Effect of stimulus mode on middle latency auditory evoked potentials in humans

Middle Latency Auditory Evoked Potentials (MLAEPs) were recorded in 35 healthy subjects; all underwent monaural stimulation and 18 of them additionally underwent binaural stimulation. The aim of the study was to determine the effect of stimulus mode on MLAEP Na, Pa and Nb components and to assess normative data for clinical purposes. MLAEPs were respectively obtained from Cz-ipsilateral ear lobe (monaural mode) and from Cz-A1 and Cz-A2 (binaural mode) by twice averaging 1000 responses to 65 dBHL alternating clicks delivered at a repetition rate of 8.1 Hz. Time base was 100 msec; analogical band-pass filter setting was 5-1000 Hz (off-line digital badpass: 20-100 Hz). The statistical analyses (paired t-test, repeated measures analysis of variance) were not able to demonstrate any differences that derived from differing sides of stimulation (monaural mode) or from differing recording derivations (binaural mode); on the contrary, we demonstrated a slight increase in waveform amplitudes when the binaural mode was employed. In particular, we observed an increase in Na-Pa peak-to-peak amplitude, whereas Pa-Nb amplitude was unmodified. This finding is explicable in terms of a binaural interaction effect. Finally, we propose some guidelines for the correct performance and evaluation of MLAEPs in clinical practice.     

Dynamics of MLAEP changes in midazolam-induced sedation

This study aimed at assessing the effects of midazolam (MDZ) sedation on auditory brainstem (BAEP) and middle latency (MLAEP) evoked potentials in intensive care conditions. Ten ventilated comatose patients were receiving an intravenous MDZ bolus dose (0.2 mg/kg) followed by a 2 h continuous infusion (0.1 mg/kg/h). MLAEPs and BAEPs elicited by clicks (90 dB HL+masking) were simultaneously and continuously monitored during the first 6 h and for 30 min the next morning. We found no effect of MDZ sedation on BAEPs. Only MLAEP components were modified. However, none of the patients presented any total abolition of the MLAEPs. Bolus injection led to very early alteration of cortical responses, beginning after 5 min and lasting almost 1 h (maximum Pa latency increase, 3.1 ms; maximum Pa-Nb amplitude decrease, 46%). During continuous infusion, MLAEPs remained slightly, although significantly, altered (Pa latency, +1.3 ms; Pa-Nb amplitude, 27%). The Nb wave seemed to be modified earlier and to return to normality later than the Pa wave. These findings incite a careful interpretation of MLAEP tracings acquired during the first hour following MDZ bolus injection. If possible, MDZ should be administered as continuous infusion for reliable interpretation of evoked potential changes in intensive care unit, or during surgery.     

Auditory evoked potentials in a patient with a unilateral lesion of the inferior colliculus and medial geniculate body

Brain-stem, middle latency and late auditory evoked potentials (BAEPs, MLAEPs and LAEPs, respectively) were recorded in a patient 2 months after removal of a tumor affecting the quadrigeminal plate. Simultaneously, MRI showed a left unilateral lesion involving the inferior colliculus, brachium colliculi and the medial geniculate body (MGB). On dichotic listening, there was complete extinction of the right ear input, without subjective auditory disturbance. BAEPs were abnormal after stimulation of the right ear alone. Wave V was delayed and reduced in amplitude, and the I–V interval was augmented. Above all, MLAEPs of both ears were very abnormal. The Pa and Na components over the left hemisphere were abolished (Pa) or very reduced in amplitude or abolished (Na) whereas both Pa and Na components over the right hemisphere were normal. LAEPs were asymmetrical, with reduced P1N1P2 complex over the left hemisphere and absence of polarity reversal over the mastoid. It has been demonstrated that a lesion affecting only the inferior colliculus and MGB unilaterally and not extending beyond the MGB can abolish Na and Pa ipsilaterally. Any discussion of Na and Pa sources should take into account the output of the MGB to the auditory radiations, the MGB, the brachium colliculi and the inferior colliculus.     

Effects of stimulus repetition rate on slow and fast components of auditory brain-stem responses

Effects of stimulus repetition rate on the slow and fast components of the auditory brain-stem response (ABR) were investigated in 10 adult subjects with normal hearing. The ABRs were recorded with click stimuli at repetition rates of 8, 13.3, 23.8, 40 and 90.9/sec and at an intensity level of 55 dB nHL. Power spectral analysis of the averaged responses was performed. Then the responses were divided into a slow component (0–400Hz) and a fast component (400–1500 Hz) by using digital filtering technique. The magnitude of the slow component was little affected with increasing stimulus rate from 8/sec to 90.9/sec, while successive waves of the fast component, including wave V, decreased in amplitude as stimulus rate was increased. The latency of the slow component and each wave of the fast component was prolonged with increasing click rates. The shift of latency became longer in the later waves than in the earlier waves.     

