The effects of dexmedetomidine/remifentanil and midazolam/remifentanil on auditory-evoked potentials and electroencephalogram at light-to-moderate sedation levels in healthy subjects

Avoidance of excessively deep sedation levels is problematic in intensive care patients. Electrophysiologic monitoring may offer an approach to solving this problem. Since electroencephalogram (EEG) responses to different sedation regimens vary, we assessed electrophysiologic responses to two sedative drug regimens in 10 healthy volunteers. Dexmedetomidine/remifentanil (dex/remi group) and midazolam/remifentanil (mida/remi group) were infused 7 days apart. Each combination of medications was given at stepwise intervals to reach Ramsay scores (RS) 2, 3, and 4. Resting EEG, bispectral index (BIS), and the N100 amplitudes of long-latency auditory-evoked potentials (ERP) were recorded at each level of sedation. During dex/remi, resting EEG was characterized by a recurrent high-power low-frequency pattern which became more pronounced at deeper levels of sedation. BIS Index decreased uniformly in only the dex/remi group (from 94 +/- 3 at baseline to 58 +/- 14 at RS 4) compared to the mida/remi group (from 94 +/- 2 to 76 +/- 10; P = 0.029 between groups). The ERP amplitudes decreased from 5.3 +/- 1.3 at baseline to 0.4 +/- 1.1 at RS 4 (P = 0.003) in only the mida/remi group. We conclude that ERPs in volunteers sedated with dex/remi, in contrast to mida/remi, indicate a cortical response to acoustic stimuli, even when sedation reaches deeper levels. Consequently, ERP can monitor sedation with midazolam but not with dexmedetomidine. The reverse is true for BIS.

Non-organic hearing loss: new and confirmed findings

Although non-organic hearing losses are relatively rare, it is important to identify suspicious findings early to be able to administer specific tests, such as objective measurements and specific counseling. In this retrospective study, we searched for findings that were specific ti or typical for non-organic hearing losses. Patient records from a 6 year period (2003-2008) from the University ENT Department of Bern, Switzerland, were reviewed. In this period, 40 subjects were diagnosed with a non-organic hearing loss (22 children, ages 7-16, mean 10.6 years; 18 adults, ages 19-57, mean 39.7 years; 25 females and 15 males). Pure tone audiograms in children and adults showed predominantly sensorineural and frequency-independent hearing losses, mostly in the range of 40-60 dB. In all cases, objective measurements (otoacoustic emissions and/or auditory-evoked potentials) indicated normal or substantially better hearing thresholds than those found in pure tone audiometry. In nine subjects (22.5%; 2 children, 7 adults), hearing aids had been fitted before the first presentation at our center. Six children (27%) had a history of middle ear problems with a transient hearing loss and 11 (50%) knew a person with a hearing loss. Two new and hitherto unreported findings emerged from the analysis: it was observed that a small air-bone gap of 5-20 dB was typical for non-organic hearing losses and that speech audiometry might show considerably poorer results than expected from pure tone audiometry.

Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 microM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.

Competition for neuronal resources: how hallucinations make themselves heard

BACKGROUND: Hallucinations are perceptions in the absence of a corresponding external sensory stimulus. However, during auditory verbal hallucinations, activation of the primary auditory cortex has been described. AIMS: The objective of this study was to investigate whether this activation of the auditory cortex contributes essentially to the character of hallucinations and attributes them to alien sources, or whether the auditory activation is a sign of increased general auditory attention to external sounds. METHOD: The responsiveness of the auditory cortex was investigated by auditory evoked potentials (N100) during the simultaneous occurrence of hallucinations and external stimuli. Evoked potentials were computed separately for periods with and without hallucinations; N100 power, topography and brain electrical sources were analysed. RESULTS: Hallucinations lowered the N100 amplitudes and changed the topography, presumably due to a reduced left temporal responsivity. CONCLUSIONS: This finding indicates competition between auditory stimuli and hallucinations for physiological resources in the primary auditory cortex. The abnormal activation of the primary auditory cortex may thus be a constituent of auditory hallucinations.

