Organization and development of brain stem auditory nuclei in the chick: Ontogeny of postsynaptic responses

The onset of responsiveness to eighth nerve stimulation was examined in n. magnocellularis and n. laminaris, (second- and third-order neurons) of the chick brainstem auditory system. Extracellular microelectrode mapping techniques were used to examine postsynaptic responses in in vitro brainstem preparations. Two specific questions were addressed. First, what is the earliest time at which postsynaptic action potentials can be evoked in n. magnocellularis and n. laminaris by eighth nerve stimulation? Second, does responsiveness to eighth nerve stimulation develop along a spatial gradient in n. magnocellularis and, if so, how does this gradient compare with other developmental events observed in the chick auditory system? Postsynaptic responses in n. magnocellularis were first recorded at 11 days of incubation. Nucleus laminaris responses to direct stimulation of n. magnocellularis were also first recorded at 11 days, although n. laminaris responses to eighth nerve stimulation were not seen until 12 days of incubation. A gradient of response development within n. magnocellularis was indicated by mapping of responsive sites on days 11–13. At 11 days, responses to eighth nerve stimulation were restricted to the most anteromedial portion of n. magnocellularis. Between 11 and 13 days, cells in increasingly more posterolateral portions of n. magnocellularis became responsive. This is anteromedial-to-posterolateral gradient in n. magnocellularis is correlated with the basal-to-apical gradient of morphogenesis observed in the basilar papilla and morphogenetic gradients previously observed in n. magnocellularis and n. laminaris.     

Permanent peripheral hearing system alteration following transient neonatal hyperthyroidism in rats

Maturation of the peripheral auditory system was monitored with the brainstem response audiometry (BSRA) technique in L-thyroxine (T4)-injected rats. Neonatal hyperthyroidism (NH) was induced by daily injections of T4 from birth to 20 days. Following an initial period of precocious onset and accelerated maturation of click-evoked cochlear activity, specific tone stimulation triggered an altered evoked activity as soon as 16 days after birth with no recovery on the last recording session at 120 days, when the animals are considered adult. These results thus indicate that NH could rapidly lead to a permanent abnormality of peripheral auditory system evoked potentials.     

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

OBJECTIVE: The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. METHODS: Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. RESULTS: Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. CONCLUSIONS: Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. SIGNIFICANCE: Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.     

Receptive Fields of Neurons in the Owl's Auditory Brainstem Change Dynamically

Binaural neurons in the barn owl's auditory brainstem have spatial receptive fields. It is shown here that both the frequency tuning of these neurons and their tuning to interaural time difference (ITD), the prime cue for azimuthal sound localization, improves with time after stimulus onset, a process I shall term 'dynamic sharpening'. Thus, the receptive fields of these neurons also have a temporal dimension. Data were collected in four hierachically ordered nuclei concerned with the computation of ITD: the nucleus ventralis lemnisci lateralis, pars anterior (VLVa), and three subnuclei in the inferior colliculus. Dynamic sharpening in the frequency tuning curves is evident from a dynamic reduction of tuning width. When stimulated with a tone, the response of all neurons varies in a cyclic manner with ITD. The ITDs at the response peaks differ by one period of the stimulus tone. The responses with noise stimulation are similar to the responses with tonal stimulation in all but the hierarchically highest nucleus, the external nucleus of the inferior colliculus. In this nucleus are found neurons that, if stimulated with noise, respond maximally only to one ITD while the responses at the other peaks are suppressed. This sidepeak suppression is a dynamic process. Dynamic sharpening of ITD tuning is also evident from a dynamic reduction of the tuning width around each of the response peaks. The proportion of neurons showing dynamic sharpening of ITD tuning is the same in all collicular subnuclei, but is lower in VLVa. Therefore, a major component of dynamic sharpening of ITD tuning occurs at the first station of the inferior colliculus. Lateral inhibition is one of the mechanisms underlying dynamic sharpening. Part of the inhibition may be mediated by GABA (Fujita and Konishi, 1988). The function of dynamic sharpening of ITD tuning may be to increase the fine representation of auditory space in single neurons.     

