Auditory evoked responses in the rat: transverse mastoid needle electrodes register before cochlear nucleus and do not reflect later inferior colliculus activity

A previously described technique putatively differentiates short-latency auditory evoked potentials in peripheral and central neural pathways of the mouse and rat [Galbraith G, Waschek J, Armstrong B, Edmond J, Lopez I, Liu W, et al. Murine auditory brainstem evoked response: putative two-channel differentiation of peripheral and central neural pathways. J Neurosci Methods 2006;153:214-20]. This technique involves recording from orthogonally oriented subdermal needle electrode pairs, using fast sample rates (100k/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 peak earlier than peaks recorded from electrodes oriented along the scalp midline (anterior and posterior to the interaural line). The absolute latency of the early mastoid component is consistent with an origin in the primary auditory nerve, while delayed midline latencies implicate activity in central neural pathways. We report here the results of recording simultaneously from transverse mastoid (M) needle electrodes and electrodes acutely implanted in cochlear nucleus (CN) and inferior colliculus (IC). The results show a highly consistent pattern in which the initial mastoid component leads CN by an average of 0.16 ms, suggesting an obligatory neural site of origin of the mastoid response that is distal to IC, namely the auditory nerve. Moreover, later IC components (beyond approximately 3.5 ms) are completely absent in mastoid recordings, indicating that the transverse mastoid recordings provide a relatively isolated measure of early auditory neural activity.     

Auditory brainstem response and somatosensory evoked potential in Machado-Joseph disease in Japanese families

To clarify physiological aspects of Machado-Joseph disease (MJD), we studied auditory brainstem response (ABR) and somatosensory evoked potential (SEP) in 17 clinically diagnosed patients with MJD aged 32-64 in Japanese families. ABR was recorded in 13 patients. In 8 patients, ABR were abnormal. In 5 patients, the latency of I wave was normal, but other waves could not be evoked. In the other 3 patients, I-III interpeak latency was prolonged. SEP was recorded in 15 patients. In SEP of median nerve, 11 patients had abnormal findings, and SEP of posterior tibial nerve revealed abnormal findings in all 15 patients. In all patients, responses from Erb's point and popliteal fossa were normal in latency, but other peaks were low in amplitude or absent, and the latency and central conduction time (CCT) were prolonged. The result of ABR indicated the involvement of the brainstem auditory pathways in MJD, and the result of SEP suggested that somatosensory pathways, particularly central pathways, would be involved in the disease process. ABR and SEP can be potential diagnostic methods for detection of subclinical abnormality in MJD patients.     

Posterior tibial and sural nerve somatosensory evoked potentials in dystrophia myotonica

Somatosensory evoked potentials (SEPs) were recorded in a group of 18 patients with dystrophia myotonica and in 28 control subjects after stimulating the right and left posterior tibial (SEP-PT) and sural (SEP-S) nerves at the ankles. Recording electrodes were placed in the popliteal fossae, overlying the L3 spinal vertebrae, and at the appropriate scalp sites. In all control subjects and dystrophia myotonica subjects SEP-PT latencies were shorter than equivalent SEP-S latencies, probably reflecting conduction along group I muscle afferents and along slower conducting cutaneous afferents, respectively. Intergroup comparisons revealed prolonged absolute and interpeak latencies in the dystrophia myotonica group, showing both peripheral and central somatosensory pathway involvement. Individual abnormal latencies which exceeded the control group mean plus 3 standard deviations were found in 66% of the dystrophia myotonica group, mainly due to prolonged peripheral conduction times. Results pointed to the concomitant involvement of both the posterior tibial and sural nerve somatosensory pathways in dystrophia myotonica.     

