Anesthesia with flunitrazepam/fentanyl and isoflurane/fentanyl. Unconscious perception and mid-latency auditory evoked potentials

There is a high incidence of intraoperative awareness during cardiac surgery. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. In the present study, we investigated MLAEP and explicit and implicit memory for information presented during cardiac anaesthesia. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 30 patients scheduled for elective cardiac surgery. Anaesthesia was induced in group I (n = 10) with flunitrazepam/fentanyl (0.01 mg/kg) and maintained with flunitrazepam/fentanyl (1.2 mg/h). The patients in group II (n = 10) received etomidate (0.25 mg/kg) and fentanyl (0.005 mg/kg) for induction and isoflurane (0.6-1.2 vol%)/fentanyl (1.2 mg/h) for maintenance of general anaesthesia. Group III (n = 10) served as a control and patients were anaesthetized as in I or II. After sternotomy an audiotape that included an implicit memory task was presented to the patients in groups I and II. The story of Robinson Crusoe was told, and it was suggested to the patients that they remember Robinson Crusoe when asked what they associated with the word Friday 3-5 days postoperatively. Auditory evoked potentials were recorded awake and during general anaesthesia before and after the audiotape presentation on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms poststimulus interval and analyzed off-line. Latencies of the peak V, Na, Pa were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. RESULTS. None of the patients had an explicit memory of intraoperative events. Five patients in group I, one patient in group II, and no patients in group III showed implicit memory of the intraoperative tape message. They remembered Robinson Crusoe spontaneously when they were asked their associations with Friday. In the awake state AEP peak latencies were in the normal range. During general anaesthesia in group I, the peaks Na, Pa did not increase in latency or decrease in amplitude before and after the audiotape presentation. The primary cortical complex Na/Pa could be identified as in the awake state. In contrast, in group II Na, Pa showed a marked increase in latency and a decrease in amplitude or were completely suppressed. CONCLUSIONS. During general anaesthesia auditory information can be processed and remembered postoperatively by an implicit memory function, when the electrophysiological conditions of primary cortical stimuli processing is preserved. Implicit memory can be observed more often when high-dose opioid analgesia is combined with receptor-binding agents like the benzodiazepines than under non-specific anaesthetics like isoflurane. Non-specific anaesthetics seem to provide a more effective suppression of auditory stimuli processing than receptor-specific agents.     

Abnormalities of auditory evoked magnetic fields and structural changes in the left hemisphere of male schizophrenics--a magnetoencephalographic-magnetic resonance imaging study

Functional and structural changes in 10 DSM-III-R male schizophrenics and 10 healthy volunteers were investigated using magnetoencephalographically (MEG) detected long-latency (N100 m) auditory evoked fields (AEFs) and magnetic resonance imaging (MRI). The AEFs were characterized by single moving equivalent dipoles, which were superimposed on MRIs. There were significant differences in dipole orientations and in AEF latencies in the left hemisphere of schizophrenics, when compared to the controls. The MEG-detected alterations were found to be associated with a bilateral volume reduction of the posterior superior temporal gyrus (pSTG), which was more pronounced in the left hemisphere. Separate analysis of white and gray matter has shown that the pSTG volume reduction resulted from decreased gray matter volumes without white matter changes. Both the functional and the morphological data indicate a left-hemispheric disturbance in our patients.     

Human auditory cortical mechanisms of sound lateralization: II. Interaural time differences at sound onset

Neuromagnetic responses were recorded over the right temporal cortex using a 24-channel gradiometer. Stimuli were binaural click trains, presented with six separate interaural time differences (ITDs). N100m to sound onset was larger and earlier for stimuli presented with left- than with right-leading ITDs. With stimulus lateralization taken into account, monaural and binaural stimuli evoked responses of roughly equal amplitude. In selective adaptation and oddball experiments, stimuli presented with different ITDs excited overlapping neuronal populations, but the amount of overlap decreased as the ITD between the stimuli increased. There were no systematic differences in the cortical source locations of the N100m as a function of ITD, however. Thus it appears that ITD-sensitive neurons in the human auditory cortex are not organized into a large-scale, orderly representation, which could be resolved by MEG.     

