Biomedical subjects

M C MacDonald

Publications and source records attributed to M C MacDonald.

16 recordsLinked to original sources

PubMed2001

Assessing working memory and language comprehension in Alzheimer's disease.

Studies of language impairments in patients with Alzheimer's disease have often assumed that impairments in linguistic working memory underlie comprehension deficits. Assessment of this hypothesis has been hindered both by vagueness of key terms such as "working memory" and by limitations of available working memory tasks, in that many such tasks either seem to have little relationship to language comprehension or are too confusing or difficult for Alzheimer's patients. Four experiments investigated the usefulness of digit ordering, a new task assessing linguistic working memory and/or language processing skill, in normal adults and patients with probable Alzheimer's disease. The digit ordering task was shown to be strongly correlated with the degree of dementia in Alzheimer's patients. The task correlated with measures of language processing on which patients and normal controls performed differently. The results are interpreted as indicating that linguistic representations, linguistic processing, and linguistic working memory are intertwined, such that a deficit of one (e.g., working memory) cannot be said to "cause" a deficit in the other. The implications of this approach are explored in terms of task demands in comprehension and memory measures, and interpretation of previous results in the literature.

Aged↗

PubMed2000

The concomitant effects of phrase length and informational content in sentence comprehension.

Recent evidence suggests that phrase length plays a crucial role in modification ambiguities. Using a self-paced reading task, we extended these results by examining the additional pragmatic effects that length manipulations may exert. The results demonstrate that length not only modulates modification preferences directly, but that it also necessarily changes the informational content of a sentence, which itself affects modification preferences. Our findings suggest that the same length manipulation affects multiple sources of constraints, both structural and pragmatic, which can each exert differing effects on processing.

Adult↗

PubMed1999

Why do Alzheimer patients have difficulty with pronouns? Working memory, semantics, and reference in comprehension and production in Alzheimer's disease.

Three experiments investigated the extent to which semantic and working-memory deficits contribute to Alzheimer patients' impairments in producing and comprehending referring expressions. In Experiment 1, the spontaneous speech of 11 patients with Alzheimer's disease (AD) contained a greater ratio of pronouns to full noun phrases than did the spontaneous speech produced by 9 healthy controls. Experiments 2 and 3 used a cross-modal naming methodology to compare reference comprehension in another group of 10 patients and 10 age-matched controls. In Experiment 2, patients were less sensitive than healthy controls to the grammatical information necessary for processing pronouns. In Experiment 3, patients were better able to remember referent information in short paragraphs when reference was maintained with full noun phrases rather than pronouns, but healthy controls showed the reverse pattern. Performance in all three experiments was linked to working memory performance but not to word finding difficulty. We discuss these findings in terms of a theory of reference processing, the Informational Load Hypothesis, which views referential impairments in AD as the consequence of normal discourse processing in the context of a working memory impairment.

Aged↗

PubMed1999

Nonlinearity parameter for tissue-mimicking materials.

A finite amplitude insert-substitution method has been used to determine the ultrasonic nonlinearity parameter B/A of nine versions of water-based, macroscopically uniform ultrasonically tissue-mimicking (TM) nonfat and fat materials. In this method, the amplitude of the second harmonic following transmission through degassed distilled water with known B/A (B/A = 5.2) and the amplitude of the second harmonic following transmission through the unknown sample are measured. The ratio of these amplitudes allows calculation of the B/A of the sample. Measured B/A values of the nonfat materials range from 5.6 to 6.6. These values compare favorably with published values for nonfat soft tissues. In contrast, the measured B/A values for two tissue-mimicking fat materials are 9.8 and 11.1; these two values represent the low and high end of B/A for most fresh fatty tissues. For comparison, B/A was measured for two commonly available uniform materials, corn oil and ethylene glycol, and the results are in good agreement with published values.

Adipose Tissue↗

PubMed1998

Sentence comprehension deficits in Alzheimer's disease: a comparison of off-line vs. on-line sentence processing.

