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Murray Grossman

Publications and source records attributed to Murray Grossman.

At least 37 records · Page 2Linked to original sources
PubMed2005

Verb agreements during on-line sentence processing in Alzheimer's disease and frontotemporal dementia.

An on-line "word detection" paradigm was used to assess the comprehension of thematic and transitive verb agreements during sentence processing in individuals diagnosed with probable Alzheimer's Disease (AD, n=15) and Frontotemporal Dementia (FTD, n=14). AD, FTD, and control participants (n=17) were asked to listen for a word in a sentence. Unbeknownst to the participants, the target word followed an agreement involving a verb's transitivity or thematic role component. Control participants took significantly longer to respond to a target word only when it immediately followed a violation of a thematic role agreement or a transitivity agreement, relative to target word detection immediately following the corresponding correct agreement. AD patients were selectively insensitive to thematic role agreement violations, although they demonstrated a normal processing pattern for transitivity agreements. This is consistent with previous observations showing selective difficulty with the thematic role component of a verb in AD. FTD patients were insensitive to violations of thematic role and transitivity agreements. FTD patients' impairment for both transitivity and thematic role agreements may reflect a broader degradation of verb knowledge that involves both grammatical and semantic representations, or difficulty processing sentence structure that also causes a thematic role deficit.

Aged↗
PubMed2005

Sentence processing in frontotemporal dementia.

Patients with frontotemporal dementia (FTD) have sentence comprehension difficulty. We examined the hypothesis that both grammatical and resource factors contribute to their impaired sentence comprehension with a traditional, off-line sentence comprehension task, and an on-line sentence processing procedure that minimizes task-related resources. This was investigated in subgroups of FTD patients with Progressive Non-fluent Aphasia (PNFA; n = 5) who have effortful speech; non-aphasic patients with an executive deficit (EXEC; n = 8); and Semantic Dementia (SD; n = 3) patients with poor single word comprehension. The results were correlated with measures of executive resources. We found that PNFA patients are significantly impaired in their off-line sentence comprehension, and that their performance correlated with auditory-verbal short-term memory. PNFA patients also demonstrated a pattern of slowed processing for the on-line sentence measure. This is consistent with the hypothesis that information relevant for constructing sentence representations during comprehension degrades in working memory as it is activated over an abnormally slowed time course. EXEC patients had modest off-line sentence comprehension difficulty, and this correlated with performance on measures of working memory, planning, and inhibitory control. On-line processing in EXEC patients demonstrated their insensitivity to sentence-based information. This raises the possibility that a limitation in material-neutral executive resources not dedicated to grammatical processing may play a role in their sentence comprehension deficit. SD patients' pattern of on-line sentence comprehension paralleled control subjects' performance. We conclude that grammatical and executive components both contribute to sentence comprehension, and that the profile of sentence comprehension difficulty varies across FTD subgroups depending on the sentence processing component that is impaired.

Aged↗
PubMed2004

The neural basis for novel semantic categorization.

We monitored regional cerebral activity with BOLD fMRI during acquisition of a novel semantic category and subsequent categorization of test stimuli by a rule-based strategy or a similarity-based strategy. We observed different patterns of activation in direct comparisons of rule- and similarity-based categorization. During rule-based category acquisition, subjects recruited anterior cingulate, thalamic, and parietal regions to support selective attention to perceptual features, and left inferior frontal cortex to helps maintain rules in working memory. Subsequent rule-based categorization revealed anterior cingulate and parietal activation while judging stimuli whose conformity with the rules was readily apparent, and left inferior frontal recruitment during judgments of stimuli whose conformity was less apparent. By comparison, similarity-based category acquisition showed recruitment of anterior prefrontal and posterior cingulate regions, presumably to support successful retrieval of previously encountered exemplars from long-term memory, and bilateral temporal-parietal activation for perceptual feature integration. Subsequent similarity-based categorization revealed temporal-parietal, posterior cingulate, and anterior prefrontal activation. These findings suggest that large-scale networks support relatively distinct categorization processes during the acquisition and judgment of semantic category knowledge.

Adult↗
PubMed2004

What's in a name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease, frontotemporal dementia and corticobasal degeneration.