Functional localization of bilateral auditory cortices using an MRI-linked whole head magnetoencephalography (MEG) system

In 20 healthy subjects, auditory evoked magnetic fields were measured over the entire head, using a helmet-shaped 66-channel MEG system linked to MRI. When the left or right ear was stimulated by 60 msec 2 kHz tones, the prominent 100 msec response (N100m) appeared significantly earlier in the contralateral hemisphere than in the ipsilateral one. In 16 cases, the N100m dipolar field patterns were clear in both hemispheres, overlapping each other across the midline. The N100m sources were estimated using a 2-dipole model in a spherical conducting medium with the size and location of the sphere determined individually according to the MRI images. No differences were found between the contralateral and ipsilateral N100m dipole positions in one hemisphere. When superimposed on MRI, the N100m dipoles were located precisely on the upper surface of bilateral temporal lobes with a standard deviation of 2.2 mm in the superior-inferior direction. In 16 right handed males, the right hemispheric N100m dipoles were 6 mm anterior to the left hemispheric dipoles. The whole head MEG is suitable to see small but significant differences of bilateral cerebral function, with exceptionally high spatial resolution, confirmed by the MRI-linked system.     

Cortical-hippocampal auditory processing identified by magnetoencephalography

We recorded magnetic and electrical responses simultaneously in an auditory detection task to elucidate the brain areas involved in auditory processing. Target stimuli evoked magnetic fields peaking at approximately the same latency of around about 400 msec (M400) over the anterior temporal, superior temporal, and parietal regions on each hemisphere. Equivalent current dipoles (ECDs) were analyzed with a time-varying multidipole model and superimposed on each subject's magnetic resonance image (MRI). Multiple independent dipoles located in the superior temporal plane, inferior parietal lobe, and mesial temporal region best accounted for the recorded M400 fields. These findings suggest that distributed activity in multiple structures including the mesial temporal, superior temporal, and inferior parietal regions on both hemispheres is engaged during auditory attention and memory updating.     

Effects of the civil war in central Mozambique and evaluation of the intervention of the International Committee of the Red Cross

Visual evoked potentials to pattern reversal and diffuse flash stimulation were recorded from 520 consecutive pediatric patients and 11 normal infants between the ages of 27 weeks post-conception and 24 months. The latency and peak-to-peak amplitude of the first reproducible positive peak of the binocular pattern visual evoked potential (P100) were measured for five check sizes subtending from 15' to 4 degrees of arc. Three developmental trends were noted: 1) a rapid increase in pattern resolution near term, 2) a subsequent decrease in the latency of P100, and 3) a gradual increase in the amplitude of P100. These three trends reflect the multiplicity of early maturation and are discussed in terms of changes in receptor growth and density, pathway myelination, and cortical synaptivity.     

High-precision neuromagnetic study of the functional organization of the human auditory cortex

Previous studies have proven that a dipole source analysis of the auditory evoked field is capable of providing evidence of the tonotopic organization of the human auditory cortex. To explore the nature of the estimated dipoles in greater detail, a single subject was extensively studied, and the estimated sources were registered in a three-dimensional reconstruction of the cortical surface derived from magnetic resonance images. The stimuli were 500-ms tone bursts with frequencies of 250, 500, 1,000, and 2,000 Hz (mean intensity of 60 dB SL). The total number of stimuli presented per condition was about 3,600 (36 independent experiments spread over 4 days). Using special postprocessing techniques, the relative localization accuracy could be enhanced to such an extent that differences in the dipole locations of 1 mm could be clearly distinguished. The results suggest that peak N1m (latency around 100 ms) arises from the planum temporale, whereas peak P2m (latency around 170 ms) appears to correspond to a center of activity in (or close to) Heschl's gyrus. The tonotopic organization found for the generator of N1m was consistent with earlier studies ("the higher the frequency the deeper the source"). However, additional findings (time dependence of the estimated sources; slightly different tonotopy obtained for field change; dependence of the estimated sources on the estimation technique) indicate that multiple areas are involved in the generation of N1m. Evidence of a frequency-dependent source location was found also for P2m.     

