The brain is organized into neural networks that control interactions across distributed areas. As the brain ages, neurodegeneration can be seen through the breakdown of these networks. This negative correlation between increased aging and decreased organization of brain networks can be seen through resting-state fMRI. Some brains may be more prone to rapid cognitive decline following focal brain events, such as a stroke or aneurysm. Cognitive decline can be characterized by difficulty with language, worsening memory, and other behaviors. The present study takes a look into directly manipulating cognitive function with lesioning regions of interest that are associated with important networks using mice models. The results of the lesion can be phenotyped with fMRI and behavioral assays throughout the lifespan of the mouse. Research from this study can be used to look into aging of healthy humans and diagnoses associated with neurodegeneration like Alzheimer’s Disease.
To study these large-scale brain networks, the lab will use fMRI to look into changes of brain network organization throughout the mouse lifespan. Mice will be surgically implanted with headposts for resting-state fMRI data. In aim 1, these mice will be scanned multiple times over the lifespan to generate the natural progression of systems segregation within the mouse brain. Between scans, mice will run through behavioral assays to collect more characteristics associated with neurodegeneration. In aim 2, mice will go through another surgery to have one of two regions of interest lesioned. The regions of interest chosen for this study target vulnerable brain network hubs and a control site in a non-hub location. The lesion procedure will either be performed earlier or later in the mouse’s life. These lesions will show how the brain maintains and rewires networks from a focal brain event. More fMRI data will be collected after the lesion to track changes within different life stages. The analyses will be done in collaboration from Gagan Wig’s lab at UT Dallas.
This study will employ conventional Open Field and Novel Object Recognition (NOR) assays, enhanced with Motion Sequencing (MoSeq), to generate a longitudinal, data-driven characterization of mouse behavior across the lifespan and in the context of the targeted cortical lesions. We will use the Open Field to measure locomotion and anxiety-like exploratory behavior. In contrast, NOR will be used as a basic assessment of cognition and memory via the animal’s differential exploration of a familiar versus a novel object. MoSeq will be implemented during Open Field exploration and NOR, analyzed from 3D/depth videography. The unsupervised algorithm of MoSeq parses the continuous movement from recorded depth videos into behavioral “syllables,” enabling the capturing of fine-grained motor/postural motifs that extend beyond the standard behavior scoring. Integrating these behavioral assays with longitudinal resting-state fMRI allows this study to link behavioral profiles to large-scale network organization (system segregation) across aging and quantify how hub versus non-hub lesions alter the trajectories of both brain networks and behavior.
Group Members: Gabriella Vill, Tyler Young, & Apoorva Vashisht