Successful Working Memory Processes and Cerebellum in an Elderly Sample: A Neuropsychological and fMRI Study

RESEARCH ARTICLE Successful Working Memory Processes and Cerebellum in an Elderly Sample: A Neuropsychological and fMRI Study Elkin O. Luis1, Gonzalo Arrondo1,4, Marta Vidorreta1, Martin Martínez1, Francis Loayza1, María A. Fernández-Seara1,3, María A. Pastor1,2,3* 1 Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain, 2 Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain, 3 CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain, 4 Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom * OPEN ACCESS Citation: Luis EO, Arrondo G, Vidorreta M, Martínez M, Loayza F, Fernández-Seara MA, et al. (2015) Successful Working Memory Processes and Cerebellum in an Elderly Sample: A Neuropsychological and fMRI Study. PLoS ONE 10(7): e0131536. doi:10.1371/journal.pone.0131536 Editor: Andrea Antal, University Medical Center Goettingen, GERMANY Received: April 12, 2015 Accepted: June 3, 2015 Abstract Background Imaging studies help to understand the evolution of key cognitive processes related to aging, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to WM processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during highdemand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition. Published: July 1, 2015 Copyright: © 2015 Luis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Methods We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: M.A.P. has been funded by CIBERNED, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain and by the UTE project Fundacion para la Investigacion Medica Aplicada FIMA, Spain. Elkin O. Luis is supported by an Education Department grant from the Government of Navarra (2011-2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Results During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parietal network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas. PLOS ONE | DOI:10.1371/journal.pone.0131536 July 1, 2015 1 / 17 Successful Working Memory Processes and Cerebellum Competing Interests: The authors have declared that no competing interests exist. Conclusion Successful WM processes in the elderly population are accompanied by an activation pattern that involves cerebellar regions working together with a fronto-parietal network. Introduction With advancing age, most adults report difficulties in generating strategies to maintain and handle information in rapidly changing social contexts. One of the most studied cognitive processes in the neuroscience of aging is working memory (WM), which has been defined as the process that maintains limited information in the mind during short periods of time [1]. An accepted model proposes that WM processes are carried out by specific subsystems: the Phonological Loop (PL), the Visuo-spatial Sketchpad (VS) and the Episodic Buffer (EB). Both the PL and VS have a passive storage system, and a loop-strategy of active maintenance of information [2]. A fourth construct called the Central Executive (CE) works over the slave subsystems through the orientation, focus and division of attentional resources [3,4]. Currently the roles of the basal ganglia (BG) and the cerebellum in WM-processing are better recognised. McNab et al. [5] demonstrated with functional magnetic resonance imaging (fMRI) that BG activity was a predictor of unnecessary storage and played a role as a filter of irrelevant information for WM. Another fMRI study conducted by Ziemus et al., [6] using a 2-back paradigm showed that cerebellar lesions affect the functioning of the fronto-parietal network, which is involved in WM. Bower [7] regards the cerebellum as a perception facilitator through the coordination of sensory information acquisition. In WM, cerebellar function has been proposed to depend on stimuli conditions, memory load or task type [8]. The cerebellar function, and particularly the function of VI/Crus I and VIIB lobules, might not be simply related to maintaining the memory footprint, but also to executive control [9]. Other studies have shown that right VI and Crus I are involved during subvocal rehearsal processes (SRP) and lobules VIIB and VIII during the phonological store (PS) [10,11]. Whereas a left predominance for visual input conditions has been reported [12], other investigations suggest that the cerebellum might serve as an interface between the two components of the phonological loop (SRP and PS), comparing the output of SRP with previously stored content [10,13,14]. Previous studies have shown a cognitive decline associated with age in tasks supported by the frontal lobes, such as WM, priming and text processing [4]. In addition, it has been proposed that age-related changes are the result of a weakening of inhibitory processes in WM (the inhibition deficit hypothesis). Recent neuroimaging studies have identified several changes in brain activation patterns during WM tasks due to aging. Such studies have demonstrated that older adults exhibit greater activation in prefrontal regions coupled with lower activations in posterior brain regions when performing WM tasks, supporting the sensory deficit hypothesis. It has also been reported that older adults during WM tasks show greater vulnerability to distractions that weaken the memory trace and an age-associated decline in their performance on WM neuropsychological tests [15,16]. Several studies have reported that aging i (...truncated)