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Murray Grossman

Publications and source records attributed to Murray Grossman.

At least 55 records · Page 3Linked to original sources
PubMed2003

Neural basis for semantic memory difficulty in Alzheimer's disease: an fMRI study.

Patients with probable Alzheimer's disease are thought to have a semantic memory deficit. We used functional MRI to evaluate the neural basis for impaired semantic memory for ANIMALS and IMPLEMENTS in 11 patients with Alzheimer's disease and 16 healthy seniors. For both categories of knowledge, Alzheimer's disease patients show reduced activation in the left posterolateral temporal-inferior parietal cortex compared with healthy seniors. Activation changes in this heteromodal association region may be related to an impairment of the category-neutral semantic processes involved in integrating feature knowledge that is represented in modality-specific association cortices. We also found increased activation of an area of the left temporal cortex for both categories of knowledge in Alzheimer's disease that was not activated in healthy seniors. Category-specific changes were also seen in Alzheimer's disease compared with healthy seniors that may be related to the neural representation of category-specific feature knowledge represented in semantic memory. For ANIMALS, the left ventral temporal cortex was activated in Alzheimer's disease in an anatomical distribution that was posterior to the left ventral recruitment for this category in healthy seniors. For IMPLEMENTS, frontal-striatal regions were activated in Alzheimer's disease in a manner that was displaced from the locus of recruitment for this category in healthy seniors. Our findings are consistent with a two-component model of semantic memory involving category-neutral processes operating on category- specific knowledge, and both components appear to be compromised in Alzheimer's disease. Components of the large-scale neural network underlying semantic memory may modify themselves to maintain performance in the face of a neurodegenerative disease.

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PubMed2003

Categorization of object descriptions in Alzheimer's disease and frontotemporal dementia: limitation in rule-based processing.

Studies of semantic memory in probable Alzheimer's disease (AD) have focused on the degradation of semantic knowledge, but other work in AD suggests an impairment in the semantic categorization processes that operate on this knowledge. We examined the categorization of object descriptions, where semantic category membership judgments were based on rule-based or similarity-based categorization processes. We found that AD patients were selectively limited in their semantic categorization under conditions requiring a rule-based approach. However, AD patients did not differ from healthy seniors under conditions based on judgments of overall similarity. We showed that this was not due to nonspecific or overall task-related difficulty associated with the rule condition by asking the subjects to use similarity-based judgments of perceptually degraded versions of the stimuli. The results of this condition did not differ from other similarity-based judgments but did differ from the rule-based condition in AD. Rule-based judgments of semantic category membership correlated with executive measures of inhibitory control and mental search, but not with measures of episodic memory or overall dementia severity, suggesting a contribution of executive resources to rule-based semantic categorization. Moreover, the pattern of limited rule-based categorization in AD closely resembled the performance profile of patients with frontotemporal dementia, further implying that executive resource limitations underlie AD patients' limited rule-based semantic categorization. These findings suggest that semantic memory difficulty in AD is due in part to a deficit in executive processes that are central to rule-based categorization in semantic memory.

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PubMed2002

Sporadic Pick's disease: a tauopathy characterized by a spectrum of pathological tau isoforms in gray and white matter.

Pick's disease is characterized neuropathologically by distinct tau-immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble tau proteins with predominantly three microtubule-binding repeat tau isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule-binding repeat, detected other tau lesions in Pick's disease. To better define the spectrum of tau pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the tau isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule-binding repeat pathological tau isoforms are present in gray and white matter of various brain regions. Using phosphorylation-dependent anti-tau antibodies, we show that major tau phosphoepitopes are present in sarcosyl-insoluble gray and white matter regions of Pick's disease brains. Also, for the first time to our knowledge, we demonstrated that isoforms with four microtubule-binding repeat tau isoforms are present in Pick bodies from selected brains. Isolated tau filaments were straight or twisted and formed by three microtubule-binding repeat or four microtubule-binding repeat tau isoforms. Major tau phosphorylation-dependent and exon 10-specific epitopes were present in filaments. Therefore, Pick's disease is characterized by an accumulations of Pick bodies in the hippocampal region and cortex as well as the presence of three and four microtubule-binding repeat tau pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.

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PubMed2002

Neural basis for sentence comprehension: grammatical and short-term memory components.

