Detection of memory‐ and learning‐related brain connectivity changes following trace eyeblink‐conditioning using resting‐state functional magnetic resonance imaging in the awake rabbit

Abstract

Animal imaging studies have the potential to further establish resting-state fMRI (rs-fMRI) and enable its validation for clinical use. The rabbit subjects used in this work are an ideal model system for studying learning and behavior and are also an excellent established test subject for awake scanning given their natural tolerance for restraint. We found that analysis of rs-fMRI conducted on a cohort of rabbits undergoing eyeblink conditioning can reveal functional brain connectivity changes associated with learning, and that rs-fMRI can be used to capture differences between subjects with different levels of cognitive performance. rs-fMRI sessions were conducted on a cohort of rabbits before and after trace eyeblink conditioning. MRI results were analyzed using independent component analysis (ICA) and network analysis. Behavioral data were collected with standard methods using an infrared reflective sensor aimed at the cornea to detect blinks. Behavioral results were analyzed, and a median split was used to create two groups of rabbits based on their performance. The cohort of rabbits undergoing eyeblink conditioning exhibited increased functional connectivity in the cingulate cortex, retrosplenial cortex, and thalamus consistent with brain reorganization associated with increased learning. Differences in the striatum and right cerebellum were also identified between rabbits in the top or bottom halves of the group as measured by the behavioral assay. Thus, rs-fMRI can provide not only a tool to detect and monitor functional brain changes associated with learning, but also to discriminate between different levels of cognitive performance.

Diet‐induced Alzheimer's‐like syndrome in the rabbit

“…The volume quadrature coil was used for transmission. The acquisition protocol included a coronal 3D‐GRE multi‐echo scan with repetition time (TR) = 68 milliseconds and echo times (TEs) as used previously 18 …”

“…Images were analyzed using FMRIB Software Library version 6.0 (Analysis Group, FMRIB), FSLNets 0.6, and MatLab R2017a (The Mathworks Inc.), as we did previously 18 …”

“…Images were acquired with a 7T ClinScan MRI scanner, as recently reported. 18 A three-channel custom-made receiver coil (RAPID MR International) designed with a central aperture was used. The volume quadrature coil was used for transmission.…”

“…We replicated the cholesterol and copper diet in aging rabbits, added a group fed a diet enriched with saturated fat and fructose, and expanded characterization of memory by adding recognition tests that can be done repeatedly simply by using different objects or locations with each repeat of the test. 17 Having shown 18 that resting state fMRI (rsfMRI) in awake rabbits provides reliable information on brain intrinsic functional connectivity networks, we acquired and compared connectivity data across groups to determine diet-related differences among functional networks. Finally, using MRI to generate R 2 * (1/T 2 *) brain maps we measured whole-brain and regional R 2 * values that were consistently higher in the diet groups compared to the control group.…”

Brain activity studied with magnetic resonance imaging in awake rabbits

“…the awake rabbit (Bertolino et al, 2021). We have also used a three-bolt version of the headbolt where one of the bolts was replaced with a plastic guide tube for a removable cannula that was targeted to the lateral ventricle for injection of magnetic nanospheres attached to an antibody (Rozema et al, 2020).…”