Electrical stimulation of the cochlear nerve in rats: analysis of c-Fos expression in auditory brainstem nuclei

We investigated functional activation of central auditory brainstem nuclei in response to direct electrical stimulation of the cochlear nerve using c-Fos immunoreactivity as a marker for functional mapping. The cochlear nerve was stimulated in the cerebellopontine angle of Lewis rats applying biphasic electrical pulses (120-250 muA, 5 Hz) for 30 min. In a control group, bilateral cochlectomy was performed in order to assess the basal expression of c-Fos in the auditory brainstem nuclei. The completeness of cochlear ablations and the response of auditory brainstem nuclei to electrical stimulation were electrophysiologically verified. C-Fos immunohistochemistry was performed using the free floating method. In anaesthetized animals with unilateral electrical stimulation of the cochlear nerve, increased expression of c-Fos was detected in the ipsilateral ventral cochlear nucleus (VCN), in the dorsal cochlear nucleus bilaterally (DCN), in the ipsilateral lateral superior olive (LSO) and in the contralateral inferior colliculus (IC). A bilateral slight increase of c-Fos expression in all subdivisions of the lateral lemniscus (LL) did not reach statistical significance. Contralateral inhibition of the nuclei of the trapezoid body (TB) was observed. Our data show that unilateral electrical stimulation of the cochlear nerve leads to increased expression of c-Fos in most auditory brainstem nuclei, similar to monaural auditory stimulation. They also confirm previous studies suggesting inhibitory connections between the cochlear nuclei. C-Fos immunoreactivity mapping is an efficient tool to detect functional changes following direct electrical stimulation of the cochlear nerve on the cellular level. This could be particularly helpful in studies of differential activation of the central auditory system by experimental cochlear and brainstem implants.     

Preservation of brainstem neurophysiological function in hydranencephaly

The preservation of central neurophysiological function was assessed in a 32-year-old woman with hydranencephaly using brainstem auditory evoked responses (BAER), auditory middle latency responses (MLR), cortical auditory evoked responses (CER), strobe electroretinograms (ERG), strobe-flash visual evoked responses (VER) and median and tibial nerve somatosensory evoked responses (SER). The BAER to the right ear stimulation revealed wave peaks I through VII with normal thresholds, morphology and latencies, while the BAER in the left ear was abnormal. The auditory MLR and CER were absent. Grossly normal strobe ERGs were acquired bilaterally with peak waves at 20 and 50 ms. Strobe VERs were poorly defined and abnormal bilaterally. Left and right median nerve SER revealed significant conduction defects in the large fiber sensory system caudal to the thalamus, above the lower pontine level. Bilateral tibial nerve stimulation revealed normal knee popliteal fossa potentials, but distinct conduction defects in the large fiber sensory system rostral to the lower spinal cord. Brainstem electrophysiological measures revealed functional auditory afferent tracts and nuclei, in the absence of cortical influence, suggesting intact unilateral auditory function, which would support clinical observations of behavioral auditory responses in hydranencephaly.     

Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss and computational model

Ever since Pliny the Elder coined the term tinnitus, the perception of sound in the absence of an external sound source has remained enigmatic. Traditional theories assume that tinnitus is triggered by cochlear damage, but many tinnitus patients present with a normal audiogram, i.e., with no direct signs of cochlear damage. Here, we report that in human subjects with tinnitus and a normal audiogram, auditory brainstem responses show a significantly reduced amplitude of the wave I potential (generated by primary auditory nerve fibers) but normal amplitudes of the more centrally generated wave V. This provides direct physiological evidence of "hidden hearing loss" that manifests as reduced neural output from the cochlea, and consequent renormalization of neuronal response magnitude within the brainstem. Employing an established computational model, we demonstrate how tinnitus could arise from a homeostatic response of neurons in the central auditory system to reduced auditory nerve input in the absence of elevated hearing thresholds.     

Far-field recorded frequency-following responses: evidence for the locus of brainstem sources.

Two experiments were performed to determine the brainstem origins of the scalp recorded auditory frequency-following response (FFR). The first was a study of FFR onset latency in which responses observed by direct recording from depth electrodes in brainstem auditory nuclei were compared with those obtained from the scalp. The mean onset latency of scalp recorded FFR (5.8 msec) closely approximated the 5.4 msec mean latency of response recorded from within the inferior colliculus (IC). In a second experiment, cooling of the IC greatly reduced or eliminated FFR both within this nucleus and at the scalp. FFR at the medial superior olive was unaffected during cooling. It was concluded that at moderate intensities of stimulation the primary source of scalp recorded FFR is the IC.     

