Investigation of cognitive and functional magnetic resonance imaging changes during attention control and memory, and their possible neurochemical and genetic mechanisms

Abstract

The aging of the population appears to be a serious threat for society. Dementia occurs in high proportion of the aging population which is typically in the form of Alzheimer’s disease (AD). It is imperative that the neurophysiologic mechanisms of aging should be thoroughly investigated in order to provide insights for the early diagnosis of age-related neurodegenerative diseases. The basic cognitive functions mostly affected by age are the competence of attention and memory. Previous cognitive studies based on functional Magnetic Resonance Imaging (fMRI) revealed that there were distinct patterns of blood-oxygen-level-dependent (BOLD) changes or functional hyperemia in aging, high-performing older adults and APOE ε4 carriers. Furthermore, the glutamatergic cycle plays an essential role in modulating memory processing through the hippocampal circuitry, which is manifested by the neurotransmitter-mediated signaling in the glial/neuronal regulation of neurovascular coupling. A cognitively-normal (Montreal Cognitive Assessment ≥ 26) cohort of 91 healthy adults (average age = 51 ± 17 years, ranging from 20 to 84 years) underwent the Magnetic Resonance (MR) scans with 3.0 T Philips scanner. Task-based (including three attentional tasks and face-name encoding/retrieval task) and resting state fMRI were performed. Three conditions were considered in each task, which were shown as follows: Condition 1: young (20 yr – 40 yr) vs. middle-aged (40 yr – 60 yr) vs. elderly (above 60 yr); Condition 2: low performance (scored below 25%) vs. high performance (scored above 25%) in the behavioral test; Condition 3: low genetic risk (non-ApoE ε4 carriers) vs. high genetic risk ( ApoE ε4 carriers). In addition, traditional seed-based and graph theory methods were applied to analyze the resting state data in genetic-related subgroups. Proton Magnetic Resonance Spectroscopy (1H-MRS) technique was adopted to measure glutamatergic level. No significant results was found in the attentional experiments. It was revealed in face name memory task that the compensation mechanism occurred in these three different conditions. Additionally, the distribution of energy usage might be underlined in the task-negative DMN brain regions to accomplish the cognitive work. Moreover, the topological property differences between ApoE ε4 carriers and non-carriers suggested that the carriers had worse local interconnectivity and information exchange efficiency. It was illustrated by the combined 1H-MRS and fMRI data that the level of left hippocampal Glx (summation of glutamate and glutamine) was indeed associated with whole brain and bilateral hippocampal activations and behavioral responses during the memory task, rather than that in the right hippocampus or control region. Further sub-group analyses demonstrated that “effective and bilateral” functional hyperemia was modulated by left hippocampal Glx in the high-performance subjects, and co-option of the right hippocampal Glx played the modulatory role in APOE ε4 carriers. Thereby, consistent with the former fMRI and animal studies, a dissociable but dynamic left-right hippocampal glutamatergic system was revealed in the experiments, which guided and orchestrated neuronal activities in human brains in the cognitive control. In addition, our findings further supported the recruitment hypothesis of the apolipoprotein E compensatory mechanism. The results might provide insights in the underlying neurochemical and genetic mechanisms of cognitive control.