No auditory conduction abnormality in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder characterized by lack of sustained attention and hyperactivity. It has been suggested that asymmetrical conduction of the auditory stimulus in the brainstem plays a role in the pathophysiological process of ADHD. In the present study, the functional integrity of the central auditory pathway was assessed using the auditory brainstem response (ABR), mid-latency response (MLR) and slow vertex response (SVR). Twenty ADHD children and twenty controls were recruited for the study and recordings were done on a computerized evoked potential recorder using the 10-20 system of electrode placement. There emerged no significant difference in absolute peak latencies, interpeak latencies and amplitude of ABR or latency of MLR in the ADHD children as compared with the controls. Prolongation of the SVR latency was found in the children with ADHD versus the controls, but the difference was statistically insignificant. The present study does not suggest any auditory conduction abnormality as a contributory factor in ADHD.     

Neurotoxic effects of n-hexane on the human central nervous system: evoked potential abnormalities in n-hexane polyneuropathy.

An outbreak of n-hexane polyneuropathy as a result of industrial exposure occurred in printing factories in Taipei area from December 1983 to February 1985. Multimodality evoked potentials study was performed on 22 of the polyneuropathy cases, five of the subclinical cases, and seven of the unaffected workers. The absolute and interpeak latencies of patterned visual evoked potential (pVEP) in both the polyneuropathy and subclinical groups were longer than in the normal controls. The pVEP interpeak amplitude was also decreased in the polyneuropathy cases. Brainstem auditory evoked potentials (BAEP), showed no difference of wave I latency between factory workers and normal controls, but prolongation of the wave I-V interpeak latencies was noted, corresponding with the severity of the polyneuropathy. In somatosensory evoked potentials (SEPs), both the absolute latencies and central conduction time (CCT) were longer in subclinical and polyneuropathy cases than in the unaffected workers and normal controls. From this evoked potentials study, chronic toxic effects of n-hexane on the central nervous system were shown.     

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. II. A cross-sectional study in childhood. Correlations with hormonal levels and developmental quotients

We report the results of somatosensory evoked potentials (SEPs) and auditory brain-stem responses (ABRs) done in 48 congenital hypothyroid (CH) treated children, early detected and aged 18 months, 3 and 5-9 years of age. We report also the results of SEP and ABR done in 9 3-year-old CH children, before and after a 1 month therapy interruption to reassess the thyroid status. The more frequent abnormalities were increased wave I latencies for 18 month and 3-year-old CH children. In some children, these increases were not associated with signs of otitis media. No significant difference was seen between CH children and controls for SEP latencies and ABR and SEP interpeak latencies (IPLs). Similarly, no significant difference was seen between the two recording sessions in the 9 3-year-old CH children for ABR and SEP. On an individual basis, we observed abnormalities of central conduction time for ABR and SEP in several CH children. Moreover, significant partial correlations were found between ABR and SEP IPLs and thyroxine (T4) serum levels at diagnosis and thyrotropin (TSH) serum levels at the time of recording. There was also a significant partial correlation between N19-P22 IPLs and the practical reasoning scale of the Griffiths test considering the whole group of CH children. These results indicate that SEP might eventually be used to detect CH children at risk of presenting developmental abnormalities.     

Multi-modality evoked potentials in hypoxaemia

The auditory nerve-brain-stem evoked response (ABR) has been shown to be insensitive to hypoxic inspiratory gas mixtures which severely depress the EEG. In order to determine the relative sensitivities of additional brain regions and pathways to hypoxaemia, anaesthetized paralysed cats were ventilated with various gas mixtures while recording the evoked responses of the auditory, somatosensory (including peripheral nerve, brain-stem and primary cortical components), visual and vestibular systems. Arterial blood pressure was maintained by dopamine infusion and pH was corrected with bicarbonate. Hypoxic gas mixtures (6-7% O2) presented for 60 min, causing severe hypoxaemia (paO2 20-30 mm Hg; O2 saturation 25-50%), were without effect on the somatosensory, vestibular and visual EPs while the auditory evoked potentials (ABR and cortical components) were depressed. However, if arterial blood pressure was allowed to fall, all of the evoked potentials became severely depressed and isoelectric. These results and others indicate that the cortical components are qualitatively similar to the more peripheral evoked potentials. The resistance of these evoked potentials to controlled hypoxaemia is probably due to their generation by oligosynaptic pathways and to a compensatory switch to anaerobic metabolism and to an elevation of cerebral blood flow.     