Gastric vagal-splanchnic interactions in the brainstem of the cat

Brainstem unitary responses to gastric vagal-splanchnic nerve interactions were evaluated in anesthetized cats during electrical stimulation of the nerves. The gastric branches of the dorsal and ventral vagal trunks which serve the proximal stomach were electrically stimulated while recording in nucleus solitarius in the brainstem to identify evoked unitary responses. The vagally evoked brainstem responses were orthodromic in nature as evidenced by a slight variability in latency, reduction in the number of spikes upon decreasing stimulus strength and failure to follow higher stimulus frequencies. Interactions between gastric vagal input from the proximal stomach and left greater splanchnic nerve were evaluated by simultaneously stimulating the nerves electrically. Forty-three (16%) of the 265 gastric vagally evoked brainstem responses recorded were inhibited by simultaneously activating the left greater splanchnic nerve. The gastric vagally evoked responses inhibited by splanchnic input were nearly equally divided between the dorsal and ventral vagal trunks. Eighty-eight percent of those vagally evoked brainstem units inhibited by splanchnic input showed complete inhibition suggesting secure synaptic coupling. In addition, 3 gastric vagally activated brainstem units were identified which were also activated by greater splanchnic input. The latency of the splanchnic evoked brainstem response in these 3 units ranged from 55 to 89 ms compared to a mean latency of 290 ms (S.D. +/- 50 ms) for the vagally evoked brainstem response. Splanchnic electrical stimulation usually produced an inhibitory effect upon the vagally evoked brainstem response which persisted for approximately 30 s following termination of splanchnic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Binaural interaction in auditory brainstem responses of mentally retarded and nonretarded individuals

The short-latency auditory brainstem responses of institutionalized mentally retarded individuals (Down syndrome and unknown etiology) and nonretarded control persons were recorded. The results showed that retarded individuals differed in the clarity of initial auditory brainstem response waves (I and II). Down syndrome individuals had significantly smaller auditory brainstem response amplitudes (Waves II and III) when compared with retarded individuals of unknown etiology. Down syndrome individuals also had significantly shorter latencies (Waves III and V) and shorter interwave conduction times (III-I and V-I) when compared with retarded individuals of unknown etiology. Retarded individuals did not differ from control subjects when amplitudes of binaural auditory brainstem responses were compared to the computer summation of such responses evoked by left and right ear stimulation; however, there was evidence for a general binaural interaction effect.     

Potentiation of amygdaloid and hippocampal auditory-evoked potentials in a discriminatory fear-conditioning task in mice as a function of tone pattern and context

According to the local memory storage hypothesis, information about the tone-shock association in an auditory fear-conditioning paradigm is stored in synapses within the lateral amygdala. Thus, fear-conditioning-induced potentiation of auditory-evoked potentials in response to a conditioned stimulus (CS+, a series of short lasting tones; patterned tone) has been interpreted as an in vivo correlate of amygdaloid synaptic plasticity. Here, we re-examine the specificity of potentiation of auditory-evoked potentials in terms of (i) local confinement to the lateral amygdala, (ii) parameters of CS+ and (iii) influence of context, using a discriminatory fear-conditioning paradigm. Adult male C57BL/6J mice were implanted with recording electrodes aimed at the lateral amygdala, the CA1 region of the hippocampus and the neck muscles for simultaneous recordings of auditory-evoked potentials and startle responses. In a neutral context, auditory-evoked potentials within lateral amygdala and CA1 as well as startle and freezing responses to the CS+ were significantly potentiated following conditioning, as compared with pre-conditioning values and responses to a neutral stimulus (CSn; tone of different frequency). Potentiation was only evident if CS+ was presented as a uniform series but not if presented mixed with CSn. Accordingly, mice failed to show intensified freezing to a patterned tone if a single lasting tone of the same frequency served as CS+. Both CA1 and lateral amygdala auditory-evoked potentials were potentiated in response to CSn if presented in the conditioning context. These findings demonstrate that (i) potentiation of auditory-evoked potentials is not restricted to the lateral amygdala, (ii) both tone frequency and pattern of tone presentation are essential for proper CS+ recognition and (iii) contextual memory leads to a general potentiation of auditory-evoked potentials.     

