Middle Latency Response Components Research Articles

Do tone duration changes that elicit the mismatch negativity also affect the preceding middle latency responses?

The human brain can automatically detect sound changes. Previous studies have reported that rare sounds presented within a sequence of repetitive sounds elicit the mismatch negativity (MMN) in the absence of attention in the latency range of 100-250ms. On the other hand, a previous study discovered that occasional changes in sound location enhance the middle latency response (MLR) elicited in the latency range of 10-50ms. Several studies have reported an increase in the amplitude of the MLR within the frame of oddball paradigms such as frequency and location changes. However, few studies have been conducted on paradigms employing a duration change. The purpose of the present study was to examine whether the peak amplitudes of the MLR components are enhanced by a change in duration. Twenty healthy Japanese men (age: 23.9±2.9years) participated in the present study. We used an oddball paradigm that contained standard stimuli with a duration of 10ms and deviant stimuli with a duration of 5ms. The peak amplitudes of the MLR for the deviant stimuli were then compared with those for the standard stimuli. No changes were observed in the peak amplitude of the MLR resulting from a duration change, whereas a definite MMN was elicited. The amplitude of the MLR was increased within the frame of oddball paradigms such as frequency and location changes. By contrast, the amplitude of the MLR was not changed within the duration change oddball paradigm that elicited the MMN.

Middle Latency Responses to Optimized Chirps in Adult Cochlear Implant Users.

Cochlear implant (CI) outcomes can be assessed using objective measures that reflect the integrity of the auditory pathway. One such measure is the middle latency response (MLR), which can provide valuable information for clinicians. Traditional stimuli for evoking MLRs, that is, clicks or tone bursts, do not stimulate all parts of the cochlea simultaneously, whereas chirp stimuli compensate for the cochlear neural delay and, therefore, produce more synchronous responses from the different neural elements of the cochlea. The purpose of the present study was to determine whether chirp stimuli can elicit reliable MLRs in CI users and whether those responses correlate with clinical outcomes and with deprivation-related factors. We presented 2,000 free-field optimized chirp stimuli to CI and control participants while their electroencephalography (EEG) was being recorded. Twenty-four adult CI users and 24 matched normal-hearing (NH) individuals (age range from 18 to 63 years) participated in this study. The EEG was recorded from 64 active electrodes placed on the scalp. EEG signals were processed using EEGLAB and ERPLAB toolboxes. We characterized the latencies and amplitudes of the different MLR components in both groups. Chirp stimuli reliably evoked qualitatively similar MLRs across all NH and CI participants with a couple of differences observed between the NH and CI group. Among the different MLR components, the Na latency was significantly shorter for the CI group. A significant amplitude difference was also found between groups for the Pa-Nb complex, with higher amplitudes observed in the NH group. Finally, there were no significant correlations between MLR latencies (or amplitudes) and clinical outcomes or deprivation-related measures. Free-field-presented optimized chirp stimuli were shown to evoke measurable and reliable MLRs in CI users. In this experiment, the MLR morphology in CI users was similar to those observed in NH participants. Even though we did not replicate here a significant relationship between MLR and speech perception measures, we were able to successfully collect acoustically evoked MLRs, which could constitute an important supplemental measure to the standard behavioral tests presently being used in postoperative clinical evaluation settings.

Are chirps better than clicks and tonebursts for evoking middle latency responses?

