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Biomedical subjects

J M Clarke

Publications and source records attributed to J M Clarke.

At least 19 recordsLinked to original sources

Identification of QTL and association of a phytoene synthase gene with endosperm colour in durum wheat.

The yellow colour of durum wheat (Triticum turgidum L. var durum) semolina is due in part to the presence of carotenoid pigments found in the endosperm and is an important end-use quality trait. We hypothesized that variation in the genes coding for phytoene synthase (Psy), a critical enzyme in carotenoid biosynthesis, may partially explain the phenotypic variation in endosperm colour observed among durum cultivars. Using rice sequence information, primers were designed to PCR clone and sequence the Psy genes from Kofa (high colour) and W9262-260D3 (medium colour) durum cultivars. Sequencing confirmed the presence of four Psy genes in each parent, corresponding to a two member gene family designated as Psy1-1, Psy1-2 and Psy2-1 and Psy2-2. A genetic map was constructed using 155 F1-derived doubled haploid lines from the cross W9262-260D3/Kofa with 194 simple sequence repeat and DArT markers. Using Psy1-1 and Psy2-1 allele-specific markers and chromosome mapping, the Psy1 and Psy2 genes were located to the group 7 and 5 chromosomes, respectively. Four quantitative trait loci (QTL) underlying phenotypic variation in endosperm colour were identified on chromosomes 2A, 4B, 6B, and 7B. The Psy1-1 locus co-segregated with the 7B QTL, demonstrating an association of this gene with phenotypic variation for endosperm colour. This work is the first report of mapping Psy genes and supports the role of Psy1-1 in elevated levels of endosperm colour in durum wheat. This gene is a target for the further development of a molecular marker to enhance selection for endosperm colour in durum wheat breeding programs.

Alkyl and Aryl Transferases↗

Effect of season and temperature on mortality in amphibians due to chytridiomycosis.

OBJECTIVE: To investigate the distribution and incidence of chytridiomycosis in eastern Australian frogs and to examine the effects of temperature on this disease. DESIGN: A pathological survey and a transmission experiment were conducted. PROCEDURE: Diagnostic pathology examinations were performed on free-living and captive, ill and dead amphibians collected opportunistically from eastern Australia between October 1993 and December 2000. We conducted a transmission experiment in the laboratory to investigate the effects of temperature: eight great barred frogs (Mixophyes fasciolatus) exposed to zoospores of Batrachochytrium dendrobatidis and six unexposed frogs were housed individually in each of three rooms held at 17 degrees C, 23 degrees C and 27 degrees C. RESULTS: Chytridiomycosis was the cause of death or morbidity for 133 (55.2%) of 241 free-living amphibians and for 66 (58.4%) of 113 captive amphibians. This disease occurred in 34 amphibian species, was widespread around the eastern seaboard of Australia and affected amphibians in a variety of habitats at high and low altitudes on or between the Great Dividing Range and the coast. The incidence of chytridiomycosis was higher in winter, with 53% of wild frogs from Queensland and New South Wales dying in July and August. Other diseases were much less common and were detected mostly in spring and summer. In experimental infections, lower temperatures enhanced the pathogenicity of B. dendrobatidis in M. fasciolatus. All 16 frogs exposed to B. dendrobatidis at 17 degrees C and 23 degrees C died, whereas 4 of 8 frogs exposed at 27 degrees C survived. However, the time until death for the frogs that died at 27 degrees C was shorter than at the lower temperatures. Infections in survivors were eliminated by 98 days. CONCLUSION: Chytridiomycosis is a major cause of mortality in free-living and captive amphibians in Australia and mortality rate increases at lower temperatures.

Amphibians↗

The Woman Friendly Hospital Initiative in Bangladesh setting: standards for the care of women subject to violence.

