Difficulty processing temporary syntactic ambiguities in Lewy body spectrum disorder

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.     

Impairments of speech fluency in Lewy body spectrum disorder

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.     

The organization of narrative discourse in Lewy body spectrum disorder

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.     

Assessing resource demands during sentence processing in Parkinson's disease

Patients with Parkinson's disease (PD) have sentence comprehension difficulty, but it is unclear whether this is due to a deficit in grammatical processing or to an executive resource limitation. To assess grammatical processing in PD while minimizing task-related demands, PD patients and healthy control subjects performed a word detection procedure that assesses sensitivity to grammatical agreements in sentences in an "on-line" fashion. With this technique, we found that control subjects and PD patients are equally sensitive to grammatical agreement violations in sentences. A traditional, resource-demanding measure of sentence comprehension was also administered to the same PD patients. In comparison to healthy controls, PD patients were significantly impaired in their relative comprehension of sentences containing object-gap subordinate clauses compared to subject-gap subordinate clauses. Performance on several executive resource measures was also impaired in PD, and this correlated with their comprehension performance. Sensitivity to grammatical agreements with the word detection procedure, in the context of sentence comprehension difficulty on a traditional measure, suggests that PD patients' executive resource limitations contribute to their sentence comprehension difficulty.     

Large-scale neural network for sentence processing

Our model of sentence comprehension includes at least grammatical processes important for structure-building, and executive resources such as working memory that support these grammatical processes. We hypothesized that a core network of brain regions supports grammatical processes, and that additional brain regions are activated depending on the working memory demands associated with processing a particular grammatical feature. We used functional magnetic resonance imaging (fMRI) to test this hypothesis by comparing cortical activation patterns during coherence judgments of sentences with three different syntactic features. We found activation of the ventral portion of left inferior frontal cortex during judgments of violations of each grammatical feature. Increased recruitment of the dorsal portion of left inferior frontal cortex was seen during judgments of violations of specific grammatical features that appear to involve a more prominent working memory component. Left posterolateral temporal cortex and anterior cingulate were also implicated in judging some of the grammatical features. Our observations are consistent with a large-scale neural network for sentence processing that includes a core set of regions for detecting and repairing several different kinds of grammatical features, and additional regions that appear to participate depending on the working memory demands associated with processing a particular grammatical feature.     

Neuropsychological Characteristics of Dementia with Lewy Bodies and Parkinson’s Disease with Dementia: Differentiation, Early Detection, and Implications for “Mild Cognitive Impairment” and Biomarkers

Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are neurodegenerative conditions sharing a disorder of α-synuclein metabolism. Temporal differences in the emergence of symptoms and clinical features warrant the continued clinical distinction between DLB and PDD. While DLB and PDD groups’ neuropsychological profiles often differ from those in Alzheimer’s disease (AD), the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. PDD and DLB neuropsychological profiles share sufficient similarity to resist accurate and reliable differentiation. Although heterogeneous cognitive changes (predominantly in memory and executive function) may manifest earlier and more frequently than previously appreciated in Parkinson’s disease (PD), and executive deficits may be harbingers of dementia, the enthusiasm to uncritically extend the concept of mild cognitive impairment (MCI) to PD should be tempered. Instead, future research might strive to identify the precise neuropsychological characteristics of the prodromal stages of PD, PDD, and DLB which, in conjunction with other potential biomarkers, facilitate early and accurate diagnosis, and the definition of neuroprotective, neurorestorative, and symptomatic treatment endpoints.     