Age-related changes in human middle latency auditory evoked potentials

We recorded middle latency auditory evoked potentials (MAEPs) in young (20–40 years) and elderly (60–80 years) subjects with normal hearing. The Pa component was prolonged in latency and markedly enhanced in amplitude in the elderly subjects. No changes were found in Na, or in the binaural interaction of the MAEP. Differences in Pa amplitude and latency were not due exclusively to changes in auditory thresholds, since they were not duplicated by changes in stimulus intensity, and persisted when MAEPs from selected young and old subjects were compared at similar SPL levels. The enhancement of Pa amplitude appears to reflect age-related central modifications in auditory processing.     

Integration and recovery processes contribute to the temporal selectivity of neurons in the midbrain of the northern leopard frog, Rana pipiens

This study examined the mechanisms underlying amplitude modulation selectivity in the anuran auditory midbrain. Single units were recorded extracellularly in the torus semicircularis of the northern leopard frog, Rana pipiens. Two physiologically distinct classes of neurons were identified, based on their response latencies and their selectivities to pulse repetition rates. Cells in one group had short response latencies (median = 31 ms) and responded best to pulse repetition rates below 40 Hz. Tuning to low amplitude modulation rates was largely determined by recovery processes and phasic response properties. Cells in the second group had much longer latencies (median=81 ms) and were generally selective for pulse repetition rates greater than 40-50 Hz. Sensitivity to higher amplitude modulation rates resulted from integration processes; these units only responded when a threshold number of pulses were presented at a minimum pulse density (amplitude modulation rate). At amplitude modulation rates above their best rate, their responses decreased, apparently due to inadequate recovery time between pulses.     

Midlatency auditory evoked responses: Differential effects of sleep in the human

Middle latency responses (MLRs) in the 10–100 msec latency range, evoked by click stimuli, were studied in 14 adult volunteer subjects during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. Evoked potentials were collected in 500 trial averages during continuos presentation of 1/sec clicks during initial awake recordings and thereafter during a 2 h afternoon nap or all-night sleep session. Continuously recorded EEG, EOG and EMG were scored for wakefulness, stages 2–4 of slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. The major components included in this study and their latency ranges, as determined by peak latency measurements from the awake records, were: ABR V, 5–8 msec, Pa, 30–40 msec, Nb, 45–55 msec, and P1, 55–80 msec. In agreement with previous reports, ABR V and Pa showed no amplitude changes from wakefulness to either SWS or REM. Not previously reported, however, was the dramatic decrease and disappearance of P1 during SWS and its reappearance during REM to an amplitude similar to that during wakefulness. This unique linkage between a particular evoked potential component and sleep-wakefulness indicates that its generator system must be functionally related to states of arousal. Relevant data from the cat model suggest that the generator substrate for P1 may be within the ascending reticular activating system.     

Detection of simple and pattern regularity violations occurs at different levels of the auditory hierarchy

Auditory deviance detection in humans is indexed by the mismatch negativity (MMN), a component of the auditory evoked potential (AEP) of the electroencephalogram (EEG) occurring at a latency of 100-250 ms after stimulus onset. However, by using classic oddball paradigms, differential responses to regularity violations of simple auditory features have been found at the level of the middle latency response (MLR) of the AEP occurring within the first 50 ms after stimulus (deviation) onset. These findings suggest the existence of fast deviance detection mechanisms for simple feature changes, but it is not clear whether deviance detection among more complex acoustic regularities could be observed at such early latencies. To test this, we examined the pre-attentive processing of rare stimulus repetitions in a sequence of tones alternating in frequency in both long and middle latency ranges. Additionally, we introduced occasional changes in the interaural time difference (ITD), so that a simple-feature regularity could be examined in the same paradigm. MMN was obtained for both repetition and ITD deviants, occurring at 150 ms and 100 ms after stimulus onset respectively. At the level of the MLR, a difference was observed between standards and ITD deviants at the Na component (20-30 ms after stimulus onset), for 800 Hz tones, but not for repetition deviants. These findings suggest that detection mechanisms for deviants to simple regularities, but not to more complex regularities, are already activated in the MLR range, supporting the view that the auditory deviance detection system is organized in a hierarchical manner.     