Somatosensory evoked response abnormalities in high-risk newborns

In a previous study from our laboratory, the prognostic significance of the auditory brainstem evoked response was assessed in high-risk neonates. An abnormal auditory brainstem evoked response predicted neurologic deficits at age 1 year; however, a normal result did not predict a normal outcome. In order to evaluate the prognostic utility of examining other sensory pathways, somatosensory evoked responses were elicited following median nerve stimulation. Testing was performed at 37–44 weeks conceptional age (defined as gestational age plus chronologic age) and at 2 and 6 months conceptional ages. Those patients studied included 34 high-risk neonates and 18 healthy, term infants as controls. Ten of the 34 patients had abnormal somatosensory evoked responses. Abnormalities included increased absolute (N19, P22) and interwave (N13–N19, N19–P22) latencies and flat potentials, alone or in combination. Three children with flat potentials demonstrated a persistence of this abnormality on subsequent examination and they later presented clinically with spastic quadriparesis. Four infants with increased latencies manifested normal responses on subsequent examination. Recently, these 4 patients exhibited tone abnormalities and mild developmental deficits; developmental outcome, however, will be assessed in a blind study at 1 year of age as part of this ongoing prospective study. Preliminary results suggest that somatosensory evoked responses may be valuable as an electrophysiologic predictor of outcome.     

Anatomic origin of P13 and P14 scalp far-field potentials.

After median nerve stimulation, noncephalic or earlobe reference montages enable one to record over the scalp a well-defined, positive far-field response, which has been labeled the P14 or P13-P14 complex. It has been ascertained that this wave is generated in the caudal brainstem. Its use is reliable and sometimes mandatory in assessing a number of diseases that affect primarily the brainstem, such as multiple sclerosis or coma. Because of its complex shape as well as discrepant findings in the literature, it is still debated whether this potential is produced by a single or by multiple serial generators. The authors present these different views and summarize the different recording methods, while bearing in mind that some recording techniques are more suitable for routine purposes and others are preferred in selected cases, when more information regarding caudal brainstem function is required.     

Linear and nonlinear changes in the auditory brainstem response of aging humans

OBJECTIVE: This experiment was designed to characterize the changes in linear and nonlinear temporal interactions in the aging auditory brainstem of humans using maximum length sequence (MLS) stimulation. METHODS: The MLS technique uses a quasi-random sequence of clicks and silences to determine the linear (linear averaging of single responses) and nonlinear (interactions between pairs or triplets of responses) temporal interactions in the auditory brainstem response (ABR). A group of 30 normal hearing females aged between 11 and 61years were tested. They were divided in three groups: young (<24years); middle (24-41years) and old (>41years). RESULTS: The linear component showed a decrease in wave 5 amplitude with age which could also be related to increased thresholds for higher frequencies. The nonlinear component of the MLS-ABR showed significant differences between middle and old groups for wave 1 and 5 latencies and inter-wave interval (1-5). CONCLUSIONS: The results suggest that the linear and nonlinear components of the MLS-ABR could be more sensitive to changes occurring in the auditory system before any functionally significant changes in hearing status. SIGNIFICANCE: The nonlinear components of the auditory brainstem could be used as an investigative tool to assess early changes in the aging auditory brainstem in young middle-aged women.     

Temporal relationship between single unit activity in superior olivary complex and scalp-derived auditory brainstem response in guinea pig

Single unit activities in the region of the superior olivary complex were recorded from 8 guinea pigs concurrently with the recording of auditory brainstem potentials from the scalp. At any one anatomical site, be it a fiber tract (e.g. trapezoid body) or a nucleus (e.g. medial nucleus of the trapezoid body), the modal latency of the onset discharge of the units encountered corresponded in time with the latencies of several different waves (waves P2-P5) of the auditory brainstem response (ABR). Moreover, at the time of occurrence of just one of the ABR waves, single units in several diverse anatomical sites in and around the superior olive were found with modal latencies of onset discharge at that same time period. The slopes of the latency/intensity functions for both the peaks of the ABR and the modal latency of the onset discharge for most of the single units studied in the superior olive and its adjacent fiber tracts were remarkably similar. These data support the hypothesis of multiple rather than single generator site(s) for components of the ABR, at least, for waves P2-P5 in the guinea pig. These data do not distinguish whether the ABR are generated in part by travelling nerve action potentials or graded synaptic events.     

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.     

