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Biomedical subjects

M W Church

Publications and source records attributed to M W Church.

At least 37 records · Page 2Linked to original sources
PubMed1988

Dose-dependent effects of atropine sulfate on the brainstem and cortical auditory evoked potentials in the rat.

Because brainstem auditory evoked potentials (BAEPs) are frequently recorded in anesthetized animals and humans, it is important to become familiar with the effects on the BAEP of drugs used during anesthesia, including pre-anesthetics. The dose-dependent and stimulus intensity-dependent effects on the BAEP of a pre-anesthetic, atropine sulfate, were studied in the unanesthetized rat. The animal subjects were 11 adult female Long-Evans rats. BAEPs in response to 0.1 ms clicks (12.5/s) were recorded from skull screw electrodes during a baseline period, as well as after saline and atropine treatments. Atropine sulfate was given i.p. in doses ranging from 0.250 to 40 mg/kg. Contrary to a prior report, doses in the standard pre-anesthetic range (i.e. 0.250-1.000 mg/kg) did not convincingly influence the BAEP. Only the highest dose (40 mg/kg) produced a significant and noteworthy change in the BAEP. This effect was characterized by significant amplitude increases in the P1, P2 and P3 components, but not in the P4, P5 and P6 components. This selective effect occurred at the highest stimulus intensity of 110 dB peak equivalent sound pressure level, but not at lower intensities. There were no convincing atropine-induced changes in BAEP latencies. Atropine-induced changes in the cortical auditory evoked potential (CAEP) were characterized by amplitude decrements. Thus, atropine seemed to have an excitatory effect on the BAEP and an inhibitory or depressive effect on the CAEP.

Animals↗
PubMed1988

Hearing disorders in children with fetal alcohol syndrome: findings from case reports.

Fourteen children with the fetal alcohol syndrome were evaluated by standard audiologic procedures. Thirteen of the 14 children had childhood histories of hearing disorders. All 13 of these children (93%) had clinically significant histories of bilateral recurrent serous otitis media (ie, they were otitis prone), and at least four children (29%) had bilateral sensorineural hearing losses in addition to being otitis prone. Many of the children with recurrent serous otitis media required repeated myringotomies with placement of ventilation tubes, and those with sensorineural hearing losses required sound amplification during childhood. Recurrent respiratory infections (secondary to immune deficiencies) and eustachian tube dysfunction (secondary to embryonic malformations of the first and second branchial arches) are discussed as possible etiologic factors in the presence of the recurrent serous otitis media. An alcohol-induced neuroectoderm syndrome and alcohol ototoxicity are discussed as possible etiologic factors in the occurrence of sensorineural hearing loss. The findings suggest that hearing disorders are a heretofore unrecognized characteristic of the fetal alcohol syndrome. Such hearing disorders may contribute to the speech and language and learning difficulties seen in children with fetal alcohol syndrome. The present study also provided confirmatory evidence of visual, health, and speech and language disorders in children with this syndrome.

Child↗
PubMed1987

Pentobarbital-induced changes in the mouse brainstem auditory evoked potential as a function of click repetition rate and time postdrug.

The effects of pentobarbital (80 mg/kg, i.p.) and saline injections on the BAEP were studied in 10 adult female BDF1 mice. Pentobarbital anesthesia induced statistically significant increases in the amplitudes and latencies of various BAEP components relative to preinjection and saline control values. These pentobarbital-induced changes were maximal shortly after drug administration and dissipated over time in a pattern similar to a drug elimination curve. Since pentobarbital and fast stimulus repetition rates are considered to be 'synaptic stressors', it was predicted that pentobarbital anesthesia and click repetition rate would have combined effects on the BAEP. This prediction was partially supported in that pentobarbital-induced changes in P4 amplitude and latency were significantly dependent on click repetition rate. The pentobarbital-induced effects on earlier BAEP components, however, proved to be largely independent of click rate. Pentobarbital-associated changes in the BAEP were not due to such factors as core temperature changes, circadian variations, and stress. The importance of anesthetic-induced changes in the BAEP for clinical and experimental studies is discussed.

Acoustic Stimulation↗
PubMed1987

Prenatal alcohol exposure shortens life span in rats.