We monitored regional cerebral activity with BOLD fMRI while subjects were presented written sentences differing in their grammatical structure (subject-relative or object-relative center-embedded clauses) and their short-term memory demands (short or long antecedent-gap linkages). A core region of left posterior superior temporal cortex was recruited during all sentence conditions in comparison to a pseudofont baseline, suggesting that this area plays a central role in sustaining comprehension that is common to all sentences. Right posterior superior temporal cortex was recruited during sentences with long compared to short antecedent-gap linkages regardless of grammatical structure, suggesting that this brain region supports passive short-term memory during sentence comprehension. Recruitment of left inferior frontal cortex was most clearly associated with sentences that featured both an object-relative clause and a long antecedent-gap linkage, suggesting that this region supports the cognitive resources required to maintain long-distance syntactic dependencies during the comprehension of grammatically complex sentences.

Adult↗
PubMed2002

Neural representation of verb meaning: an fMRI study.

The neural basis for verb comprehension has proven elusive, in part because of the limited range of verb categories that have been assessed. In the present study, 16 healthy young adults were probed for the meaning associated with verbs of MOTION and verbs of COGNITION. We observed distinct patterns of activation for each verb subcategory: MOTION verbs are associated with recruitment of left ventral temporal-occipital cortex, bilateral prefrontal cortex and caudate, whereas COGNITION verbs are associated with left posterolateral temporal activation. These findings are consistent with the claim that the neural representations of verb subcategories are distinct. Although the "sensory-motor" hypothesis may play a role in explaining activation associated with MOTION verbs, the left posterolateral temporal distribution of cortical activation associated with COGNITION verbs cannot be easily explained by the "sensory-motor" hypothesis. We suggest that left posterolateral temporal activation supports aspects of lexical semantic processing concerned with the neural representation of propositional knowledge contributing to COGNITION verbs.

Adult↗
PubMed2002

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.

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PubMed2002

Neural correlates of successful and unsuccessful verbal memory encoding.

Recent neuroimaging studies suggest that episodic memory encoding involves a network of neocortical structures which may act interdependently with medial temporal lobe (mTL) structures to promote the formation of durable memories, and that activation in certain structures is modulated according to task performance. Functional magnetic resonance imaging (fMRI) was used to determine the neural structures recruited during a verbal episodic encoding task and to examine the relationship between activation during encoding and subsequent recognition memory performance across subjects. Our results show performance-correlated activation during encoding both in neocortical and medial temporal structures. Neocortical activations associated with later successful and unsuccessful recognition memory were found to differ not only in magnitude, but also in hemispheric laterality. These performance-related hemispheric effects, which have not been previously reported, may correspond to between-subject differences in encoding strategy.

Adolescent↗
PubMed2002

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.

Aged↗
PubMed2002

Age-related changes in working memory during sentence comprehension: an fMRI study.

Sentence comprehension declines with age, but the neural basis for this change is unclear. We monitored regional brain activity in 13 younger subjects and 11 healthy seniors matched for sentence comprehension accuracy while they answered a simple probe about written sentences. The sentences varied in their grammatical features (subject-relative vs object-relative subordinate clause) and their verbal working memory (WM) demands (short vs long antecedent noun-gap linkage). We found that young and senior subjects both recruit a core written sentence processing network, including left posterolateral temporal and bilateral occipital cortex for all sentences, and ventral portions of left inferior frontal cortex for object-relative sentences with a long noun-gap linkage. Differences in activation patterns for seniors compared to younger subjects were due largely to changes in brain regions associated with a verbal WM network. While seniors had less left parietal recruitment than younger subjects, left premotor cortex, and dorsal portions of left inferior frontal cortex showed greater activation in seniors compared to younger subjects. Younger subjects recruited right posterolateral temporal cortex for sentences with a long noun-gap linkage. Seniors additionally recruited right parietal cortex for this sentence-specific form of WM. Our findings are consistent with the hypothesis that the neural basis for sentence comprehension includes dissociable but interactive large-scale neural networks supporting core written sentence processes and related cognitive resources involved in WM. Seniors with good comprehension appear to up-regulate portions of the neural substrate for WM during sentence processing to achieve comprehension accuracy that equals young subjects.