Attentional resource and processing speed limitations during sentence processing in Parkinson's disease

Several studies have suggested that patients with Parkinson's disease (PD) have sentence comprehension difficulty in part because of their limited executive resources. However, these assessments confound the executive resources contributing to sentence comprehension with the resources needed for task performance. In the present study, we used a word detection technique that minimizes task demands in order to evaluate attentional and processing speed resources during the comprehension of simple sentences without subordinate clauses and sentences containing subject-relative and object-relative center-embedded subordinate clauses. We found that PD patients have poor sensitivity to phonetic errors embedded in unbound grammatical morphemes, regardless of the clausal structure of the sentence, suggesting difficulty attending to grammatical morphemes. We also found that PD patients are significantly slowed in their sensitivity to phonetic errors in content words embedded in object-relative center-embedded sentences. Slowed sensitivity to content words in object-relative sentences was correlated with timed executive measures of planning. On a traditional measure of comprehension, these PD patients were impaired for sentences containing object-relative center-embedded clauses compared to sentences with subject-relative center-embedded clauses, and comprehension of object-relative sentences was correlated with executive measures. Our findings are consistent with the claim that limited executive resources for strategic attention and processing speed contribute to the sentence comprehension difficulties of PD patients.     

Sentence comprehension in Parkinson's disease: the role of attention and memory.

Sentence comprehension is a complex process involving at least attentional, memory, grammatical, and semantic components. We report three experiments designed to evaluate the impairments underlying sentence comprehension difficulties in nondemented patients with Parkinson's disease (PD). In the first experiment, we asked patients to answer simple questions about sentences which varied in terms of grammatical complexity and semantic constraint. We found that PD patients are significantly compromised in their ability to perform this task. Their difficulties became more prominent as grammatical complexity increased, but they were significantly assisted by semantic constraints that limited possible interpretations of a sentence. Analyses of individual patient profiles revealed heterogeneous performance across the group of PD patients and somewhat inconsistent performance for patients across testing sessions. In the second experiment, we tested the possibility that patients' heterogeneous performance on the sentence comprehension task is due to an impairment in memory or attention, cognitive domains known to be compromised in some PD patients. Although PD patients and control subjects differed on one memory measure, there were no significant correlations between attention and memory performance and the results of the sentence comprehension task. In the final experiment, we manipulated the sentences used in the first experiment in a fashion that stressed the need for memory and attention in a sentence. The results indicated that PD patients are significantly compromised in their ability to attend to certain critical grammatical features of a sentence. A regression analysis identified specific grammatical, semantic, and attentional mechanisms as significant contributors to PD patients' overall sentence comprehension, accounting for over 97% of the variance in their performance. We conclude that there are multiple sources of cognitive difficulty underlying PD patients' sentence comprehension impairment.     

Neural basis for sentence comprehension deficits in frontotemporal dementia

Many patients with frontotemporal dementia (FTD) have impaired sentence comprehension. However, the pattern of comprehension difficulty appears to vary depending on the clinical subgroup. The purpose of this study was to elucidate the neural basis for these deficits in FTD. We studied patients with two different presentations: Three patients with Progressive Non-Fluent Ahasia (PNFA), and five non-aphasic patients with a dysexecutive and social impairment (EXEC). The FTD patient subgroups were compared to a cohort of 11 healthy seniors with intact sentence comprehension. We monitored regional cerebral activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) while subjects read sentences featuring both a grammatically complex object-relative center-embedded clause and a long linkage between the head noun phrase (NP) and the gap where the NP is interpreted in the center-embedded clause. Subjects decided whether the agent of the action is a male or a female. Healthy seniors activated both ventral portions of inferior frontal cortex (vIFC) and dorsal portions of IFC (dIFC) in the left hemisphere, often associated with grammatical and working memory components of these sentences, respectively. PNFA patients differed from healthy controls since they have reduced activation of left vIFC, while EXEC patients have less recruitment of left dIFC. We conclude that FTD subgroups have distinct patterns of sentence comprehension difficulty in part because of selective interruptions of a large-scale neural network for sentence processing.     

Sentence processing strategies in healthy seniors with poor comprehension: an fMRI study

We used fMRI to examine patterns of brain recruitment in 22 healthy seniors, half of whom had selective comprehension difficulty for grammatically complex sentences. We found significantly reduced recruitment of left posterolateral temporal [Brodmann area (BA) 22/21] and left inferior frontal (BA 44/6) cortex in poor comprehenders compared to the healthy seniors with good sentence comprehension, cortical regions previously associated with language comprehension and verbal working memory, respectively. The poor comprehenders demonstrated increased activation of left prefrontal (BA 9/46), right dorsal inferior frontal (BA 44/6), and left posterior cingulate (BA 31/23) cortices for the grammatically simpler sentences that they understood. We hypothesize that these brain regions support an alternate, nongrammatical strategy for processing complex configurations of symbolic information. Moreover, these observations emphasize the crucial role of the left perisylvian network for grammatically guided sentence processing in subjects with good comprehension.     