In a study of the effects of in utero alcohol exposure on life span in rats, pregnant rats were intubated twice daily with 3.5 gm/kg alcohol on gestational days 11-21 or with an isocaloric sucrose solution. These latter animals were pair-fed and pair-watered to alcohol-treated animals. A third group served as nontreated ad lib-fed controls. At birth, all offspring were removed from their biological mothers, culled to eight per litter, and placed with nontreated surrogate dams. Alcohol-exposed animals died at a significantly younger age than pair-fed and ad lib controls and never attained the same maximum body weights as control animals. For females prenatally exposed to alcohol, life span was shortened by about 20 weeks; in male cohorts, life span was shortened by about 2.5-7 weeks.

Animals↗
PubMed1987

Effects of ketamine anesthesia on the rat brain-stem auditory evoked potential as a function of dose and stimulus intensity.

Because ketamine is both an abused substance and a commonly used veterinary anesthetic, its effects on brain and sensory functions are of interest. The present study examined the dose-dependent effects of ketamine anesthesia in the rat, using the brain-stem auditory evoked potential (BAEP) as an objective, quantitative measure of this substance's acute effects on brain and sensory electrophysiology. The animal subjects were 11 young adult female Long-Evans rats. BAEPs were recorded from skull screw electrodes during a baseline period as well as after saline and ketamine treatments. Ketamine was administered (i.p.) in 2 serial doses. The first dose (100 mg/kg) was followed 30-40 min later by a second dose (also 100 mg/kg). Equal volumes of normal saline were also injected serially. An interval of 1-2 weeks occurred between the saline and ketamine treatments, with treatment order counterbalanced. Normothermia was maintained to control for possible temperature-related effects. Ketamine produced prolongations in the latencies of all BAEP components (P1 through P6) that were statistically significant relative to baseline values. These latency shifts were progressively greater for waves P1 through P4 (shifts in P5 and P6 approximated the P4 shift). The effect of the second ketamine injection was to nearly double the latency shifts. Ketamine also had significant and complex effects on BAEP amplitudes that were dependent on dose and stimulus intensity. The results of the present study challenge the belief that the BAEP is resistant to the effects of anesthetics and suggest that the BAEP is useful in characterizing the CNS and sensory effects of these pharmacological agents.

Animals↗
PubMed1986

Age-related hearing loss in BDF1 mice as evidenced by the brainstem auditory evoked potential.

Age-related hearing loss was studied in unanesthetized female BDF1 mice using brainstem auditory evoked potential (BAEP) latency-intensity (L-I) profiles and BAEP thresholds. The mice were divided into 5 age-related groups: 3-4 months, 5.5-7 months, 9-10 months, 12 months and 18 months. Relative to the youngest group, BAEP threshold data indicated shifts in auditory sensitivity ranging from +6 dB for the 5.5- to 7-month-old group to +71 dB for the 18-month-old group. The BAEP L-I profiles of older mice were consistent with recruitment-type sensorineural (cochlear) hearing losses. No evidence of retrocochlear involvement was observed.

Aging↗
PubMed1985

A method for chronically recording brain-stem and cortical auditory evoked potentials from unanesthetized mice.

Anesthetizing or sedating animals affords control over movement artifact during electrophysiological recording. However, the use of chemical restraint leads to unwanted side effects such as drug-induced hypothermia. Hypothermia is problematic because BAEP amplitudes and latencies are affected significantly by core temperature changes. Moreover, several recent studies have indicated that anesthetics and sedatives may significantly alter the BAEP and CAEP even in thermoregulated subjects. There is a need, therefore, to develop a practical technique for obtaining chronic BAEPs and CAEPs in restrained, unanesthetized animals. The present report describes a technique that permits the gathering of consistent, reliable evoked potential recordings over time in unanesthetized mice. The preparation is useful for studying the CNS effects of pharmacological agents, pathological conditions, aging and development in the mouse and could be adapted for use with other small animals as well.

Anesthesia↗
PubMed1984

Postnatal development of the brainstem auditory evoked potential and far-field cochlear microphonic in non-sedated rat pups.

Normal postnatal development of the scalp-recorded cochlear microphonic (CM) response and brainstem auditory evoked potential (BAEP) were studied in rat pups. BAEP latencies decreased and amplitudes increased as a function of maturation. These changes occurred rapidly between 14 and 23 days of age with gradual change occurring thereafter. The observed latency changes indicated that the auditory pathway matures in a sequential manner from the most peripheral to the most rostral structures. For example, CM latency stabilized (matured) by day 17 while BAEP wave I and II latencies stabilized by days 23 and 35, respectively. BAEP waves III and IV still showed significant latency decreases between days 42 and 70. The between-litter variability for CM and BAEP wave latencies also decreased with age. In contrast to peak latency measures, CM and BAEP amplitudes followed an independent time course of postnatal development. CM amplitude did not increase significantly after day 14. Amplitudes of all 4 BAEP components increased steadily from day 14 to 29, then stabilized. Unlike latency variability, amplitude variability was independent of age. There were no significant gender-dependent differences in amplitudes or latencies between the ages of 14 and 70 days.