The Woman Friendly Hospital Initiative is part of the overall strategy aimed at overcoming a situation of high maternal mortality in Bangladesh. It has evolved from the reality of 14% of maternal deaths being associated with violence. A key of the initiative is the management of violence against women. Training courses for doctors developed through a process of multi-sectoral consultation. The focus is on effecting a change in the perceptions, emotions, attitude, knowledge and skills of providers and nurturing leadership.

Adult↗

Potential problems with fluorescein diacetate assays of cell viability when testing natural products for antimicrobial activity.

There are two potential problems in the use of fluorescein diacetate (FDA) as a measure of cell viability. The first is the hydrolysis of FDA to fluorescein in the absence of live cells and the second is the quenching of fluorescence by assay solutions. We show that common media components such as tryptone, peptone and yeast extract all promote hydrolysis of FDA in the absence of live cells, as do Tris-HCl and sodium phosphate buffers. As a consequence, various microbiological media promote hydrolysis of FDA in the absence of live cells. Different media were also shown to reduce the amount of visible fluorescence of fluorescein. Diluting the medium decreases the background hydrolysis of FDA as well as increases the amount of visible fluorescence. Both problems should be considered when using FDA as an indicator of cell viability when testing natural products for antimicrobial activity.

Anti-Infective Agents↗

Development of an ex vivo model to study adherence of Mannheimia haemolytica serovar 1 to mucosal tissues of the respiratory tract of cattle.

OBJECTIVE: To develop and validate an ex vivo model for study of adherence of Mannheimia haemolytica (formerly Pasteurella haemolytica) to respiratory tract mucosa of cattle and to use this model to confirm adherence of M haemolytica serovar 1 (Mh1) to several relevant respiratory mucosal surfaces. SAMPLE POPULATION: Excised nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue from the bovine upper respiratory tract. PROCEDURE: Mh1 was radiolabeled by use of tritiated leucine. Various concentrations of labeled bacteria were incubated with bovine upper respiratory tract tissues for various times. Tissue was washed to remove nonadherent bacteria, and percentage of bacteria adhered (percentage of adherence) was estimated using radioactivity. Using an optimal inoculum concentration and incubation time, percentage of Mh1 adherence was compared on nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue, and adherence to nasopharyngeal tissue was confirmed by scanning and transmission electron microscopy. RESULTS: The optimal Mh1 inoculum concentration was 1 X 10(7) colony forming units/ml and incubation time was 3 hours. Percentage of adherence of Mh1 to nasopharyngeal tissue was greater than adherence to other tissue types. CONCLUSIONS AND CLINICAL RELEVANCE: The ex vivo model maintained the functional and structural integrity of bovine upper respiratory tract mucosa, as confirmed by light and electron microscopy. Electron microscopy revealed participation of epithelial cell cilia and surface mucus in adherence of Mh1 to nasopharyngeal tissue. Adherence of Mh1 was confirmed in repeated assays, indicating that this organism adheres to upper respiratory tract mucosa of cattle.

Animals↗

Hemispheric interactions during a face--word Stroop-analog task.

A Stroop-analog task with faces and words was developed to investigate intrahemispheric and interhemispheric Stroop effects (SEs). Lateralized faces and words were used in an attempt to invoke right- and left-hemispheric specialization, respectively. A prototypical male face, female face, and baby face and the corresponding words man, woman, and baby were presented as congruent or incongruent face-word pairs either to the same visual field (i.e., unilateral presentations) or to separate visual fields (i.e., bilateral presentations). Bidirectional SEs were found. Word distractors interfered with the identification of face targets, and, somewhat surprisingly, an even greater SE was obtained when words were the target and faces were ignored. Laterality effects were most pronounced for bilateral trials, whereby the SE was larger for right-hemisphere than for left-hemisphere target presentations, irrespective of type of target. This finding suggests that the left hemisphere is generally better shielded than the right from interhemispheric interference effects.

Adolescent↗

Presentation of thyroid carcinoma as a thrombosed external jugular vein, with intraluminal tumour thrombus in the great veins.

