Implanted Monitor Alerting to Reduce Treatment Delay in Patients With Acute Coronary Syndrome Events.

BACKGROUND: Increased pre-hospital delay during acute coronary syndrome (ACS) events contributes to worse outcome. OBJECTIVES: The purpose of this study was to assess the effectiveness of an implanted cardiac monitor with real-time alarms for abnormal ST-segment shifts to reduce pre-hospital delay during ACS events. METHODS: In the ALERTS (AngeLmed Early Recognition and Treatment of STEMI) pivotal study, subjects at high risk for recurrent ACS events (n = 907) were randomized to control (Alarms OFF) or treatment groups for 6 months, after which alarms were activated in all subjects (Alarms ON). Emergency department (ED) visits with standard-of-care cardiac test results were independently adjudicated as true- or false-positive ACS events. Alarm-to-door (A2D) and symptom-to-door (S2D) times were calculated for true-positive ACS ED visits triggered by 3 possible prompts: alarm only, alarms + symptoms, or symptoms only. RESULTS: The Alarms ON group showed reduced delays, with 55% (95% confidence interval [CI]: 46% to 63%) of ED visits for ACS events <2 h compared with 10% (95% CI: 2% to 27%) in the Alarms OFF group (p < 0.0001). Results were similar when restricted to myocardial infarction (MI) events. Median pre-hospital delay for MI was 12.7 h for Alarms OFF and 1.6 h in Alarms ON subjects (p < 0.0089). Median A2D delay was 1.4 h for asymptomatic MI. Median S2D delay for symptoms-only MI (no alarm) in Alarms ON was 4.3 h. CONCLUSIONS: Intracardiac monitoring with real-time alarms for ST-segment shift that exceeds a subject's self-normative ischemia threshold level significantly reduced the proportion of pre-hospital delays >2 h for ACS events, including asymptomatic MI, compared with symptoms-only ED visits in Alarms OFF. (AngeLmed for Early Recognition and Treatment of STEMI [ALERTS]; NCT00781118).

A pilot feasibility study of treating overactive bladder patients with percutaneous saphenous nerve stimulation.

AIMS: Effective long-term treatment of overactive bladder (OAB) remains a significant clinical challenge. We present our initial experience with a new bladder neuromodulation method that electrically targets the saphenous nerve (SAFN). METHODS: A total of 18 OAB patients (female, 55-84 years) were provided with percutaneous SAFN stimulation. The SAFN was targeted with a needle electrode inserted below the medial condyle of the tibia. Activation of the SAFN was confirmed by the patient's perception of paresthesia radiating down the leg. Electrical stimulation was applied for 30 min and subsequently repeated weekly for 3 months. The effects of stimulation were assessed by a 4-day bladder diary and quality-of-life questionaire (OAB-q). RESULTS: Percutaneous SAFN stimulation was confirmed in all 16 patients who completed the study, and no adverse events were reported. Positive response to SAFN stimulation was achieved in 87.5% (14 of 16) of patients, as determined by either a minimum 50% reduction in bladder symptoms or a minimum 10 point increase in the HRQL total score. CONCLUSIONS: Electrical activation of the SAFN was consistently achieved using anatomical landmarks and patient feedback. The procedure was well tolerated and, based on our small cohort of patients, appears efficacious, and safe. This pilot study provides early feasibility data that points to a promising new intervention for treating OAB.

Human Envelope Following Responses to Amplitude Modulation: Effects of Aging and Modulation Depth.