Binaural interaction and the effects of stimulus intensity and repetition rate in human auditory brain-stem

Binaural interaction (BI) components in brain-stem auditory evoked potential (BAEP) and their changes with stimulus intensity and repetition rate were examined in human adult. Seven BI components were identified, which occurred between the latency range of 5 and 11 ms and coincided consistently with the latency range of BAEP waves IV–VII. Waves DV and DVII, occurring at the downslopes of BAEP-waves V and VII, respectively, were the two most prominent and reproducible BI components. Wave DVII existed consistently at high, moderate and, in most cases, low stimulus intensities, suggesting that this component is neurogenic although acoustic cross-talk may account for a part of its waveform at high stimulus intensities. The latencies of all BI components increased as a function of decreasing stimulus intensity, while the interpeak intervals, especially DV–DVII, were essentially constant at different intensity levels. The amplitudes of BI components decreased slightly with decreasing intensity. As click repetition rate increased, BI wave latencies and interpeak intervals increased slightly and amplitudes decreased slightly. When repetition rate increased to above 20/s, BI components became poorly differentiated. Lower repetition rates, e.g. 10/s, are therefore preferred for routine derivation of the BI. The changes in the latency and amplitude of BI components with stimulus intensity and repetition rate were associated or concomitant with those of the corresponding BAEP components in monaural and binaural potentials. In view of the concomitant relationship between BI and BAEP latency, we designate BI components in association with the corresponding BAEP components.     

Evoked potentials recorded from the auditory cortex in man: evaluation and topography of the middle latency components

The goal of this study is to determine and localize the generators of different components of middle latency auditory evoked potentials (MLAEPs) through intracerebral recording in auditory cortex in man (Heschl's gyrus and planum temporale).The present results show that the generators of components at 30, 50, 60 and 75 msec latency are distributed medio-laterally along Heschl's gyrus. The 30 msec component is generated in the dorso-postero-medial part of Heschl's gyrus (primary area) and the 50 msec component is generated laterally in the primary area. The generators of the later components (60–75 msec) are localized in the lateral part of Heschl's gyrus that forms the secondary areas.The localization of N100 generators is discussed.     

High-pass filter settings affect the detectability of MLRs in humans

Auditory middle latency responses (MLRs) have been recorded in 217 patients ranging in age from 6 days to 20 years. The probability of obtaining MLR components Na and Pa was higher with a high-pass filter setting of 15 Hz, 12 dB/octave as compared to 3 Hz, 6 dB/octave. This effect was found at all ages tested. Age-related latency effects were apparent with 3 Hz but not 15 Hz filtering.     

Effects of benzocaine on the kinetics of normal and batrachotoxin-modified Na channels in frog node of Ranvier.

The effects of benzocaine (0.5-1 mM) on normal Na currents, and on Na current and gating charge movement (Q) of batrachotoxin (BTX)-modified Na channels were analyzed in voltage-clamped frog node of Ranvier. Without BTX treatment the decay of Na current during pulses to between -40 and 0 mV could be decomposed into two exponential components both in the absence and in the presence of benzocaine. Benzocaine did not significantly alter the inactivation time constant of either component, but reduced both their amplitudes. The amplitude of the slow inactivating component was more decreased by benzocaine than the amplitude of the fast one, leading to an apparently faster decline of the overall Na current. After removal of Na inactivation and charge movement immobilization by BTX, benzocaine decreased the amplitude of INa with no change in time course. INa, QON, and QOFF were all reduced by the same factor. The results suggest that the rate of reaction of benzocaine with its receptor is slow compared to the rates of channel activation and inactivation. The differential effects of benzocaine on the two components of Na current inactivation in normal channels can be explained assuming two types of channel with different rates of inactivation and different affinities for the drug.     

Effects of stimulus repetition rate on ABR threshold,amplitude and latency in neonatal and adult Mongolian gerbils

The ABR wave forms of 16-day-old and adult Mongolian gerbils were evoked by click stimuli presented at rates ranging from 1 to 80/sec. Wave I and wave IV thresholds were determined for each of 5 click rates. Amplitudes and latencies of waves I and IV were measured at each of 7 click rates and 3 intensity levels (15, 40 and 65 dB above threshold). Thresholds for waves I and IV in the adult gerbil and wave I in the 16 day gerbil were unaffected by changes in stimulus repetition rate. Neonatal wave IV thresholds were unaffected by click rate for rates below 25/sec but increased approximately 7 dB/decade increase in click rate when rate exceeded 25/sec. Increasing click rate produced greater reductions in ABR amplitude among neonates than adults for both waves I and IV. Decreases in amplitude due to increasing rate were independent of intensity level in both neonatal and adult subjects. Increasing rate produced similar increases in wave I latency among 16 day and adult subjects, but produced much greater increases in wave IV latency among neonates. Stimulus intensity level and click rate acted independently on wave I and wave IV latency in adult subjects and wave I latency in neonates. However, an interaction between rate and intensity was observed with respect to neonatal wave IV latency.     

