Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson’s disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body spectrum disorder (LBSD). Thirty-three patients with LBSD were given a two-alternative, forced-choice sentence-picture matching task. Sentence type, working memory, and grammatical structure were systematically manipulated in the sentences. We found that patients with PDD and DLB were significantly impaired relative to non-demented PD patients and healthy controls. The deficit in PDD/DLB was most pronounced for sentences lengthened by the strategic placement of an additional prepositional phrase and for sentences with an additional proposition due to a center-embedded clause. However, there was no effect for subject-relative versus object-relative grammatical structure. An MRI voxel-based morphometry analysis in a subset of patients showed significant gray matter thinning in the frontal lobe bilaterally, and this extended to temporal, parietal and occipital regions. A regression analysis related sentence processing difficulty in LBSD to frontal neocortex, including inferiorprefrontal, premotor, and dorsolateral prefrontal regions, as well as right superior temporal cortex. These findings are consistent with the hypothesis that patients with PDD and DLB have difficulty processing sentences with increased working memory demands and that this deficit is related in part to their frontal disease.

Few studies have examined connected speech in demented and non-demented patients with Parkinson’s disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured narrative speech sample in order to characterize impairments of speech fluency and to determine the factors contributing to reduced speech fluency in these patients. Both demented and non-demented PD patients exhibited reduced speech fluency, characterized by reduced overall speech rate and long pauses between sentences. Reduced speech rate in LBSD correlated with measures of between-utterance pauses, executive functioning, and grammatical comprehension. Regression analyses related non-fluent speech, grammatical difficulty, and executive difficulty to atrophy in frontal brain regions. These findings indicate that multiple factors contribute to slowed speech in LBSD, and this is mediated in part by disease in frontal brain regions.

Objective

Previous work investigating deficits in self-appraisal in behavioural-variant frontotemporal degeneration (bvFTD) has focused on a single domain: social/behavioural processes. We examined whether a domain-specific versus multi-domain model best explains degraded self-appraisal in bvFTD.

Methods

49 patients with bvFTD and 73 patients with Alzheimer’s disease (AD) were administered quantitative assessments of episodic memory, naming and grammatical comprehension. Self-appraisal of cognitive test performance was assessed by asking patients to rate their performance immediately after completing each neuropsychological test. A discrepancy score was created to reflect the difference between patient performance on neuropsychological tests and self-appraisal of their test performance. Self-appraisal for each neuropsychological measure was related to grey matter (GM) density in each group using voxel-based morphometry.

Results

bvFTD patients were poor at evaluating their own performance on all cognitive tests, with no significant correlations between self-appraisal and actual performance. By contrast, poor self-appraisal in AD was restricted to episodic memory performance. Poor self-appraisal on each task in bvFTD and AD was related to reduced GM density in several ventral and rostral medial prefrontal regions. Crucially, poor self-appraisal for all domains in bvFTD was related to a specific area of reduced GM density in the subgenual cingulate (BA 25).

Conclusion

Poor self-appraisal in bvFTD affects multiple domains, and this multi-domain impairment pattern is associated with frontal disease in the subgenual cingulate.

While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson’s disease (PD), Parkinson’s dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an on-line word detection procedure, patients heard sentences with a syntactic structure that has high-compatibility or low-compatibility with the main verb’s statistically preferred syntactic structure, and half of the sentences were lengthened strategically between the onset of the ambiguity and its resolution. We found selectively slowed processing of lengthened ambiguous sentences in the PDD/DLB subgroup. This correlated with impairments on measures of executive control. Regression analyses related the working memory deficit during ambiguous sentence processing to significant cortical thinning in frontal and parietal regions. These findings emphasize the role of prefrontal disease in the executive limitations that interfere with processing ambiguous sentences in LBSD.

