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Biomedical subjects

R Batra

Publications and source records attributed to R Batra.

At least 55 records · Page 3Linked to original sources

A comparison of the interaural time sensitivity of neurons in the inferior colliculus and thalamus of the unanesthetized rabbit.

The localization of low-frequency sounds (less than 3 kHz) along the azimuth involves comparing the ongoing difference in the time of arrival of a sound at the two ears. Information about interaural time differences (ITDs) is derived from an initial comparison performed in the superior olivary complex. However, little is known about which aspects of this information are transformed as it ascends the brainstem. To address this issue, we compared the ITD sensitivity of neurons in the inferior colliculus (IC) and auditory thalamus, successive stations in the auditory pathway. We found ITD sensitivity in the IC and thalamus to be similar in several respects. At both levels, the large majority of neurons responded maximally to ITDs within the range that a rabbit would normally encounter (+/- 300 microseconds) and preferred ipsilateral delays, delays that would be created by sounds in the contralateral sound field. The range of frequencies over which ITD sensitivity was expressed was also similar in the midbrain and thalamus. Several differences were also apparent. In comparison to IC neurons, neurons in the thalamus responded over more restricted ranges of ITD, responded at lower rates, and, in response to monaural stimulation, showed an increased influence of inhibition. Finally, a greater proportion of thalamic units had characteristic delays corresponding to intermediate discharge rates. The preservation of a bias for ipsilateral delays from IC to thalamus suggests that a representation of contralateral azimuths is present at both levels. Similarities between the two levels suggest that information about ITDs is faithfully transmitted from midbrain to thalamus. Differences in ITD sensitivity, such as the sharper tuning for ITDs, suggest that the thalamus is not a simple relay. Enhanced sensitivity to ITDs should translate to better-defined azimuthal receptive fields, and therefore may be a step toward achieving an optimal representation of azimuth within the auditory pathway.

Acoustic Stimulation↗

Efferent control of temporal response properties of the Limulus lateral eye.

The sensitivity of the Limulus lateral eye exhibits a pronounced circadian rhythm. At night a circadian oscillator in the brain activates efferent fibers in the optic nerve, inducing multiple changes in the physiological and anatomical characteristics of retinal cells. These changes increase the sensitivity of the retina by about five orders of magnitude. We investigated whether this increase in retinal sensitivity is accompanied by changes in the ability of the retina to process temporal information. We measured the frequency transfer characteristic (FTC) of single receptors (ommatidia) by recording the response of their optic nerve fibers to sinusoidally modulated light. We first measured the FTC in the less sensitive daytime state and then after converting the retina to the more sensitive nighttime state by electrical stimulation of the efferent fibers. The activation of these fibers shifted the peak of the FTC to lower frequencies and reduced the slope of the low-frequency limb. These changes reduce the eye's ability to detect rapid changes in light intensity but enhance its ability to detect dim flashes of light. Apparently Limulus sacrifices temporal resolution for increased visual sensitivity at night.

Animals↗

Goldenhar's syndrome: an analysis of anaesthetic management. A retrospective study of seventeen cases.

Seventeen patients with Goldenhar's syndrome who had surgery 28 times are presented. Various authors have reported problems in the anaesthetic management of these patients, but we encountered significant difficulties in only one. Three anaesthetic techniques were used. A thorough pre-operative assessment with back-up facilities for difficult intubation are important. Additional cardiorespiratory and craniovertebral anomalies may necessitate modifications in the basic techniques.

Anesthesia↗

Temporal coding of envelopes and their interaural delays in the inferior colliculus of the unanesthetized rabbit.