Adult↗
PubMed2002

The neural basis for category-specific knowledge: an fMRI study.

Functional neuroimaging studies of healthy adults have associated different categories of knowledge with distinct activation patterns. The basis for these recruitment patterns has been controversial, due in part to the limited range of categories that has been studied. We used fMRI to monitor regional cortical recruitment patterns while subjects were exposed to printed names of Animals, Implements, and Abstract nouns. Both Implements and Abstract nouns were related to recruitment of left posterolateral temporal cortex and left prefrontal cortex, and Abstract nouns additionally recruited posterolateral temporal and prefrontal regions of the right hemisphere. Animals were associated with activation of ventral-medial occipital cortex in the left hemisphere at a level that approaches significance. These findings are not consistent with the "sensory-motor" model proposed to explain the neural representation of word knowledge. We suggest instead a neural model of semantic memory that reflects the processes common to understanding Implements and Abstract nouns and a selective sensitivity, possibly evolving from adaptive pressures, to the overlapping, intercorrelated visual characteristics of Animals.

Adult↗
PubMed2002

The neural basis for categorization in semantic memory.

We asked young adults to categorize written object descriptions into one of two categories, based on a rule or on overall similarity, while we monitored regional brain activity with functional magnetic resonance imaging (fMRI). We found significantly greater recruitment of left dorsolateral prefrontal cortex for rule-based categorization in direct comparison with similarity-based categorization. Recruitment of right ventral frontal cortex and thalamus was uniquely associated with rule-based categorization as well. These observations lend support to the claim that executive functions such as working memory, inhibitory control, and selective attention contribute to rule-based categorization. Right inferior parietal activation was uniquely associated with similarity-based categorization. This region may play an important role in overall feature configuration that is important for this form of categorization. We found other brain regions recruited for both rule-based and similarity-based categorization: Anterior cingulate cortex may support the implementation of executive functions during situations with competing response alternatives; and left inferior parietal cortex may be related to the integration of feature knowledge about objects represented in modality-specific association cortices. We also administered a degraded-similarity condition where the task of categorizing a written object description was made more difficult by perceptually degrading the stimulus materials. The degraded condition and the rule-based condition, but not the similarity-based condition, were associated with caudate activation. The caudate may support resource demands that are not specific for a particular categorization process. These findings associate partially distinct large-scale neural networks with different forms of categorization in semantic memory.

Adolescent↗
PubMed2002

Signature tau neuropathology in gray and white matter of corticobasal degeneration.

Corticobasal degeneration (CBD) is an adult-onset progressive neurodegenerative disorder characterized by L-dopa-resistant rigidity, focal cortical deficits, and variable dementia. The neuropathological hallmark of CBD is the deposition of filamentous inclusions in neurons and glia composed of hyperphosphorylated tau with only four microtubule-binding repeats (4R-tau). To characterize the regional burden of tau pathology in CBD, we studied 12 brains with the neuropathological diagnosis of CBD using biochemical and histochemical techniques. Eleven brain regions were evaluated including gray and white matter from frontal, parietal, temporal, and occipital lobes and cerebellum as well as basal ganglia. Although the distribution of tau pathology was variable, neuropathological and biochemical data showed a similar burden of tau abnormalities in frontal, temporal, and parietal lobes and basal ganglia of both hemispheres. This included abundant, sarkosyl-insoluble 4R-tau in both gray and white matter of two or more of these cortical regions and basal ganglia, and to a lesser extent, cerebellar white matter. The insoluble tau pathology in gray and white matter showed overlapping but distinct phosphorylated epitopes suggesting cell-type and subcellular localization (ie, cell bodies versus cell processes)-specific differences in tau phosphorylation. In contrast, soluble tau was composed of normal 4R/3R-tau ratios indicating no gross abnormality in tau splicing. Thus, although clinically heterogeneous, CBD is a distinct lobar and basal ganglionic tauopathy with selective aggregation of 4R-tau.

Aged↗
PubMed2002

Disturbed visual processing contributes to impaired reading in Alzheimer's disease.