Limited efficacy of adjuvant therapy with dexamethasone in preventing hearing loss due to experimental pneumococcal meningitis in the infant rat

Sensorineural hearing loss (SNHL) is the most common sequel of bacterial meningitis (BM) and is observed in up to 30% of survivors when the disease is caused by Streptococcus pneumoniae. BM is the single most important origin of acquired SNHL in childhood. Anti-inflammatory dexamethasone holds promises as potential adjuvant therapy to prevent SNHL associated with BM. However, in infant rats, pneumococcal meningitis (PM) increased auditory brainstem response (ABR) thresholds [mean difference = 54 decibels sound pressure level (dB SPL)], measured 3 wk after infection, irrespective to treatment with ceftriaxone plus dexamethasone or ceftriaxone plus saline (p < 0.005 compared with mock-infected controls). Moreover, dexamethasone did not attenuate short- and long-term histomorphologic correlates of SNHL. At 24 h after infection, blood-labyrinth barrier (BLB) permeability was significantly increased in infected animals of both treatment groups compared with controls. Three weeks after the infection, the averaged number of type I neurons per square millimeter of the Rosenthal's canal dropped from 0.3019 +/- 0.0252 in controls to 0.2227 +/- 0.0635 in infected animals receiving saline (p < 0.0005). Dexamethasone was not more effective than saline in preventing neuron loss (0.2462 +/- 0.0399; p > 0.05). These results suggest that more efficient adjuvant therapies are needed to prevent SNHL associated with pediatric PM.

Clinical evaluation of the new coat colour macchiato in a male Franches-Montagnes horse

In April 2008 a Franches-Montagnes colt was born with an unusual coat colour phenotype which had never been observed in that population before. The foal showed extended white markings on body and legs, a white head and blue eyes. As both parents have an unremarkable bay coat colour phenotype, a de novo mutation was expected in the offspring and a candidate gene approach revealed a spontaneous mutation in the microphthalmia associated transcription factor gene (MITF). A detailed clinical examination in 2010 indicated an impaired hearing capacity. As in the American Paint Horse large white facial markings in combination with blue eyes are associated with deafness, the hearing capacity of the stallion was closer examined performing brainstem auditory-evoked responses (BAER). The BAER confirmed bilateral deafness in the Franches-Montagnes colt. It is assumed that the deafness is caused by a melanocyte deficiency caused by the MITF gene mutation. Unfortunately, due to castration of the horse, the causal association between the mutation in the MITF gene and clinical findings cannot be confirmed by experimental matings.

Minimized extracorporeal circulation does not impair cognitive brain function after coronary artery bypass grafting

OBJECTIVES Objective evaluation of the impact of minimized extracorporeal circulation (MECC) on perioperative cognitive brain function in coronary artery bypass grafting (CABG) by electroencephalogram P300 wave event-related potentials and number connection test (NCT) as metrics of cognitive function. METHODS Cognitive brain function was assessed in 31 patients in 2013 with a mean age of 65 years [standard deviation (SD) 10] undergoing CABG by the use of MECC with P300 auditory evoked potentials (peak latencies in milliseconds) directly prior to intervention, 7 days after and 3 months later. Number connection test, serving as method of control, was performed simultaneously in all patients. RESULTS Seven days following CABG, cognitive P300 evoked potentials were comparable with preoperative baseline values [vertex (Cz) 376 (SD 11) ms vs 378 (18) ms, P = 0.39; frontal (Fz) 377 (11) vs 379 (21) ms, P = 0.53]. Cognitive brain function at 3 months was compared with baseline values [(Cz) 376 (11) ms vs 371 (14 ms) P = 0.09; (Fz) 377 (11) ms vs 371 (15) ms, P = 0.04]. Between the first postoperative measurement and 3 months later, significant improvement was observed [(Cz) 378 (18) ms vs 371 (14) ms, P = 0.03; (Fz) 379 (21) vs 371 (15) ms, P = 0.02]. Similar clearly corresponding patterns could be obtained via the number connection test. Results could be confirmed in repeated measures analysis of variance for Cz (P = 0.05) and (Fz) results (P = 0.04). CONCLUSIONS MECC does not adversely affect cognitive brain function after CABG. Additionally, these patients experience a substantial significant cognitive improvement after 3 months, evidentiary proving that the concept of MECC ensures safety and outcome in terms of brain function.