OBJECTIVE: To record envelope following responses (EFRs) to monaural amplitude-modulated broadband noise carriers in which amplitude modulation (AM) depth was slowly changed over time and to compare these objective electrophysiological measures to subjective behavioral thresholds in young normal hearing and older subjects. PARTICIPANTS: three groups of subjects included a young normal-hearing group (YNH 18 to 28 years; pure-tone average = 5 dB HL), a first older group ("O1"; 41 to 62 years; pure-tone average = 19 dB HL), and a second older group ("O2"; 67 to 82 years; pure-tone average = 35 dB HL). Electrophysiology: In condition 1, the AM depth (41 Hz) of a white noise carrier, was continuously varied from 2% to 100% (5%/s). EFRs were analyzed as a function of the AM depth. In condition 2, auditory steady-state responses were recorded to fixed AM depths (100%, 75%, 50%, and 25%) at a rate of 41 Hz. Psychophysics: A 3 AFC (alternative forced choice) procedure was used to track the AM depth needed to detect AM at 41 Hz (AM detection). The minimum AM depth capable of eliciting a statistically detectable EFR was defined as the physiological AM detection threshold. RESULTS: Across all ages, the fixed AM depth auditory steady-state response and swept AM EFR yielded similar response amplitudes. Statistically significant correlations (r = 0.48) were observed between behavioral and physiological AM detection thresholds. Older subjects had slightly higher (not significant) behavioral AM detection thresholds than younger subjects. AM detection thresholds did not correlate with age. All groups showed a sigmoidal EFR amplitude versus AM depth function but the shape of the function differed across groups. The O2 group reached EFR amplitude plateau levels at lower modulation depths than the normal-hearing group and had a narrower neural dynamic range. In the young normal-hearing group, the EFR phase did not differ with AM depth, whereas in the older group, EFR phase showed a consistent decrease with increasing AM depth. The degree of phase change (or phase slope) was significantly correlated to the pure-tone threshold at 4 kHz. CONCLUSIONS: EFRs can be recorded using either the swept modulation depth or the discrete AM depth techniques. Sweep recordings may provide additional valuable information at suprathreshold intensities including the plateau level, slope, and dynamic range. Older subjects had a reduced neural dynamic range compared with younger subjects suggesting that aging affects the ability of the auditory system to encode subtle differences in the depth of AM. The phase-slope differences are likely related to differences in low and high-frequency contributions to EFR. The behavioral-physiological AM depth threshold relationship was significant but likely too weak to be clinically useful in the present individual subjects who did not suffer from apparent temporal processing deficits.

A statistically based acute ischemia detection algorithm suitable for an implantable device.

This study investigates the performance of a new statistically driven acute ischemia detection algorithm that can process data from two bipolar cutaneous or subcutaneous leads. During a start-up phase, the algorithm processes electrocardiogram signals to determine a normal range of ST-segment deviation as a function of heart rate. The algorithm then generates upper and lower ST-deviation thresholds based on the dispersion of the baseline ST-deviation data. After the start-up phase, persistent ST-deviation that is beyond either the upper or lower thresholds results in detection of acute ischemia. To test the algorithm, we performed long-term (10 day) Holter monitoring in a control group of 14 subjects. We also performed Holter monitoring during balloon angioplasty, and for 2 days after surgery, in 30 subjects who underwent elective percutaneous coronary interventions ("PCI"). We determined the percentage of balloon inflations the algorithm detected without producing false positive detections within the control group 10-day daily life data. The algorithm detected 17/17 LAD occlusions, 7/8 LCX occlusions, and 8/9 RCA occlusions. Our results suggest that automatically generated, subject-specific, heart-rate dependent ST-deviation thresholds can detect PCI induced myocardial ischemia without resulting in false positive detections in a small control group.

Phase stability of auditory steady state responses in newborn infants.