Confrontation naming is impaired in neurodegenerative conditions like Alzheimer's disease (AD), frontotemporal dementia (FTD) and corticobasal degeneration (CBD). Some behavioural observations suggest a common source of impaired naming across these patient groups, while others find partially unique patterns of naming difficulty. We hypothesized that a large-scale neural network underlies naming, and that patterns of impaired naming in AD, FTD and CBD reflect cortical atrophy that interrupts this network in a manner that is partially shared and partially unique across these patient groups. We tested this hypothesis by correlating naming impairments with voxel-based morphometric (VBM) analyses of cortical atrophy in structural MRIs of 50 patients. We found significant naming deficits in all patient groups. Naming also correlated with lexical retrieval in all patient groups, including subgroups of patients with FTD. VBM analyses showed significant cortical atrophy, which was shared across AD, FTD and CBD patients in the left lateral temporal cortex; this area correlated with naming accuracy in all groups. Left lateral temporal atrophy thus appears to interfere with a lexical retrieval component of naming in AD, FTD and CBD. Impaired naming also correlated with semantic memory and visual perceptual-spatial functioning in specific groups of patients and, correspondingly, naming correlated with cortical atrophy in partially distinct neuroanatomical distributions in AD, FTD, CBD and subgroups of patients with FTD. These partially unique correlation profiles appear to reflect selective interruption of other components of the naming process, including semantic and visual perceptual-spatial functioning. These findings are consistent with the hypothesis that a large-scale neural network supports naming, and that this network is interrupted in several distinct ways in patients with neurodegenerative diseases.

Aged↗
PubMed2004

Verbal mediation of number knowledge: evidence from semantic dementia and corticobasal degeneration.

Patients with corticobasal degeneration (CBD) appear to have impaired number knowledge. We examined the nature of their number deficit while we tested the hypothesis that comprehension of larger numbers depends in part on verbal mediation. We evaluated magnitude judgments and performance on number conservation measures rooted in Piagetian theory in nonaphasic patients with CBD (n=13) and patients with a fluent form of progressive aphasia known as semantic dementia (SD; n=15). We manipulated the numbers of the arrays and the visual-spatial properties of the stimuli being compared during magnitude judgments and Piagetian conservation measures. CBD patients were consistently impaired judging the magnitudes of larger numbers (4-9), while they had minimal difficulty with smaller numbers (magnitudes < or = 3). By comparison, SD patients performed all measures of number knowledge at a ceiling level regardless of number magnitude. Neither patient group was significantly impacted by manipulations of the spatial properties of the stimuli. CBD patients' impairment with larger numbers despite minimal aphasia, and SD patients' intact performance despite an aphasia, challenge the proposal that understanding larger numbers depends on verbal mediation.

Aged↗
PubMed2004

Dissociable patterns of brain activity during comprehension of rapid and syntactically complex speech: evidence from fMRI.

Sentence comprehension is a complex task that involves both language-specific processing components and general cognitive resources. Comprehension can be made more difficult by increasing the syntactic complexity or the presentation rate of a sentence, but it is unclear whether the same neural mechanism underlies both of these effects. In the current study, we used event-related functional magnetic resonance imaging (fMRI) to monitor neural activity while participants heard sentences containing a subject-relative or object-relative center-embedded clause presented at three different speech rates. Syntactically complex object-relative sentences activated left inferior frontal cortex across presentation rates, whereas sentences presented at a rapid rate recruited frontal brain regions such as anterior cingulate and premotor cortex, regardless of syntactic complexity. These results suggest that dissociable components of a large-scale neural network support the processing of syntactic complexity and speech presented at a rapid rate during auditory sentence processing.

Adult↗
PubMed2004

Primary progressive aphasia: a review.

This review summarizes clinical and imaging features associated with primary progressive aphasia (PPA). We investigate the hypothesis that these patients can be divided into subgroups of progressive non-fluent aphasia (PNFA) and semantic dementia (SD), based on their linguistic profiles and related imaging studies, and examine whether each of these major subgroups can be further subdivided. We focus on several critical features within each progressive aphasic subgroup. In PNFA, we examine agrammatism, phonologic disorder, and impaired verb processing to determine whether this syndrome is related to a modality-specific impairment in word formation and articulation, or a conceptual deficit that interferes with grammatical processing. In SD, we examine impaired semantic memory, limited remote memory, and anomia to assess whether this syndrome is due to a modality-neutral interruption of semantic memory, or the degradation of various material-specific representations of object features and words. We conclude that there is sufficiently consistent and converging evidence from clinical and imaging studies to support the claim that PNFA and SD are distinct subgroups of PPA. However, there does not appear to be sufficient evidence at this point to support further discrimination within these progressive aphasic subgroups. Testing hypotheses about finer-grained syndromes such as progressive dysarthria or progressive anomia has important consequences for improving our understanding of language organization and the neural basis for language.