Age Factors↗
PubMed1984

Brain-stem auditory evoked potentials in the rat: effects of gender, stimulus characteristics and ethanol sedation.

Rat BAEPs varied significantly as a function of gender and ethanol sedation as well as stimulus intensity and repetition rate. All BAEP wave latencies decreased and amplitudes increased with increasing stimulus intensity. Contrary to the prevailing view, the I-IV interpeak latency changed significantly as a function of stimulus intensity. In terms of repetition rate, all BAEP wave latencies increased and amplitudes decreased with increasing repetition rate. Male rats, compared to females, had significantly longer latencies for several BAEP components and interpeak latencies as well as smaller wave II amplitudes across a broad range of stimulus intensities. Males, compared to females, also had longer BAEP wave IV latencies and I-IV interpeak latencies at a slow stimulus repetition rate (8 clicks/sec) but shorter wave IV and I-IV latencies at a fast repetition rate (120 clicks/sec). These gender-dependent differences indicate that male and female rat BAEP data should not be combined indiscriminantly. Ethanol sedation had a statistically significant effect on the I-IV interpeak latency that was judged to be largely independent of core temperature changes. This finding suggests that while sedatives and anesthetics used to immobilize animals may have apparently minor temperature-independent effects on BAEP latencies, these effects can be statistically significant.

Animals↗
PubMed1979

The effects of flurazepam hydrochloride on brain electrical activity during sleep.

To further evaluate the effects of flurazepam on EEG during sleep, following 7 nights of placebo baseline, flurazepam (30 mg) was administered to 6 young adult poor sleepers for 10 additional nights while 6 other young adult poor sleepers continued to receive placebo capsules in a double-blind paradigm. Three placebo follow-up nights were recorded 2--3 weeks post-treatment. Twelve good sleepers received only placebo capsules for the first 7 nights. Delta waves, 0.5--2 c/sec, and sleep spindles were counted on-line by a phasic detector. Delta activity was also analyzed off-line by PDP-12 computer for only the first 4 h of sleep and involved a comparison over stages of sleep. Click-evoked K-complexes during NREM sleep were analyzed for 6 good sleepers and 11 poor sleepers. Repeated use of flurazepam caused a gradual decrease in delta amplitude and count, and a gradual increase in sleep spindle rate. The decrease in delta amplitude was seen in all sleep stages, but the decrease was significant only during SWS and stage 2. The decrease in delta amplitude was significant by the 3rd drug night, but the rate of amplitude decrease tended to slow with continued treatment. The decrease in delta count was less pronounced and more gradual over drug nights than the rate of decrease in amplitude. Flurazepam also significantly reduced evoked K-complex amplitude but did not affect latency. Sleep spindle rate was significantly increased by drug night 5. Results of this study indicate that the reduction of SWS with flurazepam during the initial drug nights is due primarily to the decrease in delta amplitude, but, with continued use, the decrease in delta count also contributes to the decrease in stage 4 sleep.

Adult↗
PubMed1979

Auditory arousal thresholds of good sleepers and poor sleepers with and without flurazepam.

Auditory arousal thresholds of good (N = 12) and poor (N = 12) sleepers (sleep onset insomniacs) were obtained during stage 2, stage 4, and REM sleep at various times of the night. Despite claims of being "light" sleepers who are easily awakened by noise, poor sleeper auditory arousal thresholds were the same as those of good sleepers. Flurazepam (30 mg) increased the auditory arousal thresholds of poor sleepers (N = 6), but the increase was statistically significant only during the period of peak effect which occurred 1--2 hr after ingestion. Consistent with poor sleeper complaints of trouble falling asleep, the return to sleep (i.e., sleep latency) was significantly longer for poor than for good sleepers following stimulus arousals during the first stage 2 and first stage 4 periods of the night. Sleep latencies for good and poor sleepers did not differ significantly following subsequent arousals. The sleep latency following the first stage 2 stimulus arousal was significantly reduced in poor sleepers during flurazepam-induced sleep.

