R ITL ITR PCL PC-2-1.5-1-0.500.511.5cortical sourcelog modulationEffects of predictability on recurrent inhibition control subjectsschizophrenics