A ''neural'' response with 3-ms latency evoked by loud sound in profoundly deaf patients

A large negative deflection with a latency of 3 ms was observed in the auditory brainstem response (ABR) waveforms of some patients with peripheral profound deafness. This deflection was termed the N3 potential. In this paper, we review patients with the N3 potential and discuss the characteristics of abnormal ABR waveforms. The origin of the N3 potential was also discussed, especially with respect to vestibular evoked potentials. In most of the patients, audiograms showed no response to the maximum output of an audiometer in the high-frequency range and a residual response in the low-frequency range. The N3 potentials were noted at intensities of 80 dB nHL or greater. As the stimulus intensity increased, the amplitude of the potential increased and the latency decreased. A high repetition rate (83.3/s) of the click stimulus influenced the latency and amplitude of the N3 potential. The potential was replicated on retest within less than a month, and had a consistent latency and amplitude over the scalp. The results indicate that the N3 potential is not an electrical artifact but a physiological neural response evoked by a loud sound. The N3 potential is most likely not an auditory evoked response from cochlear or a response from a semicircular canal, because it has a 3-ms latency, a sharp waveform, and is unassociated with vertigo. The results suggest that the N3 potential may be a saccular acoustic response.     

Discriminative power of visual evoked potential characteristics in multiple sclerosis

To investigate the discriminative power of pattern-reversal visual evoked potential characteristics (peak latencies and amplitude) and to test whether the addition of visual evoked potential amplitude can increase the power of the visual evoked potential in the diagnosis of multiple sclerosis, we retrospectively studied visual evoked potentials in 59 patients with definite multiple sclerosis and 126 control subjects. Two check sizes (17' and 10') were used. Females had significantly higher amplitudes and shorter latencies than males. N80 latency showed a gradual increase and P100 amplitude a decrease with age. P100 latency was stable between the ages of 20 and 55 years but was increased in childhood and the elderly. The significance of visual evoked potential peak latencies and amplitude in separating the two groups was investigated by means of a (multivariate) discriminant analysis. The visual evoked potential with a pattern of 10' could be measured in 58% of patients with multiple sclerosis. The exclusive use of the P100 amplitude in the discriminant analysis resulted in a percentage of correctly classified cases of 84%, whereas for P100 and N80 latency it was 85% and 90%, respectively. With the 17' pattern, the N80 latency yielded also a higher correct percentage than did the P100 latency. Although N80 latency is, to a greater extent than P100 latency, influenced by age, sex and size of stimulus pattern, when these influences are accounted for, the N80 latency is a more sensitive measure than P100 latency in the classification of multiple sclerosis. Combined use of latency and amplitude for discriminant analysis yielded no significant improvement of the percentage of correctly classified cases.     

Auditory middle latency responses in patients with epilepsy

Middle latency auditory responses (MLRs) were studied in 55 normal subjects and 49 epileptic patients. We evaluated the function of the auditory system and of the temporal lobe in epileptic patients using MLRs. (1) The patients with epilepsy had significantly prolonged Pa and Nb latencies and the significantly increased amplitude of Pa-Nb component. (2) The prolongation and the increase of MLR components in latency and amplitude were more obvious in patients with intractable epilepsy than patients without intractable epilepsy. (3) The difference between left and right sides was larger in epileptic patients than normal subjects. (4) Epileptic patients with polypharmacy had reduced amplitude of Pa-Nb component and prolonged latency of Pa component than patients with monotherapy. Antiepileptic drugs (AEDs) appeared to decrease the amplitude of Pa-Nb component. It was supposed that the enhancement of amplitude of Pa-Nb component represented the abnormality of central nerve system in epileptic patients, in part.     

