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Spontaneous prediction error generation in schizophrenia.

ABSTRACT: Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.

SUBMITTER: Yamashita Y

PROVIDER: S-EPMC3364276 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Spontaneous prediction error generation in schizophrenia.

Yamashita Yuichi Y Tani Jun J

PloS one 20120530 5

Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric ...[more]

PMID: 22666398

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Project description:Current theories of cognitive dysfunction in schizophrenia emphasize an impairment in the ability of individuals suffering from this disorder to monitor their own performance, and adjust their behavior to changing demands. Detecting an error in performance is a critical component of evaluative functions that allow the flexible adjustment of behavior to optimize outcomes. The dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in error-detection and implementation of error-based behavioral adjustments. However, accurate error-detection and subsequent behavioral adjustments are unlikely to rely on a single brain region. Recent research demonstrates that regions in the anterior insula, inferior parietal lobule, anterior prefrontal cortex, thalamus, and cerebellum also show robust error-related activity, and integrate into a functional network. Despite the relevance of examining brain activity related to the processing of error information and supporting behavioral adjustments in terms of a distributed network, the contribution of regions outside the dACC to error processing remains poorly understood. To address this question, we used functional magnetic resonance imaging to examine error-related responses in 37 individuals with schizophrenia and 32 healthy controls in regions identified in the basic science literature as being involved in error processing, and determined whether their activity was related to behavioral adjustments. Our imaging results support previous findings showing that regions outside the dACC are sensitive to error commission, and demonstrated that abnormalities in brain responses to errors among individuals with schizophrenia extend beyond the dACC to almost all of the regions involved in error-related processing in controls. However, error related responses in the dACC were most predictive of behavioral adjustments in both groups. Moreover, the integration of this network of regions differed between groups, with the cerebellar regions and the dACC less connected to the network in individuals with schizophrenia compared to controls. Our findings demonstrate a blunted response to error commission in the dACC that is associated with reduced error-related behavioral adjustments in individuals with schizophrenia. This result supports the hypothesis that a failure to respond appropriately to errors in individuals with schizophrenia is linked to alterations in dACC function leading to a compromise in the implementation of cognitive control. Our findings highlight the importance of examining brain activity related to the processing of error information and supporting error-related behavioral adjustments in terms of a distributed network.

Project description:A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30-100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ.To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ.We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 31, 2012. Electroencephalograms were obtained during auditory steady-state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a resting state in 18 participants in each group.Electroencephalographic activity in the auditory cortex was estimated using dipole source localization. Auditory steady-state response (ASSR) measures included the phase-locking factor and evoked power. Spontaneous gamma power was measured as induced (non-phase-locked) gamma power in the ASSR data and as total gamma power in the resting-state data.The ASSR phase-locking factor was reduced significantly in patients with SZ compared with controls for the 40-Hz stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46?=?6.79 [P?=?.012]) but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46?=?0.006 [P?=?.938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46?=?1.605 [P?=?.212], respectively), repeating previous findings. The mean [SD] broadband-induced (30-100 Hz) gamma power was increased in patients with SZ compared with controls during steady-state stimulation (6.579 [3.783] vs 3.984 [1.843]; F1,46 = 9.128 [P = .004]; d = 0.87) but not during rest (0.006 [0.003] vs 0.005 [0.002]; F1,34?=?1.067 [P?=?.309]; d?=?0.35). Induced gamma power in the left hemisphere of the patients with SZ during the 40-Hz stimulation was positively correlated with auditory hallucination symptoms (tangential, ??=?0.587 [P?=?.031]; radial, ??=?0.593 [P?=?.024]) and negatively correlated with the ASSR phase-locking factor (baseline: ??=?-0.572 [P?=?.024]; ASSR: ??=?-0.568 [P?=?.032]).Spontaneous gamma activity is increased during auditory steady-state stimulation in SZ, reflecting a disruption in the normal balance of excitation and inhibition. This phenomenon interacts with evoked oscillations, possibly contributing to the gamma ASSR deficit found in SZ. The similarity of increased spontaneous gamma power in SZ to the findings of increased spontaneous gamma power in animal models of NMDAR hypofunction suggests that spontaneous gamma power could serve as a biomarker for the integrity of NMDARs on parvalbumin-expressing inhibitory interneurons in humans and in animal models of neuropsychiatric disorders.

Dataset Information

Spontaneous prediction error generation in schizophrenia.

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Spontaneous prediction error generation in schizophrenia.

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