Retrieval Deficiency in Brain Activity of Working Memory in Amnesic Mild Cognitive Impairment Patients: A Brain Event-Related Potentials Study

Abstract

In the early stage of Alzheimer disease (AD) or mild cognitive impairment (MCI), working memory (WM) deficiency is prominent and could be attributed to failure in encoding, maintenance or retrieval of information. However, evidence for a retention or retrieval deficit remains equivocal. It is also unclear what cognitive mechanism in WM is impaired in MCI or early AD. We enrolled 46 subjects from our Memory Clinics and community, with 24 amnesic MCI patients and 22 normal subjects. After neurological and cognitive assessments, they performed a classic delayed match to sample (DMS) task with simultaneous event-related potential (ERP) recorded. The ERPs in encoding and retrieval epoch during WM were analyzed separately. The latency and amplitude of every ERP component were compared between two groups, and then analyzed to explore their relationship with neuropsychological performance. Finally, the locations of maximal difference in cortex were calculated by standard low-resolution tomographic analysis. A total of five components were found: P1, N1, P2, N2, and P300. The amplitude of P2 and P300 was larger in normal subjects than in MCI patients only during retrieval, not encoding epoch, while the latency did not show statistical difference. The latency and amplitude of P1 and N1 were similar in two groups. P2 amplitude in the retrieval epoch positively correlated with memory test (auditory verbal learning test) and visual spatial score of Chinese Addenbrooke's Cognitive Examination-Revised (ACE-R), while P300 amplitude correlated with ACE-R. The activation difference in P2 time range was maximal at medial frontal gyrus. However, the difference in cortex activation during P300 time range did not show significance. The amplitude of P2 indicated deficiency in memory retrieval process, potentially due to dysfunction of central executive in WM model. Regarding the location of P2 during WM task, medial frontal plays important role in memory retrieval. The findings in the present study suggested that MCI patients have retrieval deficit, probably due to central executive based on medial frontal gyrus. Thus, it may provide new biomarker for early detection and intervention for aMCI.

Mapping of impaired functional connectivity during memory phases in Alzheimer's disease and its association with cortical β-amyloid

“…Importantly, we found the reduction speci cally in the maintenance and retrieval phase of memory. As in our previous work, retrieval de ciencies could be the cause of poor performance (5). An intervention study provided additional evidence for the importance of the retrieval phase in recognition (34).…”

“…It is controversial whether the observed amnesia is due to disrupted encoding or consolidation of episodic information, or an impairment in the retrieval of stored memory information. Several studies have suggested that the ineffective encoding of new information in the brain triggers episodic memory de cits (1,2), while more evidence supported retrieval de cit in early AD (3)(4)(5). Transgenic AD mouse models also suggested that direct activation of hippocampal memory engram cells resulted in memory retrieval, revealing a retrieval, rather than a storage impairment in early AD (6).…”

Monolinguals and bilinguals respond differently to a delayed matching-to-sample task: An ERP study

“…P200 latency was longer in the high-load condition than in the low-load condition, indicating the need for more processing time in the more difficult conditions. Previous studies have found no effect of task difficulty on the P200 (Li et al, 2016;Pinal et al, 2014). These conflicting findings may be due to differences in stimulus presentation: Li et al (2016) presented letters for 2000 ms whereas Pinal and Diaz, 2014 presented domino images for 1000 ms, and both studies presented all stimuli for the same time independent of memory load.…”

“…This component is typically measured during conflict monitoring tasks (Veen & Carter, 2002), but is also reflective of stimulus detection and the ability to discriminate incongruities between stimuli (Bennys, Portet, Touchon & Rondouin, 2007;Folstein & Van Petten, 2008;Patel & Azzam, 2005). Similar to the P2, in a DMS task N2b amplitude is not modulated during encoding by task difficulty (Li et al, 2016;Pinal et al, 2014). However, during the retrieval phase of a WM task, N2b amplitude continually increases with task difficulty (Patel & Azzam, 2005;Pinal et al, 2014), indicating that as the task becomes more difficult, more attention and effort is needed to retrieve the memory of the past stimulus and discriminate the current stimulus from the previous one.…”

Decreased Event-Related Beta Synchronization During Memory Maintenance Marks Early Cognitive Decline in Mild Cognitive Impairment

“…For the source localization, the low-resolution electromagnetic tomography approach was applied, which has been previously successfully used for the analysis of ERPs in MCI patients [33,34]. However, to our knowledge, this is the first study examining the sources of induced time-varying oscillations in MCI.…”