Mismatch negativity in the neurophysiologic/behavioral evaluation of auditory processing deficits: a case study

The subject of this case report is an 18-year-old woman with grossly abnormal auditory brain stem response (ABR), normal peripheral hearing, and specific behavioral auditory processing deficits. Auditory middle latency responses (MLRs) and cortical potentials N1, P2, and P300 were intact. The mismatch negativity (MMN) was normal in response to certain synthesized speech stimuli and impaired to others--consistent with her behavioral discrimination of these stimuli. Behavioral tests of auditory processing were consistent with auditory brain stem dysfunction. A neuropsychological evaluation revealed normal intellectual and academic performance. The subject was in her first year of college at the time of the evaluation. This case study is important because: (1) Although there have been several reports of absent/abnormal ABR with preserved peripheral hearing and deficits in auditory processing, little is known about the specific nature of the auditory deficits experienced by these individuals. Such information may be valuable to the clinical management of patients with this constellation of findings. (2) Of interest is the information that the mismatch negativity (MMN) cortical event-related potential can bring to the evaluation of patients with auditory processing deficits. The MMN reflects central auditory processing of small acoustic differences and may provide an objective measure of auditory discrimination. (3) From a theorectical standpoint, a patient with neural deficits affecting specific components of the auditory pathway provides insight into the relationship between evoked potentials and physiological mechanisms of auditory processing. How do various components of the auditory pathway contribute to speech discrimination? How might evoked potentials reflect the processes underlying the neural coding of specific features of speech stimuli such as timing and spectral cues?     

Response of the primary auditory cortex to electrical stimulation of the auditory nerve in the congenitally deaf white cat

Neural activity plays an important role in the development and maintenance of sensory pathways. However, while there is considerable experience using cochlear implants in both congenitally deaf adults and children, little is known of the effects of a hearing loss on the development of the auditory cortex. In the present study, cortical evoked potentials, field potentials, and multi- and single-unit activity evoked by electrical stimulation of the auditory nerve were used to study the functional organisation of the auditory cortex in the adult congenitally deaf white cat. The absence of click-evoked auditory brainstem responses during the first weeks of life demonstrated that these animals had no auditory experience. Under barbiturate anaesthesia, cortical potentials could be recorded from the contralateral auditory cortex in response to bipolar electrical stimulation of the cochlea in spite of total auditory deprivation. Threshold, morphology and latency of the evoked potentials varied with the location of the recording electrode, with response latency varying from 10 to 20 ms. There was evidence of threshold shifts with site of the cochlear stimulation in accordance with the known cochleotopic organisation of AI. Thresholds also varied with the configuration of the stimulating electrodes in accordance with changes previously observed in normal hearing animals. Single-unit recordings exhibited properties similar to the evoked potentials. Increasing stimulus intensity resulted in an increase in spike rate and a decrease in latency to a minimum of approximately 8 ms, consistent with latencies recorded in AI of previously normal animals (Raggio and Schreiner, 1994). Single-unit thresholds also varied with the configuration of the stimulating electrodes. Strongly driven responses were followed by a suppression of spontaneous activity. Even at saturation intensities the degree of synchronisation was less than observed when recording from auditory brainstem nuclei. Taken together, in these auditory deprived animals basic response properties of the auditory cortex of the congenitally deaf white cat appear similar to those reported in normal hearing animals in response to electrical stimulation of the auditory nerve. In addition, it seems that the auditory cortex retains at least some rudimentary level of cochleotopic organisation.     

Stable quantitative EEG difference in post-LSD visual disorder by split-half analysis: evidence for disinhibition

Hallucinogen persisting perceptual disorder (HPPD) may follow the ingestion of LSD or other hallucinogens in a subset of users. It is characterized by chronic, intermittent or constant visual hallucinations of many sorts persisting beyond the period of acute drug effects. We studied 44 LSD-induced HPPD subjects and 88 matched controls to search for spectral and evoked potential differences using quantitative EEG (qEEG). HPPD subjects demonstrated faster alpha frequency and shorter VER (visual evoked response) latency, consistent with prior animal and human data on response to acute LSD administration which suggest LSD-induced cortical disinhibition. AER (auditory evoked response) latency was prolonged consistent with a differential LSD effect upon visual and auditory systems. The exploratory T-statistic significance probability mapping (T-SPM) technique demonstrated HPPD-control differences mostly involving temporal and left parietal scalp regions, confirmed by a split-half analysis. Significant variables were all derived from the long latency flash VER and click AER. None were derived from spectral analyzed EEG data. Canonical correlation between SPM-derived measures and variables reflecting disease severity was highly significant. A between-group stepwise discriminant analysis based upon a full set of qEEG measures demonstrated 87% prospective classification success by jackknifing and 88% success in a separate split-half analysis.     

