EMOTIONAL ENHANCEMENT AND REPETITION EFFECTS DURING WORKING MEMORY IN PERSONS WITH MILD COGNITIVE IMPAIRMENT

This dissertation introduces a framework for understanding differences in how emotional enhancement effects might influence memory in aging adults and then summarizes the findings of three studies of how repetition effects and emotional enhancement effects influence working memory in older adults without cognitive impairment (NC), older adults with amnestic mild cognitive impairment (MCI), and older adults with mild Alzheimer’s disease (AD). In these experiments, individuals with AD showed cognitive impairment in terms of accuracy and reaction time, but individuals with MCI showed milder behavioral impairment that was confined to manipulations of working memory. Individuals with AD showed relative sparing of repetition effects in behavioral performance, and this sparing was linked to an altered cortical repetition effect using event-related potentials (ERPs). Repetition effects in MCI appear absent in emotional tasks that lack a working memory component, but are present in a neural repetition mechanism that is evoked in the presence of working memory. Finally, persons with MCI showed working memory processing similar to persons without impairment when working with stimuli of low arousal and positive hedonic valence, but when working with stimuli of high arousal and negative hedonic valence, their working memory processing more resembled the AD phenotype

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing in Persons with Mild Cognitive Impairment

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD performed an emotionally-valenced short-term memory task while encephalography was recorded. Results indicated that for persons with MCI, high arousal negative stimuli led to working memory processing patterns previously associated with MCI presumed due to AD and dementia of the Alzheimer-type. In contrast, low arousal positive stimuli evoked a processing pattern similar to MCI participants’ unaffected spouses. Our current findings suggest that low arousal positive stimuli attenuate working memory deficits of MCI due to AD

The Time Course of Age-related Emotional Preference in Task-irrelevant Affective Processing

Studies of the age-related positivity effect have demonstrated that older adults have a generalized preference to positive stimuli or avoidance to negative stimuli compared with younger adults. However, it remains unclear when and how this positive effect occurs in task-irrelevant affective processing in the aging brain. The present study investigated age-related emotional preference in one task-irrelevant affective stimuli processing by event-related brain potentials (ERPs) measurement with a specific focus on the time course of older adults' emotional processing and regulation. Younger and older adults completed a modified oddball task in which the deviant stimuli were affective faces. In the relatively early time window, the brain activities were not modulated by emotional valence in younger adults, yet the sad stimuli elicited a larger P3a than the happy and neutral ones in older adults. In the late time window, the sad stimuli elicited a larger positive slow wave than the happy stimuli in younger adults. Contrarily, at the later processing stage older adults' valence differences were eliminated. In general, we found time course differences in how older adults processed task-irrelevant affective stimuli compared, with the young, and an age-related positivity effect occurred in the late time window, manifested as a negativity preference in younger and no preferences in older adults. These results provided evidence for supporting socioemotional selectivity theory from an ERP approach

Does emotional memory enhancement assist the memory-impaired?

We review recent work on emotional memory enhancement in older adults and patients with mild cognitive impairment (MCI) or Alzheimer dementia (AD) and evaluate the viability of incorporating emotional components into cognitive rehabilitation for these groups. First, we identify converging evidence regarding the effects of emotional valence on working memory in healthy aging. Second, we introduce work that suggests a more complex role for emotional memory enhancement in aging and identify a model capable of unifying disparate research findings. Third, we survey the neuroimaging literature for evidence of a special role for the amygdala in MCI and early AD in emotional memory enhancement. Finally, we assess the theoretical feasibility of incorporating emotional content into cognitive rehabilitation given all available evidence

A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment from Normal Aging

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education. Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be easy enough for impaired participants to complete but also to generate comparable performance between subjects with NC and those with aMCI. Scalp electroencephalography, memory accuracy, and reaction times were measured. Results: Whereas memory performance separated the AD group from the others, the performance of NC and subjects with aMCI was similar. In contrast, left frontal cognitive ERP patterns differentiated subjects with aMCI from NC. Enhanced P3 responses at left frontal sites were associated with nonmatching relative to matching stimuli during working memory tasks in patients with aMCI and AD, but not in NC. The accuracy of discriminating aMCI from NC was 85% by using left frontal match/nonmatch effect combined with nonmatch reaction time. Conclusions: The left frontal cognitive ERP indicator holds promise as a sensitive, simple, affordable, and noninvasive biomarker for detection of early cognitive impairment

Social Comparison Manifests in Event-related Potentials

Social comparison, a widespread phenomenon in human society, has been found to affect outcome evaluation. The need to belong to a social group may result in distinct neural responses to diverse social comparison outcomes. To extend previous studies by examining how social comparison with hierarchical characteristics is temporally processed, electroencephalography responses were recorded in the current study. Participants played a lottery game with two pseudo-players simultaneously and received both their own and the other two players’ outcomes. Results of three event-related potential components, including the P2, the feedback-related negativity (FRN), and the late positive component (LPC), indicate that social comparison manifests in three stages. First, outcomes indicating a different performance from others elicited a larger P2 than evenness. Second, the FRN showed hierarchical sensitivity to social comparison outcomes. This effect manifested asymmetrically. Finally, large difference between the participant’s outcome and the other two players’ evoked a larger LPC than the medium difference and the even condition. We suggest that during social comparison, people detect if there is any difference between self and others, and then evaluate the information of this difference hierarchically, and finally interpret the situations in which oneself deviates from the group as most motivationally salient

Functional Human \u3cem\u3eGRIN2B\u3c/em\u3e Promoter Polymorphism and Variation of Mental Processing Speed in Older Adults

We investigated the role of a single nucleotide polymorphism rs3764030 (G \u3e A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was genotyped and participants were grouped based on the presence of the A allele into GG and AA/AG. Carriers of the A allele maintained their speed of memory retrieval over age compared to GG carriers (p = 0.026 slope of the regression line between AA and AG versus GG groups). To validate the results, 12 older adults from the same cohort participated in a different version of the short-term memory task. Reaction times were significantly slower with age in older adults with G allele (p \u3c 0.001). These findings support a role for rs3764030 in maintaining faster mental processing speed over aging

Alzheimer\u27s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially During Resting and Task States

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults

Predicting risk decisions in a modified Balloon Analogue Risk Task: Conventional and single-trial ERP analyses

Event-related potential (ERP) has the potential to reveal the temporal neurophysiological dynamics of risk decision-making, but this potential has not been fully explored in previous studies. When predicting risk decision with ERPs, most studies focus on between-trial analysis that reflects feedback learning, while within-trial analysis that could directly link option assessment with behavioral output has been largely ignored. Suitable task design is crucial for applying within-trial prediction. In this study, we used a modified version of the classic Balloon Analogue Risk Task (BART). In each trial of the task, participants made multiple rounds of decisions between a risky option (pump up the balloon) and a safe option (cash out). Behavioral results show that as the level of economic risk increased, participants were less willing to make a risky decision and also needed a longer response time to do so. In general, the ERP results showed distinct characteristics compared with previous findings based on between-trial prediction, particularly about the role of the P1 component. Specifically, both the P1 (amplitude and latency) and P3 (amplitude) components evoked by current outcomes predicted subsequent decisions. We suggest that these findings indicate the importance of selective attention (indexed by the P1) and motivational functions (indexed by the P3), which may help clarify the cognitive mechanism of risk decision-making. The theoretical significance of these findings is discussed