Functional Connectivity fMRI of the Rodent Brain: Comparison of Functional Connectivity Networks in Rat and Mouse

Jonckers, Elisabeth; Audekerke, Johan Van; Visscher, Geofrey De; Linden, Annemie Van der; Verhoye, Marleen

doi:10.1371/journal.pone.0018876

Cited by 209 publications

(250 citation statements)

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“…Furthermore, we successfully applied a modelfree probabilistic independent component analysis strategy to identify a group-based functional bilateral sensorimotor cortical network in rat brain, in addition to other networks such as a bilateral cingulate-thalamic network. Despite differences in rat strain, anesthesia, ICA algorithm, and number of components, our findings are largely in agreement with previous studies that also demonstrated predominantly bilateral functional networks in rat brain (Hutchison et al, 2010;Jonckers et al, 2011). Subsequent analyses demonstrated that both interhemispheric functional connectivity and ipsilesional intrahemispheric signal coherence in sensorimotor cortex and cingulate-thalamic network were significantly reduced after medium and large stroke, particularly at subacute stages.…”

Section: Discussionsupporting

confidence: 92%

“…fmrib.ox.ac.uk/fsl), to extract a group-averaged functional network that included the bilateral sensorimotor cortex. This data-driven approach allows unbiased identification of whole functional networks from included animals, without the need to coregister to an extrinsic rat brain atlas to select diverse brain regions that are assumed to be part of a larger functional network (Hutchison et al, 2010;Jonckers et al, 2011). We found that analysis with seven components yielded a component of which the anatomical pattern most ideally matched with the bilateral sensorimotor cortices (see Fig.…”

Section: Methodsmentioning

confidence: 97%

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Extent of Bilateral Neuronal Network Reorganization and Functional Recovery in Relation to Stroke Severity

et al. 2012

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Remodeling of neuronal structures and networks is believed to significantly contribute to (partial) restoration of functions after stroke. However, it has been unclear to what extent the brain reorganizes and how this correlates with functional recovery in relation to stroke severity. We applied serial resting-state functional MRI and diffusion tensor imaging together with behavioral testing to relate longitudinal modifications in functional and structural connectivity of the sensorimotor neuronal network to changes in sensorimotor function after unilateral stroke in rats. We found that gradual improvement of functions is associated with wide-ranging changes in functional and structural connectivity within bilateral neuronal networks, particularly after large stroke. Both after medium and large stroke, brain reorganization eventually leads to (partial) normalization of neuronal signal synchronization within the affected sensorimotor cortical network (intraregional signal coherence), as well as between the affected and unaffected sensorimotor cortices (interhemispheric functional connectivity). Furthermore, the bilateral network configuration shifts from subacutely increased "small-worldness," possibly reflective of initial excessive neuronal clustering and wiring, toward a baseline small-world topology, optimal for global information transfer and local processing, at chronic stages. Cortical network remodeling was accompanied by recovery of initially disrupted structural integrity in corticospinal tract regions, which correlated positively with retrieval of sensorimotor functions. Our study demonstrates that the degree of functional recovery after stroke is associated with the extent of preservation or restoration of ipsilesional corticospinal tracts in combination with reinstatement of interhemispheric neuronal signal synchronization and normalization of smallworld cortical network organization.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 97%

Extent of Bilateral Neuronal Network Reorganization and Functional Recovery in Relation to Stroke Severity

et al. 2012

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“…Using this technique, functional connectivity (FC) is defined as the temporal correlation of these fluctuations between different brain regions [26]. Coherence of low frequency fluctuations of the BOLD signal has been shown in different mammalian species including mice [27], rats [28], monkeys [29], and humans [26]. This paper shows the first application of rsfMRI in a non-mammalian species, a pigeon.…”

Section: Introductionmentioning

confidence: 99%

Functional MRI and functional connectivity of the visual system of awake pigeons

Groof

Jonckers

Güntürkün

et al. 2013

Behavioural Brain Research

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h i g h l i g h t sFirst study to image the whole brain of awake pigeons. We show a habituation program for MR-sessions under awake and head-fixed conditions. Movement under these conditions is minimal. First measurement of functional connectivity in a non-mammalian species. Analyses of BOLD-response and functional connectivity are feasible. a r t i c l e i n f o b s t r a c tAt present, functional MRI (fMRI) is increasingly used in animal research but the disadvantage is that the majority of the imaging is applied in anaesthetized animals. Only a few articles present results obtained in awake rodents. In this study both traditional fMRI and resting state (rsfMRI) were applied to four pigeons, that were trained to remain still while being imaged, removing the need for anesthesia. This is the first time functional connectivity measurements are performed in a non-mammalian species. Since the visual system of pigeons is a well-known model for brain asymmetry, the focus of the study was on the neural substrate of the visual system. For fMRI a visual stimulus was used and functional connectivity measurements were done with the entopallium (E; analog for the primary visual cortex) as a seed region. Interestingly in awake pigeons the left E was significantly functionally connected to the right E. Moreover we compared connectivity maps for a seed region in both hemispheres resulting in a stronger bilateral connectivity starting from left E then from right E. These results could be used as a starting point for further imaging studies in awake birds and also provide a new window into the analysis of hemispheric dominance in the pigeon.