Auditory evoked potentials from the primary auditory cortex of the cat: topographic and pharmacological studies

Wave VI (8.4 msec) of the brain-stem auditory evoked potential (BAEP) was maximal in a discrete region of primary auditory cortex (AI) of the anesthetized cat. Wave VI underwent rapid amplitude decreas over millimeter distances in the AI region and followed high stimulation rates. Wave VI did not show intracortical polarity inversion nor was it abolished by epicortical or intracortical GABA administration. The data are compatible with a wave VI source in the terminal axons of the thalamo-cortical radiations.Middle latency auditory responses (MAEPs) generated 10–40 msec after auditory stimulation were also recorded in a circumscribed area of AI. In contrast to wave VI, these primary auditory cortex potentials (Pa 18.3 msec; Nb 31.9 msec) underwent transcortical polarity inversion, correlated with intracortical multi-unit activity in the AI region and were reversibly altered or abolished by epicortical or intracortical GABA adminstration to the AI region. The data suggest that the Pa and Nb components of the cat MAEP are intracortically generated by neuronal elements in the AI region.     

Differential production of chirping behavior evoked by electrical stimulation of the weakly electric fish, Apteronotus leptorhynchus

Aperonotus leptorhynchus (Gymnotiformes) produces wave-like electric organ discharges distinguished by a high degree of constancy. Transient frequency and amplitude modulations of these discharges occur both spontaneously and during social interactions, which can be mimicked by external electrical stimulation. The so-called chirps can be divided into four different types. Independent of the type of chirp produced under spontaneous conditions, the fish generate only significant numbers of type-2 chirps under evoked conditions. The rate of production of chirps of this type is largely determined by the frequency relative to the fish's frequency and signal intensity. Frequencies of + 10 Hz of the fish's own discharge frequency most effectively elicit chirps. Type-2 chirps can also be evoked through stimulation at or near the higher harmonic frequencies of the fish's frequency, but the chirp rate decreases with increasing number of the higher harmonic component. Over a certain range, the rate of production of type-2 chirps increases with increasing stimulus intensity. At very high intensities the generation of type-2 chirps is accompanied by the production of a novel type of electrical signal ("abrupt frequency rise") characterized by a frequency increase of approximately 20 Hz and high repetition rates of roughly 10 s(-1). We hypothesize that the different types of electric modulations subserve different behavioral functions.     

Effect of stimulus rate on the cortical posterior tibial nerve SEPs: a topographic study

We performed topographical mapping of somatosensory evoked potentials (SEPs) in response to posterior tibial nerve stimulation delivered at 2, 5 and 7.5 Hz in 15 healthy subjects. P37 was significantly attenuated at 5 and 7.5 Hz and the N50 component attenuated only at 5 Hz, its amplitude remaining stable for further increases in stimulus frequency. Frontal N37 and P50 potentials showed no significant decrease when the stimulus repetition frequency was changed from 2 to 7.5 Hz. P60 showed an attenuation of the amplitude only at 7.5 Hz. Latency and scalp topographies of all cortical components examined remained uncharged for the 3 stimulus rates tested The optimal stimulus rate for mapping of tibial nerve SEPs was lower than 5 Hz. The distinct recovery function of the contralateral N37-P50 and ipsilateral P37-N50 responses suggests that these potentials arise from separate generators     

Discrimination of insect wingbeat-frequencies by the batRhinolophus ferrumequinum

