Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

Abstract: In this review we are concerned specifically with the putative role of the default-mode network (DMN) in the pathophysiology of mental disorders. First, we define the DMN concept with regard to its neuro-anatomy, its functional organisation through low frequency neuronal oscillations, its relation to other recently discovered low frequency resting state networks, and the cognitive functions it is thought to serve. Second, we introduce methodological and analytical issues and challenges. Third, we describe putative mechanisms proposed to link DMN abnormalities and mental disorders. These include interference by network activity during task performance, altered patterns of antagonism between task specific and non-specific elements, altered connectively and integrity of the DMN, and altered psychological functions served by the network DMN. Fourth, we review the empirical literature systematically. We relate DMN dysfunction to dementia, schizophrenia, epilepsy, anxiety and depression, autism and attention deficit/hyperactivity disorder drawing out common and unique elements of the disorders. Finally, we provide an integrative overview and highlight important challenges and tasks for future research.

Abstract: We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.

Abstract: Neuropsychiatric disorders are associated with abnormal function of the default mode network (DMN), a distributed network of brain regions more active during rest than during performance of many attention-demanding tasks and characterized by a high degree of functional connectivity (i.e., temporal correlations between brain regions). Functional magnetic resonance imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks. In schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected. In schizophrenia this may relate to overly intensive self-reference and impairments in attention and working memory. In depression, DMN hyperactivity may be related to negative rumination. These findings are considered in terms of what is known about psychological functions supported by the DMN, and alteration of the DMN in other neuropsychiatric disorders.

Abstract: A considerable body of evidence has accumulated over recent years on the functions of the default-mode network (DMN) – a set of brain regions whose activity is high when the mind is not engaged in specific behavioral tasks and low during focused attention on the external environment. In this review, we focus on DMN suppression and its functional role in health and disease, summarizing evidence that spans several disciplines, including cognitive neuroscience, pharmacological neuroimaging, clinical neuroscience, and theoretical neuroscience. Collectively, this research highlights the functional relevance of DMN suppression for goal-directed cognition, possibly by reducing goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and illustrates the functional significance of DMN suppression deficits in severe mental illness.

Abstract: Models of Network Growth All networks, whether they are social, technological, or biological, are the result of a growth process. Many of these networks continue to grow for prolonged periods of time, continually modifying their connectivity structure throughout their entire existence. For example, the World Wide Web has grown from a small number of cross-linked documents in the early 1 990s to an estimated 30 billion indexed web pages in 2009.3 The extraordinary growth of the Web continues unabated and has occurred without any top-down design, yet the topology of its hyperlink structure exhibits characteristic statistical patterns (Pastor-Satorras and Vespig­ nani, 2004). Other technological networks such as the power grid, global transportation networks, or mobile communication networks continue to grow and evolve, each displaying characteristic patterns of expansion and elaboration. Growth and change in social and organizational

Abstract: Book on statistical decision theory and sensory processes in signal detection theory and psychophysics

Abstract: The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIB's Software Library (FSL).

Abstract: A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

Abstract: Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.

Abstract: Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.