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“…Although there are similarities, many discordant results are observed between studies. One reason for this may be that different labs adopted different anaesthetic regimens (Jonckers et al, 2011;Grandjean et al, 2014b;Mechling et al, 2014;Sforazzini et al, 2014;Liska et al, 2015;Zerbi et al, 2015).…”

Section: MVmentioning

confidence: 99%

“…Its inventor shared the Nobel Prize in Physiology or Medicine in 2003 (Huettel et al, 2009). Discovered in rats (Ogawa et al, 1990), the application areas of BOLD fMRI have been expanded not only to humans (Kwong et al, 1992), but also monkeys (Vincent et al, 2007) and now mice (Jonckers et al, 2011). Its contributions to both clinical and scientific research are still growing steadily.…”

Section: Blood-oxygen-level-dependent (Bold) Functional Mrimentioning

confidence: 99%

Functional network study on the wild type and DISC1 transgenic mice

Wu¹

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Major mental disorders such as schizophrenia (SZ), bipolar disorder and major depression create a heavy social burden and remain poorly treated. Recent reports examining the genetic and molecular structure of brain disorders discovered the gene Disrupted-in-Schizophrenia 1 (DISC1) to be significantly associated with these disorders and plays a substantial role in influencing a range of shared endophenotypes underlying these disorders. This has led to a powerful gateway to explore the underlying pathology and to achieve better diagnosis and treatments of major mental diseases. Characterising the phenotypes of DISC1 in brain functions would provide valuable insights into the mechanism of how this gene influences the brain.Resting-state fMRI (rs-fMRI) is a powerful technique being applied to more than 30 different kinds of brain disorders and different species. Findings from rs-fMRI studies on humans provide ample evidence of abnormal functional patterns in patients with mental illnesses. Specifically, altered functional connectivity (FC) and network topologies are proposed to be plausible imaging endophenotypes of psychotic disorders. However, little is known about the direct effects of gene dysfunction, such as DISC1 mutations, on restingstate brain activations. One aim of this thesis is to investigate the impacts of DISC1 on variations of resting-state functional networks (RSNs) in anaesthetized mouse brains using DISC1 transgenic mice and rs-fMRI.Before characterizing disease phenotypes in mouse models, it is necessary to understand how the mouse brain functions in normal states. Anaesthesia is currently an integrated part of most mouse rs-fMRI experiment. However, it influences blood-oxygenation-leveldependent (BOLD) fMRI signals via modulation of neurovascular coupling and brain metabolism, and therefore alters FC and topologies of RSNs. Investigating FC and its changes associated with genes therefore initially requires an understanding of the anaesthetics. Furthermore, various anaesthetic protocols are adopted by different labs leading to difficulties in result comparisons. The brain is a complex and hierarchical system, whereby its RSN architecture can be characterised from mutiple perspectives at regional or global levels. Previous mouse rs-fMRI studies have focused on long-distance FC, however, given the non-uniform influence of anaesthesia on the brain, mapping functional activations across scales in mice under different anaesthetics remain sparsely explored. Establishing this relationahsip would provide a reliable reference to study mouse brain functions in abnormal states and facilitate comparisons across laboratories. | P a g eIn the first aim of this thesis, I investigated the local connectivity in wide type (WT) mice under six commonly used anaesthetic regimens. I identified that the regional connectivity altered across the brain as a function of the expression density of receptors relative to specific agents. In addition, the depth of anaesthesia influences local synchronization.In the seco...

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Functional Connectivity fMRI of the Rodent Brain: Comparison of Functional Connectivity Networks in Rat and Mouse

Cited by 209 publications

References 46 publications

Extent of Bilateral Neuronal Network Reorganization and Functional Recovery in Relation to Stroke Severity

Extent of Bilateral Neuronal Network Reorganization and Functional Recovery in Relation to Stroke Severity

Functional MRI and functional connectivity of the visual system of awake pigeons

Functional network study on the wild type and DISC1 transgenic mice

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