The influence of different brain states on the default mode-like network in rodents

The default mode network (DMN) is a large-scale brain network that is thought to play a fundamental role in internally oriented cognition, self-referential thought, mind-wandering and autobiographical memory. This brain network has consistently been shown in humans to be highly active and synchronized during rest. However, during an attentive brain state, e.g. during the performance of an external attention demanding task, DMN deactivates and desynchronizes. This functionality of the DMN is thought to facilitate task performance by suppressing internally based processing and task-independent brain activity during a task. Furthermore, it allows to shift additional cognitive processing resources towards the execution of the task. In recent years, preclinical imaging studies have discovered the existence of a default mode-like network (DMLN) in rodents. This DMLN consist out of anatomical homologous regions to the DMN in humans, however the resemblance in functionality remains to be proven. In this thesis, we investigated the functionality of the DMLN in rodents by using functional magnetic resonance imaging (fMRI) techniques during a visual attentive brain state. Here we could demonstrate that similarly as the human DMN, DMLN in rats was shown to deactivate and desynchronize during a visual attentive brain state. This result provides evidence that DMLN in rodents is functionally alike to the DMN in humans. As both networks show high correspondence in anatomy and functionality, results coming from DMLN animal studies could aid to some extent in the understanding of the DMN in humans. Next, we investigated a potential mechanism through which attention might modulate the DMLN i.e. the cholinergic system. As such, we used chemogenetics to stimulate cholinergic neurons in the basal forebrain inducing a cholinergic stimulated brain state and its effect was investigated using fMRI techniques. Results coming from this experiment demonstrated a clear roll of the cholinergic system in the control of synchronization and activity of the DMLN. Due to the strong link between attention and the cholinergic system, we hypothesize that the cholinergic system is the neuromodulatory system through which the attention system exert its modulation on the DMLN. Lastly, in the final part of the thesis, we focused on improving analysis methods for fMRI techniques. To do so, we developed a probabilistic vascular mouse brain atlas to objectively detect vascular influences within fMRI data. The vascular atlas was applied to fMRI data and was demonstrated to be an effective method to objectively identify vascular influences.

Jaar van publicatie:2020

Trefwoorden:Doctoral thesis

Toegankelijkheid:Open