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Biomedical subjects

A Marantz

Publications and source records attributed to A Marantz.

At least 19 recordsLinked to original sources

A magnetoencephalographic component whose latency reflects lexical frequency.

Magnetoencephalography (MEG) measured subjects' brain responses during a lexical decision task. The words employed come from six frequency categories, which were defined in terms of a linear decrease in log-frequency. Although frequency effects in reaction-time are well-documented in studies of lexical access, a neural component whose latency predicts reaction time has not been discovered. This study identifies an MEG component (the M350) whose latency mirrors the frequency-effect.

Adult↗

Phase II study of gemcitabine, 5-fluorouracil, and leucovorin in patients with pancreatic cancer.

The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.

Antineoplastic Combined Chemotherapy Protocols↗

Reconstructing spatio-temporal activities of neural sources using an MEG vector beamformer technique.

We have developed a method suitable for reconstructing spatio-temporal activities of neural sources by using magnetoencephalogram (MEG) data. The method extends the adaptive beamformer technique originally proposed by Borgiotti and Kaplan to incorporate the vector beamformer formulation in which a set of three weight vectors are used to detect the source activity in three orthogonal directions. The weight vectors of the vector-extended version of the Borgiotti-Kaplan beamformer are then projected onto the signal subspace of the measurement covariance matrix to obtain the final form of the proposed beamformer's weight vectors. Our numerical experiments show that both spatial resolution and output signal-to-noise ratio of the proposed beamformer are significantly higher than those of the minimum-variance-based vector beamformer used in previous investigations. We also applied the proposed beamformer to two sets of auditory-evoked MEG data, and the results clearly demonstrated the method's capability of reconstructing spatio-temporal activities of neural sources.

Brain Mapping↗

A syntactic specialization for Broca's area.

Despite numerous aphasia and functional imaging studies, the exact correlation between cortical language areas and subcomponents of the linguistic system has not been established. Here, we used functional MRI to identify cortical areas specifically involved in syntactic processing. An experimental design contrasted sentences containing grammatical errors with sentences containing spelling errors. The ungrammatical sentences produced more activation in cortical language areas than did the sentences with spelling errors, and the difference in activation was significantly greater in Broca's area than in Wernicke's area or in the angular gyrus/supramarginal gyrus. The present findings provide direct evidence of a syntactic specialization for Broca's area and establish the existence of distinct modules for our knowledge of language.

Adult↗

The selectivity of the occipitotemporal M170 for faces.

Evidence from fMRI, ERPs and intracranial recordings suggests the existence of face-specific mechanisms in the primate occipitotemporal cortex. The present study used a 64-channel MEG system to monitor neural activity while normal subjects viewed a sequence of grayscale photographs of a variety of unfamiliar faces and non-face stimuli. In 14 of 15 subjects, face stimuli evoked a larger response than non-face stimuli at a latency of 160 ms after stimulus onset at bilateral occipitotemporal sensors. Inverted face stimuli elicited responses that were no different in amplitude but 13 ms later in latency than upright faces. The profile of this M170 response across stimulus conditions is largely consistent with prior results using scalp and subdural ERPs.

Acoustic Stimulation↗

Auditory cortex accesses phonological categories: an MEG mismatch study.

The studies presented here use an adapted oddball paradigm to show evidence that representations of discrete phonological categories are available to the human auditory cortex. Brain activity was recorded using a 37-channel biomagnetometer while eight subjects listened passively to synthetic speech sounds. In the phonological condition, which contrasted stimuli from an acoustic /dae/-/tae/ continuum, a magnetic mismatch field (MMF) was elicited in a sequence of stimuli in which phonological categories occurred in a many-to-one ratio, but no acoustic many-to-one ratio was present. In order to isolate the contribution of phonological categories to the MMF responses, the acoustic parameter of voice onset time, which distinguished standard and deviant stimuli, was also varied within the standard and deviant categories. No MMF was elicited in the acoustic condition, in which the acoustic distribution of stimuli was identical to the first experiment, but the many-to-one distribution of phonological categories was removed. The design of these studies makes it possible to demonstrate the all-or-nothing property of phonological category membership. This approach contrasts with a number of previous studies of phonetic perception using the mismatch paradigm, which have demonstrated the graded property of enhanced acoustic discrimination at or near phonetic category boundaries.