The relationship between visual processing dysfunction and oral reading impairment was investigated in 17 patients with probable or possible Alzheimer's disease (AD). When dementia severity was controlled, a significant relationship was found between single word oral reading impairments and difficulties discriminating words written in different fonts and photographs of objects in different orientations, which are all functions believed to be dependent on the integrity of left ventral temporal-occipital visual association regions. By contrast, there was no significant relationship between reading performance and the score on a test of spatial localization, believed to be more dependent on parietal lobe function. There was also no relationship between reading ability and discrimination of unfamiliar faces, a function thought to engage right inferotemporal lobe structures. In contrast to the significant association between impaired reading and certain visual processes, when dementia severity was controlled, there was no relationship between reading and lexical semantic impairment. These results highlight the contribution of visual processing deficits to impaired oral reading in AD and further suggest that this association may derive from neuropathological changes in areas of the left temporal occipital lobes specialized for high-level visual processing.

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PubMed2002

Frontotemporal dementia: a review.

This review summarizes the clinical, imaging, and pathological features of frontotemporal dementia (FTD). Clinicians have become increasingly sensitive to FTD in the differential diagnosis of Alzheimer's disease. Clinical subgroups of FTD patients have been recognized, including patients with progressive non-fluent aphasia, semantic dementia, and behavioral disorder with executive difficulty. The clinical, neuroimaging and neuropathological profiles associated with these clinically defined subgroups are examined.

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PubMed2002

Information processing speed and sentence comprehension in Parkinson's disease.

This study tests the hypothesis that sentence comprehension difficulty in Parkinson's disease (PD) is related in part to altered information processing speed that plays a crucial role in grammatical processing. The authors measured information processing speed in 32 PD patients without dementia using a lexical list-priming paradigm in which the interstimulus interval (ISI) between the prime and the target varied. Sentence comprehension accuracy was also assessed in 22 of these patients. Sentence comprehension accuracy for object-relative center-embedded sentences was impaired in a subgroup of PD patients. This subgroup of PD patients primed at an abnormally long ISI. Similarly, only PD patients who primed at a long ISI had greater difficulty understanding sentences with an object-relative clause than a subject-relative clause. Findings suggest that slowed information processing speed contributes to sentence comprehension difficulty in PD.

Aged↗
PubMed2002

Progressive aphasic syndromes: clinical and theoretical advances.

PURPOSE OF REVIEW: Knowledge of the neural basis for language and related aspects of cognition has been advanced through detailed studies of patients with primary progressive aphasia. This brief review highlights some recent work. RECENT FINDINGS: The impairment of semantic knowledge in patients with semantic dementia appears to influence performance in a wide variety of linguistic and cognitive domains, including morphological agreements such as the irregular past tense. Computational studies modeling the deficits of these patients have advanced interpretations of the impairments in semantic dementia. Imaging analyses have confirmed the presence of temporal atrophy cross-sectionally and longitudinally in these patients. In patients with semantic dementia, it appears that both the left temporal and right temporal regions contribute in different proportions to naming and comprehension, although the nature of the process underlying the consolidation of knowledge in semantic memory continues to be actively debated. In patients with progressive non-fluent aphasia, recent work has emphasized an impairment with verbs. Functional neuroimaging work with progressive non-fluent aphasics, compared directly to non-aphasic patients with frontotemporal dementia, has demonstrated a dissociation for grammatical and working memory aspects of sentence processing within the left frontal cortex. SUMMARY: These findings will improve diagnostic accuracy, prognostic ability, and therapeutic potential in patients with progressive aphasia.

Aphasia, Primary Progressive↗
PubMed2002

Memory encoding and retrieval in frontotemporal dementia and Alzheimer's disease.

Memory encoding and retrieval strategies were assessed in patients with behavior-executive variant frontotemporal dementia (FTD), language variant FTD, and Alzheimer's disease (AD) using verbal and visuospatial supraspan learning tests. FTD patients obtained higher free recall, cued recall, and recognition scores than AD patients. Comparison of free recall scores with cued recall and recognition scores was similar in the 3 dementia groups. Groups did not differ in semantic clustering strategies during learning, but serial-order recall was more common in FTD patients. These data do not support the idea that FTD patients' poor memory is due to a selective retrieval disorder, though FTD patients may fail to implement sophisticated organizational strategies during learning. FTD patients' retained capacity for encoding new information into long-term declarative memory is likely due to relatively spared medial temporal lobe involvement.

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