Cochlear implant candidates with psychogenic hearing loss.

Abstract Conclusions: Specific requests for cochlear implantations by persons with psychogenic hearing loss are a relatively new phenomenon. A number of features seems to be over-represented in this group of patients. The existence of these requests stresses the importance of auditory brainstem response (ABR) measurements before cochlear implantation. Objective: To describe the phenomenon of patients with psychogenic hearing losses specifically requesting cochlear implantation, and to gain first insights into the characteristics of this group. Methods: Analysis of all cases seen between 2004 and 2013 at the University Hospital of Bern, Switzerland. Results: Four cochlear implant candidates with psychogenic hearing loss were identified. All were female, aged 23-51 years. Hearing thresholds ranged from 86 dB to 112 dB HL (pure-tone average 500-4000 Hz). ABRs and otoacoustic emissions (OAEs) showed bilaterally normal hearing in two subjects, and hearing thresholds between 30 and 50 dB in the other two subjects. Three subjects suffered from depression and one from a pathologic fear of cancer. Three had a history of five or more previous surgeries. Three were smokers and three reported other close family members with hearing losses. All four were hearing aid users at the time of presentation.

Minimized Extracorporeal Circulation does not impair cognitive brain function after coronary artery bypass grafting

Gebiet: Chirurgie Abstract: Minimized Extracorporeal Circulation does not impair cognitive brain function after coronary artery bypass grafting – – Objectives – Objective evaluation of the impact of minimized extracorporeal circulation (MECC) on perioperative cognitive brain function in coronary bypass grafting (CABG) by Electroencephalogram (EEG) P 300 wave event related potentials (ERP) and number connection test ( NCT) as metrics of cognitive function. – – Methods – Cognitive brain function was assessed in 31 patients with a mean age of 65y (Standard Deviation/SD 10) undergoing coronary artery bypass grafting (CABG) by the use of MECC with P300 auditory evoked potentials (peak latencies in milliseconds [ms]) directly prior to intervention, 7 days after and 3 month later. Number connection test (NCT), serving as method of control, was performed simultaneously in all patients. – – Results – Seven days following CABG, cognitive P300 evoked potentials were comparable to preoperative baseline values (vertex [Cz] 376 (SD 11) ms vs. 378 (18) ms, p=0.39, frontal [Fz] 377 (11) vs. 379 (21) ms, p=0.53). Cognitive brain function showed at 3 months compared to baseline values ([Cz] 376 (11) ms vs. 371 (14 ms) p=0.09, [Fz] 377 (11) ms vs. 371 (15) ms, p=0.04. Between the first postoperative measurement and 3 months later, significant improvement was observed ([Cz] 378 (18) ms vs. 371 (14) ms, p=0.03, [Fz] 379 (21) vs. 371 (15) ms, p=0.02). Similar clearly corresponding patterns could be obtained via number connection test. Results could be confirmed in repeated measures analysis of variance for Cz (p = 0.05) and (Fz) results (p = 0.04). – – Conclusions

Enhancing BOLD response in the auditory system by neurophysiologically tuned fMRI sequence

Auditory neuroscience has not tapped fMRI's full potential because of acoustic scanner noise emitted by the gradient switches of conventional echoplanar fMRI sequences. The scanner noise is pulsed, and auditory cortex is particularly sensitive to pulsed sounds. Current fMRI approaches to avoid stimulus-noise interactions are temporally inefficient. Since the sustained BOLD response to pulsed sounds decreases with repetition rate and becomes minimal with unpulsed sounds, we developed an fMRI sequence emitting continuous rather than pulsed gradient sound by implementing a novel quasi-continuous gradient switch pattern. Compared to conventional fMRI, continuous-sound fMRI reduced auditory cortex BOLD baseline and increased BOLD amplitude with graded sound stimuli, short sound events, and sounds as complex as orchestra music with preserved temporal resolution. Response in subcortical auditory nuclei was enhanced, but not the response to light in visual cortex. Finally, tonotopic mapping using continuous-sound fMRI demonstrates that enhanced functional signal-to-noise in BOLD response translates into improved spatial separability of specific sound representations.