P300 latency: abnormal in sleep apnea with somnolence and idiopathic hypersomnia, but normal in narcolepsy

To evaluate cognitive abnormalities in excessive daytime sleepiness (EDS) using cognitive evoked potentials (P300), and to evaluate if P300 measures differentiate among disorders of EDS, a series of EDS subjects were administered a polysomnogram, auditory and visual P300 testing using 31 scalp electrodes, and a multiple sleep latency test. P300 variables were compared with those of normal subjects. Forty normal subjects ages 16 to 65 years, and 69 EDS patients ages 16 to 65 years were used. Of these, 39 had profound obstructive sleep apnea (OSA, Respiratory Disturbance Index or RDI > 80/h sleep) with severe somnolence (Mean Sleep Latency < 5 min). Twenty-two had idiopathic hypersomnia (IH). Eight had narcolepsy. The normals and the three EDS groups did not differ in age. IH and profound OSA patients had longer visual P300 latency than normals or narcolepsy patients (p < 0.05). (p < 0.05). IH and profound OSA patients had longer auditory P300 latency than normals. They had smaller auditory P300 amplitude than narcolepsy patients. There were visual P300 latency topographic differences between normals and profound OSA patients. In conclusion, IH and profound OSA patients show cognitive evoked potential evidence of cognitive dysfunction. Narcolepsy patients do not show such evidence. Visual P300 latency differentiates among disorders of EDS.     

Case report: A rare complication of Hickman line insertion

The objective evaluation of smell is the least used functional ear, nose and throat exploration. Evoked potentials can be recorded after chemical olfactory stimulation using a method similar to recording cortical auditory evoked potentials. Our results with this technique and peppermint oil as the stimulant were fully satisfactory. In 10 patients with normal smell, a characteristic wave with a long latency was recorded in the absence of auditory and visual stimuli. In contrast, in 10 anosmic patients this characteristic recording was absent. The easy recording technique proposed here can be useful for olfactory assessment of objective disorders, detection of malingers, and medical-legal reports.     

Electrically evoked auditory brainstem response in peripherally myelin-deficient mice

The integrity of the myelin sheath is important for normal electrophysiological function and survival of neurons that make up the auditory nerve. It is hypothesized that myelin deficiency of the auditory nerve may change the electrophysiologic characteristics of the auditory system, especially the temporal properties. In this study, the electrically evoked auditory brainstem response (EABR) was systematically evaluated in TrJ and Po-DT-A mice. Both of these mice have a deficit of their peripheral myelin. Correlation between the EABR and degree of myelin deficiency was also evaluated. The EABR in both strains of poorly myelinated mice exhibited prolonged latency, decreased amplitude, elevated threshold of wave I evoked by short-duration stimuli (20 microseconds/phase). A 2-pulse stimulation paradigm was used to evaluate refractory properties. Myelin-deficient mice exhibited slower recovery from the refractory state than controls. Long-duration stimuli (4 ms/phase) were used to assess integration properties. Myelin-deficient mice demonstrated prolonged wave I latency and more gradual latency changes with current level. Myelin thickness showed a strong correlation with EABR threshold for short-duration stimulation (r = -0.784), maximum wave I latency (r = -0.778) and the time constant of the wave I latency-current level function (r = -0.736) for long-duration stimulation and normalized wave I recovery functions (r = -0.718). These findings suggest that EABR measurement may be a promising tool to assess the electrically stimulated properties of auditory neurons, particularly related to the status of myelin sheath.     

