We examine the anatomic basis for abstract and concrete lexical representations in semantic memory by assessing patients with focal neurodegenerative disease. Prior evidence from healthy adult studies suggests that there may be an anatomical dissociation between abstract and concrete representations: abstract words more strongly activate the left inferior frontal gyrus relative to concrete words, while concrete words more strongly activate left anterior-inferior temporal regions. However, this double dissociation has not been directly examined. We test this dissociation in two patient groups with focal cortical atrophy in each of these regions, the behavioral variant of Frontotemporal Degeneration (bvFTD) and the semantic variant of Primary Progressive Aphasia (svPPA). We administered an associativity judgment task for abstract and concrete words, where subjects select which of two words is best associated with a given target word. Both bvFTD and svPPA patients were significantly impaired in their overall performance compared to controls. While controls treated concrete and abstract words equally, we found a category-specific double dissociation in patients’ judgments: bvFTD patients showed a concreteness effect (CE), with significantly worse performance for abstract compared to concrete words, while svPPA patients showed reversal of the CE, with significantly worse performance for concrete over abstract words. Regression analyses also revealed an anatomic double dissociation: The CE is associated with inferior frontal atrophy in bvFTD, while reversal of the CE is associated with left anterior-inferior temporal atrophy in svPPA. These results support a cognitive and anatomic model of semantic memory organization where abstract and concrete representations are supported by dissociable neuroanatomic substrates.

Poor hearing acuity reduces memory for spoken words, even when the words are presented with enough clarity for correct recognition. An "effortful hypothesis" suggests that the perceptual effort needed for recognition draws from resources that would otherwise be available for encoding the word in memory. To assess this hypothesis, we conducted a behavioral task requiring immediate free recall of word-lists, some of which contained an acoustically masked word that was just above perceptual threshold. Results show that masking a word reduces the recall of that word and words prior to it, as well as weakening the linking associations between the masked and prior words. In contrast, recall probabilities of words following the masked word are not affected. To account for this effect we conducted computational simulations testing two classes of models: associative linking models and short-term memory buffer models. Only a model that integrated both contextual linking and buffer components matched all of the effects of masking observed in our behavioral data. In this Linking-Buffer model, the masked word disrupts a short-term memory buffer, causing associative links of words in the buffer to be weakened, affecting memory for the masked word and the word prior to it, while allowing links of words following the masked word to be spared. We suggest that these data account for the so-called "effortful hypothesis", where distorted input has a detrimental impact on prior information stored in short-term memory.

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Recall of recently heard words is affected by the clarity of presentation: even if all words are presented with sufficient clarity for successful recognition, those that are more difficult to hear are less likely to be recalled. Such a result demonstrates that memory processing depends on more than whether a word is simply “recognized” versus “not-recognized”. More surprising is that when a single item in a list of spoken words is acoustically masked, prior words that were heard with full clarity are also less likely to be recalled. To account for such a phenomenon, we developed the Linking by Active Maintenance Model (LAMM). This computational model of perception and encoding predicts that these effects are time dependent. Here we challenge our model by investigating whether and how the impact of acoustic masking on memory depends on presentation rate. We find that a slower presentation rate causes a more disruptive impact of stimulus degradation on prior, clearly heard words than does a fast rate. These results are unexpected according to prior theories of effortful listening, but we demonstrate that they can be accounted for by LAMM.

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is characterized by the accumulation of TAR-DNA-binding protein 43 (TDP-43) aggregates in older adults. LATE coexists with Lewy body disease (LBD) as well as other neuropathological changes including Alzheimer's disease (AD). We aimed to identify the pathological, clinical, and genetic characteristics of LATE in LBD (LATE-LBD) by comparing it with LATE in AD (LATE-AD), LATE with mixed pathology of LBD and AD (LATE-LBD + AD), and LATE alone (Pure LATE). We analyzed four cohorts of autopsy-confirmed LBD (n = 313), AD (n = 282), LBD + AD (n = 355), and aging (n = 111). We assessed the association of LATE with patient profiles including LBD subtype and AD neuropathologic change (ADNC). We studied the morphological and distributional differences between LATE-LBD and LATE-AD. By frequency analysis, we staged LATE-LBD and examined the association with cognitive impairment and genetic risk factors. Demographic analysis showed LATE associated with age in all four cohorts and the frequency of LATE was the highest in LBD + AD followed by AD, LBD, and Aging. LBD subtype and ADNC associated with LATE in LBD or AD but not in LBD + AD. Pathological analysis revealed that the hippocampal distribution of LATE was different between LATE-LBD and LATE-AD: neuronal cytoplasmic inclusions were more frequent in cornu ammonis 3 (CA3) in LATE-LBD compared to LATE-AD and abundant fine neurites composed of C-terminal truncated TDP-43 were found mainly in CA2 to subiculum in LATE-LBD, which were not as numerous in LATE-AD. Some of these fine neurites colocalized with phosphorylated α-synuclein. LATE-LBD staging showed LATE neuropathological changes spread in the dentate gyrus and brainstem earlier than in LATE-AD. The presence and prevalence of LATE in LBD associated with cognitive impairment independent of either LBD subtype or ADNC; LATE-LBD stage also associated with the genetic risk variants of TMEM106B rs1990622 and GRN rs5848. These data highlight clinicopathological and genetic features of LATE-LBD.