Two studies explored whether sentence comprehension impairments in Alzheimer's disease (AD) are due to deficits in syntactic processing or memory. Study 1 used a picture-pointing sentence comprehension task to measure the final outcome of comprehension in an off-line fashion. It showed the comprehension of 30 patients with AD to be impaired, but suggested that the deficits could not be attributed solely to syntactic impairments. Study 2 investigated the effects of memory on sentence comprehension by comparing off-line (grammaticality judgment) with on-line (cross-modal naming) language processing in 11 AD and 9 control subjects. The results revealed impaired performance in the off-line task but normal performance in the on-line task using the same sentences. Performance on the off-line task correlated with independent measures of verbal working memory. These data are used to argue that sentence comprehension impairments are related to verbal working memory deficits in AD.

Aged↗

PubMed1998

Relation of a common mutation in methylenetetrahydrofolate reductase to plasma homocysteine and early onset coronary artery disease.

OBJECTIVE: In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. METHODS: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. RESULTS: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). CONCLUSION: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.

Age of Onset↗

PubMed1996

Pseudohomophone effects and models of word recognition.

Two experiments examined factors that influence the processing of pseudohomophones (nonwords such as brone or joap, which sound like words) and nonpseudohomophones (such as brone and joap, which do not sound like words). In Experiment 1, pseudohomophones yielded faster naming latencies and slower lexical-decision latencies than did nonpseudohomophones, replicating results of R. S. McCann and D. Besner (1987) and R. S. McCann, D. Besner, and E. Davelaar (1988). The magnitude of the effect was related to subjects' speed in lexical decision but not naming. In Experiment 2, both immediate and delayed naming conditions were used. There was again a significant pseudohomophone effect that did not change in magnitude across conditions. These results indicate that pseudohomophone effects in the lexical-decision and naming tasks have different bases. In lexical decision, they reflect the pseudohomophone's activation of phonological and semantic information associated with words. In naming, they reflect differences in ease of articulating familiar versus unfamiliar pronunciations. Implications of these results concerning models of word recognition are discussed, focusing on how pseudohomophone effects can arise within models that do not incorporate word-specific representations, such as the M. S. Seidenberg and J. L. McClelland (1989) model.

Humans↗

PubMed1994

The lexical nature of syntactic ambiguity resolution [corrected].

Ambiguity resolution is a central problem in language comprehension. Lexical and syntactic ambiguities are standardly assumed to involve different types of knowledge representations and be resolved by different mechanisms. An alternative account is provided in which both types of ambiguity derive from aspects of lexical representation and are resolved by the same processing mechanisms. Reinterpreting syntactic ambiguity resolution as a form of lexical ambiguity resolution obviates the need for special parsing principles to account for syntactic interpretation preferences, reconciles a number of apparently conflicting results concerning the roles of lexical and contextual information in sentence processing, explains differences among ambiguities in terms of ease of resolution, and provides a more unified account of language comprehension than was previously available.

Cognition↗

PubMed1993

Age- and dose-related NMDA induction of Fos-like immunoreactivity and c-fos mRNA in the arcuate nucleus of immature female rats.

Glutamate and the N-methyl-D-aspartate (NMDA) receptor are important regulatory components of the hypothalamic control of luteinizing hormone (LH) secretion. Peripheral injection of prepubertal rats with NMDA induces maximal secretion of LH within 8 min as well as the expression of the proto-oncogene, c-fos, within the mediobasal hypothalamus (MBH). Because the induction of the c-fos gene is recognized as a sensitive marker of neuronal activity, the detection and characterization of c-fos mRNA and Fos protein may be particularly useful in the analysis of the GnRH (gonadotropin releasing hormone) neuronal system. This study has examined the effect of different doses of NMDA on c-fos mRNA and Fos-like immunoreactivity (Fos-lir); the time-course of induction of c-fos mRNA and the appearance of Fos-lir expression and the ontogeny of NMDA-induced Fos-lir. Our results indicate that NMDA-induced c-fos mRNA and protein are maximal by 60 and 120 min, respectively. Both c-fos mRNA and protein attain peak levels using NMDA doses between 20 and 40 mg/kg. Ontological studies demonstrated that Fos-lir could be detected at 5 days after birth, but declined after sexual maturation. The data presented here indicate that the immunohistochemical localization of c-fos gene expression, in conjunction with in situ hybridization, is a useful technique for mapping NMDA-sensitive pathways and may provide anatomical and physiological evidence that better defines the glutamatergic control of sexual maturation.