OBJECTIVES: This study examined the phases of auditory steady state responses (ASSRs) evoked by exponentially amplitude-modulated (AM) tones in 44 newborn infants (within 3 days of birth) and in 15 older infants (within 3 to 15 wks of birth). Our hypothesis was that the phases of the ASSRs would show orderly changes with modulation rate/carrier frequency and that this stability could be used with phase-biasing statistical techniques to augment response detection. DESIGN: Multiple ASSRs were recorded to four modulated tonal carriers with intensities of 50 dB SPL, which were combined and presented simultaneously. The carriers of 0.5, 1, 2, and 4 kHz were modulated at rates between 78 and 95 Hz. Recordings lasted 12.3 mins. Data were analyzed offline with particular attention to phase and its possible exploitation in response detection using a phase-weighted t test (PWT). Population normative phase values were compared with self-normative values. The latter uses phase estimates from ASSRs that are detected at an earlier time to estimate expected phases of ASSRs, which have not yet been detected. This was implemented as an interstimulus phase-weighted t test (iPWT). A secondary analysis compared using fixed test durations where data were evaluated once at the end of the recording with variable test durations where data were evaluated after every sweep. RESULTS: Average phases were not statistically different between the newborn and older infants. The mean ASSR phases across both infant groups were 10°, 36°, 83°, and 110° in the left ear and 78°, 97°, 135°, and 138° in the right ear for the four modulated carriers, respectively. Of a total of 172 detected ASSRs across the four carriers, 63% (109/172), 84% (144/172), and 99% (170/172) of the phase values fell within ±30°, ±45°, and ±90° of the population mean values, respectively. Self-normative phase values were slightly closer to actual measured phases, than population normative values. Compared with the F test, with a fixed duration, the iPWT technique did slightly better (71.7% versus 77.1% detected). Compared with the F test, with variable test duration, test time was reduced using the iPWT technique for normal and weighted averaging by 4 and 2.9 sweeps (66 and 48 secs), respectively, while false-positive rates were maintained. Compared with tests that relied on the F-ratio and a fixed time of 12.3 mins, using variable test times and the iPWT approach resulted in a halving of test time, while slightly improving comparable ASSR detection rates (66.7% versus 72.5%). An inter-ear average phase difference of 52° was found, which was not accounted for by modulation rates used for left/right ears. Converting phase to latency yielded similar results to prior studies. CONCLUSIONS: The phase responses of ASSRs evoked by AM tones are stable in newborn and young infants. When using the multiple auditory steady state response (MASTER) technique, it is possible to employ phase-biasing methods to reduce test time and increase detection rates. Using self-normative intrastimulus phase difference values provides better estimated phases than average population phases for purposes of response detection.

Initial clinical results using intracardiac electrogram monitoring to detect and alert patients during coronary plaque rupture and ischemia.

OBJECTIVES: We report the first clinical studies of intracardiac ST-segment monitoring in ambulatory humans to alert them to significant ST-segment shifts associated with thrombotic occlusion. BACKGROUND: Despite improvements in door-to-balloon times, delays in symptom-to-door times of 2 to 3 h remain. Early alerting of the presence of acute myocardial infarction could prompt patients to seek immediate medical evaluation. METHODS: Intracardiac monitoring was performed in 37 patients at high risk for acute coronary syndromes. The implanted monitor continuously evaluated the patients' ST segments sensed from a conventional pacemaker right ventricle apical lead, and alerted patients to detected ischemic events. RESULTS: During follow-up (median 1.52 years, range 126 to 974 days), 4 patients had ST-segment changes of ≥3 SDs of their normal daily range, in the absence of an elevated heart rate. This in combination with immediate hospital monitoring led to angiogram and/or intravascular ultrasonography, which confirmed thrombotic coronary occlusion/ruptured plaque. The median alarm-to-door time was 19.5 min (6, 18, 21, and 60 min, respectively). Alerting for demand-related ischemia at elevated heart rates, reflective of flow-limiting coronary obstructions, occurred in 4 patients. There were 2 false-positive ischemia alarms related to arrhythmias, and 1 alarm due to a programming error that did not prompt cardiac catheterization. CONCLUSIONS: Shifts exceeding 3 SD from a patient's daily intracardiac ST-segment range may be a sensitive/specific marker for thrombotic coronary occlusion. Patient alerting was associated with a median alert-to-door time of 19.5 min for patients at high risk of recurrent coronary syndromes who typically present with 2- to 3-h delays.

Evaluating the modulation transfer function of auditory steady state responses in the 65 Hz to 120 Hz range.