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.     

Peripheral and central conduction abnormalities in diabetes mellitus

OBJECTIVES: To investigate peripheral and central somatosensory conduction in patients with diabetes. METHODS: The authors recorded sensory nerve action potentials and 5-channel somatosensory evoked potentials (SEPs) with noncephalic reference after median nerve stimulation in 55 patients with diabetes and 41 age- and height-matched normal subjects. The authors determined onset or peak latencies of the Erb's potential (N9) and the spinal N13-P13 and the cortical N20-P20 components, and obtained the central conduction time (CCT) by onset-to-onset and peak-to-peak measurements. RESULTS: Both onset and peak latencies of all SEP components were prolonged in patients with diabetes. The mean onset CCT in the diabetic group was 6.3 +/- 0.5 msec (mean +/- SD)-significantly longer than that in the control group (6.1 +/- 0.2 msec)-whereas no significant difference was found in the peak CCT. The amplitudes of N9 and N13-P13 components (but not N20-P20) were significantly smaller in the diabetic group. The peripheral sensory conduction velocity was also decreased in the diabetic group, but there was no significant correlation between peripheral conduction slowing and the onset of CCT prolongation. CONCLUSIONS: Diabetes affects conductive function in the central as well as peripheral somatosensory pathways. The CCT abnormality does not coincide with lowering of the peripheral sensory conduction. The current results do not favor a hypothesis that a central-peripheral distal axonopathy plays an important role in development of diabetic polyneuropathy.     

Auditory function in Pelizaeus–Merzbacher disease

Pelizaeus–Merzbacher disease (PMD; MIM 312080), an inherited defect of central nervous system myelin formation, affects individuals in many ways, including their hearing and language abilities. The aim of this study was to assess the auditory abilities in 18 patients with PMD by examining the functional processes along the central auditory pathways using auditory brainstem responses (ABR) and cortical auditory evoked potentials (CAEP) in response to speech sounds. The significant ABR anomalies confirm the existence of dyssynchrony previously described at the level of the brainstem in patients with PMD. Despite the significant auditory dyssynchrony observed at the level of the brainstem, CAEPs were present in most patients, albeit somehow abnormal in terms of morphology and latency, resembling a type of auditory neuropathy spectrum disorder.     

Influence of reference electrodes, stimulation characteristics and task paradigms on auditory P50

Abstract To clarify the nature of auditory P50, middle latency auditory evoked potentials were recorded by using different conditions of reference electrodes (linked earlobes, LE; balanced non-cephalic, BN), stimulation characteristics (tone burst, human voice) and tasks (counting, simple reaction) in 10 right-handed males (aged 21–36 years). EEG was recorded from Fz, Cz, Pz, C3, C4, T3 and T4 according to the 10–20 system. Two groups of electrode sites were made for the statistical analysis: a midline group, Fz, Cz and Pz; and a lateral group, T3, C3, Cz, C4 and T4. The results were that the P50 amplitudes with BN electrodes were significantly higher than those with LE in both groups (midline, P < 0.01; lateral, P < 0.01); the P50 amplitudes by voice stimulation were significantly higher than those by tone stimulation in the lateral group ( P < 0.05), and the P50 latencies under a simple reaction paradigm were significantly shorter than those under a counting task in both groups (midline, P < 0.05; lateral, P < 0.05). These results suggest that various factors including motor response affect the P50 amplitudes and latencies.     