Acoustic Stimulation↗

MEG spatio-temporal analysis using a covariance matrix calculated from nonaveraged multiple-epoch data.

We propose a magnetoencephalographic (MEG) spatio-temporal analysis in which the measurement-covariance matrix is calculated using nonaveraged multiple epoch data. The proposed analysis has two advantages. First, a very narrow time window can be used for the source estimation. Second, accurate localization is possible even when the source activation has a time jitter. Experiments using auditory evoked MEG data clearly demonstrate these advantages.

Algorithms↗

Comparison of covariance-based and waveform-based subtraction methods in removing the interference from button-pressing finger movements.

A covariance matrix-based subtraction method has recently been proposed to remove interference using two MEG measurements: The first has both target and interfering activities and the second only has the interference. This paper compared covariance matrix-based subtraction with conventional waveform-based subtraction, which requires that the waveforms of interference be equal at every time point between the two measurements. Our analysis showed that covariance-subtraction only requires that the time-average of the squared intensity of interference be equal between the two measurements. As a result, the method is still effective when the onset of interference differs or even their measured waveforms differ between the two measurements. The covariance- and waveform-subtraction methods were both applied to remove the interference caused by response-button-pressing finger movements in auditory-evoked MEG measurements. The results of this application demonstrated the superiority of the covariance-subtraction method over the conventional waveform-subtraction method.

Algorithms↗

MEG covariance difference analysis: a method to extract target source activities by using task and control measurements.

A method is proposed for extracting target dipolesource activities from two sets of evoked magnetoencephalographic (MEG) data, one measured using task stimuli and the other using control stimuli. The difference matrix between the two covariance matrices obtained from these two measurements is calculated, and a procedure similar to the MEG-multiple signal classification (MUSIC) algorithm is applied to this difference matrix to extract the target dipole-source configuration. This configuration corresponds to the source-configuration difference between the two measurements. Computer simulation verified the validity of the proposed method. The method was applied to actual evoked-field data obtained from simulated task-and-control experiments. In these measurements, a combination of auditory and somatosensory stimuli was used as the task stimulus and the somatosensory stimulus alone was used as the control stimulus. The proposed covariance difference analysis successfully extracted the target auditory source and eliminated the disturbance from the somatosensory sources.

Algorithms↗

Processing of vowels in supratemporal auditory cortex.

The auditory evoked neuromagnetic fields elicited by synthesized vowels of two different fundamental frequencies F0 were recorded in six subjects over the left and right temporal cortices using a 37-channel biomagnetometer. Single equivalent current dipole modeling of the fields elicited by all vowel types localized activity to a well-circumscribed area in supratemporal auditory cortex in both hemispheres. There were hemisphere asymmetries in the amplitude and latency of the M100 response. We also observed changes in M100 latency related to vowel type, but not to F0. There was no clear effect of vowel type or F0 on dipole localization for the M100, but a possible vowel type by latency interaction. These M100 data provide further evidence that vowels are processed independently of their pitch.

Adult↗

Noise covariance incorporated MEG-MUSIC algorithm: a method for multiple-dipole estimation tolerant of the influence of background brain activity.

This paper proposes a method of localizing multiple current dipoles from spatio-temporal biomagnetic data. The method is based on the multiple signal classification (MUSIC) algorithm and is tolerant of the influence of background brain activity. In this method, the noise covariance matrix is estimated using a portion of the data that contains noise, but does not contain any signal information. Then, a modified noise subspace projector is formed using the generalized eigenvectors of the noise and measured-data covariance matrices. The MUSIC localizer is calculated using this noise subspace projector and the noise covariance matrix. The results from a computer simulation have verified the effectiveness of the method. The method was then applied to source estimation for auditory-evoked fields elicited by syllable speech sounds. The results strongly suggest the method's effectiveness in removing the influence of background activity.

Algorithms↗

Task-induced asymmetry of the auditory evoked M100 neuromagnetic field elicited by speech sounds.

