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Mechanistic classification of neural circuit dysfunctions: insights from neuroeconomics research in animals.

ABSTRACT: Many psychiatric conditions present complex behavioral symptoms, and the type and magnitude of underlying neural dysfunction may vary drastically. This review introduces a classification scheme for psychiatric symptoms, describing them in terms of the state of a dysfunctional neural circuit. We provide examples of two kinds of functional deficits: variance-shifted functionality, in which a damaged circuit continues to function albeit suboptimally, and state-shifted functionality, resulting in an absent or qualitatively different functional state. We discuss, from the perspective of neuroeconomics and related areas of behavioral investigation, three broad classes of commonly occurring symptoms in psychopathology based on selected studies of decision making in animals: temporal discounting, social preferences, and decision making under environmental volatility. We conclude that the proposed mechanistic categorization scheme offers promise for understanding neural circuit dysfunctions underlying psychopathology.

SUBMITTER: Chang SW

PROVIDER: S-EPMC3383404 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Mechanistic classification of neural circuit dysfunctions: insights from neuroeconomics research in animals.

Chang Steve W C SW Barack David L DL Platt Michael L ML

Biological psychiatry 20120320 2

Many psychiatric conditions present complex behavioral symptoms, and the type and magnitude of underlying neural dysfunction may vary drastically. This review introduces a classification scheme for psychiatric symptoms, describing them in terms of the state of a dysfunctional neural circuit. We provide examples of two kinds of functional deficits: variance-shifted functionality, in which a damaged circuit continues to function albeit suboptimally, and state-shifted functionality, resulting in an ...[more]

PMID: 22440615

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Project description:A surge of data has reproducibly identified strong associations of OSA with cardiac arrhythmias. As an extension of epidemiologic and clinic-based findings, experimental investigations have made strides in advancing our understanding of the putative OSA and cardiac arrhythmogenesis mechanistic underpinnings. Although most studies have focused on the links between OSA and atrial fibrillation (AF), relationships with ventricular arrhythmias have also been characterized. Key findings implicate OSA-related autonomic nervous system fluctuations typified by enhanced parasympathetic activation during respiratory events and sympathetic surges subsequent to respiratory events, which contribute to augmented arrhythmic propensity. Other more immediate pathophysiologic influences of OSA-enhancing arrhythmogenesis include intermittent hypoxia, intrathoracic pressure swings leading to atrial stretch, and hypercapnia. Intermediate pathways by which OSA may trigger arrhythmia include increased systemic inflammation, oxidative stress, enhanced prothrombotic state, and vascular dysfunction. Long-term OSA-associated sequelae such as hypertension, atrial enlargement and fibrosis, ventricular hypertrophy, and coronary artery disease also predispose to cardiac arrhythmia. These factors can lead to a reduction in atrial effective refractory period, triggered and abnormal automaticity, and promote slowed and heterogeneous conduction; all of these mechanisms increase the persistence of reentrant arrhythmias and prolong the QT interval. Cardiac electrical and structural remodeling observed in OSA animal models can progress the arrhythmogenic substrate to further enhance arrhythmia generation. Future investigations clarifying the contribution of specific OSA-related mechanistic pathways to arrhythmia generation may allow targeted preventative therapies to mitigate OSA-induced arrhythmogenicity. Furthermore, interventional studies are needed to clarify the impact of OSA pathophysiology reversal on cardiac arrhythmogenesis and related adverse outcomes.

Dataset Information

Mechanistic classification of neural circuit dysfunctions: insights from neuroeconomics research in animals.

Publications

Mechanistic classification of neural circuit dysfunctions: insights from neuroeconomics research in animals.

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