Carcinoma of the thyroid most commonly presents as an asymptomatic thyroid nodule. Some types of thyroid carcinoma show vascular invasion, but this is usually microscopic.(1,2)It is rare for such invasion to involve the great veins and be macroscopic. There are 18 such reports in the literature to date.(3-12)We report a case of a carcinoma of the thyroid that presented due to the presence of tumour thrombus within the external jugular vein, where thrombus was also seen within the great veins.

Aged↗

Development of an in vitro fluorometric assay to study adherence of Pasteurella haemolytica to bovine cells.

OBJECTIVE: To develop an in vitro fluorometric assay to assess Pasteurella haemolytica adherence to bovine respiratory and epithelial cells and compare adherence of single strains of P. haemolytica serovars A1 and A2 (PhA1 and PhA2, respectively). SAMPLE POPULATION: Monolayers of bovine turbinate and Madin Darby bovine kidney (MDBK) cells. PROCEDURE: To determine optimal inoculum concentration and incubation time, various concentrations of P. haemolytica were labeled with fluorescein isothiocyanate and incubated with monolayers of bovine cells for various times. Bovine cells were washed to remove nonadherent bacteria, and percentage of bacteria adhered (percentage of adherence) was estimated fluorometrically. Percentage of adherence of PhA1 was compared with that of PhA2. RESULTS: The optimal inoculum concentration that resulted in measurable fluorescence of adherent bacteria was 1 x 10(8) colony-forming units/ml, and the optimal incubation time was 45 minutes. Percentage of adherence of PhA1 to MDBK and turbinate cells was significantly greater than that determined for PhA2. CONCLUSIONS: The in vitro fluorometric assay is a time-efficient, inexpensive, and labor-saving method for evaluation of P. haemolytica adherence to bovine cells. The concentration of bacteria used to inoculate bovine cells in this assay is similar to that typically used in other types of in vitro adherence assays. The predominance of PhA1 over PhA2 during the early stages of bovine respiratory disease may be attributable to the ability of PhA1 to adhere more avidly to nasopharyngeal tissue.

Animals↗

Open access carotid duplex scanning: throughput and resultant surgical workload.

It is now generally accepted that high-quality duplex scanning obviates the need for pre-operative angiography in the assessment of most cases of carotid disease. An information leaflet was circulated to all general practitioners and hospital doctors in early 1996. Indications, results of treatment and details of the open access service were described. This paper outlines the workload that followed, for both imaging and surgical departments.

Adolescent↗

Effect of left renal vein division during aortic surgery on renal function.

A total of 398 consecutive patients underwent surgery for an aneurysm or occlusive disease of the aorta at Norfolk and Norwich Hospital between December 1994 and October 1998. It was necessary to divide the left renal vein in 58 (14.6%) cases. We examined the effect of this division on the mortality rate and renal function. Renal function was assessed by measuring serum creatinine pre-operatively, peri-operatively and long-term postoperatively. There was no significant difference in the mortality rate between patients who had the left renal vein divided (LRVD) and in whom the left renal vein remained intact (LRVI)--31% versus 32%, P = 0.83. There was no significant difference in the pre-operative serum creatinine level between both groups (107 +/- 21 mumol/l in LRVD versus 103 +/- 29 mumol/l in LRVI, P = 0.14). There was an insignificant rise in the mean serum creatinine 7 days postoperatively (111 +/- 21 mumol/l in LRVD versus 107 +/- 31 mumol/l in LRVI, P = 0.05). The mean serum creatinine returned back to the pre-operative level at 30 days postoperatively (106 +/- 16 mumol/l in LRVD and 105 +/- 29 mumol/l, P = 0.20). After 1 month, there was no significant difference in the number of patients who had a sustained elevation of serum creatinine level (7.5% in LRVD versus 2.7% in LRVI, P = 0.11). We feel that division of the left renal vein is a safe and helpful procedure during juxtarenal aortic surgery.

Aged↗

Intracranial ERPs in humans during a lateralized visual oddball task: I. Occipital and peri-Rolandic recordings.