1. The difference in the time of arrival of a sound at the two ears can be used to locate its source along the azimuth. Traditionally, it has been thought that only the on-going interaural temporal disparities (ITDs) produced by sounds of lower frequency (approximately less than 2 kHz) could be used for this purpose. However, ongoing ITDs of low frequency are also produced by envelopes of amplitude-modulated (AM) tones. These ITDs can be detected and used to lateralize complex high-frequency sounds (1, 8, 12, 15, 22, 24, 26). Auditory neurons synchronize to the modulation envelope, but do so at progressively lower modulation frequencies at higher levels of the auditory pathway. Some neurons of the cochlear nucleus synchronize best to frequencies as high as 700 Hz, but those of the inferior colliculus (IC) exhibit their best synchrony below 200 Hz. Even though synchrony to higher modulation frequencies is reduced at higher levels of the auditory pathway, is information about ITDs retained? 2. We answered this question by extracellularly recording the responses of neurons in the IC of the unanesthetized rabbit. We used an unanesthetized preparation because anesthesia alters the responses of neurons in the IC to both monaurally presented tones and ITDs. The unanesthetized rabbit is ideal for auditory research. Recordings can be maintained for long periods, and the acoustic stimulus to each ear can be independently controlled. 3. We studied the responses of 89 units to sinusoidally AM tones presented to the contralateral ear. For each unit, we recorded the response at several modulation frequencies. The degree of phase locking to the envelope at each frequency was measured using the synchronization coefficient. Two measures were used to assess the range of modulation frequencies over which phase locking occurred. The "best AM frequency" was the frequency at which we observed the greatest phase locking. The "highest AM frequency" was the highest frequency at which significant phase locking (0.001 level) was observed. We could not assess synchrony to ipsilateral AM tones directly, because most units did not respond to ipsilateral stimulation. 4. We studied the sensitivity of 63 units to ITDs produced by the envelopes of AM tones. Sensitivity to ITDs was tested by presenting AM tones to the two ears that had the same carrier frequency, but modulation frequencies that differed by 1 Hz. Units that were sensitive to ITDs responded to this stimulus by varying their response rate cyclically at the difference frequency, i.e., 1 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Monaural and binaural response properties of neurons in the inferior colliculus of the rabbit: effects of sodium pentobarbital.

1. We studied the effects of sodium pentobarbital on 22 neurons in the inferior colliculus (IC) of the rabbit. We recorded changes in the sensitivity of these neurons to monaural stimulation and to ongoing interaural time differences (ITDs). Monaural stimuli were tone bursts at or near the neuron's best frequency. The ITD was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. 2. We assessed a neuron's ITD sensitivity by calculating three measures from the responses to binaural beats: composite delay, characteristic delay (CD), and characteristic phase (CP). To obtain the composite delay, we first derived period histograms by averaging, showing the response at each stimulating frequency over one period of the beat frequency. Second, the period histograms were replotted as a function of their equivalent interaural delay and then averaged together to yield the composite delay curve. Last, we calculated the composite peak or trough delay by fitting a parabola to the peak or trough of this composite curve. The composite delay curve represents the average response to all frequencies within the neuron's responsive range, and the peak reflects the interaural delay that produces the maximum response. The CD and CP were estimated from a weighted fit of a regression line to the plot of the mean interaural phase of the response versus the stimulating frequency. The slope and phase intercept of this regression line yielded estimates of CD and CP, respectively. These two quantities are thought to reflect the mechanism of ITD sensitivity, which involves the convergence of phase-locked inputs on a binaural cell. The CD estimates the difference in the time required for the two inputs to travel from either ear to this cell, whereas the CP reflects the interaural phase difference of the inputs at this cell. 3. Injections of sodium pentobarbital at subsurgical dosages (less than 25 mg/kg) almost invariably altered the neuron's response rate, response latency, response pattern, and spontaneous activity. Most of these changes were predictable and consistent with an enhancement of inhibitory influences. For example, if the earliest response was inhibitory, later excitation was usually reduced and latency increased. If the earliest response was excitatory, the level of this excitation was unaltered or slightly enhanced, and changes in latency were minimal. 4. The neuron's response pattern also changed in a predictable way. For example, a response with an inhibitory pause could either change to a response with a longer pause or to a response with an onset only.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Interaural phase-sensitive units in the inferior colliculus of the unanesthetized rabbit: effects of changing frequency.