A central nerve conduction study in hypothyroidism: before and after thyroxine replacement

Employing a Nicolet CA 100 machine, 20 patients of primary hypothyroidism were selected for electrophysiological studies, including somato-sensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP), and visual evoked potential (VEP), to assess the central nerve conduction before and after administration of the thyroid hormone. Before thyroxine replacement therapy, the latencies of N9, N13, and N20 in SSEP showed significant delay, while the central conduction time (CCT) merely had a tendency of prolongation. In BAEP, the peak and interpeak latencies delayed significantly. Additionally, the latency and amplitude of VEP also had significant difference between patients and controls. After thyroxine replacement, the SSEP, BAEP, and VEP studies revealed significant improvement, in correlation with clinical amelioration. In conclusion, the central nerve conduction would be affected in primary hypothyroidism and the improvement was usually the case, reflecting the clinical recovery after appropriate treatment. The electrophysiological study provides an objective method for monitoring the function of central nervous system in hypothyroidism before and after thyroxine treatment.     

The early component of the visual evoked magnetic field

Several EEG studies have reported an early component of the visual evoked potential. However, it is controversial whether this component is cortical or subcortical. Our study has aimed to clarify this problem using MEG and EEG in nine normal volunteers. A total of 4000 stimuli were presented to the monocular visual hemifield through a light-proof stimulating goggle and the visual evoked magnetic field and visual evoked potential was measured above the occipital lobe. The early component was observed in three of the nine subjects. The latency ranged from 40 to 45 ms in MEG and from 39 to 47 ms in EEG. The result of dipole localization analysis showed that its origin was cortical, and specifically, the striate cortex.     

Differential effect of two calcium channel blockers--nifedipine and diltiazem--on atherogenesis in hypercholesterolemic hamster

Previous studies report that background luminance flicker, which is asynchronous with signal averaging, reduces the amplitude and increases the latency of the pattern-onset visual evoked potential (VEP). This effect has been attributed to saturation of the magnocellular (m-) pathway by the flicker stimulus. In the current study, we evaluate this hypothesis and further characterize this effect. We found that flicker had similar effects on the pattern-onset and pattern-reversal VEP, suggesting that the reversal and onset responses have similar generators. Chromatic flicker decreased latency of the chromatic VEP whereas luminance flicker increased peak latency to luminance targets. This result indicates that luminance flicker saturates a rapidly conducting m-pathway whereas chromatic flicker saturates a more slowly conducting parvocellular (p-) pathway. Finally, evoked potentials to chromatic and luminance stimuli were recorded from 34 electrodes over the scalp in the presence of static and asynchronously modulated backgrounds. An equivalent dipole model was used to assess occipital, parietal, and temporal lobe components of the surface response topography. Results showed that chromatic flicker reduced activity to a greater extent in the ventral visual pathway whereas luminance flicker reduced activity to a greater extent in the dorsal visual pathway to parietal lobe. We conclude that the VEP to isoluminant color and luminance stimuli contains both m- and p-pathway components. Asynchronous flicker can be used to selectively reduce the contribution of these pathways to the surface recorded VEP. Our results provide evidence of parallel pathways in the human visual system, with a dorsal luminance channel projecting predominantly to the posterior parietal lobe and a ventral color channel projecting predominantly to inferior temporal lobe.     

Neural conduction velocity of the human auditory nerve: bipolar recordings from the exposed intracranial portion of the eighth nerve during vestibular nerve section

We measured the conduction velocity of the intracranial portion of the auditory nerve in 3 patients undergoing vestibular nerve section to treat Ménière's disease. The conduction velocity varied from patient to patient, with an average value of 15.1 m/sec. The latency of peak III of the brain-stem auditory evoked potentials (BAEPs) increased by an average of 0.5 msec as a result of exposure of the eighth nerve, and if that increase is assumed to affect the entire length of the auditory nerve (2.6 cm) evenly, then the corrected estimate of conduction velocity would be 22.0 m/sec. Estimates of conduction velocity based on the interpeak latencies of peaks I and II of the BAEP, assuming that peak II is generated by the mid-portion of the intracranial segment of the auditory nerve, yielded similar values of conduction velocities (about 20 m/sec).