Working memory components in written sentence generation

College students wrote either simple or complex sentences using 2 prompt nouns while components of working memory were distracted with a concurrent task. Loads on the visual and spatial components of working memory (retain a shape) and verbal component (retain 3 or 6 digits) were compared with a no-load control. Only the 6-digit load reliably reduced sentence length relative to the control, suggesting that unimpeded sentence generation requires verbal working memory. The sentence length effect may arise from a failure to retrieve and maintain lexical representations during grammatical encoding. Memory load had no effect on grammatical and spelling errors, implying that syntactic and orthographic processing were undisturbed. Other possibilities locate the difficulty in planning conceptual content or in phonological encoding, but some evidence speaks against them.     

The roles of sequencing and verbal working memory in sentence comprehension deficits in Parkinson's disease

Studies of sentence comprehension deficits in Parkinson's disease (PD) patients suggest that language processing involves circuits connecting subcortical and cortical regions. Anatomically segregated neural circuits appear to support different cognitive and motor functions. To investigate which functions are implicated in PD comprehension deficits, we tested comprehension, verbal working memory span, and cognitive set-switching in a non-linguistic task in 41 PD patients; we also obtained speech measurements reflecting motor sequencing processes that may be involved in articulatory rehearsal within working memory. Comprehension of sentences with center-embedded or final relative clauses was impaired when they could not be understood from lexical semantic content alone. Overall comprehension error rates correlated strongly with impaired set-switching and significantly with reduced working memory span and speech motor sequencing deficits. Correlations with comprehension of different sentence structures indicate that these impairments do not represent a single deficit; rather, PD comprehension deficits appear to arise from several independent mechanisms. Deficits in cognitive set-switching or underlying inhibitory processes may compromise the ability to process relative clauses. Deficits in verbal working memory appear to impair comprehension of long-distance dependencies. Speech sequencing correlated with neither set-switching nor verbal working memory span, consistent with their being supported by independent, segregated cortico-subcortical circuits.     

The Sum and Substance of It: The Appreciation of Mass and Count Quantifiers in Parkinson′s Disease

We performed three experiments in order to determine whether patients with Parkinson′s disease (PD) have a sentence comprehension impairment. In the first experiment, we found that nondemented PD patients were impaired at matching a short sentence containing a mass or count quantifier (e.g., "Point to the jar with many") with one of four pictures. Patients erred by pointing to the incorrect mass or count type of substance, but pointed correctly to the large or small amount of a substance in the picture. In the second experiment, we asked the same PD patients to judge short sentences containing mass or count nouns modified by mass or count adjectives (e.g., *"The glass contains many milk"). PD patients were significantly impaired at detecting errors in the agreement between a noun and a quantifying adjective and errors in the appropriate use of the plural associated with a noun. A sentence completion task was performed in order to determine whether patients impaired on both sentence-picture matching and sentence judgment tasks are also compromised in their expression of quantifiers. Some patients impaired on both tasks also had difficulty expressing quantifiers, and it is these patients who may have difficulty performing grammatical computations. Other patients were selectively impaired in their sentence-picture matching or their sentence judgments, suggesting a performance deficit concerned with a particular task. We conclude that sentence comprehension impairments in PD are multifactorial in nature.     