Selective attention affects human brain stem frequency-following response

Selective attention modifies long-latency cortical event-related potentials. Amplitudes are typically enhanced and/or latencies reduced when evoking stimuli are attended. However, there is controversy concerning the effects of selective attention on short-latency brain stem evoked potentials. The objective of the present study was to assess possible attention effects on the brain stem auditory frequency-following response (FFR) elicited by a periodic tone. Young adult subjects heard a repetitive auditory stimulus while detecting infrequent target stimuli in either an auditory or visual detection task. Five channels of high frequency electroencephalographic (EEG) activity were recorded along the scalp midline with the center electrode positioned at the vertex. The FFR was elicited by the repetitive tone during both tasks. There were significant individual differences in the electrode sites yielding maximum response amplitudes, but overall FFR amplitudes were significantly larger during the auditory attention task. These results suggest that selective attention in humans can modify signal processing in sensory (afferent) pathways at the level of the brain stem. This may reflect top-down perceptual preprocessing mediated by extensive descending (efferent) pathways that originate in the cortex. Overall, the FFR appears to be a robust indicator of early auditory neural processing and shows effects not seen in brain stem auditory evoked response studies employing transient (click) acoustic stimuli.     

Auditory and Visual Evoked Potentials to Irrelevant Stimuli During Conditioning to a Visual Stimulus

Amplitude changes of evoked responses to irrelevant auditory (click) and visual (optic tract stimulation) stimuli were examined during appetitive conditioning to a flashing light. Four female cats, with chronically implanted electrodes along the visual and auditory pathways, were conditioned with pairings of a flashing light and food reinforcement. The results showed that, as conditioning progressed, the auditory evoked potentials were attenuated while the visual evoked potentials did not change significantly. The data seem to indicate possible differences in the neural processing of irrelevant information.     

Auditory and visual evoked potentials to irrelevant stimuli during conditioning to a visual stimulus

Amplitude changes of evoked responses to irrelevant auditory (click) and visual (optic tract stimulation) stimuli were examined during appetitive conditioning to a flashing light. Four female cats, with chronically implanted electrodes along the visual and auditory pathways, were conditioned with pairings of a flashing light and food reinforcement. The results showed that, as conditioning progressed, the auditory evoked potentials were attenuated while the visual evoked potentials did not change significantly. The data seem to indicate possible differences in the neural processing of irrelevant information.     

Auditory brainstem responses in autism: Brainstem dysfunction or peripheral hearing loss?

The advent of electrophysiological techniques for audiologic and neurologic assessment in the late 60s has generated at least 11 auditory brainstem response (ABR) studies in autism designed to test the integrity of the auditory brainstem pathways. The results reported are contradictory, involving prolongation, shortening, and no abnormalities in central transmission latencies. When sample and methodological factors influencing the ABR are taken into consideration in the interpretation of results, the ABR data available at present can be seen as only suggestive, rather than supportive, of brainstem involvement in autism. Paradoxically, these studies revelated the presence of peripheral hearing impairment in a nonnegligible number of autistic individuals. Additional evidence of auditory abnormalities as well as the implications for the clinician are considered.The author is grateful to Isabelle Rapin and Terence W. Picton for their comments on an earlier draft of this paper, and particularly to David R. Stapells for his numerous and extremely valuable suggestions.     

Measurement of lingual and palatine somatosensory evoked potentials.

OBJECTIVE: A technique is presented for generating and recording lingual and palatine nerve somatosensory evoked potentials (SEPs). METHODS: Pairs of thin, stainless steel disk electrodes were mounted onto mandibular or maxillary acrylic splints, similar to orthodontic retainers. Mandibular splint electrodes were oriented to contact the under surface of the tongue along the course of the right and left lingual nerves and maxillary splint electrodes were oriented to contact the hard palate bilaterally along the course of the palatine nerves. SEP recording electrodes were placed on the scalp 1 cm posterior to C5 and C6 (C5' and C6', respectively) using the combinatorial nomenclature of the International 10-20 system. Two reference electrode locations, Fz and C5' or C6', over the cortical hemisphere opposite that of the recording electrode, were used. RESULTS: Right and left lingual and palatine nerve SEPs were recorded from five normal adults. SEP latencies were similar to the N13 and P18 cortical peak latencies recorded in previous studies of trigeminal nerve branches to the lips regardless of reference electrode position. CONCLUSIONS: A more precise method of stimulating the intraoral lingual and palatine nerves was accomplished using dental splints. SEPs were easier to obtain using a contralateral cortex reference electrode location.     