Summary Five Greater Horseshoe bats,Rhinolophus ferrumequinum, were trained in a two-alternative forced-choice procedure to discriminate between artificial echoes of insects fluttering at different wingbeat rates. The stimuli were electronically produced phantom targets simulating fluttering insects with various wingbeat frequencies (Figs. 3, 4). Difference thresholds for wingbeat rates of 50 Hz and 100 Hz were determined. For an S+ of 50 Hz the difference threshold values lay between 2.8 and 4.6 Hz for individual bats; with an S+ of 100 Hz they increased to between 9.8 and 12.0 Hz (Figs. 5, 6, Table 1).Three bats, previously trained to discriminate between a S+ of 50 Hz and a S– with a lower wingbeat rate, were tested with higher frequency stimuli. When they had to decide between their old S+ of 50 Hz and either a 60 or 70 Hz echo two bats continued to select the 50 Hz stimulus while the third bat now preferred the faster fluttering insects (Table 2).During the discrimination task the echolocation behavior of the bats was monitored. When the phantom targets were presented all bats increased their duty-cycle of sound emission from about 40% to sometimes near 70%. They did so by either emitting longer echolocation calls or by increasing the sound repetition rate (Figs. 7, 8).The results show that Greater Horseshoe bats can determine the wingbeat rate of flying insects with an accuracy between 6 and 12%. Possible cues for flutter rate determination by cf-fm bats from natural and artificial insect echoes are discussed.Abbreviations DC duty-cycle - PD pulse duration - PI pulse interval - cf constantfrequency - fm frequency modulation     

Inconsistency of auditory middle latency and steady-state responses in infants

Auditory middle latency and steady-state responses (MLR/SSRs) were recorded in normal infants (aged 3 weeks to 28 months) and adults. SSR amplitudes were maximum using stimulus presentation rates near 40 Hz in adults. By contrast, the infant data showed no consistent amplitude maximum across the rates tested (9–59 Hz). With the exception of the brain-stem response wave V to MLR Na deflection, MLR components in infant's responses to 10.85 Hz clicks did not show any consistent pattern. To investigate the hypothesis that the 40 Hz SSR is derived from overlapping of the 10 Hz MLR components, 43.4 Hz SSRs were synthesized from the responses recorded at 10.85 Hz and compared with those recorded at 43.4 Hz. The predictive accuracy of the synthesized 43.4 Hz SSRs was significantly better in adults than in infants. The results of these studies indicate the presence of large age-related differences in the auditory MLR and SSR, and in the relationship between the two responses.     

KILLER WHALE (ORCINUS ORCA) AUDITORY EVOKED POTENTIALS TO RHYTHMIC CLICKS

Temporal auditory mechanisms were measured in killer whales ( Orcinus orca ) by recording auditory evoked potentials (AEPs) to clicks. Clicks were presented at rates from 10/sec to 1,600/sec. At low rates, clicks evoked an AEP similar to the auditory brainstem response (ABR) of other odontocetes; however, peak latencies of the main waves were 3–3.7 msec longer than in bottlenose dolphins. Fourier analysis of the ABR showed a prominent peak at 300–400 Hz and a smaller one at 800–1,200 Hz. High-rate click presentation (more than 100/sec) evoked a rate-following response (RFR). The RFR amplitude depended little on rate up to 400/sec, decreased at higher rates and became undetectable at 1,120/sec. Fourier analysis showed that RFR fundamental amplitude dependence on frequency closely resembled the ABR spectrum. The fundamental could follow clicks to around 1,000/sec, although higher harmonics of lower rates could arise at frequencies as high as 1,200 Hz. Both RFR fundamental phase dependence on frequency and the response lag after a click train indicated an RFR group delay of around 7.5 msec. This corresponds to the latency of ABR waves PIII-NIV, which indicates the RFR originates as a rhythmic, overlapping ABR sequence. The data suggest the killer whale auditory system can follow high click rates, an ability that may have been selected for as a function of high-frequency hearing and the use of rapid clicks in echolocation.     

BAEP subcomponents and wave form — relation to click phase and stimulus rate

The latency distributions of normal brain-stem auditory evoked potential (BAEP) components elicited by condensation (C) and rarefaction (R) clicks at 10 and 50 Hz were found to be double- or multi-peaked for II (10 and 50 Hz), III (50 Hz), IV (10 and 50 Hz) and V (10 Hz). A bifid component III was found in 3.5% (10 Hz) and 7.4% (50 Hz) of BAEPs. A bifid II and triple IV/V configuration were occasionally noted. The prevalences of the different IV/V complex configurations were significantly dependent upon click phase and rate. These results suggest that several subcomponent might participate in the generation of the single BAEP components and that a single generator may contribute to different BAEP components in different subjects.Early subcomponents between I and II (Ib) were found in 13% of 10 Hz BAEPs and 27% of 50 Hz BAEPs (P = 0.002) and the latency distribution of Ib seemed to be bimodal. Ib/I relative amplitude frequently increased with 50 Hz stimulation.We suggest that the generator of Ib is partially cochlear (CM) and partially neural (equivalent to N2 of the ECochG-AP) in origin.The existence of subcomponents must be recognized in clinical use of BAEPs both to avoid misinterpretation and to decrease the normal variability in monophasic click evoked BAEP studies.