Anatomical Correlates of Sentence Comprehension and Verbal Working Memory in Neurodegenerative Disease

Amici, Serena; Brambati, Simona Maria; Wilkins, David P.; Ogar, Jennifer M.; Dronkers, Nina; Miller, Bruce L.; Gorno‐Tempini, Maria Luisa

doi:10.1523/jneurosci.1331-07.2007

Cited by 97 publications

(101 citation statements)

References 73 publications

(93 reference statements)

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“…One study associated impaired sentence comprehension with posterior-inferior frontal and anterior-superior temporal regions of the left hemisphere 7. In mixed groups of neurodegenerative patients, grammatical comprehension was related to left inferior frontal atrophy 23 24. The present study found that difficulty understanding cleft sentences in naPPA is related to left anterior-superior temporal GM atrophy.…”

Section: Discussionsupporting

confidence: 51%

Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia

Charles

Olm

Powers

et al. 2013

Journal of Neurology, Neurosurgery & Psychiatry

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Importance Grammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable. Objective To develop a measure of grammatical comprehension and examine this comparatively in PPA variants and behavioural-variant frontotemporal degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in white matter tracts. Design Case–control study. Setting Academic medical centre. Participants 39 patients with variants of PPA (naPPA=12, lvPPA=15 and svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls. Main outcome measure Grammatical comprehension accuracy. Results Patients with naPPA had selective difficulty understanding cleft sentence structures, while all PPA variants and patients with bvFTD were impaired with sentences containing a centre-embedded subordinate clause. Patients with bvFTD were also impaired understanding sentences involving short-term memory. Linear regressions related grammatical comprehension difficulty in naPPA to left anterior-superior temporal atrophy and reduced FA in corpus callosum and inferior frontal-occipital fasciculus. Difficulty with centre-embedded sentences in other PPA variants was related to other brain regions. Conclusions and relevance These findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.

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Section: Discussionsupporting

confidence: 51%

Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia

Charles

Olm

Powers

et al. 2013

Journal of Neurology, Neurosurgery & Psychiatry

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“…This inferior frontal involvement is not unexpected given the presence of agrammatic aphasia in this group and the known association between Broca area and agrammatic aphasia. 29,30 Similarities were also noted with the DTI analysis. In contrast to PPAOS and dominant AOS, the agPPA group showed widespread abnormalities for all imaging modalities.…”

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confidence: 70%

Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA

et al. 2013

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Objective: We assessed whether clinical and imaging features of subjects with apraxia of speech (AOS) more severe than aphasia (dominant AOS) are more similar to agrammatic primary progressive aphasia (agPPA) or to primary progressive AOS (PPAOS).Methods: Sixty-seven subjects (PPAOS 5 18, dominant AOS 5 10, agPPA 5 9, age-matched controls 5 30) who all had volumetric MRI, diffusion tensor imaging, F18-fluorodeoxyglucose and C11-labeled Pittsburgh compound B (PiB)-PET scanning, as well as neurologic and speech and language assessments, were included in this case-control study. AOS was classified as either type 1, predominated by sound distortions and distorted sound substitutions, or type 2, predominated by syllabically segmented prosodic speech patterns. Results:The dominant AOS subjects most often had AOS type 2, similar to PPAOS. In contrast, agPPA subjects most often had type 1 (p 5 0.01). Both dominant AOS and PPAOS showed focal imaging abnormalities in premotor cortex, whereas agPPA showed widespread involvement affecting premotor, prefrontal, temporal and parietal lobes, caudate, and insula. Only the dominant AOS and PPAOS groups showed midbrain atrophy compared with controls. No differences were observed in PiB binding across all 3 groups, with the majority being PiB negative. Conclusion:These results suggest that dominant AOS is more similar to PPAOS than agPPA, with dominant AOS and PPAOS exhibiting a clinically distinguishable subtype of progressive AOS compared with agPPA. Neurology â 2013;81:337-345 GLOSSARY agPPA 5 agrammatic primary progressive aphasia; AOS 5 apraxia of speech; ASRS 5 Apraxia of Speech Rating Scale; DTI 5 diffusion tensor imaging; FA 5 fractional anisotropy; FDG 5 F18-fluorodeoxyglucose; MD 5 mean diffusivity; NOS 5 not otherwise specified; PiB 5 Pittsburgh compound B; PPA 5 primary progressive aphasia; PPAOS 5 primary progressive apraxia of speech; PSPS 5 progressive supranuclear palsy syndrome; TDP-43 5 TAR DNA binding protein of 43 kDa; WAB 5 Western Aphasia Battery.The term apraxia of speech (AOS) is used to denote a motor speech disorder in which abnormalities reflect deficits in the programming of movements for speech production.1,2 Although usually caused by left hemisphere stroke, AOS can also be associated with neurodegenerative disease, and when it is the only sign or symptom, it is labeled primary progressive AOS (PPAOS).3,4 Unlike PPAOS, the term primary progressive aphasia (PPA) is reserved for a neurodegenerative disorder in which the most salient feature is language dysfunction. 5-7 Agrammatic PPA (agPPA) is one subtype of PPA, characterized by specific abnormalities that affect grammar and syntax in verbal or written expression. 8,9 Although it is recognized that many subjects with agPPA may have AOS, the most salient feature of agPPA is aphasia. In fact, to be diagnosed with any variant of PPA, 8 language difficulty must be the most prominent clinical feature at symptom onset and for the initial phases of the disease; deficits cannot be due to "disruption o...