Aphasia, Primary Progressive↗
PubMed2004

Frontotemporal dementia: genetics and genetic counseling dilemmas.

BACKGROUND: Frontotemporal dementia (FTD) is a neurodegenerative disease with early symptoms of personality change and/or language disorder. Approximately 40% of individuals with FTD have a family history of dementia; however, in our experience, less than 10% have clear autosomal dominant inheritance. Mutations in the microtubule-associated protein tau (MAPT) gene have been reported in up to 50% of hereditary cases, but are unusual except in families with more than 3 individuals with FTD. The genetics of FTD is complicated by clinical heterogeneity, variable expression, phenocopies, misdiagnoses, and lost family histories. The objective of this paper is to enable physicians to recognize hereditary patterns and genetic concerns of FTD families and to understand genetic counseling strategies. REVIEW SUMMARY: The complexity of FTD genetics and genetic counseling are illustrated using 4 case histories. Case 1 demonstrates the difficulty obtaining a reliable FTD family history. Case 2 illustrates how psychiatric phenocopies can make family linkage studies difficult. The lack of genotype and phenotype correlation and issues of predictive genetic testing within FTD families are the subject of case 3, and case 4 shows how normal aging language difficulties and cognitive changes can be misinterpreted when a family history of dementia is present. CONCLUSIONS: Physicians seeing patients with possible FTD should be aware of the risk of a genetic etiology. A 3-generation family history should be obtained with attention to neurologic, psychiatric, and behavioral symptoms. Variable expression and phenocopies are confounding factors when assessing a possible genetic etiology. Referral of the patient and family for genetic counseling is recommended.

Dementia↗
PubMed2004

Confrontation naming and morphometric analyses of structural MRI in frontotemporal dementia.

We studied the neural basis for confrontation naming difficulty in 29 patients with frontotemporal dementia (FTD) by correlating naming with voxel-based morphometric analyses of gray matter volume in structural MRI. We found that naming is significantly impaired in FTD, including patients with semantic dementia (SD), progressive nonfluent aphasia (PNFA), and nonaphasic patients (NON-APH) with a disorder of social and executive functioning. Significant cortical atrophy was found in the left anterior temporal cortex in all three FTD subgroups relative to healthy seniors. We also found significant cortical atrophy in unique anatomic distributions in each FTD subgroup. This included: lateral, ventral, and parahippocampal regions of the left temporal lobe in SD; inferior, orbital, dorsolateral, and premotor regions of the left frontal lobe in PNFA, and bilateral frontal regions in NON-APH. Direct correlations between confrontation naming and gray matter volume revealed distinct patterns in each FTD subgroup. SD patients showed a significant correlation in the left lateral temporal cortex, PNFA patients in several left frontal regions, and NON-APH patients in the right dorsolateral prefrontal cortex. These findings suggest that confrontation naming is supported by a large-scale neural network, and that naming is compromised in FTD due to interruption of the network in several different ways.

Aged↗
PubMed2003

Novel concepts mediate word retrieval from human episodic associative memory: evidence from event-related potentials.

Effects of conceptual fusion on episodic associative retrieval were examined. Subjects attempted to fuse sequentially displayed (800 ms offset) word pairs; pairs subjects were unable to fuse were instead considered associated by juxtaposition. Next, dense-array event-related potentials (ERPs) were recorded while the pairs were redisplayed, half reversed in order. Subjects pressed a button to indicate whether each pair was presented in the previous order. Behavioral results showed that retrieval of fused pairs was faster and more accurate than for juxtaposed pairs. ERP topography to the first word of fused pairs was different from juxtaposed pairs, indicating that fusion can mediate associative retrieval of constituent items. Estimates of current source density at the cortical surface showed that fusion-mediated retrieval elicited left inferior-prefrontal/anterior-temporal activity not typically observed in episodic memory retrieval studies.

Adolescent↗
PubMed2003

Calculation impairment in neurodegenerative diseases.