Murine auditory brainstem evoked response: putative two-channel differentiation of peripheral and central neural pathways

Standard noninvasive recordings of the auditory brainstem evoked response (ABR) from a single pair of obliquely oriented electrodes (typically midline vertex referenced to mastoid) confound inherently distinct signals propagating over peripheral and central neural pathways differing in location and spatial orientation. We describe here a technique for recording short-latency auditory evoked potentials that putatively differentiates peripheral and central neural activity in the mouse and rat. The technique involves recording from two orthogonally oriented electrode pairs using fast sample rates (100 k/s) to accurately measure differences in neural timing and waveform morphology. Electrodes oriented in a transverse plane (mastoid-to-mastoid) register an initial positive-going ABR peak (P1T) earlier than a series of peaks recorded from electrodes oriented along the midline (anterior and posterior to the inter-aural line). The absolute P1T latency is consistent with an origin in the primary auditory nerve, while the delayed midline latencies implicate activity farther along central neural pathways. Differences between these latencies (midline minus transverse) provide new and precise measures of central conduction time (CCT), which in one case is as brief as 0.10 ms. Results in wild type (WT) and knockout (KO) mice, as well as rats, show significant differences in absolute latencies as well as CCT.     

Cortical hemispheric asymmetries are present at young ages and further develop into adolescence

Specialization of the auditory cortices for pure tone listening may develop with age. In adults, the right hemisphere dominates when listening to pure tones and music; we thus hypothesized that (a) asymmetric function between auditory cortices increases with age and (b) this development is specific to tonal rather than broadband/non‐tonal stimuli. Cortical responses to tone‐bursts and broadband click‐trains were recorded by multichannel electroencephalography in young children (5.1 ± 0.8 years old) and adolescents (15.2 ± 1.7 years old) with normal hearing. Peak dipole moments indicating activity strength in right and left auditory cortices were calculated using the Time Restricted, Artefact and Coherence source Suppression (TRACS) beamformer. Monaural click‐trains and tone‐bursts in young children evoked a dominant response in the contralateral right cortex by left ear stimulation and, similarly, a contralateral left cortex response to click‐trains in the right ear. Responses to tone‐bursts in the right ear were more bilateral. In adolescents, peak activity dominated in the right cortex in most conditions (tone‐bursts from either ear and to clicks from the left ear). Bilateral activity was evoked by right ear click stimulation. Thus, right hemispheric specialization for monaural tonal stimuli begins in children as young as 5 years of age and becomes more prominent by adolescence. These changes were marked by consistent dipole moments in the right auditory cortex with age in contrast to decreases in dipole activity in all other stimulus conditions. Together, the findings reveal increasingly asymmetric function for the two auditory cortices, potentially to support greater cortical specialization with development into adolescence.     

The action of norepinephrine in the rat hippocampus. IV. The effects of locus coeruleus stimulation on evoked hippocampal unit activity.

Activity of neurons in the hippocampus (HPC) was recorded in awake, freely moving rats. Most cells were inhibited by either a loud auditory stimulus (tone) or by electrical stimulation of the nucleus locus coeruleus (LC). The inhibitory responses to the tone were antagonized by drugs that interfere with central noradrenergic transmission. When LC stimulation was used as the unconditioned stimulus in a classical conditioning paradigm, previously inhibitory responses to the tone were reinstituted. When behaviorally subthreshold LC stimulation preceded a tone which was correlated with food, the existing conditioned response to the tone was potentiated. These data suggest that the generalized inhibitory response of HPC neurons to a tone is modulated by the noradrenergic pathway and that experimental activation of LC can potentiate HPC responses to behaviorally significant conditioned stimuli.     

Sound‐specific plasticity in the primary auditory cortex as induced by the cholinergic pedunculopontine tegmental nucleus

Brain cholinergic modulation is essential for learning‐induced plasticity of the auditory cortex. The pedunculopontine tegmental nucleus (PPTg) is an important cholinergic nucleus in the brainstem, and appears to be involved in learning and subcortical plasticity. This study confirms the involvement of the PPTg in the plasticity of the auditory cortex in mice. We show here that electrical stimulation of the PPTg paired with a tone induced drastic changes in the frequency tunings of auditory cortical neurons. Importantly, the changes in frequency tuning were highly specific to the frequency of the paired tone; the best frequency of auditory cortical neurons shifted towards the frequency of the paired tone. We further demonstrated that such frequency‐specific plasticity was largely eliminated by either thalamic or cortical application of the muscarinic acetylcholine receptor antagonist atropine. Our finding suggests that the PPTg significantly contributes to auditory cortical plasticity via the auditory thalamus and cholinergic basal forebrain.