Quantifiers are very common in everyday speech, but we know little about their cognitive basis or neural representation. The present study examined comprehension of three classes of quantifiers that depend on different cognitive components in patients with focal neurodegenerative diseases. Patients evaluated the truth-value of a sentence containing a quantifier relative to a picture illustrating a small number of familiar objects, and performance was related to MRI grey matter atrophy using voxel-based morphometry. We found that patients with corticobasal syndrome (CBS) and posterior cortical atrophy (PCA) are significantly impaired in their comprehension of Cardinal Quantifiers (e.g. “At least three birds are on the branch”), due in part to their deficit in quantity knowledge. MRI analyses related this deficit to temporal-parietal atrophy found in CBS/PCA. We also found that patients with behavioral variant frontotemporal dementia (bvFTD) are significantly impaired in their comprehension of Logical Quantifiers (e.g. “Some the birds are on the branch”), associated with a simple form of perceptual logic, and this correlated with their deficit on executive measures. This deficit was related to disease in rostral prefrontal cortex in bvFTD. These patients were also impaired in their comprehension of Majority Quantifiers (e.g. “At least half of the birds are on the branch”), and this too was correlated with their deficit on executive measures. This was related to disease in the basal ganglia interrupting a frontal-striatal loop critical for executive functioning. These findings suggest that a large-scale frontal-parietal neural network plays a crucial role in quantifier comprehension, and that comprehension of specific classes of quantifiers may be selectively impaired in patients with focal neurodegenerative conditions in these areas.

Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy Body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB.

Objective

To understand the scope of semantic impairment in semantic dementia.

Design

Case study.

Setting

Academic medical center.

Patient

A man with semantic dementia, as demonstrated by clinical, neuropsychological, and imaging studies.

Main Outcome Measures

Music performance and magnetic resonance imaging results.

Results

Despite profoundly impaired semantic memory for words and objects due to left temporal lobe atrophy, this semiprofessional musician was creative and expressive in demonstrating preserved musical knowledge.

Conclusion

Long-term representations of words and objects in semantic memory may be dissociated from meaningful knowledge in other domains, such as music.

We investigated the cognitive and neural bases of impaired speech fluency, a central feature of primary progressive aphasia. Speech fluency was assessed in 35 patients with frontotemporal lobar degeneration (FTLD) who presented with progressive non-fluent aphasia (PNFA, n=11), semantic dementia (SemD, n=12), or a social and executive disorder without aphasia (SOC/EXEC, n=12). Fluency was quantified as the number of words per minute in an extended, semi-structured speech sample. This was related to language characteristics of the speech sample and to neuropsychological measures. PNFA patients were significantly less fluent than controls and other FTLD patients. Fluency correlated with grammatical expression but not with speech errors or executive difficulty. SemD and SOC/EXEC patients were also less fluent than controls. In SemD, fluency was associated with semantically limited content. In SOC/EXEC, fluency was associated with executive limitations. Voxel-based morphometry analyses of high-resolution MRI related fluency to gray matter volume in left inferior frontal, insula, and superior temporal regions for the entire cohort of FTLD patients. This region overlapped partially distinct atrophic areas in each FTLD subgroup. It thus appears to play a crucial role in speech fluency, which can be interrupted in different ways in different FTLD subgroups.

Recent investigations have supported the suggestion that phonological speech errors may reflect the simultaneous activation of more than one phonemic representation. This presents a challenge for speech error evidence which is based on the assumption of well-formedness, because we may continue to perceive well-formed errors, even when they are not produced. To address this issue, we present two tongue-twister experiments in which the articulation of onset consonants is quantified and compared to baseline measures from cases where there is no phonemic competition. We report three measure of articulatory variability: changes in tongue-to-palate contact using electropalatography (EPG, Experiment 1), changes in midsagittal spline of the tongue using ultrasound (Experiment 2), and acoustic changes manifested as voice-onset-time (VOT). These three sources provide converging evidence that articulatory variability increases when competing onsets differ by one phonological feature, but the increase is attenuated when onsets differ by two features. This finding provides clear evidence, based solely on production, that the articulation of phonemes is influenced by cascading activation from the speech plan.