The middle latency response (MLR) is considered a valid clinical tool for assessing the integrity of cortical and subcortical structures. Several investigators have demonstrated that a rising frequency chirp stimulus is capable of eliciting not only larger wave V amplitudes but larger MLR components as well. However, the chirp has never been specifically examined in a hemispheric electrode montage setup that is typical for neurodiagnostic application and site-of-lesion testing. The purpose of this study was to examine the effect of chirp, click, and toneburst stimuli on MLR waveform peak latency and peak-to-peak amplitude in a hemispheric electrode montage setup. This study used a repeated-measures design. A total of 10 young adult participants (3 males, 7 females) with normal hearing were recruited and had negative histories of audiologic, otologic, and neurologic involvement, and no reported language or learning difficulties. MLR latencies (Na, Pa, Nb, and Pb) and peak-to-peak amplitudes (Na-Pa, Pa-Nb, and Nb-Pb) were measured for all conditions and were statistically evaluated for left hemisphere-right ear (C3-A2) and right hemisphere-left ear (C4-A1) recordings. Statistical analyses revealed no significant difference between C3-A2 and C4-A1 peak-to-peak amplitudes; therefore, data were collapsed. Stimulus comparisons revealed that Na evoked by tonebursts were statistically prolonged compared with both chirp and click, and that both Na-Pa and Pa-Nb peak-to-peak amplitudes were statistically larger for chirps compared with both clicks and tonebursts, and for clicks compared with tonebursts. The results of this study support the hypothesis that a chirp would offer a clinical advantage to the click and toneburst in overall peak-to-peak amplitude. As expected, normal-hearing participants did not exhibit hemispheric differences when comparing C3-A2 and C4-A1 peak-to-peak amplitudes demonstrating symmetric auditory brain function. However, chirp-evoked MLRs will require further study to determine its usefulness in clinical practice.

P b(P 1) resonance at 40 Hz: Effects of high stimulus rate on auditory middle latency responses (MLRs) explored using deconvolution

Objective In this study, the effects of high stimulus rate on middle latency response (MLR) components P a and P b (P 1 or P50) were studied using high rate clicks in normal hearing awake subjects were investigated. Methods Five jittered click sequences at different mean rates (24.4, 39.1, 58.6, 78.1, 97.7 Hz) were presented to 10 subjects. Overlapping MLRs were deconvolved using the frequency domain continuous loop averaging deconvolution (CLAD) [Özdamar Ö., Bohórquez, J., Signal to noise ratio and frequency analysis of continuous loop averaging deconvolution (CLAD) of overlapping evoked potentials. J. Acoust. Soc. Am., 119:429–438, 2006]. In addition conventional auditory transient MLRs at 4.88 Hz were obtained using conventional averaging. Results P a amplitude, latency and waveshape remained fairly constant up to 78.1 Hz. P b component, however, showed a variable waveshape with latencies covering a wide range (50–70 ms) and N b–P b amplitudes increasing at 39.1 and 58.6 Hz and decreasing at other rates. Conclusions Recordings show that both P a and P b MLR components can be consistently recorded at all rates up to 100 Hz. P b amplitude shows an increase at around 40 Hz showing a resonance at that frequency. Significance The dramatic increase of the P b component at around 40 Hz may account for the high amplitude of the 40 Hz ASSR.

Amplitude–intensity functions for auditory middle latency responses in hearing-impaired subjects

Results from animal studies show that hearing loss can result in increased neural responsiveness within the central auditory system. This study employed auditory middle latency evoked responses to compare central auditory responsiveness in human males with and without hearing loss. Measurements of auditory middle latency responses (MLRs) recorded from 14 normal hearing males were compared with MLR measures from 14 males with high-frequency, sensorineural hearing loss. Sixteen toneburst stimuli (four frequencies×four intensities) were used. Slopes of the amplitude–intensity functions for the several components of the MLR were obtained for each subject at frequencies below, near, and above the audiometric edge. Analysis of variance (ANOVA) revealed a significant group effect for MLR component Pa–Na, with less steep slopes at all frequencies for the hearing-impaired group. The ANOVA also showed a trend towards a significant group effect for Pb–Nb. Two-sample t-tests performed for Pb–Nb for each of the four tonebursts showed a frequency-specific effect. For Pb–Nb there was a statistically greater mean slope for the hearing-impaired group at the toneburst frequency associated with the audiometric edge.

