Relationship between hippocampal structure and memory function in elderly humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection

Reinforcement Learning, Error-Related Negativity, and Genetic Risk for Alzheimer\u27s Disease

Reinforcement learning (RL) has been widely used as a model of animal and human learning and decision-making. The neural networks underlying RL involve many of the same structures primarily affected by Alzheimer’s disease (AD) such as the hippocampus. Yet, RL and non-invasive evaluation of its neural underpinnings have been underutilized as a framework for understanding disease pathology and its pre-clinical states. This study aimed to provide a novel approach for assessing subtle changes in asymptomatic apolipoprotein-E (APOE) carriers and non-carriers. Electroencephalography was collected from forty APOE genotyped older adults (Male n = 11; Mage = 79.30; Meducation = 14.88 years) during an RL task comprised of distinct phases (RL, implicit). Neural components associated with the error detection system involved in RL, the response error-related negativity (ERN) and the feedback error-related negativity (FRN), were examined for individuals at low (APOE ε4-; n=20) and high risk (APOE ε4+; n=20). RL task performance did not differ between risk groups. However, the high-risk group consistently elicited greater peak amplitudes than the low-risk group. The pattern of results indicated that the high-risk group deviated from typical RL processes such that peak amplitudes did not differ between early and late learning. Additionally, despite intact learning, latent hippocampal atrophy is believed to have disrupted the transfer and use of learned information to novel situations thus altering the hippocampal-frontostriatal circuit responsible for adaptive behavior and the corresponding neural signal. The results indicate that disease related changes can be identified prior to clinical diagnosis or functional decline using RL and a non-invasive assessment of neural function, which may prove to inform clinical conceptualization, assessment, and treatment

Is faster better? Effects of response deadline on ERP correlates of recognition memory in younger and older adults

Aging studies generally suggest that recollection is impaired whereas familiarity-based recognition remains relatively preserved in healthy older adults. The present event-related potential (ERP) study explores whether age-related impairments in recognition memory can be reduced under conditions in which recognition decisions are primarily driven by familiarity. Old and young adults performed an item recognition task with perceptually rich visual stimuli. A response deadline procedure was employed following previous studies which have shown that limiting response times attenuates recollection but leaves familiarity relatively unaffected. Age effects on memory performance were large in the non-speeded response condition in which recollection contributes to performance. When response time was limited, performance differences between groups were negligible. In the non-speeded condition the ERP correlate of recollection was not detectable in old adults. Conversely, in the speeded condition ERP correlates of familiarity were obtained in both age groups, though attenuated for old adults. For old adults in the speeded condition a temporally extended posterior negativity was obtained which was more pronounced for low performing participants. The results suggest that even though the neural generators of the familiarity signal degrade with age, familiarity is an important contributor to recognition memory in older adults and can lead to a disproportional benefit in memory in conditions designed to specifically enhance familiarity-based responding

The monitoring role of right lateral prefrontal cortex: evidence from variable foreperiod and source memory tasks

The main purpose of this research project was to investigate the monitoring function of the right dorsolateral prefrontal cortex using different tasks in two domains. To that purpose, the architecture of the cognitive processes required to perform each task was extracted by means of different approaches of functional dissociation. A variable foreperiod (FP) task was initially adopted. In such a task, simple/choice RTs are required while FPs of different duration vary on a trial-by-trial basis equiprobably in a rectangular distribution but randomly. As a result, the conditional probability is higher later in the FP range and RT is faster as the FP increases. This is the variable FP effect, which a recent neuropsychological study shows to be impaired in right lateral prefrontal patients. Another phenomenon usually obtained with such a paradigm is that of the sequential effects: RT becomes slower as the FP on the preceding trial gets longer. Contrasting views in the literature propose either multi-process strategic accounts, or a single-process conditioning account. In the project, these alternative theories were tested using behavioural studies on adults and children. The findings of these studies were not fully compatible with the previous views. A composite dual-process account, which shares some aspects with the previous accounts, was put forward and discussed. On this account, sequential effects are due to automatic processes acting on the arousal level, whereas the FP effect is due to a strategic process monitoring the conditional probability of stimulus occurrence. Results of two TMS experiments confirm that the right dorsolateral prefrontal cortex is responsible for the FP effect, but not for the sequential effects. A neuropsychological study on tumor patients further corroborates this finding and suggests that left premotor areas are more likely to be the locus of the sequential effects. In order to test whether the explicit temporal judgment has an influence on the nature of the FP phenomena, a series of behavioural experiments was conducted using a modified version of the variable FP paradigm. In the basic task, explicit judgments about the FP length were required. No modulation of the FP phenomena was obtained. However, a new stimulus-response compatibility effect was found: RT was faster when short and long FPs had to be responded to with left and right response-keys, respectively, than with the opposite stimulus-response mapping. This effect suggests that elapsing time is represented, in some circumstances, by means of spatial coordinates. Control experiments enable us to reject accounts based on hand/hemispheric asymmetries, but not accounts based on more categorical factors such as the linguistic markedness of the words used to label the stimuli and the responses. The last part of the project aimed at extending results about a monitoring role (intended in a broad sense) of the right prefrontal cortex to a domain different from non-specific preparation. Two experiments in the source memory domain were run recording ERPs in the retrieval phase. The results show that prefrontal ERPs are not modulated by retrieval success, but by retrieval confidence, with low-confidence responses being associated with more positive waves than high-confidence ones, bilaterally, in the anterior prefrontal sites. Moreover, prefrontal waves were asymmetrically more positive in the right than in the left scalp regions, independently of confidence and accuracy. On the basis of these results, we could reject accounts linked to retrieval success. The results are instead interpreted in terms of different prefrontally-located monitoring processes in source memory retrieval. Overall, the project represents an instantiation of the fractionation approach recently adopted to study the supervisory functions of the prefrontal cortex. This approach was used here in order to understand the differential role of a particular prefrontal area (i.e., the right dorsolateral prefrontal cortex) in a rather specific function (i.e., monitoring). This goal was developed in synchrony with the attainment of a better functional description of the tasks employed

Disentangling older adults´ difficulties in person memory neurophysiological studies on face and name processing

Complaints about difficulties in person perception and memory are very common among older adults, and the ability to learn and recognize faces and names is known to decline with increasing age. However, it is not clear at present to what degree these deficits result from less efficient processing at early perceptual, representational, or episodic memory-related stages. In this thesis five experiments are presented, which aimed at investigating this issue by analyzing event-related brain potential correlates of person perception and memory. Overall, the results indicate that early perceptual face processing (as reflected in the N170) is relatively less affected by aging than later representational and memory-related stages (as reflected in N250, N400, and episodic old/new effects)

Risk factors for incident cognitive decline and dementia in a very elderly hypertensive population : a two year prospective cohort study

Imperial Users onl