Repeatability of sound-evoked triceps myogenic potentials.

OBJECTIVE: To investigate the repeatability of sound-evoked vestibular evoked myogenic potentials recorded from the triceps (tVEMPs) with and without visual feedback. DESIGN: tVEMP responses to 95 dB nHL 500-Hz tone bursts were recorded in a longitudinal, repeated measures study where P1 and N1 latencies and amplitudes were measured on three separate occasions from the same individuals. Analysis of variance, intra-class correlations, and limits of repeatability analyses were used to assess tVEMP repeatability and effects of visual feedback. STUDY SAMPLE: Fifteen participants (nine women) aged between 18 and 41 years took part. RESULTS: Response rates of 63% and 68% were obtained for tVEMPs with eyes open and closed, respectively. When present, tVEMP latencies and amplitudes exhibited fair to good repeatability. Repeatability of tVEMP latencies and amplitudes measured using Bland-Altman methods was poorer with eyes closed. CONCLUSIONS: Sound-evoked tVEMP response rates are too low to support their clinical utility at the moment. tVEMP response rate may be improved by refining the balance task to include a force related target. Better tVEMP repeatability with eyes open supports the hypothesis that the response is modulated by visual feedback, and is consistent with studies reporting triceps responses to galvanic stimulation.

Balance appointment information leaflets: employing performance-based user-testing to improve understanding.

OBJECTIVE: To use performance-based user-testing to evaluate the effectiveness of balance appointment patient information leaflets (PILs) in conveying important information. DESIGN: The study used a sequential groups design. Twenty participants were asked to find and demonstrate understanding of 11 key points of information contained within two NHS leaflets, A and B (10 participants each), through individual structured-interviews. Participants' views of the leaflets were explored through a short semi-structured interview. Following analysis, a revised leaflet was developed and tested on a further 20 participants. STUDY SAMPLE: 40 participants (25F/15M, aged 46-72) with no experience of balance problems or balance assessment appointments. RESULTS: Participants exhibited difficulties with finding and/or understanding 5/11 and 6/11 points of information within leaflets A and B, respectively. Five out of eleven points of the revised leaflet also posed problems. Ten out of eleven points were understood by > 90% of participants testing the revised leaflet compared with 6/11 points for leaflets A and B. CONCLUSIONS: Some balance appointment PILs contain information which is difficult to find and/or understand for some readers. PILs should be evaluated prior to use using performance-based methods, since poor information provision may lead to increased patient anxiety and appointment non-attendance, cancellation, or postponement.

Hearing aid instruction booklets: employing usability testing to determine effectiveness.

PURPOSE: This study implemented performance-based usability and literature testing to determine whether people could use 2 instruction booklets for hearing aids (HAs) to carry out basic maintenance tasks and find and understand key facts. METHOD: Using a cross-sectional study design, researchers recruited 40 participants (25 women, 15 men, ages 46-72 years) with no experience of HAs or audiology services to test instruction booklets for a Danalogic and Unitron HA (20 participants each). Participants were asked to follow instructions provided within the booklets to complete common HA tasks (e.g., cleaning the HA and mold and changing the battery) and demonstrate understanding of information. Participants' views of the booklets were then obtained within a short individual interview. RESULTS: Participants experienced problems in completing all tasks while following instructions provided by the Danalogic and Unitron booklets. Individual interviews highlighted further issues regarding layout, diagrams, and content, including missing information. CONCLUSIONS: Some HA instruction booklets contain information that some users may find difficult to find, understand, and follow. These limitations may negatively impact on HA satisfaction and use. It is recommended that written information for clients be evaluated prior to use. This study supports the premise that performance-based usability and literature testing are appropriate methods to use.

The effect of varying stimulus phase between frequency and amplitude modulation on auditory steady-state responses in neonates.

OBJECTIVE: To compare auditory steady-state responses (ASSRs) to air-conducted amplitude, frequency, and mixed modulated stimuli (AM, FM, and MM, respectively) in neonates. DESIGN: Multiple ASSRs to AM, FM, and MM to 0.5, 1, 2, and 4 kHz tones modulated between 0.078 and 0.092 kHz were recorded and compared. MM phase settings across the cycle at 45° intervals were used and optimum phase settings were predicted using a sinusoidal model. STUDY SAMPLE: Twenty neonates with click ABR thresholds of ≤ 40 dB nHL. RESULTS: ASSR amplitudes were significantly larger to AM than FM stimuli. MM phase setting had a significant effect on amplitude at 1, 2, and 4 kHz but not 0.5 kHz. MM phase settings (± 95% confidence intervals) of 276° (± 9.5°) and 270° (± 19.1°) were predicted for 1 and 2 kHz, respectively. The 0.5 and 4 kHz data were not sufficient to model any effect of phase. MM and AM response latencies increased with decreasing carrier frequency. Some MM response latencies were significantly different from AM response latencies, however no consistent trend was apparent. Test times were significantly affected by phase setting. CONCLUSIONS: MM phase settings have a significant effect on ASSR response amplitude and latencies in neonates.