OBJECTIVES: This study investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. This first of two articles focuses on recordings from visual and motor cortices. METHODS: Intracranial event-related potentials (ERPs) were recorded from occipital and/or peri-Rolandic sites in 8 patients with intractable epilepsy while they performed a lateralized visual oddball task. RESULTS: As expected, lateralized visual (N150, P200, N250) and motor (N/P400, N/P550) ERP effects were found for occipital and peri-Rolandic recordings, respectively. These reflect an advantage for direct over indirect sensory/motor pathways. More surprisingly, some occipital recordings were paradoxically larger in amplitude for indirect than for direct visual stimulus lateralization, and other occipital sites were sensitive to motor response factors. Likewise, one peri-Rolandic site exhibited a slow wave component that was sensitive to visual sensory factors. There was also pervasive bilaterally-symmetric ERP activity as reflected by P3-like and slow wave-like components. CONCLUSIONS: These findings argue against a hemispheric independence model of information processing. With the exception of initial stimulus input and final response output pathway effects, the processing in this simple task engages both hemispheres in a roughly symmetrical fashion, even though a single hemisphere may be adequate for task performance.

Brain Mapping↗

Intracranial ERPs in humans during a lateralized visual oddball task: II. Temporal, parietal, and frontal recordings.

OBJECTIVE: We investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. While our companion article ( Clarke et al. 1999) focused on visual and motor event-related potentials (ERPs) recorded from occipital and peri-Rolandic sites, the present article is concerned with ERP correlates of intermediate stages of information processing from remaining cerebral regions. METHODS: Intracranial ERPs were recorded from temporal, parietal and frontal lobe sites in 13 patients with intractable epilepsy while they performed a lateralized visual oddball task. RESULTS: Visually-responsive N2 and/or P3 effects were recorded from medial temporal and supramarginal sites that appear to reflect activity along ventral and dorsal visual streams, respectively. Likewise, certain prefrontal sites, that are probably involved in working memory, were also visually-responsive. The majority of sites exhibiting N2, P3 and/or slow wave components, however, were unaffected by lateralized visual field or response hand effects. Target-evoked P3-like components were most frequently recorded from medial temporal and prefrontal sites. Post-response slow wave components were pervasive, and polarity reversals were present in the insula/operculum region, apparently reflecting somatosensory activity from SII. CONCLUSIONS: The general absence of lateralized ERP effects despite lateralized stimulus input and response output suggests the importance of interhemispheric integration over hemispheric independence in the processing of this type of task.

Adult↗

Pharmacokinetics of cefepime and comparison with those of ceftiofur in horses.

OBJECTIVE: To determine pharmacokinetics of i.v., i.m., and oral administration of cefepime in horses and to compare pharmacokinetics of i.m. administration of cefepime with those of ceftiofur sodium. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Horses received 3 doses of cefepime (11 mg/kg of body weight, PO; 2.2 mg/kg, i.v.; and 2.2 mg/kg, i.m.) and 1 dose of ceftiofur (2.2 mg/kg, i.m.). Two horses also received L-arginine, p.o. and i.v., at doses identical to those contained in the cefepime dihydrochloride-L-arginine preparations previously administered. Blood samples were collected for 24 hours after administration of cefepime or ceftiofur and were assayed for cefepime and ceftiofur concentrations. RESULTS: Pharmacokinetic analysis of disposition data indicated that i.v. administration data were best described by a 2-compartment open model, whereas i.m. administration data were best described by a 1-compartment absorption model. Median elimination half-life and volume of distribution after i.v. administration of cefepime were 125.7 minutes and 225 ml/kg, respectively. After i.m. administration of cefepime, mean maximal plasma concentration of (8.13 microg/ml) was reached at a mean time of 80 minutes. Absorption of cefepime after i.m. administration was complete, with a median bioavailability of 1.11. Intramuscular administration of ceftiofur resulted in similar mean maximal plasma concentration (7.98 microg/ml) and mean time to this concentration (82 minutes). Cefepime was not detected in samples collected after oral administration. Adverse effects consisting principally of gastrointestinal disturbances were observed after oral and i.m. administration of cefepime and after 1 i.m. administration of ceftiofur. CONCLUSIONS AND CLINICAL RELEVANCE: Cefepime, administered i.v. or i.m. at a dosage of 2.2 mg/kg, every 8 hours is likely to provide effective antibacterial therapy for cefepime-sensitive organisms in horses. Further studies are needed to evaluate adverse effects on the gastrointestinal tract.

