Connectivity, Pharmacology and Computation: Towards a Mechanistic Understanding of Neural System Dysfunction in Schizophrenia

Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks. Functional neuroimaging tools have evolved sufficiently to reliably detect system-level disturbances in neural networks. This review focuses on recent findings in schi...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in psychiatry Vol. 4
Main Authors:	Alan eAnticevic, Michael W Cole, Grega eRepovš, Aleksandar eSavic, Naomi R Driesen, Genevieve eYang, Youngsun T Cho, John David Murray, David C Glahn, Xiao-Jing eWang, John H Krystal
Format:	Journal Article
Language:	English
Published:	Frontiers Media S.A 01-12-2013
Subjects:	computational modeling functional connectivity Glutamate Pharmacology Schizophrenia Thalamus
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks. Functional neuroimaging tools have evolved sufficiently to reliably detect system-level disturbances in neural networks. This review focuses on recent findings in schizophrenia and bipolar illness using resting-state neuroimaging, an advantageous approach for biomarker development given its ease of data collection and lack of task-based confounds. These benefits notwithstanding, neuroimaging does not yet allow the evaluation of individual neurons within local circuits, where pharmacological treatments ultimately exert their effects. This limitation constitutes an important obstacle in translating findings from animal research to humans and from healthy humans to patient populations. Integrating new neuroscientific tools may help to bridge some of these gaps. We specifically discuss two complementary approaches. The first is pharmacological manipulations in healthy volunteers, which transiently mimic some cardinal features of psychiatric conditions. We specifically focus on recent neuroimaging studies using the NMDA receptor antagonist, ketamine, to probe glutamate synaptic dysfunction associated with schizophrenia. Second, we discuss the combination of human pharmacological imaging with biophysically-informed computational models developed to guide the interpretation of functional imaging studies and to inform the development of pathophysiologic hypotheses. To illustrate this approach, we review clinical investigations in addition to recent findings of how computational modeling has guided inferences drawn from our studies involving ketamine administration to healthy subjects. Thus, this review asserts that linking experimental studies in humans with computational models will advance to effort to bridge cellular, systems, and clinical neuroscience approaches to psychiatric disorders.
ISSN:	1664-0640
DOI:	10.3389/fpsyt.2013.00169