OBJECTIVE: Auditory steady state response (ASSR) tests allow frequency-specific assessment of the auditory system. The responses can be elicited with long-duration tones that are modulated at particular rates. The literature has reported that some rates may evoke larger responses than others. Modulation transfer functions (MTFs), which show ASSR response as a function of modulation rate, can be created by presenting a fixed carrier with a modulation rate that is swept over time. Here, we explore the profiles of MTFs with particular effort made toward examining (1) the rates in the MTF that provided the maximum and minimum values, (2) the means and ranges of ASSRs within each MTF, and (3) MTF test-retest repeatability. Because recording ASSRs to a 500-Hz carrier frequency is often difficult at 60 dB SPL or less, we focused our efforts on this frequency. The main objective of this study was to evaluate the possibility of using MTFs for the purpose of identifying both optimal and unfavorable modulation rates. DESIGN: Fifty-four normal hearing adult subjects were allocated to one of four experimental conditions. The first two conditions used a 500-Hz carrier and generated MTFs where modulation rate was varied continuously across a low (66 to 102 Hz) or high (86 to 121 Hz) range. In two additional conditions, a 500-Hz carrier having a modulation rate fixed at 82 Hz and a 2000-Hz carrier having a swept modulation rate (66- to 102-Hz range) were also obtained for comparison. Stimuli were presented at 60 dB SPL. The two ranges of modulation were used because these have implications for the generators and characteristics of the evoked responses. Responses were analyzed for each condition using a Fourier analyzer. To assess the stability of the MTF, two recordings, of 25 mins each, were obtained for each subject. RESULTS: MTF profiles and modulation rates associated with maximum and minimum amplitudes clearly demonstrated repeatability between the two recordings. More specifically, modulation rates for the maximum and minimum amplitudes showed correlations above 0.92 between the two recordings. Using combined data from the two replications, we found that differences between maximum and minimum amplitudes were between 34 and 51 nV when modulation rate was varied. For the fixed modulation rate condition, the difference was only 22 nV, which was due to fluctuations in noise. Response amplitude and noise estimates obtained in this study suggest that approximately 30% of individuals would require at least 10 mins more recording time if an actual hearing test was performed using the modulation rate associated with the ASSR amplitude minimum rather than the maximum. For some individuals, the ASSR would not be detected in a practical amount of time if the wrong modulation rate were relied upon during a clinical test. CONCLUSIONS: In research applications requiring repeated measurements, or clinical contexts such as intraoperative monitoring or assessment of aided hearing, setting stimulus modulation rate parameters based on a previous analysis of an individual's MTF could be extremely beneficial. Sufficient time must be spent in recording the MTF to adequately attenuate the contribution of noise to the ASSR amplitude estimates.

The Guardian: an implantable system for chronic ambulatory monitoring of acute myocardial infarction.

The AngelMed Guardian is an implantable medical device that records cardiac data and detects ischemic events using a standard pacemaker intracardiac lead positioned in the right ventricular apex. The Guardian has been implanted in 55 people in the United States and Brazil and is currently undergoing a Food and Drug Administration phase 2 pivotal trial in the United States. The Guardian detects acute ischemic events by analyzing ST-segment shifts. The ST-segment shifts are calculated as the difference between the ST deviation of a current 10-second electrogram window and a baseline ST deviation value. If the ST-segment shift is greater than a heart rate-dependent programmable threshold, then the device generates an emergency alert signal. Results thus far have demonstrated that (i) the intracardiac electrogram is relatively noise-free and (ii) the ST-shift technique used by the Guardian is effective for detecting acute ischemic events.

Multiple auditory steady state responses (80-101 Hz): effects of ear, gender, handedness, intensity and modulation rate.