Administration, Oral↗

Penetration of parenterally administered ceftiofur into sterile vs. Pasteurella haemolytica-infected tissue chambers in cattle.

The effect of bacterial infection on antibiotic activity and penetration of parenterally administered ceftiofur into implanted tissue chambers was studied in cattle. Tissue chambers were implanted subcutaneously in the paralumbar fossae of eight calves (256-290 kg body weight). Approximately 80 days after implantation, the two chambers on one side of each animal were inoculated with Pasteurella haemolytica (10(6) CFU/chamber). Eighteen hours after inoculation, ceftiofur sodium was administered intravenously (5 mg/kg) to each of the calves. Non-infected chamber fluid, infected chamber fluid and heparinized blood samples were collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur metabolites and ceftiofur-equivalent microbiological activity were measured by high-pressure liquid chromatography and microbiological assay respectively. Concentrations of ceftiofur and desfuroylceftiofur metabolites and anti-microbial activity in P. haemolytica-infected tissue chambers were significantly higher than those in non-infected tissue chambers at all sampling times, indicating that ceftiofur, regardless of the method used for analysis, localizes at higher concentrations at tissue sites infected with P. haemolytica. Antibiotic activity-concentration ratios were lower in plasma and infected chamber fluid compared with non-infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamber fluid compared with the non-infected chamber fluid, suggests that active drug is reversibly bound to proteins. Protein-bound desfuroylceftiofur may represent a reservoir for release of active drug at the site of infection in the animal.

Animals↗

Cell surface polypeptide CshA mediates binding of Streptococcus gordonii to other oral bacteria and to immobilized fibronectin.

Isogenic mutants of Streptococcus gordonii DL1 (Challis) in which the genes encoding high-molecular-mass cell surface polypeptides CshA and/or CshB were inactivated were deficient in binding to four strains of Actinomyces naeslundii and two strains of Streptococcus oralis. Lactose-sensitive interactions of S. gordonii with A. naeslundii ATCC 12104 and PK606 were associated with expression of cshA but not of cshB. Lactose-insensitive interactions of S. gordonii with A. naeslundii T14V and WVU627, and with S. oralis C104 and 34, were dependent on expression of cshA and cshB. S. gordonii DL1 cells bound to immobilized human fibronectin (Fn), but not to soluble Fn, in a dose-dependent manner, and binding was noninhibitable by heparin. S. gordonii cshA and cshB mutants were also deficient in binding to immobilized human Fn. Antibodies to an NH2-terminal nonrepetitive region (amino acid residues 42 to 886) of recombinant CshA inhibited binding of S. gordonii DL1 cells to A. naeslundii T14V and PK606 and to immobilized Fn. Conversely, antibodies to an amino acid repeat block segment of the COOH-terminal domain (amino acid residues 2026 to 2508) were not inhibitory to adherence. Assays using CshA-specific antibodies revealed that surface expression of CshA was reduced in cshB mutants. The results suggest that CshA acts as a multifunctional adhesin in S. gordonii and that major adhesion-mediating sequences are specified within the nonrepetitive NH2-terminal region of the polypeptide.

Animals↗

Intracerebral potentials to rare target and distractor auditory and visual stimuli. I. Superior temporal plane and parietal lobe.