Acoustic Stimulation↗
PubMed1978

Evoked K-complexes and cardiovascular responses to spindle-synchronous and spindle-asynchronous stimulus clicks during NREM sleep.

The hypothesis that the functional role of the sleep spindle is to preserve sleep by inhibiting sensory input (Yamadori 1971) was examined. Series of 44 dB, 10 msec, 1000 c/sec 'clicks' were presented to 12 subjects at a 30-sec ISI during stage 2 sleep either during spindle bursts (i.e. spindle-synchronous clicks) or during interburst periods (i.e. spindle-asynchronous clicks). Contrary to the spindle inhibitory hypothesis, cortical EEG and cardiovascular responses showed no evidence of spindle 'suppression'. Evoked K-complexes were potentiated by the spindle-synchronous stimulation. A second study with 7 subjects replicated this result and extended the finding to include stage 3--4 sleep. It was suggested that the potentiation of evoked K-complexes was due to phasic reductions in inhibitory action during sleep spindles resulting in increased transmission of sensory events or, perhaps, an increase in the lability of certain EEG response systems.

Adolescent↗
PubMed1975

Changes in frequency and amplitude of delta activity during sleep.

Modified period analysis was applied to all-night sleep recordings from 14 young adult males. The modifications involved addition of measures of integrated amplitude and of time in frequency band to the zero crossings and zero counts of the first derivative. The analysis was directed toward changes in the characteristics of delta activity (0--3 c/sec) across the night. Delta shifted toward lower frequencies and decreased in amplitude as sleep progressed. These trends were apparent in mean values for successive periods of slow-wave sleep (SSWPs). For epochs of record classified as stage 4 EEG, these trends were seen both within and across SSWPs. The physiological significance of these changes is unknown. We suggest that they may reflect the kinetics of the metabolic processes underlying sleep. Whatever their theoretical significance, the present results provide new, normative features of the sleep EEG which are not evident in sleep stage classification. The trends we observed appear sufficiently reliable to merit empirical investigation as a function of age, clinical state, or the administration of drugs in addition to further studies aimed at determining their biological significance.

Adult↗
PubMedDate not supplied

Effects of cocaine on the brain-stem auditory evoked potential in the Long-Evans rat.

The present study examined the effects of an acute psychoactive dose of cocaine hydrochloride (HCl) in the rat, using the brain-stem auditory evoked potential (BAEP) as an objective, quantitative measure of this substance's effects on brain and auditory electrophysiology. The animals were 8 adult Long-Evans rats (4 female, 4 male). BAEPs were recorded from skull screw electrodes during a baseline period as well as 30-90 min after cocaine HCl treatment (10 mg/kg, i.p.). Normothermia was maintained to control for possible temperature-related effects. Cocaine's effects on the BAEP were examined over a broad range of stimulus intensities (intensity profiles) and repetition rates (rate profiles). Cocaine prolonged latencies of several BAEP components at low stimulus intensities and shortened these latencies at high stimulus intensities. The average BAEP threshold was also increased by cocaine treatment. These results were not strong, but were suggestive of a recruitment type change in auditory function. Cocaine treatment had no convincing effects on the BAEP as a function of stimulus repetition rate.

Animals↗
PubMedDate not supplied

Chronic in utero alcohol exposure affects auditory function in rats and in humans.

In one experiment, brainstem auditory evoked potentials (BAEPs) were used to study the postnatal development of the peripheral and brainstem auditory pathways in rat pups prenatally exposed to alcohol. The results indicated that prenatal alcohol exposure retards development of the peripheral and brainstem auditory pathways and that prolonged auditory transmission times, despite a "catch-up" trend, persist in maturity. BAEP latency-intensity profiles demonstrated that a significant proportion (19%) of the alcoholized rats had recruitment-type sensorineural hearing loss. In a second study, a group of 12 fetal alcohol syndrome (FAS) children were evaluated for auditory function. These children showed unusually high incidence rates of sensorineural hearing loss (33%) and conductive hearing loss secondary to recurrent serous otitis media (92%). A final study used the cortical auditory evoked potential (CAEP) and found evidence of dysfunctional processing of auditory information at the cortical level in rats prenatally exposed to alcohol. The implications of these findings for the evaluation and treatment of FAS children and for evoked potential studies on children of alcoholics and learning disabled children are discussed.

Age Factors↗