OBJECTIVE: To evaluate how the amplitudes and latencies of auditory steady state responses (ASSRs) to multiple stimuli presented at rates between 80 and 101 Hz vary with the ear of stimulation, the handedness or gender of a subject, and the rate and intensity of the stimuli. DESIGN: ASSRs were recorded in a group of 56 young adults (27 females, 13 left handed) using several stimulus conditions. In the two main conditions, four sinusoidally amplitude-modulated tones (each uniquely modulated using rates between 80 and 105 Hz) with carrier frequencies of 500, 1000, 2000, and 4000 Hz, were presented concurrently to each ear (eight total). In the first condition the modulation rates for the left ear were slower than those for the right and in the second condition this relationship was reversed. Other conditions evaluated the responses to single stimuli, to multiple stimuli presented in one ear only and to multiple stimuli presented dichotically (four in each ear) with rates that decreased rather than increased with increasing carrier frequency. Stimuli were presented at an intensity of 73 dB SPL except in two conditions wherein the intensity was 53 dB SPL. RESULTS: At 73 dB SPL, multiple-stimulus ASSRs were significantly reduced (monotic or dichotic) compared with single-stimulus ASSRs, especially at 1000 and 2000 Hz. There were significant differences between monotic and dichotic stimulation. When the stimuli were presented dichotically, the amplitude of the response varied with the relative rates of modulation for the stimuli presented in each ear. ASSRs were larger in the ear with the higher rate when the carrier frequencies were 500 and 1000 Hz and when the modulation rates were <90 Hz. There were no consistent effects of gender or ear of stimulation. There were also no significant effects of handedness. CONCLUSIONS: Presenting multiple stimuli at 73 dB SPL in the same ear decreases the amplitude of the ASSR compared with when the stimuli are presented singly. This is caused by the masking effect of low on higher carrier frequencies and some other inhibitory effect of high on lower frequencies. Dichotic stimulation can increase the amplitude of the response to stimuli modulated more rapidly (and concomitantly decrease the responses to the stimuli modulated more slowly). This effect occurs only for carrier frequencies <2000 Hz and for modulation frequencies <90 Hz. Dichotic stimulation also causes a small but highly significant decrease in the latency of the response compared with monotic stimulation.

The Guardian: an implantable system for chronic ambulatory monitoring of acute myocardial infarction

The AngelMed Guardian is an implantable medical device that records cardiac data and detects ischemic events using a standard pacemaker intracardiac lead positioned in the right ventricular apex. The Guardian has been implanted in 55 people in the United States and Brazil and is currentlyundergoing a Food and Drug Administration phase 2 pivotal trial in the United States. The Guardiandetects acute ischemic events by analyzing ST-segment shifts. The ST-segment shifts are calculated as the difference between the ST deviation of a current 10-second electrogram window and a baseline ST deviation value. If the ST-segment shift is greater than a heart rate–dependent programmable threshold, then the device generates an emergency alert signal. Results thus far have demonstrated that (i) the intracardiac electrogram is relatively noise-free and (ii) the ST-shifttechnique used by the Guardian is effective for detecting acute ischemic events.

Human auditory steady-state responses during sweeps of intensity.

OBJECTIVE: To record steady-state responses to amplitude-modulated tones that change their intensity over time and to see how well behavioral thresholds can be estimated from such responses. DESIGN: The intensity of the stimuli used in this experiment increased from 25 to 75 dB SPL for 8 sec and then decreased back to 25 dB HL during the subsequent 8 sec. Responses to this intensity sweep were averaged and then analyzed using a short-time Fast-Fourier Transform to measure how the amplitude and phase of the responses changed with intensity. One experimental condition presented single 2-kHz tones to the left ear; a second condition examined the use of simultaneously presented multiple tones (0.5, 1, 2, and 4 kHz) to the left ear; a third condition used multiple tones presented dichotically; and a fourth condition presented the multiple dichotic tones in masking noise to simulate either low-frequency (less than 1400 Hz) or high-frequency (greater than 1400 Hz) hearing loss. Physiological thresholds were determined using six different algorithms and the relations between physiological and behavioral thresholds were evaluated to see how well behavioral thresholds could be estimated. RESULTS: The amplitude-intensity functions for the 1 and 2 kHz responses both demonstrated a plateau at higher intensities in the multiple-stimulus conditions but not in the single-stimulus condition. The slope of the amplitude-intensity functions varied significantly with the carrier frequency of the stimulus: 1.30 at 500 Hz, 0.87 at 1000 Hz, 0.75 at 2000 Hz, and 1.40 at 4000 Hz. The slope of the phase-intensity function averaged 1.16 degrees per dB and did not vary with carrier frequency. Estimates of latency, however, indicated that latency increased with decreasing carrier frequency and with decreasing intensity. The performance of the threshold estimating algorithms differed between normal hearing and simulated hearing loss, since the amplitude- and phase-intensity functions in the latter condition were not linear. Physiological-behavioral threshold differences were generally greater for normal hearing than for simulated hearing loss. Linear regression provided the least physiological-behavioral difference but was quite variable during simulated hearing loss. Simply defining threshold as the lowest intensity above which all responses were significantly different from residual EEG noise was the most accurate method in terms of yielding the least standard deviation of the physiological-behavioral difference with an average standard deviation of 10 dB, provided EEG noise levels were low enough in the normal hearing condition. CONCLUSIONS: Thresholds can be estimated using intensity sweeps with about the same accuracy as recording separate responses to discrete intensities. Sweep recordings provide additional information about the responses at suprathreshold intensities by clearly determining amplitude- and phase- intensity functions at these intensities.

