Cerebral Activation during Working Memory in Multiple Sclerosis with the APOE Epsilon-4 Allele
Open Access
- Author:
- Bradson, Megan Lynn
- Area of Honors:
- Psychology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Peter Andrew Arnett, Thesis Supervisor
Dr. Frank Gerard Hillary, Thesis Honors Advisor - Keywords:
- Multiple Sclerosis
Neuroimaging
Brain Activation
fMRI
Working Memory - Abstract:
- INTRODUCTION: Increased cerebral activation patterns have been demonstrated during working memory tasks using functional magnetic resonance imaging (fMRI) in individuals diagnosed with multiple sclerosis (MS) and in cognitively intact persons genetically at risk for Alzheimer’s disease. Few studies have compared brain activation patterns associated with working memory as a function of apolipoprotein E (APOE) genotype in individuals with MS, despite evidence suggesting APOE’s role in myelin formation, myelin repair, and neuronal plasticity processes. The purpose of this study was to determine whether the ε4 allele of the APOE gene influences brain activation in a sample of cognitively similar patients with MS. METHOD: The sample (N = 41) was composed of 13 APOE-ε4+ and 28 APOE-ε4- patients with MS. All participants completed a full neuropsychological assessment battery prior to undergoing fMRI to perform the N-back task used to probe working memory-related brain activity. Using Statistical Parametric Mapping 8 (SPM8), a two-sample t-test was used to compare brain activation in APOE genotype groups. RESULTS: Independent samples t-tests verified APOE group equivalences in demographic characteristics and on neuropsychological performance variables. The APOE-ε4 positive group exhibited greater activity in the medial frontal regions bilaterally and in the right dorsolateral prefrontal cortex, (p < .001, uncorrected with a minimum cluster size of 30 voxels). DISCUSSION: Given that APOE groups were equivalent demographically and cognitively, group differences in brain activation can be attributed to APOE genotype. The greater activation observed in APOE-ε4 carriers may suggest a compensatory mechanism to offset inefficient cognitive processes that occur when the brain is impacted by MS and the APOE-ε4 allele.