Functional Magnetic Resonance Imaging of Semantic Memory as a Presymptomatic Biomarker of Alzheimer’s Disease Risk

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer\u27s disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease

Memory in autism spectrum disorder: a meta-analysis of experimental studies

To address inconsistencies in the literature on memory in Autism Spectrum Disorder (ASD), we report the first ever meta-analysis of short-term (STM) and episodic long-term (LTM) memory in ASD, evaluating the effects of type of material, type of retrieval and the role of inter-item relations. Analysis of 64 studies comparing individuals with ASD and typical development (TD) showed greater difficulties in ASD compared to TD individuals in STM (Hedges’ g=-0.53 [95%CI -0.90; -0.16], p=.005, I²=96%) compared to LTM (g=-0.30 [95%CI -0.42; -0.17], p<.00001, I²=24%), a small difficulty in verbal LTM (g=-0.21, p=.01), contrasting with a medium difficulty for visual LTM (g= -0.41, p=.0002) in ASD compared to TD individuals. We also found a general diminution in free recall compared to cued recall and recognition (LTM, free recall: g=-0.38, p<.00001, cued recall: g=-0.08, p=.58, recognition: g=-0.15, p=.16; STM, free recall: g=-0.59, p=.004, recognition: g=-0.33, p=.07). We discuss these results in terms of their relation to semantic memory. The limited diminution in verbal LTM and preserved overall recognition and cued recall (supported retrieval) may result from a greater overlap of these tasks with semantic long-term representations which are overall preserved in ASD. By contrast, difficulties in STM or free recall may result from less overlap with the semantic system or may involve additional cognitive operations and executive demands. These findings highlight the need to support STM functioning in ASD and acknowledge the potential benefit of using verbal materials at encoding and broader forms of memory support at retrieval to enhance performance

Semantic memory

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Common and unique neural activations in autobiographical, episodic, and semantic retrieval

This study sought to explore the neural correlates that underlie autobiographical, episodic, and semantic memory. Autobiographical memory was defined as the conscious recollection of personally relevant events, episodic memory as the recall of stimuli presented in the laboratory, and semantic memory as the retrieval of factual information and general knowledge about the world. Our objective was to delineate common neural activations, reflecting a functional overlap, and unique neural activations, reflecting functional dissociation of these memory processes. We conducted an event-related functional magnetic resonance imaging study in which we utilized the same pictorial stimuli but manipulated retrieval demands to extract autobiographical, episodic, or semantic memories. The results show a functional overlap of the three types of memory retrieval in the inferior frontal gyrus, the middle frontal gyrus, the caudate nucleus, the thalamus, and the lingual gyrus. All memory conditions yielded activation of the left medial-temporal lobe; however, we found a functional dissociation within this region. The anterior and superior areas were active in episodic and semantic retrieval, whereas more posterior and inferior areas were active in autobiographical retrieval. Unique activations for each memory type were also delineated, including medial frontal increases for autobiographical, right middle frontal increases for episodic, and right inferior temporal increases for semantic retrieval. These findings suggest a common neural network underlying all declarative memory retrieval, as well as unique neural contributions reflecting the specific properties of retrieved memories

Episodic encoding is more than the sum of its parts: An fMRI investigation of multifeatural contextual encoding

Episodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced

Prospective memory impairments in Alzheimer's Disease and behavioral variant frontotemporal dementia: Clinical and neural correlates

BACKGROUND: Prospective memory (PM) refers to a future-oriented form of memory in which the individual must remember to execute an intended action either at a future point in time (Time-based) or in response to a specific event (Event-based). Lapses in PM are commonly exhibited in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD), however, the neurocognitive mechanisms driving these deficits remain unknown. OBJECTIVE: To investigate the clinical and neural correlates of Time- and Event-based PM disruption in AD and the behavioral-variant FTD (bvFTD). METHODS: Twelve AD, 12 bvFTD, and 12 healthy older Control participants completed a modified version of the Cambridge Prospective Memory test, which examines Time- and Event-based aspects of PM. All participants completed a standard neuropsychological assessment and underwent whole-brain structural MRI. RESULTS: AD and bvFTD patients displayed striking impairments across Time- and Event-based PM relative to Controls, however, Time-based PM was disproportionately affected in the AD group. Episodic memory dysfunction and hippocampal atrophy was found to correlate strongly with PM integrity in both patient groups, however, dissociable neural substrates were also evident for PM performance across dementia syndromes. CONCLUSION: Our study reveals the multifaceted nature of PM dysfunction in neurodegenerative disorders, and suggests common and dissociable neurocognitive mechanisms, which subtend these deficits in each patient group. Future studies of PM disturbance in dementia syndromes will be crucial for the development of successful interventions to improve functional independence in the patient's daily life