Effect of varying phase between frequency and amplitude modulation on bone conduction auditory steady state responses.

OBJECTIVES: Auditory steady state response (ASSR) testing provides a means to objectively estimate hearing levels in newborns and adults for whom behavioral tests prove difficult. When testing these patient groups, it is preferable that clear responses to both air and bone conduction stimuli are obtained in a short amount of time. Much of the literature addressing ASSRs, such as investigations of stimulus and recording parameters, have focused on air conduction ASSRs. The aim of this investigation was to study the amplitudes, latencies, and test times of bone conduction ASSRs elicited using amplitude- (AM), frequency- (FM), and mixed-modulated (MM) stimuli and provide suggestions for optimum recording parameters. DESIGN: Bone and air conduction multiple ASSRs were recorded from two groups of 20 normal-hearing adults using the Multiple Auditory Steady State Response research system. AM, FM, and MM sinusoidal tones were used (0.5-, 1-, 2-, and 4-kHz carrier frequencies), which were modulated between 78 and 92 Hz. AM depth was 100% and FM depth was 20%. ASSR amplitudes and latencies (calculated using the "preceding cycles" technique) were analyzed for MM phase settings across the cycle from 0° at 45° intervals and compared with AM responses. Optimum phase settings for bone and air conduction ASSRs were calculated using a sinusoidal model based on the amplitude data. RESULTS: Similar effects of stimulus type and carrier frequency were observed for bone and air conduction ASSRs. AM responses were larger in amplitude compared with FM responses. MM (at all phase settings tested) and AM response latencies increased with decreasing carrier frequency. MM phase setting had a significant (p < 0.01) sinusoidal effect on ASSR amplitudes, compared with AM responses, at 1, 2, and 4 kHz but not 0.5 kHz for air conduction and 1 and 2 kHz but not 0.5 and 4 kHz for bone conduction. Using a sinusoidal function to model this effect, MM phase settings (±95% confidence intervals) of 318° (295 to 350°) and 295° (290 to 310°) are predicted to evoke the largest responses for bone conduction ASSRs at 1 and 2 kHz, respectively. Phase settings of 293° (285 to 310°), 300° (280 to 310°), and 280° (255 to 330°) are predicted for air conduction ASSRs at 1, 2, and 4 kHz, respectively. MM phase setting had little effect on estimated latency. Test times were significantly (p < 0.01) affected by phase setting with both increases and decreases being observed. Test times for ASSRs at 1, 2, and 4 kHz could be significantly reduced if the estimated optimum phase settings are used. CONCLUSIONS: Different stimuli can significantly affect the amplitudes of bone conduction ASSRs. These effects are similar to those observed for air conduction ASSRs. MM stimuli with specific phase settings evoke larger bone conduction ASSRs compared with AM and FM stimuli alone, and calculations show that the time taken to obtain these responses is reduced. Implementation of the suggested optimum settings will promote efficient collection of bone conduction, and indeed air conduction, ASSR data.

Immunohistochemical localisation of the voltage gated potassium ion channel subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord.

Voltage gated K+ channels (Kv) are a diverse group of channels important in determining neuronal excitability. The Kv superfamily is divided into 12 subfamilies (Kv1-12) and members of the Kv3 subfamily are highly abundant in the CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique expression pattern. Since the localisation of Kv subunits is important in defining the roles they play in neuronal function, we have used immunohistochemistry to determine the distribution of the Kv3.3 subunit in the medulla oblongata and spinal cord of rats. Kv3.3 subunit immunoreactivity (Kv3.3-IR) was widespread but present only in specific cell populations where it could be detected in somata, dendrites and synaptic terminals. Labelled neurones were observed in the spinal cord in laminae IV and V, in the region of the central canal and in the ventral horn. In the medulla oblongata, labelled cell bodies were numerous in the spinal trigeminal, cuneate and gracilis nuclei whilst rarer in the lateral reticular nucleus, hypoglossal nucleus and raphe nucleus. Regions containing autonomic efferent neurones were predominantly devoid of labelling with only occasional labelled neurones being observed. Dual immunohistochemistry revealed that some Kv3.3-IR neurones in the ventral medullary reticular nucleus, spinal trigeminal nucleus, dorsal horn, ventral horn and central canal region were also immunoreactive for the Kv3.1b subunit. The presence of Kv3.3 subunits in terminals was confirmed by co-localisation of Kv3.3-IR with the synaptic vesicle protein SV2, the vesicular glutamate transporter VGluT2 and the glycine transporter GlyT2. Co-localisation of Kv3.3-IR was not observed with VGluT1, tyrosine hydroxylase, serotonin or choline acetyl transferase. Electron microscopy confirmed the presence of Kv3.3-IR in terminals and somatic membranes in ventral horn neurones, but not motoneurones. This study provides evidence supporting a role for Kv3.3 subunits in regulating neuronal excitability and in the modulation of excitatory and inhibitory synaptic transmission in the medulla oblongata and spinal cord.