Aging↗

PubMed1993

Resolution of quantifier scope ambiguities.

Various processing principles have been suggested to be governing the resolution of quantifier scope ambiguities in sentences such as Every kid climbed a tree. This paper investigates structural principles, that is, those which refer to the syntactic or semantic positions of the quantified phrases. To test these principles, the preferred interpretations for three grammatical constructions were determined in a task in which participants made speeded judgments of whether a sentence following a doubly quantified sentence was a reasonable discourse continuation of the quantified sentence. The observed preferences cannot be explained by any single structural principle, but point instead to the interaction of several principles. Contrary to many proposals, there is little or no effect of a principle that assigns scope according to the linear order of the phrases. The interaction of principles suggests that alternative interpretations of the ambiguity may be initially considered in parallel, followed by selection of the single interpretation that best satisfies the principles. These results are discussed in relation to theories of ambiguity resolution at other levels of linguistic representation.

Adult↗

PubMed1992

Working memory constraints on the processing of syntactic ambiguity.

We propose a model that explains how the working-memory capacity of a comprehender can constrain syntactic parsing and thereby affect the processing of syntactic ambiguities. The model's predictions are examined in four experiments that measure the reading times for two constructions that contain a temporary syntactic ambiguity. An example of the syntactic ambiguity is The soldiers warned about the dangers . . . ; the verb warned may either be the main verb, in which case soldiers is the agent; or the verb warned may introduce a relative clause, in which case soldiers is the patient of warned rather than the agent, as in The soldiers warned about the dangers conducted the midnight raid. The model proposes that both alternative interpretations of warned are initially activated. However, the duration for which both interpretations are maintained depends, in part, on the reader's working-memory capacity, which can be assessed by the Reading Span task (Daneman & Carpenter, 1980). The word-by-word reading times indicate that all subjects do additional processing after encountering an ambiguity, suggesting that they generate both representations. Furthermore, readers with larger working-memory capacities maintain both representations for some period of time (several words), whereas readers with smaller working-memory capacities revert to maintaining only the more likely representation.

Adult↗

PubMed1991

Occurrence of sexual maturation in chronic opiate-treated female rats.

We have investigated the consequences of chronic morphine or fentanyl exposure on the timing of puberty in female Sprague-Dawley rats. The mu-receptor agonists morphine and fentanyl were either added to the drinking water or, in the case of fentanyl, in osmotic mini-pumps. Morphine and fentanyl treatment, beginning at postnatal day 22, delayed the time of the first ovulation/vaginal opening (VO). For example, morphine included in the drinking water (800 mg/l) delayed VO by 5 days. Fentanyl gave similar results but at lower concentrations (30 mg/l). Surprisingly, these treatments delayed but did not prevent VO; i.e. in the face of continued opiate treatment most rats ovulated normally. In contrast, identical doses of morphine blocked oestrous cyclicity in drug-naive adults rats. However, morphine-dependent rats, which have reached VO (and first ovulation) then became briefly acyclic before beginning regular cycles even though opiate treatment was continued. The effects of fentanyl on immature rats were identical with those of morphine, i.e. VO was delayed but ovulation occurred in spite of continued drug treatment. On the other hand, fentanyl did not prevent cyclicity subsequent to VO. Our observation that immature female rats can reach first ovulation despite chronic opiate treatment suggests that some degree of tolerance to opiates may develop. Such a mechanism could operate in normal drug-free rats, via endogenous opioid peptides, in the timing of puberty.

Animals↗

PubMed1990

Expression of c-fos protein by N-methyl-D-aspartic acid in hypothalamus of immature female rats: blockade by MK-801 or neonatal treatment with monosodium glutamate.