Maturation of human central auditory system activity: separating auditory evoked potentials by dipole source modeling

Objectives: Previous studies have shown that observed patterns of auditory evoked potential (AEP) maturation depend on the scalp location of the recording electrodes. Dipole source modeling incorporates the AEP information recorded at all electrode locations. This should provide a more robust description of auditory system maturation based on age-related changes in AEPs. Thus, the purpose of this study was to evaluate central auditory system maturation based dipole modeling of multi-electrode long-latency AEPs recordings. Methods: AEPs were recorded at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Regional dipole source analysis, using symmetrically located sources, was used to generate a spatio-temporal source model of age-related changes in AEP latency and magnitude. Results: The regional dipole source model separated the AEPs into distinct groups depending on the orientation of the component dipoles. The sagittally oriented dipole sources contained two AEP peaks, comparable in latency to Pa and Pb of the middle latency response (MLR). Although some magnitude changes were noted, latencies of Pa and Pb showed no evidence of age-related change. The tangentially oriented sources contained activity comparable to P 1, N 1b, and P 2. There were various age-related changes in the latency and magnitude of the AEPs represented in the tangential sources. The radially oriented sources contained activity comparable to the T-complex, including Ta, and Tb, that showed only small latency changes with age. In addition, a long-latency component labeled TP 200 was observed. Conclusions: It is possible to distinguish 3 maturation groups: one group reaching maturity at age 6 and comprising the MLR components Pa and Pb, P 2, and the T-complex. A second group that was relatively fast to mature (50%/year) was represented by N 2. A third group was characterized by a slower pattern of maturation with a rate of 11–17%/year and included the AEP peaks P 1, N 1b, and TP 200. The observed latency differences combined with the differences in maturation rate indicate that P 2 is not identical to TP 200. The results also demonstrated the independence of the T-complex components, represented in the radial dipoles, from the P 1, N 1b, and P 2 components, contained in the tangentially oriented dipole sources.

Primary auditory pathway and reticular activating system dysfunction in Alzheimer's disease.

Patients with Alzheimer's disease (AD) have pathologic involvement of several important components of the primary auditory pathway, including the inferior colliculus, medial geniculate body, primary auditory cortex, and secondary auditory cortex. The main components of the brainstem auditory evoked response (BAER) and middle latency response (MLR) reflect the function of portions of the primary auditory pathway, including those affected pathologically in AD. The amplitude of the P1 component of the MLR reflects the degree of neuronal activity of midbrain portions of the ascending reticular activating system (ARAS) with cortical cholinergic projections. To determine whether there is dysfunction of the primary auditory pathway and ARAS in AD, we compared simultaneous BAER and MLR component latency and amplitude measurements in patients with mild-moderate AD (n = 35) and age-matched healthy elderly controls (n = 34). There were significant latency delays in brainstem transmission time (BAER I-V interpeak latency; p < 0.05) and in primary auditory cortex evoked potential generation (MLR Pa latency; p < 0.05) in the AD group compared with controls. In addition, there was a significant reduction in the P1 component amplitude of the MLR in the AD group (p < 0.01). These results indicate dysfunction of the primary auditory pathway and ARAS in patients with mild-moderate AD and support the hypothesis that impairment of auditory function and of arousal are intrinsic features of AD.

Binaural response patterns in subdivisions of the medial geniculate body

Auditory evoked potentials (AEPs) to binaural click stimulation were examined in the ventral (MGv) and caudomedial (MGcm) subdivisions of the medial geniculate body (MG) in guinea pigs. Binaural stimulation caused a decrease in amplitude for the response component recorded from the MGv, but an increase in amplitude for the AEP component recorded from the MGcm. Findings suggest that the evoked responses recorded from MGv and MGcm are functionally distinct. The inhibitory binaural response (BR) pattern seen in MGv was similar to that of the middle latency response (MLR) component recorded over the temporal cortex, while the additive BR pattern typical of the MGcm was similar to that of the surface midline MLR component. Furthermore, these data imply that the binaural response patterns seen in the primary and non-primary auditory cortex may be processed and encoded at the thalamic level. It is concluded that the distinct BR patterns noted for the two MG subdivisions reflect the predominant type of binaurally responsive neurons within the respective pathways.

