TY - JOUR
T1 - P.2.009 - Dopamine modulates belief updating but not surprise in the midbrain and ventral striatum
T2 - Abstracts of the ECNP Workshop for Junior Scientists in Europe 15-18 March 2017, Nice, France
AU - Nour, M.
AU - Dahoun, T.
AU - Schwartenbeck, P.
AU - Adams, R.
AU - Coello, C.
AU - Wall, M.
AU - FitzGerald, T.
AU - Dolan, R.
AU - Howes, O.
PY - 2018/3
Y1 - 2018/3
N2 - Dopamine may be critical for processing the meaningful information content of observations, which drives belief updating about the (hidden) states of the world [1–3]. In human functional magnetic resonance imaging (fMRI) studies, neuronal activity encoding the magnitude of belief updates has been detected in dopamine-rich midbrain regions, namely the substantia nigra and ventral tegmental area (SN/VTA) [1-3]. Yet, there is no direct evidence linking dopamine function to belief updating signals in humans. This question is relevant to our understanding of the relationship between dopamine, aberrant inference and the generation of psychotic symptoms such as paranoia [4]. We investigated the dopaminergic basis of belief update signals using fMRI and positron emission tomography (PET) imaging. 39 healthy participants (mean age 26y, 22 male) performed an fMRI task that decomposed sensory information into information-theoretic surprise (unexpected but not necessarily meaningful information content) and Bayesian surprise (magnitude of belief updates due to meaningful information) [1]. A Bayesian observer computational model was fitted to participants’ behavior, allowing the derivation of trial-wise regressors for information-theoretic and Bayesian surprise for fMRI analysis. 36 participants also had a [11C]-(+)-4-propyl-9-hydroxy-naphthoxazine ([11C]-(+)-PHNO) PET scan to quantify dopamine-2/3 receptor (D2/3R) availability. 17 participants additionally had a second [11C]-(+)-PHNO PET scan 3hrs following 0.5mg/kg oral dexamphetamine, to quantify striatal dopamine release capacity. Our analyses focused on the relationship between measures of neuronal activity (fMRI) and dopamine function (PET) in the bilateral SN/VTA complex and ventral striatum (VS). Our computational model closely predicted participant behaviour (R2= .67), and there was a negative correlation between subclinical paranoid thoughts and the degree to which participant behavior approximated the predictions of an ideal Bayesian observer (rho = -0.60, P<0.001). The magnitude of belief updates (Bayesian surprise) was encoded in the SN/VTA and VS (both PFWE<0.05), putatively reflecting dopaminergic activity. Neuronal activation encoding Bayesian surprise was inversely correlated with D2/3R availability in the SN/VTA (rho = -0.43, P=0.009), consistent with studies indicating that midbrain D2/3R inhibit dopamine neurons [5]. Moreover, neuronal activation encoding Bayesian surprise was inversely related to dopamine release capacity in the VS (rho = -0.66, P=0.005), indicating that subjects with high dopamine release capacity showed blunted striatal activation in response to belief-changing information (as is also found in schizophrenia [4]). Neuronal activation encoding information-theoretic surprise was not present in the SN/VTA or VS, and showed no association with dopaminergic measures. Our results indicate that the SN/VTA and VS are involved in processing the meaningful information of observations, as reflected in Bayesian belief updating [1-3]. Crucially, we provide direct evidence that neuronal signals encoding (unsigned) belief updates depend on dopaminergic activity, at variance with classical interpretations of dopamine function in terms of (signed) reward prediction errors. Moreover, our results suggest that a reduced behavioural sensitivity to meaningful information is related to subclinical paranoia. Together, these results are highly relevant for dopaminergic theories of psychosis, such as the aberrant salience hypothesis, which posit that mesostriatal dopamine dysfunction results in the formation of false beliefs about the causes of sensory information, leading to hallucinations and delusions [4].
AB - Dopamine may be critical for processing the meaningful information content of observations, which drives belief updating about the (hidden) states of the world [1–3]. In human functional magnetic resonance imaging (fMRI) studies, neuronal activity encoding the magnitude of belief updates has been detected in dopamine-rich midbrain regions, namely the substantia nigra and ventral tegmental area (SN/VTA) [1-3]. Yet, there is no direct evidence linking dopamine function to belief updating signals in humans. This question is relevant to our understanding of the relationship between dopamine, aberrant inference and the generation of psychotic symptoms such as paranoia [4]. We investigated the dopaminergic basis of belief update signals using fMRI and positron emission tomography (PET) imaging. 39 healthy participants (mean age 26y, 22 male) performed an fMRI task that decomposed sensory information into information-theoretic surprise (unexpected but not necessarily meaningful information content) and Bayesian surprise (magnitude of belief updates due to meaningful information) [1]. A Bayesian observer computational model was fitted to participants’ behavior, allowing the derivation of trial-wise regressors for information-theoretic and Bayesian surprise for fMRI analysis. 36 participants also had a [11C]-(+)-4-propyl-9-hydroxy-naphthoxazine ([11C]-(+)-PHNO) PET scan to quantify dopamine-2/3 receptor (D2/3R) availability. 17 participants additionally had a second [11C]-(+)-PHNO PET scan 3hrs following 0.5mg/kg oral dexamphetamine, to quantify striatal dopamine release capacity. Our analyses focused on the relationship between measures of neuronal activity (fMRI) and dopamine function (PET) in the bilateral SN/VTA complex and ventral striatum (VS). Our computational model closely predicted participant behaviour (R2= .67), and there was a negative correlation between subclinical paranoid thoughts and the degree to which participant behavior approximated the predictions of an ideal Bayesian observer (rho = -0.60, P<0.001). The magnitude of belief updates (Bayesian surprise) was encoded in the SN/VTA and VS (both PFWE<0.05), putatively reflecting dopaminergic activity. Neuronal activation encoding Bayesian surprise was inversely correlated with D2/3R availability in the SN/VTA (rho = -0.43, P=0.009), consistent with studies indicating that midbrain D2/3R inhibit dopamine neurons [5]. Moreover, neuronal activation encoding Bayesian surprise was inversely related to dopamine release capacity in the VS (rho = -0.66, P=0.005), indicating that subjects with high dopamine release capacity showed blunted striatal activation in response to belief-changing information (as is also found in schizophrenia [4]). Neuronal activation encoding information-theoretic surprise was not present in the SN/VTA or VS, and showed no association with dopaminergic measures. Our results indicate that the SN/VTA and VS are involved in processing the meaningful information of observations, as reflected in Bayesian belief updating [1-3]. Crucially, we provide direct evidence that neuronal signals encoding (unsigned) belief updates depend on dopaminergic activity, at variance with classical interpretations of dopamine function in terms of (signed) reward prediction errors. Moreover, our results suggest that a reduced behavioural sensitivity to meaningful information is related to subclinical paranoia. Together, these results are highly relevant for dopaminergic theories of psychosis, such as the aberrant salience hypothesis, which posit that mesostriatal dopamine dysfunction results in the formation of false beliefs about the causes of sensory information, leading to hallucinations and delusions [4].
U2 - 10.1016/j.euroneuro.2017.12.048
DO - 10.1016/j.euroneuro.2017.12.048
M3 - Meeting abstract
SN - 0924-977X
VL - 28, Supplement 1
SP - S27-S28
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -
