Default mode network functional and structural connectivity after traumatic brain injury.
TL;DR: The results support a direct relationship between white matter organization within the brain's structural core, functional connectivity within the default mode network and cognitive function following brain injury.
Abstract: Traumatic brain injury often results in cognitive impairments that limit recovery. The underlying pathophysiology of these impairments is uncertain, which restricts clinical assessment and management. Here, we use magnetic resonance imaging to test the hypotheses that: (i) traumatic brain injury results in abnormalities of functional connectivity within key cognitive networks; (ii) these changes are correlated with cognitive performance; and (iii) functional connectivity within these networks is influenced by underlying changes in structural connectivity produced by diffuse axonal injury. We studied 20 patients in the chronic phase after traumatic brain injury compared with age-matched controls. Network function was investigated in detail using functional magnetic resonance imaging to analyse both regional brain activation, and the interaction of brain regions within a network (functional connectivity). We studied patients during performance of a simple choice-reaction task and at ‘rest’. Since functional connectivity reflects underlying structural connectivity, diffusion tensor imaging was used to quantify axonal injury, and test whether structural damage correlated with functional change. The patient group showed typical impairments in information processing and attention, when compared with age-matched controls. Patients were able to perform the task accurately, but showed slow and variable responses. Brain regions activated by the task were similar between the groups, but patients showed greater deactivation within the default mode network, in keeping with an increased cognitive load. A multivariate analysis of ‘resting’ state functional magnetic resonance imaging was then used to investigate whether changes in network function were present in the absence of explicit task performance. Overall, default mode network functional connectivity was increased in the patient group. Patients with the highest functional connectivity had the least cognitive impairment. In addition, functional connectivity at rest also predicted patterns of brain activation during later performance of the task. As expected, patients showed widespread white matter damage compared with controls. Lower default mode network functional connectivity was seen in those patients with more evidence of diffuse axonal injury within the adjacent corpus callosum. Taken together, our results demonstrate altered patterns of functional connectivity in cognitive networks following injury. The results support a direct relationship between white matter organization within the brain's structural core, functional connectivity within the default mode network and cognitive function following brain injury. They can be explained by two related changes: a compensatory increase in functional connectivity within the default mode network; and a variable degree of structural disconnection that modulates this change in network function.
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TL;DR: An efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data, and improves on the state-of-the‐art for all three applications.
2,842 citations
TL;DR: A novel model of the posterior cingulate cortex's function is synthesized into a model that influences attentional focus by 'tuning' whole-brain metastability and so adjusts how stable brain network activity is over time, and is tested within the framework of complex dynamic systems theory.
Abstract: The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer’s disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region’s function (the ‘Arousal, Balance and Breadth of Attention’ model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by ‘tuning’ whole-brain metastability and so adjusts how stable brain network activity is over time.
1,710 citations
Cites background or result from "Default mode network functional and..."
...However, in certain situations increased PCC activity or its functional connectivity is associated with improved behavioural performance, even when attention is externally directed (Hampson et al., 2006; Hahn et al., 2007; Sharp et al., 2011)....
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...Our own work has consistently shown abnormal PCC function following traumatic brain injury that relates to the pattern of cognitive impairment (Bonnelle et al., 2011, 2012; Sharp et al., 2011)....
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...Our own work and others have consistently shown abnormalities in the PCC following traumatic brain injury (Kim et al., 2010; Mayer et al., 2011; Sharp et al., 2011; Bonnelle et al., 2011, 2012)....
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..., 2007), and increased functional connectivity of the PCC within the DMN is associated with faster reaction times to external stimuli in the healthy brain and following traumatic brain injury (Hampson et al., 2006; Sharp et al., 2011)....
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...Activity within the PCC has clearly been shown to correlate with the efficiency of cognitive processing in various contexts (Hampson et al., 2006; Weissman et al., 2006; Gilbert et al., 2007; Hahn et al., 2007; Kelly et al. 2008; Singh and Fawcett, 2008; Sharp et al., 2011)....
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TL;DR: The results indicate that the precuneus plays a core role not only in DMN, but also more broadly through its engagement under a variety of processing states, suggesting a heightened specialization for resting-state cognition.
Abstract: Efforts to understand the functional architecture of the brain have consistently identified multiple overlapping large-scale neural networks that are observable across multiple states. Despite the ubiquity of these networks, it remains unclear how regions within these large-scale neural networks interact to orchestrate behavior. Here, we collected functional magnetic resonance imaging data from 188 human subjects who engaged in three cognitive tasks and a resting-state scan. Using multiple tasks and a large sample allowed us to use split-sample validations to test for replication of results. We parceled the task-rest pairs into functional networks using a probabilistic spatial independent components analysis. We examined changes in connectivity between task and rest states using dual-regression analysis, which quantifies voxelwise connectivity estimates for each network of interest while controlling for the influence of signals arising from other networks and artifacts. Our analyses revealed systematic state-dependent functional connectivity in one brain region: the precuneus. Specifically, task performance led to increased connectivity (compared to rest) between the precuneus and the left frontoparietal network (lFPN), whereas rest increased connectivity between the precuneus and the default-mode network (DMN). The absolute magnitude of this effect was greater for DMN, suggesting a heightened specialization for resting-state cognition. All results replicated within the two independent samples. Our results indicate that the precuneus plays a core role not only in DMN, but also more broadly through its engagement under a variety of processing states.
