Quasi-Periodic brain activity in mice and its significance in pre-clinical neuroimaging research
26 June 2018
Auditorium O1 (UAntwerp, Campus Drie Eiken, Building O) - Universiteitsplein 1 - 2610 Wilrijk (Antwerp) (route: UAntwerpen, Campus Drie Eiken
4:00 PM - 6:00 PM
Marleen Verhoye, Annemie Van der Linden
PhD defence Michaël Belloy - Department of Biomedical Sciences
Resting state functional MRI (rsfMRI) is a non-invasive technique used to study functional connectivity (FC) between different brain areas, within a subject at rest, absent attention-demanding stimuli. RsfMRI also allows investigation of time-resolved brain dynamics, such as Quasi-Periodic Patterns (QPPs). QPPs are hypothesized to represent an important contributor to brain FC. They describe a recurring opposition of two major networks, the Default Mode (DMN) and Task Positive network (TPN), respectively important for internally versus outwardly oriented cognitive processes. The major goal of thesis was to determine if QPPs exist in mice and establish if their properties are relevant to advance preclinical rsfMRI research.
First, we validated in young healthy control animals that QPPs exist in mice and that they display dynamic anti-correlation of two networks homologous to the DMN and TPN. We determined that multiple subtypes exist and that they coincide with global brain dynamics. Global signal fluctuations and DMN-TPN anti-correlations have prior been related to arousal dynamics.
Then, we determined if QPPs could provide novel insight into Alzheimer’s disease (AD). We imaged old TG2576 mice, a mouse model of amyloidosis, and age-matched healthy controls. While control animals displayed normal patterns, AD mice were marked by QPPs in which components of the DMN network were anti-correlated. We then showed how QPPs reflected a large fraction of DMN-TPN FC, and that this information could be used as a biomarker of Alzheimer’s disease pathology.
Lastly, we investigated the role of QPPs in brain function. In control mice, we acquired rsfMRI followed by visual stimulation fMRI. We determined that QPPs occur during the task state and interact with visual processing. On one side, QPPs before the onset of a stimulus modulated the evoked response magnitude. On the other side, visual stimuli triggered activation of QPPs. By removing the contribution of QPPs from the data, we showed that QPPs contributed to the magnitude and variance of visual responses. The timing of QPPs at the start of the stimulus suggested an arousal-based mechanism. Such process can be mediated by neuromodulatory input from the brainstem, which appeared involved within QPPs. The same neuromodulatory systems are important for global brain dynamics.
Overall, this thesis showed the existence of QPPs in mice and indicated their relevance for pre-clinical research. A common emerging element from our work is the close relationship between global brain dynamics, QPPs, arousal and potentially neuromodulatory systems. Future work may more closely investigate these ties.