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Ketamine affects prediction errors about statistical regularities: a computational single-trial analysis of the mismatch negativity
- Source :
- J Neurosci, Weber, L A, Diaconescu, A O, Mathys, C, Schmidt, A, Kometer, M, Vollenweider, F & Stephan, K E 2020, ' Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity ', The Journal of Neuroscience, vol. 40, no. 29, pp. 5658-5668 . https://doi.org/10.1523/jneurosci.3069-19.2020
- Publication Year :
- 2022
- Publisher :
- Society for Neuroscience, 2022.
-
Abstract
- The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the “Bayesian brain” notion that the brain continuously updates a hierarchical model to infer the causes of its sensory inputs. Specifically, predictive coding views perceptual inference as an NMDAR-dependent process of minimizing hierarchical precision-weighted prediction errors (PEs). Disturbances of this putative process play a key role in hierarchical Bayesian theories of schizophrenia.Here, we provide empirical evidence for this clinical theory, demonstrating the existence of multiple, hierarchically related PEs in a “roving MMN” paradigm. We applied a computational model, the Hierarchical Gaussian Filter (HGF), to single-trial EEG data from healthy volunteers that received the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject fashion. Using an unrestricted analysis of the entire time-sensor space, our computational trial-by-trial analysis indicated that low-level PEs (about stimulus transitions) are expressed early (102-207ms post-stimulus), while high-level PEs (about transition probability) are reflected by later components (152-199ms, 215-277ms) of single-trial responses. Furthermore, we find that ketamine significantly diminished the expression of high-level PE responses, implying that NMDAR antagonism disrupts inference on abstract statistical regularities.Our findings are consistent with long-standing notions that NMDAR dysfunction may cause positive symptoms in schizophrenia by impairing hierarchical Bayesian inference about the world’s statistical structure. Beyond their relevance for schizophrenia, our results illustrate the potential of computational single-trial analyses for assessing potential disease mechanisms.
- Subjects :
- Male
Computer science
Inference
Mismatch negativity
Hierarchical database model
hierarchical Gaussian filter
0302 clinical medicine
Models
Receptors
HGF
predictive coding
Evoked Potentials
Auditory
Research Articles
0303 health sciences
General Neuroscience
2800 General Neuroscience
Brain
Electroencephalography
Schizophrenia
Neurological
mismatch negativity
Auditory Perception
Evoked Potentials, Auditory
NMDA receptor
schizophrenia
Female
Ketamine
Single trial
Psychology
N-Methyl-D-Aspartate
Adult
Bayesian probability
Models, Neurological
Sensory system
610 Medicine & health
Stimulus (physiology)
Bayesian inference
Receptors, N-Methyl-D-Aspartate
03 medical and health sciences
Young Adult
Double-Blind Method
medicine
Humans
10237 Institute of Biomedical Engineering
030304 developmental biology
Predictive coding
Motivation
Bayes Theorem
medicine.disease
Settore M-PSI/02 - Psicobiologia e Psicologia Fisiologica
Acoustic Stimulation
10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Neurosci, Weber, L A, Diaconescu, A O, Mathys, C, Schmidt, A, Kometer, M, Vollenweider, F & Stephan, K E 2020, ' Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity ', The Journal of Neuroscience, vol. 40, no. 29, pp. 5658-5668 . https://doi.org/10.1523/jneurosci.3069-19.2020
- Accession number :
- edsair.doi.dedup.....f73d2ff2b7a9471ca86c923f475ad01e