Kv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals.

Voltage-gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light- and electron-microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end-plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05-0.5 mM), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large-conductance calcium-activated potassium channel blockers iberiotoxin (25-150 nM) and Penitrem A (100 nM), suggesting a selective action on Kv3 subunits. Consistent with this, 15-microM 4-aminopyridine, which blocks Kv3 but not large-conductance calcium-activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood-depressing substance-I, a toxin selective for Kv3.4 subunits, had no effect at 0.05-1 microM. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ.

Input-specific modulation of neurotransmitter release in the lateral horn of the spinal cord via adenosine receptors.

Activation of adenosine A2A receptors (A2ARs) in the CNS produces a variety of neuromodulatory actions dependent on the region and preparation examined. In autonomic regions of the spinal cord, A1R activation decreases excitatory synaptic transmission, but the effects of A2AR stimulation are unknown. We sought to determine the location and function of the A2ARs in the thoracic spinal cord, focusing on the intermediolateral cell column (IML). A2AR immunoreactivity was observed throughout the gray matter, with particularly dense immunostaining in regions containing sympathetic preganglionic neurons (SPNs), namely, the IML and intercalated nucleus. Electron microscopy revealed A2AR immunoreactivity within presynaptic terminals and in postsynaptic structures in the IML. To study the functional relevance of these A2ARs, visualized whole-cell patch-clamp recordings were made from electrophysiologically identified SPNs and interneurons within the IML. The A2AR agonist c2-[p-(carboxyethyl)phenethylamino]-5'-N-ethylcarboxyamidoadenosine (CGS 21680) had no significant effect on EPSPs but increased the amplitude of IPSPs elicited by stimulation of the lateral funiculus. These effects were attributable to activation of presynaptic A2ARs because CGS 21680 application altered the paired pulse ratio. Furthermore, neurons in the IML that have IPSPs increased via A2AR activation also receive excitatory inputs that are inhibited by A1R activation. These data show that activating A2ARs increase inhibitory but not excitatory transmission onto neurons in the IML. Simultaneous activation of A1Rs and A2ARs therefore could facilitate inhibition of the postsynaptic neuron, leading to an overall reduction of sympathetic nervous activity.

Spinal cord interneurones labelled transneuronally from the adrenal gland by a GFP-herpes virus construct contain the potassium channel subunit Kv3.1b.

Interneurones in the spinal cord are likely to play an important role in the generation of activity in sympathetic preganglionic neurones (SPNs) and, therefore, sympathetic outflow. Although the properties of these interneurones have rarely been studied directly, here we show that neurones antecedent to SPNs contain the voltage-gated potassium channel subunit Kv3.1b, while SPNs do not. SPNs and interneurones were labelled by injection of a green fluorescent protein expressing herpes simplex virus (HSV-GFP) into the adrenal gland. SPNs identified by concomitant tracing with Fluorogold did not contain Kv3.1b immunoreactivity. Significantly, neurones that did not contain Fluorogold and which were unlikely to be SPNs were double labelled for Kv3.1b and GFP. This indicates that spinal cord intemeurones antecedent to SPNs contain Kv3.1b. To test the role of Kv3.1b whole cell patch clamp recordings were made from SPNs and interneurones in spinal cord slices. Selective blockade of Kv3.1b containing channels with 30 microM 4-amino-pyridine (4-AP) or 500 microM tetraethylammonium chloride (TEA) revealed that this Kv subunit contributes to fast repolarisation and fast firing frequencies of interneurones in the vicinity of the IML, allowing them to fire action potentials at much higher frequencies than SPNs. This is the first time that transneuronal labelling with this viral construct has been combined with immunohistochemical detection of ion channels. In conjunction with our electrophysiological data, this highlights a role for the Kv3.1b subunit in shaping the activity of intemeurones involved in sympathetic control.