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“…To cope with this limitation, the syntactic computational unit may require additional memory resources provided by the LIFS to deal with the partial products of parsing of doubly embedded sentences. Indeed, a recent voxel-based morphometry study found that gray-matter volume reduction in the LIFS correlates with a deterioration in the comprehension of center-embedded sentences (38).…”

Section: Functional Coupling and Structural Connectivity Between The mentioning

confidence: 99%

Segregating the core computational faculty of human language from working memory

Makuuchi

Bahlmann

Anwander

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

318

289

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In contrast to simple structures in animal vocal behavior, hierarchical structures such as center-embedded sentences manifest the core computational faculty of human language. Previous artificial grammar learning studies found that the left pars opercularis (LPO) subserves the processing of hierarchical structures. However, it is not clear whether this area is activated by the structural complexity per se or by the increased memory load entailed in processing hierarchical structures. To dissociate the effect of structural complexity from the effect of memory cost, we conducted a functional magnetic resonance imaging study of German sentence processing with a 2-way factorial design tapping structural complexity (with/without hierarchical structure, i.e., center-embedding of clauses) and working memory load (long/short distance between syntactically dependent elements; i.e., subject nouns and their respective verbs). Functional imaging data revealed that the processes for structure and memory operate separately but co-operatively in the left inferior frontal gyrus; activities in the LPO increased as a function of structural complexity, whereas activities in the left inferior frontal sulcus (LIFS) were modulated by the distance over which the syntactic information had to be transferred. Diffusion tensor imaging showed that these 2 regions were interconnected through white matter fibers. Moreover, functional coupling between the 2 regions was found to increase during the processing of complex, hierarchically structured sentences. These results suggest a neuroanatomical segregation of syntax-related aspects represented in the LPO from memory-related aspects reflected in the LIFS, which are, however, highly interconnected functionally and anatomically.DTI ͉ fMRI ͉ hierarchical structure L anguage appears to be a trait specific to humans-at least in its core computational component, that is, grammar. Defining language as a sequence of symbols, Chomsky (1) proposed a hierarchy of grammars as language production mechanisms with increasing generative powers. The lowest-level grammar is finite state grammar (FSG). FSG can be fully specified by transition probabilities between a finite number of states (e.g., words), being not powerful enough to generate structures of natural human languages. Phrase structure grammar (PSG) has more generative power than FSG. A key difference between FSG and PSG is that only PSG can generate the sequence A n B n , where A and B denote symbols and n the number of repetitions. The ability to process the sequence A n B n is crucial for the processing of center-embedded sentences, such as ''The man the boy the dog bit greeted is my friend.'' where subjects (i.e., the man, the boy, and the dog) are A-symbols and the verbs (bit, greeted, and is) are B-symbols. Surprisingly, tests on monkeys (2) and on songbirds (3) showed that whereas songbirds can process A n B n sequences, monkeys cannot. However, even if the birds could correctly discriminate A n B n sequences from A n B m , (4 Ͼ n, m Ͼ0, n m),...

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Anatomical Correlates of Sentence Comprehension and Verbal Working Memory in Neurodegenerative Disease

Cited by 97 publications

References 73 publications

Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia

Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia

Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA

Segregating the core computational faculty of human language from working memory

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