Reticular formation influences on primary and non-primary auditory pathways as reflected by the middle latency response

Ongoing studies are aimed at identifying the neural pathways responsible for the middle latency response (MLR). These studies involve the analysis of surface and intracranial potentials following pharmacologic inactivation (with lidocaine) of discrete regions of the guinea pig brain. Previous investigations have shown that MLR surface waves recorded over thetemporal lobe originate from pathways anatomically and functionally distinct from those that generate MLR waves recorded over the midline, and that both primary and non-primary auditory thalamo-cortical pathways contribute to the guinea pig MLR. The present investigation examines the role of the mesencephalic reticular formation (mRF) in the MLR generating system. Inactivation of the mRF was associated with disruption of the midline response. These waves have been shown to reflect activity from non-primary subdivisions of the thalamo-cortical pathway. Components recorded over the temporal lobe were also affected, consisting of amplitude reduction and latency prolongation without changes in response morphology. Changes in temporal MLR components with mRF inactivation were smaller than those associated with direct inactivation of primary and non-primary subdivisions of the medial geniculate body. These findings indicate that mRF input is essential for normal generation of those components of the MLR thought to reflect both primary and non-primary auditory pathway activity.

Binaural stimulation reveals functional differences between midline and temporal components of the middle latency in guinea pigs

Two morphologically distinct auditory middle latency response (MLR) wave forms can be recorded from the surface of the guinea pig brain. The temporal response is recorded from the temporal lobe contralateral to the stimulus ear, and the midline response is recorded over the posterior midline. Experimental evidence suggests that different neural generators contribute to the two responses. Furthermore, it appears that the temporal response principally reflects activity of the primary auditory pathway while the midline response reflects non-primary pathways. Although it is known that neurons throughout the auditory pathway exhibit distinct binaural interaction (BI) properties, thus far there have been no systematic attemps to differentiate the MLR wave forms in response to binaural stimulation. The purpose of this study was to determine if binaural click stimulation could functionally differentiate the midline and temporal MLR responses in the guinea pig. Binaural click stimulation caused a significant decrease in temporal MLR peak amplitudes, and a significant increase in midline MLR amplitudes. The fact that different BI patterns were observed suggests that the two MLR components are functionally distinct. The data further support the hypothesis that the midline and temporal MLR in guinea pigs reflect different neural generators and pathways.

Detectability of auditory evoked response components in preterm infants

In determining the detectability of brainstem, middle latency and cortical auditory evoked responses in preterm newborns, one has to deal with the ongoing maturation of the auditory system. In the preterm period the detectability of evoked responses is closely related to the appearance of the individual evoked response components. The detectability of the individual evoked response components in preterm infants is important, because low detectability rates make the absence of a particular evoked response component irrelevant with respect to the clinical-neurophysiological correlation. In a longitudinal study we determined the detectability and cumulative detectability, i.e. the presence of individual evoked response components in one or more recordings of evoked response components in 37 low risk preterm infants between 30 and 41 weeks conceptional age (CA). On the basis of their detectability it is concluded that evoked response components, determined between 30 and 34 weeks CA, are generally of limited use for clinical application, except for auditory brainstem response (ABR) components I, IIn, V and Vc and middle latency response (MLR) component Na. Our study made clear that improvement can be achieved by performing more than one examination within a period of approximately 4 weeks between the recording sessions. The cumulative detectability rates after two recordings showed improvement for all components involved in this study. The cumulative detectability rates of ABR components I, II, IIN, III, V, IIc, IIINc, Vc, MLR components Na and P0, and auditory cortical response (ACR) components PbP1 and N2p are sufficient to use as measures in the neurophysiological judgement of functional integrity of the central auditory pathway in preterm infants.

