Experimental magnetic resonance imaging modalities as tools to evaluate brain function, structure and networks : exercise and cocaine induced adaptations

Psychiatric disease is common, costly and globally spread. Currently there are few efficient treatments that help patients to be remitted to a high degree. There is a need for improvement of robust objective diagnostic markers that can help the physicians to diagnose, follow-up or monitor treatment schedules. In the field of depression, only about 50% of patients experience medical relief by pharmacological treatment, and with psychostimulant use disorders there are no routinely used pharmacological treatments available. Therefore, it would be valuable to have better robust tools to be used for evaluation of new putative treatments as well as gaining a more comprehensive understanding of the etiology and pathophysiology of psychiatric diseases.

The aim of this study was to further evaluate the translational potential of resting state functional connectivity (rsfMRI) brain networks by Magnetic Resonance Imaging (MRI) with special focus on rodent models for psychiatric disease.

MRI can be utilized to analyze both structure and function of the brain. The images obtained by an MRI scan with EPI (Echo Planar Imaging) pulse sequences have the right contrast to enable analysis of different functional brain networks. In the case of rsfMRI, subjects are asked to close their eyes, not think about any specific and lay still inside an MRI scanner. For rodents, this technique can be utilized on lightly anaesthetized animals. This study demonstrates how wheel running induces enlargement of hippocampus in rats. Also, it shows how remarkably similar resting state functional connectivity networks are in rats and humans. It was further discovered that 14 days cocaine administration to rats induced alterations of functional brain networks. The data obtained was processed with the novel method Quantitative Data-driven Analysis (QDA), where connection strength and numbers of connections in the whole brain was measured. This was the first time QDA was applied in rodent rsfMRI.

Finally, we used QDA to show that functional brain network connections involving insular cortex were correlated to the behavioral response of rats in a novel environment.

List of scientific papers

I. Hippocampal morphology in a rat model of depression: the effects of physical activity. Sierakowiak, A., A. Mattsson, M. Gomez-Galan, T. Femenía, L. Graae, S. N. Aski, P. Damberg, M. Lindskog, S. Brené and E. Åberg (2014). Open Neuroimaging Journal 9: 1-6.
https://doi.org/10.2174/1874440001509010001

II. Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI. Sierakowiak, A., C. Monnot, S. N. Aski, M. Uppman, T. Q. Li, P. Damberg and S. Brené (2015). PLoS One 10(3): e0120345.
https://doi.org/10.1371/journal.pone.0120345

III. Cocaine Increases and Decreases Functional Coupling of the Rodent Brain in Prelimbic Cortex and Dorsal Striatum Respectively. Adam Sierakowiak, Tie-Qiang Li, Cyril Monnot, Josefine Klein-Dahlgren, Sahar Nikkhou Aski, Peter Damberg, Stefan Brené. [Manuscript]

IV. Resting State Functional Coupling in the Rat Insular Cortex is Correlated to Behavior in a Novel Environment. By: Adam Sierakowiak, Tie-Qiang Li, Cyril Monnot, Teresa Femenía, Sahar Nikkhou Aski, Peter Damberg, Sarah Holst, Stefan Brené. [Manuscript]