We examined oral calculation in patients with corticobasal degeneration (CBD; N=17), frontotemporal dementia (FTD; N=17), and Alzheimer's disease (AD; N=20), as well as 17 healthy seniors matched for age and education. Our calculation model involves at least three components: numerosity, combinatorial processes, and executive resources such as working memory. We assessed addition, subtraction, multiplication, and division involving small numbers (small, single-digit answers) and large numbers (larger, single- and double-digit answers). We also assessed dot counting for small numbers (2-5) and large numbers (6-9), as well as a measure of working memory. All patient groups differed from healthy seniors in oral calculation. CBD (36% correct) and FTD (65% correct) demonstrated a significant overall impairment in oral calculation relative to AD (76% correct). CBD (66% correct) had more difficulty counting dots overall relative to AD (94% correct) and FTD (86% correct), consistent with our hypothesis that the calculation deficit in CBD is due in large part to a numerosity deficit. FTD had more difficulty relative to AD in their performance of reverse digit span, consistent with our hypothesis that FTD patients' executive resource limitation contributes to their pattern of calculation impairment.

Aged↗
PubMed2003

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.

Aged↗
PubMed2003

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.

Aged↗
PubMed2003

Category-specific medial temporal lobe activation and the consolidation of semantic memory: evidence from fMRI.

Semantic memory consolidation was studied by comparing medial temporal lobe (MTL) fMRI activation to ANIMAL, IMPLEMENT and ABSTRACT nouns in healthy seniors to that of young adults. Relative to healthy seniors, young adults were predicted to show greater MTL activation for IMPLEMENTS, but not ANIMALS, because the ANIMALS category consists of highly intercorrelated and overlapping features that should require less MTL-mediated binding than IMPLEMENTS over a shorter period of time during concept consolidation. ABSTRACT meanings are context-dependent and do not consist of fixed feature sets. Thus it was predicted that ABSTRACT words would not involve age-related feature binding mediated by the MTL. These predictions were confirmed by the results. Our observations are consistent with the hypothesis that the structure of a category influences the consolidation of knowledge in semantic memory.

Adult↗
PubMed2003

Alzheimer's disease and frontotemporal dementia exhibit distinct atrophy-behavior correlates: a computer-assisted imaging study.

RATIONALE AND OBJECTIVES: The purpose of this study was to test the hypothesis that distinct patterns of gray matter atrophy are responsible for unique interruptions of the naming process in Alzheimer's disease (AD) and frontotemporal dementia (FTD). MATERIALS AND METHODS: Voxel-based morphometry (VBM) was performed to characterize at the voxel level the neuroanatomic changes that occur in AD and FTD based on high-resolution T1-weighted three-dimensional (3D) spoiled-gradient echo images of patients (AD, n = 12; FTD, n = 29) and healthy control subjects (n = 12). The cortical atrophy measurements were correlated with performance on behavioral measures of naming and related processes to identify brain regions that may contribute to this language function. RESULTS: Both AD and FTD have significant naming difficulty, and this difficulty in naming correlates with a measure of lexical retrieval in both patient groups as well. However, only FTD patients showed a correlation with semantic memory. Areas of cortical atrophy common to AD and FTD were found in the anterior temporal, posterolateral temporal, and dorsolateral prefrontal regions of the left hemisphere. Correlation with naming in both AD and FTD was seen in the left anterior temporal cortex, suggesting that this area may play a role in the lexical retrieval component of naming. We also observed several unique areas of cortical atrophy in temporal and frontal cortices of these patients. Right anterior temporal and left posterolateral temporal regions of atrophy correlated with naming difficulty in FTD, suggesting that these areas may contribute to the semantic memory component of naming. Cortical areas correlating with naming that are not atrophic may represent regions that play an optional role in naming. CONCLUSION: VBM provides an important first step in analyzing brain-behavior relations in vivo in patients with neurodegenerative diseases. More refined analyses of brain morphology via high-dimensional normalization methods that are capable of modeling local as well as global variability in neuroanatomical structure promise to be even more informative.

Aged↗
PubMed2003

Neural basis for verb processing in Alzheimer's disease: an fMRI study.

Patients with probable Alzheimer's disease (AD) have difficulty understanding verbs. To investigate the neural basis for this deficit, the authors used functional magnetic resonance imaging to examine patterns of neural activation during verb processing in 11 AD patients compared with 16 healthy seniors. Subjects judged the pleasantness of verbs, including MOTION verbs and COGNITION verbs. Healthy seniors and AD patients both activated posterolateral temporal and inferior frontal regions during judgments of verbs. These activations were relatively reduced and somewhat changed in their anatomic distribution in AD patients compared with healthy seniors, particularly for the subcategory of MOTION verbs, but AD patients showed minimal activation in association with COGNITION verbs. These findings imply that poor performance with verbs in AD is due in part to altered activation of the large-scale neural network that supports verb processing.

Aged↗