| 1. |
- Olofsson, Jonas K., et al.
(författare)
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A cortical pathway to olfactory naming : evidence from primary progressive aphasia
- 2013
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 136, s. 1245-1259
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Tidskriftsartikel (refereegranskat)abstract
- It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language 'deficit' is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching. In identifying the critical role of the temporal pole and inferior frontal gyrus in transmodal linking and verbalization of olfactory objects, our findings provide a new neurobiological foundation for understanding why even common odours are hard to name.
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| 2. |
- Olofsson, Jonas K., et al.
(författare)
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A Designated Odor-Language Integration System in the Human Brain
- 2014
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 34:45, s. 14864-14873
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Tidskriftsartikel (refereegranskat)abstract
- Odors are surprisingly difficult to name, but the mechanism underlying this phenomenon is poorly understood. In experiments using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), we investigated the physiological basis of odor naming with a paradigm where olfactory and visual object cues were followed by target words that either matched or mismatched the cue. We hypothesized that word processing would not only be affected by its semantic congruency with the preceding cue, but would also depend on the cue modality (olfactory or visual). Performance was slower and less precise when linking a word to its corresponding odor than to its picture. The ERP index of semantic incongruity (N400), reflected in the comparison of nonmatching versus matching target words, was more constrained to posterior electrode sites and lasted longer on odor-cue (vs picture-cue) trials. In parallel, fMRI cross-adaptation in the right orbitofrontal cortex (OFC) and the left anterior temporal lobe (ATL) was observed in response to words when preceded by matching olfactory cues, but not by matching visual cues. Time-series plots demonstrated increased fMRI activity in OFC and ATL at the onset of the odor cue itself, followed by response habituation after processing of a matching (vs nonmatching) target word, suggesting that predictive perceptual representations in these regions are already established before delivery and deliberation of the target word. Together, our findings underscore the modality-specific anatomy and physiology of object identification in the human brain.
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| 3. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 4. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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