We studied the interaural phase sensitivity of 85 units in the inferior colliculus (IC) of the unanesthetized rabbit. We assessed this sensitivity at several frequencies within each unit's responsive range. The interaural phase disparity was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. We analyzed each unit's response to different frequencies by calculating four measures: characteristic delay (CD), characteristic phase (CP), composite peak delay, and mean peak delay. We estimated the CD and CP from the slope and phase intercept, respectively, of the regression line fitted to a plot of the mean interaural phase against stimulating frequency. The composite peak delay was estimated from the peak of a composite delay curve. This was generated by replotting the response to changes in interaural phase, as a function of the equivalent interaural delay and averaging the resultant interaural delay curves. The composite delay curve reflects the unit's average response to interaural delays across frequencies. Last, we calculated a mean peak delay, derived by converting the mean interaural phase of the response at each frequency to an equivalent delay and then averaging these delays. Interaural phase sensitivity was observed to frequencies as high as 2,150 Hz. However, the majority of units showed such sensitivity below 1,500 Hz. For most units, the interaural delay curves measured at several frequencies coincided near the peak discharge. This result is consistent with a neural model, where excitatory inputs from each ear converge upon a binaural cell, evoking maximum discharge only when the two inputs arrive simultaneously. As a first approximation, our data fit this model, indicating that IC neurons can act like coincidence detectors or cross-correlators. The distributions of CD, composite peak delay, and mean peak delay showed that most units preferred ipsilateral stimulus delays, which in the natural situation corresponds to sounds emanating from the contralateral field. Moreover, most units preferred delays that were within the estimated physiological range of the rabbit. These results support the viewpoint that neurons in the IC participate in sound localization. The distributions of CP and CD differ substantially from those found in the IC of the anesthetized cat. These differences may reflect species differences, the effects of anesthesia, or a difference in the population of units sampled. For each unit, we assessed the linearity of the plot of mean interaural phase against frequency of stimulation using a chi 2 method. For most units the plots were significantly nonlinear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The frequency-following response to continuous tones in humans.

Previous studies of the frequency-following response (FFR) in man suggest that it has multiple sources. Identification of these sources has been complicated by the use of tone bursts to evoke FFRs and the lack of precise methods to calculate their amplitude and latency. Tone bursts produce transient responses which confound measurements of the FFR. The use of continuous tones avoids this problem and the Fast Fourier Transform can be used to assess accurately and efficiently the presence, amplitude and phase angle of the FFR. In this study we systematically examined the frequency and intensity range over which FFRs to continuous tones could be evoked using FFRs to tone bursts for comparison. We then analyzed FFRs to continuous tones to determine the sources of this potential. FFRs to both stimuli have similar thresholds (65-90 dB SPL) and can be evoked by the same range of frequencies. Neurogenic FFRs in man occur only below 1000 Hz. The source for this potential has a latency of 8.2 +/- 0.1 ms (mean +/- SD) and is consistent with a midbrain source. At higher frequencies FFRs have a latency of less than 1 ms and are most likely cochlear microphonic. The small variation in the latency of the neurogenic FFR suggests this as a possible tool for assessing neurological disorders.

Adolescent↗

Scalp potentials of normal and hearing-impaired subjects in response to sinusoidally amplitude-modulated tones.