Event-related potentials were recorded from 537 sites in the superior temporal plane and parietal lobe of 41 patients. Depth electrodes were implanted to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli ("standard oddball paradigm"). In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Variants included an analogous visual discrimination task, or auditory tasks where the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. Three general response patterns could be distinguished on the basis of their wave forms, latencies and task correlates. First, potentials apparently related to rarity per se, as opposed to differences in sensory characteristics, or in habituation, were observed in the posterior superior temporal plane, beginning with a large positivity superimposed on early components. This positivity peaked at 150 msec after stimulus onset and inverted in sites superior to the Sylvian fissure. Subsequent components could be large, focal and/or inverting in polarity, and usually included a positivity at 230 msec and a negativity at 330 msec. All components in this area were specific to the auditory modality. Second, in the posterior cingulate and supramarginal gyri, a sharp triphasic negative-positive-negative wave form with peaks at about 210-300-400 msec was observed. This wave form was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. Third, a broad, often monophasic, wave form peaking at about 380 msec was observed in the superior parietal lobe, similar to that which has been recorded in the hippocampus. This wave form could be of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli and was also evoked by repeating words and faces. The early endogenous activity in auditory cortex may embody activity that is antecedent to the other patterns in multimodal association cortex. The "triphasic" pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The later broad pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

Acoustic Stimulation↗

Intracerebral potentials to rare target and distractor auditory and visual stimuli. II. Medial, lateral and posterior temporal lobe.

Event-related potentials were recorded from 1221 sites in the medial, lateral and posterior aspects of the temporal lobe in 39 patients. Depth electrodes were implanted for about 4 days in order to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli. In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Some subjects also received an analogous visual discrimination task, or auditory tasks in which the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. A complex field was recorded, indicating multiple components with overlapping time-courses, task correlates and generators. Two general patterns could be distinguished on the basis of their waveforms, latencies and task correlates. In the temporal pole and some middle temporal, posterior parahippocampal and fusiform gyrus sites, a sharp triphasic negative-positive-negative waveform with peaks at about 220-320-420 msec was usually observed. This wave was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. A second broad, often monophasic, waveform peaking at about 380 msec was generated in the hippocampus, a limited region of the superior temporal sulcus, and (by inference) in the anterobasal temporal lobe (possible rhinal cortex). This waveform was of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli, was greatly diminished when the stimuli were ignored, and was also evoked by repeating words and faces. Preceding this waveform was a non-modality-specific negativity, possibly generated in rhinal cortex, and a visual-specific negativity in inferotemporal cortex. The early triphasic pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The late monophasic pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

Acoustic Stimulation↗

Intracerebral potentials to rare target and distractor auditory and visual stimuli. III. Frontal cortex.

Evoked potentials (EPs) were recorded from 991 frontal and peri-rolandic sites (106 electrodes) in 36 patients during an auditory discrimination task with target and non-target (distractor) rare stimuli. Variants of this task explored the effects of attention, dishabituation and stimulus characteristics (including modality). Rare stimuli evoked a widespread triphasic waveform with negative, positive and negative peaks at about 210, 280 and 390 msec, respectively. This waveform was identified with the scalp EP complex termed the N2a/P3a/slow wave and associated with orienting. It was evoked by rare target and distractor auditory and visual stimuli, as well as by rare stimulus repetitions or omissions. Across most frontal trajectories, N2a/P3a/SW amplitudes changed only slowly with distance. However, large (120 microV) P3as with steep voltage gradients were observed laterally, especially near the inferior frontal sulcus, and clear inversions of the P3a were noted in the orbito-frontal and the anterior cingulate cortices. The frontal P3a was earlier to distractor than to target stimuli, but only in some sites and with a latency difference much smaller than that observed at the scalp. Frontal P3a latencies were significantly shorter than those recorded simultaneously at the scalp and often were also shorter than P3a latency in the parietal or temporal lobes. In summary, this study demonstrates an early P3a-like activity that polarity inverts over short distances in the medial frontal lobe, and that it has a significantly shorter latency than similar potentials recorded in the temporal and parietal cortices.

Acoustic Stimulation↗