The ventral medial prefrontal cortex (vmPFC) has been implicated in social and affectively influenced decision-making. Disease in this region may have clinical consequences for social judgments in patients with frontotemporal lobar degeneration (FTLD). To test this hypothesis, regional cortical activation was monitored with fMRI while healthy adults judged the acceptability of brief social scenarios such as cutting into a movie ticket line or going through a red light at 2 AM. The scenarios described: (i) a socially neutral condition, (ii) a variant of each scenario containing a negatively-valenced feature, and (iii) a variant containing a positively-valenced feature. Results revealed that healthy adults activated vmPFC during judgments of negatively-valenced scenarios relative to positive scenarios and neutral scenarios. In a comparative behavioral study, the same social decision-making paradigm was administered to patients with a social disorder due to FTLD. Patients differed significantly from healthy controls, specifically showing less sensitivity to negatively-valenced features. Comparative anatomical analysis revealed considerable overlap of vmPFC activation in healthy adults and vmPFC cortical atrophy in FTLD patients. These converging results support the role of vmPFC in social decision-making where potentially negative consequences must be considered.

The nature and frequency of speech production errors in neurodegenerative disease have not previously been precisely quantified. In the present study, 16 patients with a progressive form of nonfluent aphasia (PNFA) were asked to tell a story from a wordless children’s picture book. Errors in production were classified as either phonemic, involving language-based deformations that nevertheless result in possible sequences of English speech segments; or phonetic, involving a motor planning deficit and resulting in non-English speech segments. The distribution of cortical atrophy as revealed by structural MRI scans was examined quantitatively in a subset of PNFA patients (N=7). The few errors made by healthy seniors were only phonemic in type. PNFA patients made more than four times as many errors as controls. This included both phonemic and phonetic errors, with a preponderance of errors (82%) classified as phonemic. The majority of phonemic errors were substitutions that shared most distinctive features with the target phoneme. The systematic nature of these substitutions is not consistent with a motor planning deficit. Cortical atrophy was found in prefrontal regions bilaterally and peri-Sylvian regions of the left hemisphere. We conclude that the speech errors produced by PNFA patients are mainly errors at the phonemic level of language processing and are not caused by a motor planning impairment.

Objective

To investigate the cognitive and neural correlates of discourse impairment in corticobasal syndrome (CBS).

Background

Difficulty communicating is a frequent clinical manifestation in patients with CBS. However, the mechanisms underlying this disabling problem are not well understood.

Methods

Twenty patients with CBS and 8 healthy seniors narrated a picture story. Narratives were analyzed for maintenance of the narrative theme, identification of the overall point of the story (global connectedness), and connectedness between consecutive events (local connectedness). Discourse measures were correlated with performance on cognitive tasks and with cortical atrophy as determined by magnetic resonance imaging voxel-based morphometry.

Results

Patients with CBS referred to the narrative theme significantly less frequently than controls. Global connectedness was intact in only 6 of 20 CBS patients (30%), but preserved in all controls. Local connectedness was significantly diminished in patients relative to controls. Discourse performance in CBS was related to tasks requiring higher-order integration of visual material, but not to basic visuospatial/visuoperceptual, language, or memory function. Discourse impairment was directly related to atrophy in the right parietal lobe and bilateral dorsolateral prefrontal cortex.

Conclusions

Our findings suggest that impaired information integration in CBS, related to parieto-frontal disease, interferes with patients’ ability to narrate a coherent story.

To investigate the basis for impaired sentence comprehension in patients with frontotemporal dementia (FTD) we assessed grammatical comprehension and verbal working memory in 88 patients with three distinct presentations: progressive nonfluent aphasia (PNFA), semantic dementia (SD), and nonaphasic patients with a disorder of social comportment and executive processing (SOC/EXEC). We related sentence comprehension and working memory performance to regional cortical volume in a subgroup of 29 patients with structural MRI scans using voxel-based morphometry. PNFA patients exhibited the greatest difficulty with sentence comprehension and were especially impaired with grammatically complex sentences, which correlated with atrophy in left inferior frontal cortex. Working memory performance in these same patients correlated with a proximal but distinct left inferior frontal region. SD patients’ sentence comprehension scores correlated with left inferolateral temporal lobe damage, which we hypothesize and reflect impairments in lexical processing. We did not observe any consistent relationship between cortical atrophy and sentence comprehension impairment in SOC/EXEC patients, suggesting the deficits in this subgroup may be due to more variable declines in executive resources.