Effects of chloral hydrate, pentobarbital, ketamine, and curare on the auditory middle latency response

Changes in threshold, latency, and amplitude of the auditory middle latency response (MLR) with anesthesia and neuromuscular paralysis were studied in guinea pigs. Although each component of the surface-recorded MLR was altered by barbiturate and nonbarbiturate agents, the early positive wave (wave A) was always present, and the later waves were generally identifiable at moderate levels of anesthesia. MLR threshold was not affected by anesthesia or curare. Pentobarbital, chloral hydrate, and ketamine each caused an increase in the latency of all MLR components, with increases progressively marked for later waves. Amplitude changes were more complex. Wave A increased in amplitude with anesthesia, while wave C decreased or disappeared temporarily. Wave B showed mixed amplitude changes. Changes in MLR associated with anesthesia were generally more pronounced at a stimulation rate of 10/sec as compared to 4/sec. No changes in waveform morphology or latency were seen with neuromuscular paralysis. The results provide evidence in support of separate neurogenic substrates for the different components of the guinea pig temporal lobe MLR. The presence of the MLR with moderate levels of anesthesia indicates that this animal is an appropriate model for studying the MLR in experiments requiring anesthesia and immobilization.

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.

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.

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

Middle latency responses (MLRs) in the 10–100 msec latency range, evoked by click stimuli, were studied in 8 adult cats during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. In particular, we wanted to determine whether the 20–22 msec positivity recorded at the vertex, ‘wave A,’ shown in previous studies to reflect a generator substrate within the ascending reticular formation, was tightly linked to changes in sleep-wakefulness, as reported for single neurons in the ascending reticular activating system. Evoked potentials were collected in 100 trial averages during continuous presentation of 1/sec clicks during initial awake recordings and thereafter during all-night sleep sessions. Continuously recorded EEG, EOG and EMG were scored for wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. Recordings were obtained from electrodes implanted at the vertex and overlying the primary auditory cortex referenced to frontal sinus or to neck. In agreement with others, components of the auditory brain-stem response and the 12 msec primary cortical response showed no change in amplitude from wakefulness to either SWS or REM. Only wave A, among the components evaluated in the 1–100 msec range, decreased and disappeared during SWS and dramatically reappeared during REM to an amplitude equal to that during wakefulness. These data lend particular support to a functional relation between wave A and the ascending reticular activating system and suggest that this potential may provide a unique and dynamic probe of tonic brain activity. Moreover, this animal model provides a hypothetical basis for expecting a similar surface recorded potential in the human, a potential which has consequently been discovered.

Auditory middle latency responses in children: Effects of age and diagnostic category

The nature of auditory middle latency responses (MLRs) in children has been the subject of considerable debate. In order to study MLRs as a function of age, MLRs were obtained in 217 subjects ranging in age from 6 days to 20 years, all with normal auditory brain-stem responses (ABRs). Subjects were classified into several diagnostic categories: normal; communicative disorders (language delay, learning disability); mentally retarded, multiply handicapped; and post-meningitic. Age effects, the effects of diagnostic category, and possible differences in MLRs of males vs. females and right vs. left ears were examined. The detectability of both Na and Pa was found to increase significantly as a function of age. Detection of these MLR components became similar to adult values (approaching 100% detectability) at approximately 10 years of age. No significant differences were found among diagnostic categories. There were also no significant differences in the detectability of MLRs in males as compared to females, and there were no right vs. left ear differences. The strong age effect which appears to exist in the MLR influences their clinical use. When responses are present, they may be useful indicators of hearing sensitivity, but the absence of MLRs in children cannot be taken as an indication of hearing loss. Similarly, absent or abnormal MLRs cannot be interpreted as a manifestation of auditory pathway dysfunction, since there appears to be little difference in MLRs in normal subjects and MLRs in patients with a wide range of neurologic, cognitive, and speech and language disorders.