None of the current electrical audiometric procedures, alone or in combination, has yet achieved the precision of conventional audiometric testing that is used to assess hearing in verbally capable children and adults. The reason for this, in part, lies in the use of stimuli which have a wide frequency content. We have measured scalp potentials which follow the envelopes of sinusoidally amplitude-modulated tones: a frequency-specific stimulus. In normal subjects such amplitude-modulation following responses (AMFRs) appear to be generated by two sources. One source has a latency of about 30 ms, generates large responses and is only observed at modulations below 55 Hz, while the other source has a latency of 7-9 ms, generates smaller responses, and is only observed at modulations from 100-350 Hz. The latencies of these two sources are consistent with origins in the cortex and midbrain, respectively. We examined AMFRs to low frequency (50 Hz) modulations as a possible audiometric tool. In normal subjects, the amplitude of the AMFR increased as a function of intensity, decreased as a function of carrier frequency, and could be evoked across the whole audiometric range (250-8000 Hz). In hearing-impaired subjects, the AMFR amplitudes as a function of carrier frequency accurately reflected the pattern of hearing loss on a frequency-by-frequency basis. In most subjects, the threshold for evoking the AMFR was within 0-25 dB of hearing threshold. It therefore appears that the AMFR may be a potentially useful tool to assess hearing in those unable to undergo conventional audiometric testing.

Acoustic Stimulation↗

Central connections of Limulus ventral photoreceptors revealed by intracellular staining.

We stained the central terminations of Limulus ventral photoreceptors by intracellular injection of cobalt chloride into the cell bodies. Axons of these photoreceptors enter the protocerebrum via the ventral optic nerve and pass to the medulla. As they reach the surface of the medullar neuropil they branch profusely in fine processes with intermittent varicosities. Each axonal arborization covers about 0.01-0.02 mm2 of this surface immediately adjacent to the medullar ganglion cell layer. Each point on the surface of the medullar neuropil receives, on the average, input from about 6 ventral photoreceptor axons.

Axons↗

Lens calcium and selenite-induced cataract.

Subcutaneous injection of sodium selenite into young rats produces a nuclear cataract within 72 hours. A three-fold elevation in lens calcium and a two-fold increase in lens inorganic phosphate have been found to precede opacification. Scanning electron micrographs suggested weakened cell-to-cell adhesion in the cataractous nuclear zone.

Animals↗

Epoxidation of acrylonitrile by rat and human cytochromes P450.

The cytochromes P450 (P450) involved in the epoxidation of the rat carcinogen acrylonitrile (ACN) to the mutagen 2-cyanoethylene oxide (CEO) have been investigated in hepatic microsomes from F-344 rats and humans. Induction of P450 2E1 by acetone treatment increased the Vmax for rat microsomal CEO formation 5-fold, while ACN treatment had little effect. Treatment with beta-naphthoflavone, dexamethasone, and phenobarbital had little effect upon Vmax but increased the KM 3- to 5-fold. The P450 ligand 1-phenylimidazole and substrate ethanol were potent inhibitors of ACN epoxidation after all treatments. 2-(Diethylamino)ethyl 2,2-diphenylvalerate (SKF 525A; 0.1 mM) was not an effective inhibitor with microsomes from untreated or acetone-treated rats, but inhibited approximately 50% following dexamethasone or phenobarbital treatment. Antibodies to P450 2E1 inhibited > 85% of the ACN epoxidation activity in microsomes from untreated or beta-naphthoflavone- or acetone-treated rats, but only produced 40% and 60% inhibition following dexamethasone or phenobarbital treatments, respectively. These results indicate that P450 2E1 is the major catalyst of ACN epoxidation in untreated rats and that other forms of P450 can also epoxidize ACN. Diethyldithiocarbamate (0.1 mM) was a potent irreversible inhibitor of ACN epoxidation after all of the induction treatments, indicating that it is not specific for P450 2E1. Chlorzoxazone (2 mM) produced 75-90% inhibition after all of the induction treatments, indicating that it interacts with several rodent P450 isoforms in addition to 2E1. Human hepatic microsomes (n = 6) epoxidized ACN with Vmax'S ranging from 129 to 315 pmol of CEO formed/(min.mg of protein) and KM's from 12 to 18 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylonitrile↗

Functional characterisation of Dictyostelium myosin II with conserved tryptophanyl residue 501 mutated to tyrosine.