Simultaneous latency estimations for distortion product otoacoustic emissions and envelope following responses.

The purpose of this research was to simultaneously estimate processing delays in the cochlea and brainstem using the same acoustic stimuli. Apparent latencies were estimated from ear canal measurements of 2f1-f2 distortion product otoacoustic emissions (DPOAEs), and scalp recordings of the f2-f1 envelope following response (EFR). The stimuli were equal level tone pairs (65 dB SPL) with the upper tone f2 set at either 900 or 1800 Hz to fix the initiation site of the DPOAE and EFR. The frequency of f1 was swept continuously between frequency limits chosen to keep the EFR response between 150 and 170 Hz. The average DPOAE latencies were 9.6 and 6.2 ms for f2 =900 and 1800 Hz, and the corresponding EFR latencies were 12.4 and 8.8 ms. In a control condition, a third (suppressor) tone was added near the DPOAE response frequency to evaluate whether the potential source at fdp was contributing significantly to the measured emission. DPOAE latency is the sum of both inward and outward cochlear delays. The EFR apparent latency is the sum of inward cochlear delay and neural processing delay. Neural delay was estimated as approximately 5.3 ms for both frequencies of stimulation.

Recording auditory steady-state responses in young infants.

OBJECTIVES: This study examined the auditory steady-state responses evoked by amplitude-modulated (AM), mixed-modulated (MM), exponentially-modulated (AM2), and frequency-modulated (FM) tones in 50 newborn infants (within 3 days of birth) and in 20 older infants (within 3-15 wk of birth). Our hypothesis was that MM and AM2 tonal stimuli would evoke larger responses than either the AM or FM tones, and that this increased size would make the responses more readily detectable. DESIGN: Multiple auditory steady-state responses were recorded to four tonal stimuli presented simultaneously to each ear at 50 dB SPL. The carrier frequencies of the stimuli were 500, 1000, 2000, and 4000 Hz and the modulation rates were between 78 and 95 Hz. Recordings lasting 12 minutes were obtained for each of the three types of modulation: 100% AM, MM (100% AM and 20% FM) and AM2. In six infants, responses to 20% FM were also recorded. RESULTS: In newborn infants, MM and AM2 stimuli produced responses that were on average 15% larger than AM stimuli. For AM, MM, and AM2 stimuli, the percentage of significant responses was 67%, 73%, 76%, respectively. Responses to FM stimuli were clearly evident in newborn infants and were about half the amplitude of the AM responses. Responses recorded in the older infants were 17% larger when evoked by MM and AM2 stimuli, rather than AM stimuli. Responses in the older infants were, on average, 32% larger and showed a higher incidence of significant responses than for infants in the first 3 days of life. For AM, MM, and AM2 stimuli, the percentage of significant responses was 82%, 82%, 84%, respectively. In both newborn and older infants, the overall percentage of significant responses was decreased by the 500 Hz results, which showed lower amplitudes and were less frequently detected than responses evoked by other frequencies. CONCLUSIONS: The responses to MM and AM2 tones were larger than those evoked by AM tones. Using these stimuli will increase the reliability and efficiency of evoked potential audiometry in infancy. Responses at 50 dB SPL are more easily detected at 3-15 wk of age than in the first few days after birth. Comprehensive frequency-specific testing of hearing using steady-state responses will likely be more accurate if postponed until after the immediate neonatal period.