Know-how, intellectualism, and memory systems

ABSTRACTA longstanding tradition in philosophy distinguishes between knowthatand know-how. This traditional “anti-intellectualist” view is soentrenched in folk psychology that it is often invoked in supportof an allegedly equivalent distinction between explicit and implicitmemory, derived from the so-called “standard model of memory.”In the last two decades, the received philosophical view has beenchallenged by an “intellectualist” view of know-how. Surprisingly, defenders of the anti-intellectualist view have turned to the cognitivescience of memory, and to the standard model in particular, todefend their view. Here, I argue that this strategy is a mistake. As it turns out, upon closer scrutiny, the evidence from cognitivepsychology and neuroscience of memory does not support theanti-intellectualist approach, mainly because the standard modelof memory is likely wrong. However, this need not be interpretedas good news for the intellectualist, for it is not clear that theempirical evidence necessarily supp..

Cognitive support at encoding attenuates age differences in recollective experience among adults of lower frontal lobe function

Free recall and recollective experience were investigated in relation to neuropsychological measures of frontal lobe function (FLF) among 105 healthy adults divided into three age groups; young (M = 21.82 years), young-old (M = 64.69 years), and old-old (M = 70.69 years). Participants were tested on free recall and recognition of word lists in each of two study conditions. In the first, semantically related words were organizable into one of four taxonomic categories, whereas in the second (random) condition, words were semantically unrelated. Results in respect of free recall showed memory performance was inferior with increasing age, lower FLF, and random encoding condition. There were no interactions involving those variables. With regard to recollective experience, a similar pattern of results was obtained. However, analyses also identified a significant interaction, suggesting old-old adults of lower FLF to exhibit poorer recollective experience. This interaction was significantly modified when semantic organization was available at study. Recognition measures classified as familiar did not vary as a function of age, neuropsychological function, or encoding condition. The results are consistent with the view that autonoetic consciousness, supported by the neural systems of the prefrontal cortex, underpins recollective experience. Further, among older adults, cognitive support at encoding attenuates the detrimental effects of individual differences in those neural systems, in relation to recognition performance

Why musical memory can be preserved in advanced Alzheimer's disease

Musical memory is relatively preserved in Alzheimer's disease and other dementias. In a 7 Tesla functional MRI study employing multi-voxel pattern analysis, Jacobsen et al. identify brain regions encoding long-term musical memory in young healthy controls, and show that these same regions display relatively little atrophy and hypometabolism in patients with Alzheimer's disease.See Clark and Warren (doi:10.1093/brain/awv148) for a scientific commentary on this article. Musical memory is relatively preserved in Alzheimer's disease and other dementias. In a 7 Tesla functional MRI study employing multi-voxel pattern analysis, Jacobsen et al. identify brain regions encoding long-term musical memory in young healthy controls, and show that these same regions display relatively little atrophy and hypometabolism in patients with Alzheimer's disease.See Clark and Warren (doi:10.1093/awv148) for a scientific commentary on this article

Differentiation of functional networks during long-term memory retrieval in children and adolescents.

The processes that characterize the neural development of long-term memory (LTM) are largely unknown. In young adults, the degree of activation of a single large-scale memory network corresponds to the level of contextual detail involved; thus, differentiating between autobiographical, episodic, and semantic retrieval. In contrast to young adults, children and adolescents retrieve fewer contextual details, suggesting that they might not yet engage the entire memory circuitry and that this brain recruitment might lack the characteristic contextual differentiation found in adults. Twenty-one children (10-12 years of age), 20 adolescents (14-16 years of age), and 22 young adults (20-35 years of age) were assessed on a previously validated LTM retrieval task, while their brain activity was measured with functional magnetic resonance imaging. The results demonstrate that children, adolescents, and adults recruit a left-lateralized subset of the large-scale memory network, comprising semantic and language processing regions, with neither developmental group showing evidence of contextual differentiation within this network. Additionally, children and adolescents recruited occipital and parietal regions during all memory recall conditions, in contrast to adults who engaged the entire large-scale memory network, as described previously. Finally, a significant covariance between age and brain activation indicates that the reliance on occipital and parietal regions during memory retrieval decreases with age. These results suggest that both children and adolescents rely on semantic processing to retrieve long-term memories, which, we argue, may restrict the integration of contextual detail required for complex episodic and autobiographical memory retrieval