Effects of aging on central conduction in somatosensory evoked potentials: evaluation of onset versus peak methods.

OBJECTIVES: To investigate effects of aging on peripheral and central somatosensory conduction, and evaluate onset-to-onset and peak-to-peak measurements of each component and central conduction time (CCT) in somatosensory evoked potentials (SEPs). METHODS: We recorded SEPs with non-cephalic reference from the Erb's point, the posterior (cv 6) and anterior neck, and scalp (Fz and P4) after left median nerve stimulation in 138 normal subjects aged between 20 and 78 years. We determined onset or peak latencies of the Erb's potential (N9), the spinal N13-P13 in cv 6-to-anterior neck montage and the N20-P20 in scalp leads. Onset CCT was defined as a transit time from N13-P13 onset to N20-P20 onset. In each subject, interpeak latencies of the 'N13' component in cv 6-to-Fz montage and the N20-P20 in P4-to-Fz montage were also defined as conventional peak CCT. RESULTS: Using multiregression analysis, we found that the onset or peak latencies of each SEP component were correlated with the subject's height and age. So were the onset CCTs: Onset CCT (in ms) = 2.549+2.041x(height in meters) + 0.005 x (age in years) (P<0.0001). The conventional peak CCTs as well as onset-to-peak durations of the N20-P20 were correlated with the subject's age but not height: Peak CCT(in ms) = 5.458+0.012x (age in years) (P<0.0005). CONCLUSION: Conductive function is affected by normal aging in the central as well as peripheral somatosensory pathways. The peak CCT is more affected by aging than the onset CCT. However, the onset-to-peak duration of the N20-P20 increased by 0.8 ms between the 4th and 7th decades, suggesting that the peak CCT increase in older people reflects the age-related changes in N20-P20 profile but not in the fastest central conduction. We therefore conclude that the onset CCT measurement is preferable to the peak CCT measurement when assessing the central somatosensory conduction.     

A fiber tract model of auditory brain-stem responses

The hypothesis that auditory brain-stem responses (ABRs) are generated by action potentials in fiber tracts was tested by recording from frog sciatic nerves in a volume conductor. Far-field recording of the sciatic nerve action potentials confirmed the rule that the initial response of the electrode toward which the action potentials are traveling is positive with respect to the electrode from which they are retreating. This rule explained the initial polarity of response for transverse and longitudinal recordings in humans, and why right and left ear clicks evoke responses of opposite polarity for transverse recording, but the same polarity for longitudinal recording. This result was true for all of the waves evoked, up to 8 msec latency. A later myogenic potential known as the postauricular response did not invert with the ear stimulated. The possibility of a dendritic contribution to the ABR was discussed. It was concluded that the components of the ABR are more satisfactorily explained by action potentials than by somatic or dendritic synaptic activity.     

Latency alterations of the auditory brainstem response in audiogenic seizure-prone Long-Evans rats

Audiogenic seizure susceptibility in the normally seizure-resistant Long-Evans rat may result from altered processing in the auditory pathway. Representative waveform latencies of the auditory brainstem responses (ABR) were recorded to examine generator alterations at different levels of the auditory neuraxis. Male Long-Evans rats primed for audiogenic seizures (AGS) on PND 14 with a 10 kHz pure tone at 120 dB SPL for 8 min were tested for AGS on PND 28 with 120 dB SPL continuous white noise. Primed subjects displayed wild running culminating in clonic convulsions. Following behavioral testing at 4-6 months, vertex recordings of ABR waves Ia-VI were made in anesthetized subjects using pure tone stimulus bursts. AGS subjects showed marginally elevated ABR thresholds. Shorter ABR wave latencies were elicited in AGS subjects for peripheral and central auditory components with stimulus intensities above 50 dB PeSPL at 8 and 40 kHz. Interpeak intervals were reduced for waves Ia-V and III-V in AGS subjects. These results reveal that intense sound stimulation during a sensitive period of development later reduces processing time at higher intensity levels.     

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.