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      Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury

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          Abstract

          Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.

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          Most cited references31

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          Remembering the past and imagining the future: common and distinct neural substrates during event construction and elaboration.

          People can consciously re-experience past events and pre-experience possible future events. This fMRI study examined the neural regions mediating the construction and elaboration of past and future events. Participants were cued with a noun for 20s and instructed to construct a past or future event within a specified time period (week, year, 5-20 years). Once participants had the event in mind, they made a button press and for the remainder of the 20s elaborated on the event. Importantly, all events generated were episodic and did not differ on a number of phenomenological qualities (detail, emotionality, personal significance, field/observer perspective). Conjunction analyses indicated the left hippocampus was commonly engaged by past and future event construction, along with posterior visuospatial regions, but considerable neural differentiation was also observed during the construction phase. Future events recruited regions involved in prospective thinking and generation processes, specifically right frontopolar cortex and left ventrolateral prefrontal cortex, respectively. Furthermore, future event construction uniquely engaged the right hippocampus, possibly as a response to the novelty of these events. In contrast to the construction phase, elaboration was characterized by remarkable overlap in regions comprising the autobiographical memory retrieval network, attributable to the common processes engaged during elaboration, including self-referential processing, contextual and episodic imagery. This striking neural overlap is consistent with findings that amnesic patients exhibit deficits in both past and future thinking, and confirms that the episodic system contributes importantly to imagining the future.
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            The contribution of astrocytes and microglia to traumatic brain injury.

            Traumatic brain injury (TBI) represents a major cause of death and disability in developed countries. Brain injuries are highly heterogeneous and can also trigger other neurological complications, including epilepsy, depression and dementia. The initial injury often leads to the development of secondary sequelae; cellular hyperexcitability, vasogenic and cytotoxic oedema, hypoxia-ischaemia, oxidative stress and inflammation, all of which influence expansion of the primary lesion. It is widely known that inflammatory events in the brain following TBI contribute to the widespread cell death and chronic tissue degeneration. Neuroinflammation is a multifaceted response involving a number of cell types, both within the CNS and in the peripheral circulation. Astrocytes and microglia, cells of the CNS, are considered key players in initiating an inflammatory response after injury. These cells are capable of secreting various cytokines, chemokines and growth factors, and following injury to the CNS, undergo changes in morphology. Ultimately, these changes can influence the local microenvironment and thus determine the extent of damage and subsequent repair. This review will focus on the roles of microglia and astrocytes following TBI, highlighting some of the key processes, pathways and mediators involved in this response. Additionally, both the beneficial and the detrimental aspects of these cellular responses will be examined using evidence from animal models and human post-mortem TBI studies.
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              Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development.

              Brain structural and functional development, throughout childhood and into adulthood, underlies the maturation of increasingly sophisticated cognitive abilities. High-level attentional and cognitive control processes rely on the integrity of, and dynamic interactions between, core neurocognitive networks. The right fronto-insular cortex (rFIC) is a critical component of a salience network (SN) that mediates interactions between large-scale brain networks involved in externally oriented attention [central executive network (CEN)] and internally oriented cognition [default mode network (DMN)]. How these systems reconfigure and mature with development is a critical question for cognitive neuroscience, with implications for neurodevelopmental pathologies affecting brain connectivity. Using functional and effective connectivity measures applied to fMRI data, we examine interactions within and between the SN, CEN, and DMN. We find that functional coupling between key network nodes is stronger in adults than in children, as are causal links emanating from the rFIC. Specifically, the causal influence of the rFIC on nodes of the SN and CEN was significantly greater in adults compared with children. Notably, these results were entirely replicated on an independent dataset of matched children and adults. Developmental changes in functional and effective connectivity were related to structural connectivity along these links. Diffusion tensor imaging tractography revealed increased structural integrity in adults compared with children along both within- and between-network pathways associated with the rFIC. These results suggest that structural and functional maturation of rFIC pathways is a critical component of the process by which human brain networks mature during development to support complex, flexible cognitive processes in adulthood.
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                Author and article information

                Contributors
                wuxuehai2013@163.com
                georg.northoff@theroyal.ca
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 March 2017
                24 March 2017
                2017
                : 7
                : 387
                Affiliations
                [1 ]ISNI 0000 0004 1757 8861, GRID grid.411405.5, Department of Neurosurgery, , Huashan Hospital of Fudan University, ; NO. 12 Wulumuqi mid Road, Jing’an District Shanghai, 200040 China
                [2 ]ISNI 0000 0001 2230 9154, GRID grid.410595.c, Center for Cognition and Brain Disorders (CCBD), , Hangzhou Normal University. NO. 19#3 Shuyuan, ; NO. 58 Haishu Road, Yuhang district, Hangzhou, Zhejian Province 310000 China
                [3 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Institute of Mental Health Research, , University of Ottawa, ; 1145 Carling Avenue, Room 6435, Ottawa, ON K1Z 7K4 Canada
                [4 ]School of Life Science, South China Normal University, Key Laboratory of Ecology and Environmental Science in Higher Education of Guangdong Province, Guangzhou, 510631 PR China
                [5 ]ISNI 0000 0004 0368 7397, GRID grid.263785.d, Guangdong Key Laboratory of Mental Health and Cognitive Science, , South China Normal University, ; Guangzhou, 510631 China
                [6 ]ISNI 0000 0004 0368 7397, GRID grid.263785.d, Centre for Studies of Psychological Applications, , South China Normal University, ; Guangzhou, 510631 China
                [7 ]ISNI 0000 0004 0368 7397, GRID grid.263785.d, School of Psychology, , South China Normal University, ; Guangzhou, 510631 China
                Article
                392
                10.1038/s41598-017-00392-5
                5428308
                28341824
                7062cec8-faad-4cf6-a7c3-eca4b6d01c32
                © The Author(s) 2017

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 11 July 2016
                : 21 February 2017
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