We created a Dictyostelium discoideum myosin II mutant in which the highly conserved residue Trp-501 was replaced by a tyrosine residue. The mutant myosin alone, when expressed in a Dictyostelium strain lacking the functional myosin II heavy chain gene, supported cytokinesis and multicellular development, processes which require a functional myosin in Dictyostelium. Additionally, we expressed the W501 Y mutant in the soluble myosin head fragment M761-2R (W501Y-2R) to characterise the kinetic properties of the mutant myosin motor domain. The affinity of the mutant myosin for actin was approximately 6-fold decreased, but other kinetic properties of the protein were changed less than 2-fold by the W501Y mutation. Based on spectroscopic studies and structural considerations, Trp-501, corresponding to Trp-510 in chicken fast skeletal muscle myosin, has been proposed to be the primary ATP-sensitive tryptophanyl residue. Our results confirm these conclusions. While the wild-type construct displayed a 10% fluorescence increase, addition of ATP to W501Y-2R was not followed by an increase in tryptophan fluorescence emission.

Amino Acid Substitution↗

Radiofrequency catheter ablation of common atrial flutter--acute and follow-up results.

Atrial flutter with a structurally well-defined macro-reentrant circuit in the right atrium has recently become amenable to radiofrequency ablation with the recognition of isthmus as a narrow zone of slow conduction. This study describes 20 consecutive and symptomatic patients with atrial flutter (15 males, 5 females; mean age 38.5 +/- 10.2 years) who underwent radiofrequency ablation in our institute in the last 18 months. Fourteen patients had structurally normal hearts, while the remaining six patients had specific disorders (prior surgery for closure of atrial septal defect-2, idiopathic restrictive cardiomyopathy-1, primary sinus node dysfunction-2, tachycardiomyopathy-1). The endpoints of a complete isthmus block and conversion to sinus rhythm were achieved in 19 of the 20 patients. Total number of pulses needed to attain the endpoints was a mean of 4.2 (range 1-5), each pulse being delivered for 90 seconds. At a mean follow up of 9.4 +/- 3.2 months (range 6-12 months), recurrence of atrial flutter was seen in one patient, atrial fibrillation in two and sinus node reentrant tachycardia in one. These results are comparable to those reported in the literature. Achievement of a complete isthmus block appears to be an important endpoint in obtaining optimal results. The issues of alternative sites of ablation, long-term results and advantages of an 8 mm tip catheter need to be examined further. In conclusion, radiofrequency ablation appears to be the preferred mode of treatment for patients with atrial flutter with excellent short-term and mid-term results.

Adolescent↗

Recording of double atrial potentials as a marker for isthmus block during ablation of atrial flutter.

Radiofrequency ablation is an established method for treatment of type I atrial flutter. The assessment of creation of complete bidirectional isthmus block following linear ablation of the isthmus is an integral part of ablation procedure. Conventionally, bidirectional isthmus block is tested by pacing on either side of ablation line and looking for reversal of activation sequence in the right atrium. We looked at the feasibility of recording double potentials, separated by an isoelectric interval along the ablation line as an alternative method to demonstrate bidirectional isthmus block. An attempt was made to record the double potentials following linear ablation of the cavotricuspid isthmus. Following ablation, bidirectional isthmus block was also tested by pacing from the coronary sinus os and the low-lateral right atrium. We could demonstrate double potentials in 9 of the 11 patients in whom we attempted to record them following linear ablation of flutter. The presence of bidirectional block by pacing from coronary sinus os and low lateral right atrium could be demonstrated in 10 (91%) patients. Thus, double atrial potentials, separated by an isoelectric interval can be demonstrated following ablation of atrial flutter. Double potentials, if demonstrable on coronary sinus os and low lateral right atrium pacing, could serve as an alternative marker of isthmus block.

Action Potentials↗