Cortical mapping of the auditory middle latency response in the unanesthetized guinea pig

Auditory middle latency responses (MLRs) were mapped on the cortical surface of the unanesthetized guinea pig. The MLR consists of two positive peaks, designated A and C, with latencies of approximately 11 and 29 msec respectively, and a negative trough B, at 18 msec. Results suggest that each MLR component appears to have different generator sites and specific stimulus-response characteristics. The present work suggests that positive MLR components A and C have different generator sources because each component was maximally recorded from a different location over the contralateral temporal lobe. Little MLR activity was evident outside an area roughly 4 mm × 4 mm for each component.

Auditory middle-latency responses in humans.

Middle-latency responses (MLR) in humans were studied using an unconventional recording technique with wide bandpass filters. Such filtering permitted simultaneous recording of the auditory brain stem response (ABR) thus facilitating comparisons between the two responses. Effects of sedation (chloral hydrate and diazepam), stimulus-related properties and the coronal distribution of MLRs were examined. Mild sedatives did not appear to affect either MLRs or ABRs. MLRs differed from ABRs in their stimulus-related properties, implying that the neuronal mechanisms underlying their generation are not the same. The amplitude of the MLR component, Pa, was largest at the vertex and symmetrically distributed over the temporal lobes. MLR components Na and Pa and ABR wave V were reliably obtained in all subjects at moderate and high stimulus intensities. At low stimulus levels, however, the detectability of wave V was more robust than the middle-latency components. Thus ABR appears to be the test of choice when hearing sensitivity is in question. MLRs are likely to be most clinically useful in patients with neurological or central auditory processing disorders.

Auditory middle latency responses (MLRs) in patients with cortical lesions

Auditory middle latency responses (MLRs) and auditory brain stem responses (ABRs) were simultaneously recorded in 24 patients with cortical primarily affecting the temporal lobes. Site of lesion was documented by computerized tomography (CT) scan and behavioral profiles assessing language and other higher cortical functions were obtained. In patients with normal ABRs and either left or right hemisphere lesions, MLR components N a and P a obtained at the vertex were of normal shape and latency. Exceptions to this occurred in 2 patients: one with bilateral temporal lobe lesions, the second with an infraventricular left temporal lobe lesion extending into the thalamic radiations. Although N a and P a shape and latency were for the most part unaltered, P a amplitude tended to cluster at the low end and below normal values. MLR recorded in the coronal plate showed P a amplitude to be attenuated or absent over the damaged temporal lobe relative to the vertex or the intact hemisphere. This finding contrasts with data from normal subjects where P a amplitude is largest at the vertex and essentially symmetrical about the temporal lobes. Patients showing an atypical amplitude distribution tended to have lesions involving auditory cortex and adjacent white matter projections. No obvious correlations between MLR abnormalities and behavioral findings regarding receptive and expressive language processes were found. P a appears to be affected by temporal lobe lesions involving auditory cortex and thalamic projections. Our findings support the hypothesis that P a is bilaterally generated by two symmetrical, vertically oriented dipole sources located about the temporal lobes.

Auditory brain stem and middle latency responses in a patient with cortical deafness

Auditory brain stem (ABR) and middle latency responses (MLR) were recorded in a patient with bilateral temporal lobe lesions. Audiological and higher cortical functions were assessed using conventional behavioral methods. Roentgenological findings were presented for localizing the lesions. Initially the patient showed no behavioral response to sound. Subsequently the patient reported inconsistent awareness of environmental sounds and pure tone sensitivity was impaired to a severe degree. Higher cortical function was essentially intact and the patient was not aphasic. ABR and acoustic reflex findings were consistent with normal functioning of the auditory periphery and brain stem pathways. MLR component P a was absent bilaterally. These findings suggest that MLR component P a is bilaterally generated in the temporal lobes. Auditory cortex appears to play a role in auditory sensitivity in humans.