662 citations
TL;DR: PCC subregions showed distinct patterns of activity modulation during the performance of an attentionally demanding task, suggesting that parts of the dorsal PCC interact with frontoparietal networks to regulate the balance between internally and externally directed cognition.
Abstract: There is considerable uncertainty about the function of the posterior cingulate cortex (PCC). The PCC is a major node within the default mode network (DMN) and has high metabolic activity and dense structural connectivity to widespread brain regions, which suggests it has a role as a cortical hub. The region appears to be involved in internally directed thought, for example, memory recollection. However, recent nonhuman primate work provides evidence for a more active role in the control of cognition, through signaling an environmental change and the need to alter behavior. For an organism to flexibly react to a changing environment, information processed in functionally distinct brain networks needs to be integrated by such a cortical hub. If the PCC is involved in this process, its brain activity should show a complex and dynamic pattern that partially reflects activity in other brain networks. Using fMRI in humans and a multivariate analysis, we demonstrate that the PCC shows this type of complex functional architecture, where echoes of multiple other brain networks are seen in separable yet overlapping subregions. For example, a predominantly ventral region shows strong functional connectivity to the rest of the DMN, whereas two subregions within the dorsal PCC show high connectivity to frontoparietal networks involved in cognitive control. PCC subregions showed distinct patterns of activity modulation during the performance of an attentionally demanding task, suggesting that parts of the dorsal PCC interact with frontoparietal networks to regulate the balance between internally and externally directed cognition.
545 citations
Cites background from "Default mode network functional and..."
...Previous structural and functional imaging analyses suggest that there are other hub regions outside the PCC, including medial structures such as the thalamus or the anterior cingulate....
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...The analysis was performed on voxels that were both anatomically part of the PCC, and functionally part of the DMN (see Materials and Methods, above)....
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...Within the PCC, 10 partially overlapping subregions were identi- fied, eachofwhichhadadistinct timecourseofBOLDfluctuation(four of these regions and the overlap of all regions are illustrated in Fig....
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...To better understand PCC functionality, it is necessary to investigate how other task demands (e.g., internally directed attention such as autobiographical memory) modulate the other signals observed within the PCC, as this may reveal further functional specialization....
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TL;DR: It is shown that structural properties, including the length, number, and spatial location of white matter streamlines, are indicative of and can be inferred from the strength of resting-state and task-based functional correlations between brain regions.
Abstract: Magnetic resonance imaging enables the noninvasive mapping of both anatomical white matter connectivity and dynamic patterns of neural activity in the human brain. We examine the relationship between the structural properties of white matter streamlines (structural connectivity) and the functional properties of correlations in neural activity (functional connectivity) within 84 healthy human subjects both at rest and during the performance of attention- and memory-demanding tasks. We show that structural properties, including the length, number, and spatial location of white matter streamlines, are indicative of and can be inferred from the strength of resting-state and task-based functional correlations between brain regions. These results, which are both representative of the entire set of subjects and consistently observed within individual subjects, uncover robust links between structural and functional connectivity in the human brain.
537 citations
Cites background from "Default mode network functional and..."
...Disruptions to interhemispheric connections could similarly reduce rsFC, as is observed in patients with axonal injury in the corpus callosum (36)....
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References
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TL;DR: It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Abstract: A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
35,518 citations
TL;DR: A review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB) on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data.
12,097 citations
"Default mode network functional and..." refers background or methods in this paper
...1), and no overlap in the location of the microbleeds....
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...Structural connectivity: diffusion tensor imaging Standard diffusion tensor imaging preprocessing methods were employed using the FMRIB software library (Smith et al., 2004)....
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TL;DR: A baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF is identified, suggesting the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
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.
10,708 citations
"Default mode network functional and..." refers background in this paper
...…well as the default mode network, which consists of a set of brain regions that show highly correlated brain activity during ‘rest’ and a reduced level of activation during most attentionally demanding tasks (Shulman et al., 1997; Gusnard et al., 2001; Raichle et al., 2001; Buckner et al., 2008)....
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...…the posterior cingulate cortex, the retrosplenial cortex and parts of the ventromedial prefrontal cortex, have high metabolic demands at rest (Raichle et al., 2001), and are densely interconnected by white matter tracts that form part of the brain’s core structural network (Hagmann et al.,…...
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...metabolic demands at rest (Raichle et al., 2001), and are densely...
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TL;DR: Past observations are synthesized to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment, and for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
Abstract: Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations These two subsystems converge on important nodes of integration including the posterior cingulate cortex The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease
8,448 citations
11 Feb 2013
TL;DR: It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Abstract: A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
7,515 citations