Avoiding electromagnetic artifacts when recording auditory steady-state responses.

Electromagnetic artifacts can occur when recording multiple auditory steady-state responses evoked by sinusoidally amplitude modulated (SAM) stimuli. High-intensity air-conducted stimuli evoked responses even when hearing was prevented by masking. Additionally, high-intensity bone-conducted stimuli evoked responses that were completely different from those evoked by air-conducted stimuli of similar sensory level. These artifacts were caused by aliasing since they did not occur when recordings used high analog-digital (AD) conversion rates or when high frequencies in the electroencephalographic (EEG) signal were attenuated by steep-slope low-pass filtering. Two possible techniques can displace aliased energy away from the response frequencies: (1) using an AD rate that is not an integer submultiple of the carrier frequencies and (2) using stimuli with frequency spectra that do not alias back to the response frequencies, such as beats or "alternating SAM" tones. Alternating SAM tones evoke responses similar to conventional SAM tones, whereas beats produce significantly smaller responses.

Auditory steady-state responses and word recognition scores in normal-hearing and hearing-impaired adults.

OBJECTIVE: The number of steady-state responses evoked by the independent amplitude and frequency modulation (IAFM) of tones has been related to the ability to discriminate speech sounds as measured by word recognition scores (WRS). In the present study IAFM stimulus parameters were adjusted to resemble the acoustic properties of everyday speech to see how well responses to these speech-modeled stimuli were related to WRS. DESIGN: We separately measured WRS and IAFM responses at a stimulus intensity of 70 dB SPL in three groups of subjects: young normal-hearing, elderly normal-hearing, and elderly hearing-impaired. We used two series of IAFM stimuli, one with modulation frequencies near 40 Hz and the other with modulation frequencies near 80 Hz. The IAFM stimuli, consisting of four carrier frequencies each independently modulated in frequency and amplitude, could evoke up to eight separate responses in one ear. We recorded IAFM responses and WRS measurements in quiet and in the presence of speech-masking noise at 67 dB SPL or 70 dB SPL. We then evaluated the hearing-impaired subjects with and without their hearing aids to see whether an improvement in WRS would be reflected in an increased number of responses to the IAFM stimulus. RESULTS: The correlations between WRS and the number of IAFM responses recognized as significantly different from the background were between 0.70 and 0.81 for the 40 Hz stimuli, between 0.73 and 0.82 for the 80 Hz stimuli, and between 0.76 and 0.85 for the combined assessment of 40 and 80 Hz responses. Response amplitudes at 80 Hz were smaller in the hearing-impaired than in the normal-hearing subjects. Response amplitudes for the 40 Hz stimuli varied with the state of arousal and this effect made it impossible to compare amplitudes across the different groups. Hearing aids increased both the WRS and the number of significant IAFM responses at 40 Hz and 80 Hz. Masking decreased the WRS and the number of significant responses. CONCLUSIONS: IAFM responses are significantly correlated with WRS and may provide an objective tool for examining the brain's ability to process the auditory information needed to perceive speech.

Human auditory steady-state responses: the effects of recording technique and state of arousal.