Memory effects in syntactic ERP tasks

The study presented here investigated the role of memory in normal sentence processing by looking at ERP effects to normal sentences and sentences containing grammatical violations. Sentences where the critical word was in the middle of the sentence were compared to sentences where the critical word always occurred in sentence-final position. Grammaticality judgments were required at the end of the sentence. While the violations in both conditions result in the expected increase in the P600 component (reflecting the fact that the syntactic violation is being processed), the sentences with the sentence-medial critical word also result in a late frontal negativity effect. It is hypothesized that this effect is due to greater memory requirements that are needed to keep the violation in mind until a response can be made at the end of the sentence. The maintenance of the decision that a sentence is ungrammatical must be kept in memory longer for sentence-medial violations as opposed to when the violation occurs at the end of the sentence (immediately preceding the moment at which the judgment can be made).     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Phonology and syntax in specific language impairment: evidence from a connectionist model

Difficulties in resolving pronominal anaphora have been taken as evidence that Specific Language Impairment (SLI) involves a grammar-specific impairment. The present study explores an alternative view, that grammatical deficits in SLI are sequelae of impaired speech perception. This perceptual deficit specifically affects the use of phonological information in working memory, which in turn leads to poorer than expected syntactic comprehension. This hypothesis was explored using a connectionist model of sentence processing that learned to map sequences of words to their meanings. Anaphoric resolution was represented in this model by recognizing the semantics of the correct antecedent when a bound pronoun was input. When the model was trained on distorted phonological inputs-simulating a perceptual deficit-it exhibited marked difficulty resolving bound anaphors. However, many other aspects of sentence comprehension were intact; most importantly, the model could still resolve pronouns using gender information. In addition, the model's deficit was graded rather than categorical, as it was able to resolve pronouns in some sentences, but not in others. These results are consistent with behavioral data concerning syntactic deficits in SLI. The model provides a causal demonstration of how a perceptual deficit could give rise to grammatical deficits in SLI.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Processing complexity and sentence memory: evidence from amnesia.

This study examines sentence memory as a function of linguistic processing complexity in amnesic patients. Sentence length as well as lexical and syntactic complexity were manipulated in two sentence repetition experiments. It was found that the amnesic patients performed considerably worse than the control subjects and that performance decreased: (1) when sentence length was increased by the addition of adjuncts compared to arguments of the verb; (2) when the verb selected more thematic frames; and (3) when sentences involved "empty" argument positions that must be linked to antecedents, particularly across clausal boundaries. These data showed how linguistic complexity affects sentence memory and implied that the amnesic deficit did not involve a generalized difficulty for materials of similar length, rather, the deficit was specific to certain representational types and processing routines.     

Articulatory and phonological deficits in short-term memory and their relation to syntactic processing

The relationships between sentence comprehension deficits and deficits in the articulatory or phonological components of short-term memory were investigated. Nonfluent agrammatic patients showed very poor comprehension of syntax while a group of nonfluent patients who were not agrammatic showed good comprehension, despite both groups showing similar degrees of deficits in an articulatory component of memory. The results imply that a disruption of inner rehearsal has little consequence for auditory sentence comprehension, and that the syntactic comprehension deficits of the agrammatic patients could not be attributed to their memory deficit. A patient with a disruption in phonological storage showed good comprehension for many sentences, but was impaired when a difficult syntactic structure was encountered early in a sentence. It was proposed that phonological storage serves to hold words in a phonological form when sentence processing cannot keep pace with sentence input. Although a role for phonological storage was postulated, the impressive degree of syntactic processing that could be carried out by patients with very restricted memory spans implies that there is little overlap between the memory systems disrupted in these patients and the working memory system presumed to be involved in sentence comprehension.     

Similarity-based interference during language comprehension: Evidence from eye tracking during reading

The nature of working memory operation during complex sentence comprehension was studied by means of eye-tracking methodology. Readers had difficulty when the syntax of a sentence required them to hold 2 similar noun phrases (NPs) in working memory before syntactically and semantically integrating either of the NPs with a verb. In sentence structures that placed these NPs at the same linear distances from one another but allowed integration with a verb for 1 of the NPs, the comprehension difficulty was not seen. These results are interpreted as indicating that similarity-based interference occurs online during the comprehension of complex sentences and that the degree of memory accessibility conventionally associated with different types of NPs does not have a strong effect on sentence processing.