The auditory evoked neuromagnetic fields elicited by synthesized speech sounds (consonant-vowel syllables) were recorded in six subjects over the left and right temporal cortices using a 37-channel SQUID-based magnetometer. The latencies and amplitudes of the peaks of the M100 evoked responses were bilaterally symmetric for passively presented stimuli. In contrast, when subjects were asked to discriminate among the same syllabic stimuli, the amplitude of the M100 increased in the left and decreased in the right temporal cortices. Single equivalent current dipole modeling of the activity elicited by all stimulus-types localized to a well-circumscribed area in supratemporal auditory cortex. The results suggest that attentional modulation affects the two supratemporal cortices in a differential manner. Task-conditioned attention to speech sounds is reflected in lateralized supratemporal cortical responses possibly concordant with hemispheric language dominance.

Acoustic Stimulation↗

Prevention of adriamycin-induced cardiotoxicity by prenylamine: a pilot double blind study.

Adriamycin (ADM) is an effective antineoplastic drug. However, the amount of ADM that can be administered must be limited because of the risk of developing a severe dose-dependent myocardiopathy. Prenylamine (PNL), a calcium antagonistic drug, provided partial protection against ADM-induced cardiotoxicity in mice and in the rabbit. Thus, it was considered important to evaluate the cardioprotective potential of PNL in patients given ordinary doses of ADM. Twenty-six patients were selected and randomized in two groups, and a double-blind trial was begun. Group A (n = 13): patients received ADM, i.v. at standard oncological doses up to 550 mg/m2, plus placebo, orally. Group B (n = 13): ADM was administered as in Group A, but PNL 200 mg/day was given instead of placebo. Standard ECG and chest radiographs were performed at the beginning of treatment and every two months. Mode-M echocardiograms and 24-hour ambulatory ECGs were obtained previously to the beginning of the ADM treatment and two months after the administration of the last dose of the drug. In Group A, three patients died from oncological causes, total ADM dose was 359 +/- 100 mg/m2, and the mean age was 59.7 years. One patient in this group developed a congestive myocardiopathy while another patient developed a severe supraventricular arrhythmia. In Group B, four patients died from oncological causes, total ADM dose was 367 +/- 132 mg/m2, and the mean age was 63.8 years. No myocardiopathy was found in this group. These findings suggest that simultaneous administration of PNL may mitigate ADM cardiotoxicity, but larger trials are needed to draw definite conclusions.

Aged↗

A controlled trial of the effect of 4-hydroxypyrazolopyrimidine (allopurinol) on the toxicity of a single bolus dose of 5-fluorouracil.

We have evaluated, in a controlled study, the modification of the toxicity of a single bolus dose of 5-fluorouracil (5-FU) by allopurinol. Patients first received a single dose of 5-FU and were monitored for toxicity. If a measurable nadir in WBC or platelet count occurred, then the same dose of 5-FU was repeated with concurrent allopurinol, given for four consecutive days at an initial dose of 300 mg twice daily, starting the day before the administration of 5-FU. With this schedule, each evaluable patient received courses of 5-FU with and without allopurinol that could be compared for toxicity. Twenty patients received initial 5-FU doses of either 1,200 mg/m2 or 1,500 mg/m2 and later had the same dose repeated with allopurinol. Nineteen of these patients had a higher WBC count with allopurinol than without it. In several patients who received a further course of 5-FU with 900-mg/d allopurinol, the WBC count was yet higher than with 600-mg/d allopurinol. The myelosuppression produced by 5-FU was characterized by a decrease in granulocyte levels that was much greater than the decrease in lymphocyte levels, and the result of allopurinol treatment was to attenuate this effort on granulocytes. In a second part of the trial, the goal was to establish the maximum tolerated dose of 5-FU given with concurrent allopurinol. In this part of the study, all patients entered were given 5-FU, usually 1,200 mg/m2, with allopurinol, usually 600 mg/d for four days. Escalations of one or the other drugs were made on subsequent treatments. The data for 22 patients showed that 1,800 mg/m2 of 5-FU was well tolerated if given with 600 to 1,200 mg of allopurinol per day, and that the WBC count nadirs were no more severe than those of 1,200-mg/m2 5-FU without allopurinol. Neurotoxicity became limiting in some patients treated at these higher doses. We conclude that allopurinol given in the proper dose and schedule can diminish the granulocytopenia produced by bolus doses of 5-FU, thereby allowing a 50% increase in the maximal tolerated dose of 5-FU.

Adult↗