Significant NMDA-induced cellular activity in the median eminence-arcuate region of immature female rats was immunocytochemically localized via c-fos protein-like immunoreactivity. The production of this protein was completely prevented by pre-injection of MK-801 or APV, antagonists of the NMDA receptor-coupled ion channel. Treatment of newborn rats with monosodium glutamate (MSG), which destroys glutamate-sensitive neurons, significantly attenuated NMDA-induced c-fos when tested in the peripubertal period. These results implicate NMDA receptors in the expression of c-fos protein-like immunoreactivity in cells of the arcuate nucleus-median eminence of immature female rats.

Aging↗

PubMed1990

Peripubertal treatment with N-methyl-D-aspartic acid or neonatally with monosodium glutamate accelerates sexual maturation in female rats, an effect reversed by MK-801.

Recent reports from several laboratories have implicated the excitatory neurotransmitter glutamate as a component in the neural regulation of sexual maturation. In the rat we have previously proposed that a hypothalamic opioid restraint mechanism may ultimately be overridden by maturation of an excitatory drive, culminating in first ovulation. We have now investigated whether glutamate may be the excitatory factor. Treatment of immature female rats with single, daily injections of two N-methyl-D-aspartate (NMDA) antagonists--dextrorphan (18 mg/kg) and MK-801 (0.1 mg/kg)--beginning on the 27th postnatal day, significantly delayed the timing of vaginal opening (VO). Interestingly, treated rats reached VO in spite of continued antagonist treatment. The antagonist effect was reversed by preinjection of NMDA, suggesting that endogenous glutamate exerts its effect via an NMDA-subtype glutamate receptor. Injection of NMDA alone (15 mg/kg; once daily) produced a striking synchronization of VO such that all treated rats showed VO over a 24-hour period compared to a normal distribution of several days for control rats. In a model of first ovulation, i.e., rats induced to ovulate by pregnant mare serum, MK-801 (1 mg/kg) arrested treated rats at proestrus. This was readily reversible after discontinuing injections. A lower dose of MK-801 (0.1 mg/kg/day) was ineffective in delaying ovulation. In a second series of experiments we studied the consequences of a neonatal hypothalamic lesion which destroys glutamate-sensitive neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Changes in activation levels with negation.

Three experiments investigated the effects of negation during on-line language processing. It was hypothesized that negation of a noun (e.g., no bread) would affect the activation level of the mental representation of that noun. Experiment 1 manipulated the location of the negation in sentences that were followed by a probe recognition task. Subjects were slower to indicate that a probe had been in the sentence when the probe corresponded to a negated noun. Experiment 2 replicated these results with a probe naming task. Experiment 3 replicated the result that reading the phrase no bread inhibits responses to bread in the probe task but found no evidence of inhibition of the response to an associate probe, such as butter. The results of these three studies suggest that negation affects the discourse focus of a noun phrase, and hence the activation level of its representation.

Adult↗

PubMed1986

Rapid extraction of plasmids from Clostridium perfringens.

Two rapid methods were evaluated for their extraction of plasmids from Clostridium perfringens. The first method involved lysis of 1 to 2 ml of C. perfringens culture by treatment with hyaluronidase, lysozyme, and sarcosyl. DNA, extracted with phenol-chloroform, was treated with RNase, boiled, and electrophoresed in a 1.2% agarose gel. The second method involved lysis of 2 ml of culture by lysozyme treatment and extraction with alkaline sodium dodecyl sulfate (SDS). Extracted DNA was treated with RNase, boiled, and electrophoresed in a 0.7% agarose gel. Of 57 strains of C. perfringens analyzed by both extraction procedures, 11 were shown to have plasmids by the alkaline SDS method which were missed by the phenol-chloroform extraction method. These new plasmids were of higher molecular mass and ranged up to 68 megadaltons. Use of the DNase inhibitor diethyl pyrocarbonate did not further improve the yield of plasmid DNA. An additional 159 isolates of C. perfringens screened by the alkaline SDS method revealed plasmids up to 80 megadaltons in mass and an overall plasmid carriage rate of 69%.

Clostridium perfringens↗