The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model

Hübner, Neele S.; Mechling, Anna E.; Lee, Hsu‐Lei; Reisert, Marco; Bienert, Thomas; Hennig, Jürgen; Elverfeldt, Dominik von; Harsan, Laura‐Adela

doi:10.1016/j.neuroimage.2016.11.008

Cited by 69 publications

(72 citation statements)

References 80 publications

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“…From rodent model, the results of the study conducted by Hübner et al (2017) inducing brain demyelination, showed that functional connectivity was also altered, and the areas most affected were the posterior centers of DMN. In humans, myelination and functional connectivity develop parallel from birth until late adolescence (Stevens et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

Algarı́n

Karunakaran

Reyes

et al. 2017

Front. Aging Neurosci.

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Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the DMN are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between IDA in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (±1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the DMN. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas they exhibited increased anterior DMN connectivity to the right PCC. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, IDA in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood.

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Section: Introductionmentioning

confidence: 99%

Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

Algarı́n

Karunakaran

Reyes

et al. 2017

Front. Aging Neurosci.

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“…Several investigators have used in vivo MRI to investigate structural connectivity in genetically engineered mice. Practical problems of life support limit the resolution in these studies to ~100x100x500 um with ~30 angular samples [19,20]. Scans of post mortem specimens enable longer, higher resolution studies.…”

Section: Discussionmentioning

confidence: 99%

Heritability of the Mouse Brain Connectome

Wang

Ashbrook

Gopalakrishnan

et al. 2019

Preprint

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MRI provides an opportunity to link neuroanatomic phenotypes to genetic expression. Genome-wide associative studies in the ENIGMA consortium and the UK Biobank have demonstrated significant links between brain structure and specific genes. Similar studies in rodents are challenging because of the scale. We report whole brain diffusion connectomes of four strains of mice (C57BL/6J, DBA/2J, CAST/EiJ, and BTBR) at spatial resolution 20,000 times higher than the human connectome. We derived volumes and scalar diffusion metrics for 322 regions of the brain. Volume was the most heritable trait followed by FA, RD, and AD. These traits were heritable in > 60% of the regions when comparing all four strains. Many were also highly heritable when the BTBR was not included. Using a unique statistical approach to limit false discovery allowed us to identify a number of specific brain nodes in which connectivity was highly heritable.

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“…Since its onset in 2011 (Jonckers et al, 2011), mouse rsfMRI has developed in a number of centres and has grown to become a routine method with a number of applications, reviewed in (Chuang and Nasrallah, 2017;Gozzi and Schwarz, 2016;Hoyer et al, 2014;Jonckers et al, 2015Jonckers et al, , 2013Pan et al, 2015). Prominently, mouse rsfMRI has been used to investigate an extensive list of models, including Alzheimer's disease (Grandjean et al, 2014b, Shah et al, 2013, 2016cWiesmann et al, 2016;Zerbi et al, 2014), motor (DeSimone et al, 2016;Li et al, 2017), affective (Grandjean et al, 2016a), autism spectrum Haberl et al, 2015;Liska et al, 2018;Liska and Gozzi, 2016;Michetti et al, 2017;Sforazzini et al, 2016;Zerbi et al, 2018;Zhan et al, 2014), schizophrenia (Errico et al, 2015;Gass et al, 2016), pain (Buehlmann et al, 2018;Komaki et al, 2016), reward (Charbogne et al, 2017;Mechling et al, 2016), and demyelinating disorders (Hübner et al, 2017). Another application of mouse rsfMRI is the elucidation of large-scale functional alterations exerted by pharmacological agents (Razoux et al, 2013;Shah et al, 2016aShah et al, , 2015.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, the method has been used to address fundamental questions. These include the investigation of the structural basis underlying FC Grandjean et al, 2017b;Hübner et al, 2017;Schroeter et al, 2017;Sforazzini et al, 2016;Stafford et al, 2014), the nature of the dynamical event encoded in the resting-state signal (Belloy et al, 2018a(Belloy et al, , 2018bBukhari et al, 2018;Grandjean et al, 2017a;Sethi et al, 2017), as well as strain (Jonckers et al, 2011;Schroeter et al, 2017;Shah et al, 2016b), and the impact of sedation or awake conditions on the underlying signal and connectivity patterns (Bukhari et al, 2017;Grandjean et al, 2014a;Jonckers et al, 2014;Yoshida et al, 2016). This body of work obtained mainly over the past 5 years reflects the growth and interest into this modality as a translational tool to understand mechanisms underlying RSNs organisation in the healthy and diseased states, with the promise to highlight relevant targets in the drug development process and to advance fundamental knowledge in neuroscience.…”

Section: Introductionmentioning

confidence: 99%

“…field strength, hardware design), animal handling protocols and sedation regimens employed to control for motion and stress. Discrepancies between reports, such as the anatomical and spatial extent of a rodent homologue of the human default-mode network (DMN) (Becerra et al, 2011;Gozzi and Schwarz, 2016;Guilfoyle et al, 2013;Hübner et al, 2017;Liska et al, 2015;Lu et al, 2012;Sforazzini et al, 2014;Stafford et al, 2014;Upadhyay et al, 2011), or the organisation of murine RSNs (Jonckers et al, 2011), have stark consequences for the interpretations of the results. To meet a growing need to establish standards and points of comparison in rodent fMRI, we carried out a multi-centre comparison of mouse rsfMRI datasets.…”

Section: Introductionmentioning

confidence: 99%

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Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Grandjean¹,

Canella

Anckaerts

et al. 2019

Preprint

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Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

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The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model

Cited by 69 publications

References 80 publications

Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

Heritability of the Mouse Brain Connectome

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

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