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Review
. 2019 Sep 11;45(5):1092-1100.
doi: 10.1093/schbul/sby154.

Towards a Unifying Cognitive, Neurophysiological, and Computational Neuroscience Account of Schizophrenia

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Free PMC article
Review

Towards a Unifying Cognitive, Neurophysiological, and Computational Neuroscience Account of Schizophrenia

Andreas Heinz et al. Schizophr Bull. .
Free PMC article

Abstract

Psychotic experiences may be understood as altered information processing due to aberrant neural computations. A prominent example of such neural computations is the computation of prediction errors (PEs), which signal the difference between expected and experienced events. Among other areas showing PE coding, hippocampal-prefrontal-striatal neurocircuits play a prominent role in information processing. Dysregulation of dopaminergic signaling, often secondary to psychosocial stress, is thought to interfere with the processing of biologically important events (such as reward prediction errors) and result in the aberrant attribution of salience to irrelevant sensory stimuli and internal representations. Bayesian hierarchical predictive coding offers a promising framework for the identification of dysfunctional neurocomputational processes and the development of a mechanistic understanding of psychotic experience. According to this framework, mismatches between prior beliefs encoded at higher levels of the cortical hierarchy and lower-level (sensory) information can also be thought of as PEs, with important consequences for belief updating. Low levels of precision in the representation of prior beliefs relative to sensory data, as well as dysfunctional interactions between prior beliefs and sensory data in an ever-changing environment, have been suggested as a general mechanism underlying psychotic experiences. Translating the promise of the Bayesian hierarchical predictive coding into patient benefit will come from integrating this framework with existing knowledge of the etiology and pathophysiology of psychosis, especially regarding hippocampal-prefrontal-striatal network function and neural mechanisms of information processing and belief updating.

Keywords: computational modeling; delusions; dopamine; hallucinations; prediction error; reward; schizophrenia.

Figures

Fig. 1.
Fig. 1.
Circuit model of frontal and hippocampal control of dopamine neuron firing. The ventral hippocampus exerts potent control over dopamine neurons firing spontaneously. The number firing determines the amplitude, and hence salience, of the signal. Dopamine neurons are normally inhibited by the ventral pallidum, which in turn is inhibited by the nucleus accumbens. When the ventral hippocampus is activated, it activates the nucleus accumbens, which in turn inhibits the ventral pallidum and releases dopamine neurons from inhibition, allowing them to initiate firing. The ventral hippocampus is potently regulated by the PFC via the thalamus. The (infralimbic) PFC normally holds the ventral hippocampus in a less-active state. However, when infralimbic PFC activity is decreased, the primary effect is deactivation of the reticular nucleus of the thalamus, which in turn disinhibits the thalamic nucleus reuniens. This increases the tonic excitatory drive of the nucleus reuniens on the ventral hippocampus, disinhibiting dopamine firing, which impacts cognitive control via the associative striatum. The human analogue of the infralimbic cortex is the subgenual cingulate area 25. The arrows from the VTA to cortical and subcortical regions denote modulatory dopaminergic projections.
Fig. 2.
Fig. 2.
(A) Schematic model of altered hierarchical inference in the visual system. Sensory input represents processing in early visual cortex. Low-level “sensory” beliefs are encoded at the next higher hierarchical level, eg, mid- or high-level visual areas, and high-level “conceptual” beliefs at the highest cortical levels, eg, PFC. Arrows represent top-down signaling of prior beliefs and bottom-up signaling of prediction errors (PEs), with arrow thickness representing their respective precisions. The putative decrease in precision of low-level beliefs may lead to increased weighting of the sensory input, thus enhancing PEs, potentially compensated by increased precision of conceptual high-level beliefs. Brain image courtesy of Flickr/IsaacMao. (B) Schematic representation of the Hierarchical Gaussian Filter (adapted from Mathys et al). Levels x1(k)x2(k)x3(k) represent hidden environmental states at time k. They depend on their immediately preceding values x2(k1)x3(k1) and on the parameters κ (coupling of levels 2 and 3), ω (step size at level 2), and ϑ (learning speed about environmental volatility). The probability at each level is determined by the variables and parameters at the level above. The levels relate to each other by determining the step size of a random walk. Note that the levels of this model are not equivalent to those in (A). However, reduced learning speed about environmental volatility might contribute to a stronger top-down influence of high-level beliefs.

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