Effect of ketamine on the limb withdrawal reflex evoked by transcutaneous electrical stimulation in ponies anaesthetised with isoflurane

The purpose of this study was to evaluate the anti-nociceptive activity of ketamine and isoflurane in horses using a limb withdrawal reflex (WR) model. Single and repeated stimulations were applied to the digital nerve of the left forelimb in ponies anaesthetised with isoflurane before, during and after intravenous administration of racemic ketamine. Surface electromyographic activity was recorded from the deltoid muscle. Higher stimulation intensity was required to evoke a reflex during ketamine administration. Furthermore, the amplitudes of response to stimulations were significantly and dose-dependently depressed and a flattening of the stimulus-response curves was observed. The reflex activity recovered partially once the ketamine infusion finished. The results demonstrated that the limb WR can be used to quantify the temporal effect of ketamine on the sensory-motor processing in ponies anaesthetised with isoflurane.

Cerebral blood flow identifies responders to transcranial magnetic stimulation in auditory verbal hallucinations

Auditory hallucinations comprise a critical domain of psychopathology in schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown promise as an intervention with both positive and negative reports. The aim of this study was to test resting-brain perfusion before treatment as a possible biological marker of response to repetitive TMS. Twenty-four medicated patients underwent resting-brain perfusion magnetic resonance imaging with arterial spin labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined as a reduction in the hallucination change scale of at least 50%. Responders (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus (STG) (P<0.05, corrected) before treatment. Resting-brain perfusion in the left STG predicted the response to repetitive TMS in this study sample, suggesting this parameter as a possible bio-marker of response in patients with schizophrenia and auditory hallucinations. Being noninvasive and relatively easy to use, resting perfusion measurement before treatment might be a clinically relevant way to identify possible responders and nonresponders to repetitive TMS.

The effects of isoflurane minimum alveolar concentration on withdrawal reflex activity evoked by repeated transcutaneous electrical stimulation in ponies

The aim of this study was to quantify the effects of isoflurane at approximately the minimum alveolar concentration (peri-MAC) on the temporal summation (TS) of reflex activity in ponies. TS was evoked by repeated electrical stimulations applied at 5 Hz for 2 s on the digital nerve of the left forelimb of seven ponies. Surface electromyographic activity was recorded from the deltoid and common digital extensor muscles. TS thresholds and amplitude of response to stimulations of increasing intensities were assessed during anaesthesia at 0.85, 0.95 and 1.05 times the individual MAC, and after anaesthesia in standing animals. Under isoflurane anaesthesia, TS thresholds increased significantly in a concentration-dependent fashion and at each isoflurane MAC, the responses increased significantly for increasing stimulation intensities. A concentration-dependent depression of evoked reflexes with a reduction in the slopes of the stimulus-response function was observed for both muscles. The results demonstrated that with this model it is possible to describe and quantify the effects of anaesthetics on spinal sensory-motor processing in ponies.

Auditory motion direction encoding in auditory cortex and high-level visual cortex

The aim of this functional magnetic resonance imaging (fMRI) study was to identify human brain areas that are sensitive to the direction of auditory motion. Such directional sensitivity was assessed in a hypothesis-free manner by analyzing fMRI response patterns across the entire brain volume using a spherical-searchlight approach. In addition, we assessed directional sensitivity in three predefined brain areas that have been associated with auditory motion perception in previous neuroimaging studies. These were the primary auditory cortex, the planum temporale and the visual motion complex (hMT/V5+). Our whole-brain analysis revealed that the direction of sound-source movement could be decoded from fMRI response patterns in the right auditory cortex and in a high-level visual area located in the right lateral occipital cortex. Our region-of-interest-based analysis showed that the decoding of the direction of auditory motion was most reliable with activation patterns of the left and right planum temporale. Auditory motion direction could not be decoded from activation patterns in hMT/V5+. These findings provide further evidence for the planum temporale playing a central role in supporting auditory motion perception. In addition, our findings suggest a cross-modal transfer of directional information to high-level visual cortex in healthy humans.