UNLABELLED: There is some controversy in the literature about whether auditory steady-state responses (ASSRs) can be reliably recorded in all subjects and whether these responses consistently decrease in amplitude during drowsiness. In 10 subjects, 40-Hz ASSRs became significantly different from background electroencephalogram activity with a probability of P < 0.01 and an average time of 22 s (range, 2-92 s), provided that the responses were analyzed with time-domain averaging rather than spectral averaging. In a second experiment with 10 subjects, 40-Hz ASSRs recorded between the vertex and posterior neck consistently decreased in amplitude during drowsiness and sleep. Findings that the ASSR may occasionally increase during drowsiness may be explained by postauricular muscle responses recorded from a mastoid reference. These may occur during drowsiness in association with rolling-eye movements. ASSRs recorded between the vertex and posterior neck are not distorted by these reflexes. These findings combine with previous literature on the effects of general anesthetics on the ASSR to confirm that the ASSR is a valid option for monitoring the hypnotic effects of general anesthetics. IMPLICATIONS: Auditory steady-state responses to stimuli presented at rates near 40 Hz can be used to monitor anesthesia. These responses can be quickly and reliably recorded during both sleep and wakefulness, provided that appropriate averaging techniques are used.

Human auditory steady-state responses.

Steady-state evoked potentials can be recorded from the human scalp in response to auditory stimuli presented at rates between 1 and 200 Hz or by periodic modulations of the amplitude and/or frequency of a continuous tone. Responses can be objectively detected using frequency-based analyses. In waking subjects, the responses are particularly prominent at rates near 40 Hz. Responses evoked by more rapidly presented stimuli are less affected by changes in arousal and can be evoked by multiple simultaneous stimuli without significant loss of amplitude. Response amplitude increases as the depth of modulation or the intensity increases. The phase delay of the response increases as the intensity or the carrier frequency decreases. Auditory steady-state responses are generated throughout the auditory nervous system, with cortical regions contributing more than brainstem generators to responses at lower modulation frequencies. These responses are useful for objectively evaluating auditory thresholds, assessing suprathreshold hearing, and monitoring the state of arousal during anesthesia.

Concurrent measurement of distortion product otoacoustic emissions and auditory steady state evoked potentials.

Distortion product otoacoustic emissions (DPOAEs) and auditory steady state evoked response potentials (ASSRs) can both be evoked by tone pairs with frequencies f(1) and f(2). The DPOAE is maximal at 2f(1)-f(2) and the ASSR is maximal at f(2)-f(1). Since DPOAE magnitude depends on the ratio f(2)/f(1), but ASSR amplitude depends on the beat frequency f(2)-f(1), compromises are necessary when recording both responses concurrently. Tone pairs with f(2) of 900, 1800 and 3600 Hz were presented simultaneously at either 40 or 50 dB sound pressure level (SPL). The f(1) frequency of each pair was approximately 85 or 180 Hz lower than f(2). Phase measurements were used to calculate apparent latencies at 40 dB SPL. For increasing f(2), DPOAE latencies were 14.5, 9.7 and 6.3 ms for 85 Hz beats, and 11.5, 9.0 and 4.3 ms for 180 Hz beats. ASSR latencies were 22.0, 15.7 and 17.8 ms at 85 Hz, and 17.7, 11.3 and 9.6 ms at 180 Hz. From a model of the mechanical transmission in the cochlea, delays between the basilar membrane and the generator of the ASSR were estimated as 15.4, 12.2 and 15.3 ms at 85 Hz and 8.6, 7.6 and 8.0 ms at 180 Hz.

Advantages and caveats when recording steady-state responses to multiple simultaneous stimuli.

This article considers the efficiency of evoked potential audiometry using steady-state responses evoked by multiple simultaneous stimuli with carrier frequencies at 500, 1000, 2000, and 4000 Hz. The general principles of signal-to-noise enhancement through averaging provide a basis for determining the time required to estimate thresholds. The advantage of the multiple-stimulus technique over a single-stimulus approach is less than the ratio of the number of stimuli presented. When testing two ears simultaneously, the advantage is typically that the multiple-stimulus technique is two to three times faster. One factor that increases the time of the multiple-response recording is the relatively small size of responses at 500 and 4000 Hz. Increasing the intensities of the 500- and 4000-Hz stimuli by 10 or 20 dB can enhance their responses without significantly changing the other responses. Using multiple simultaneous stimuli causes small changes in the responses compared with when the responses are evoked by single stimuli. The clearest of these interactions is the attenuation of the responses to low-frequency stimuli in the presence of higher-frequency stimuli. Although these interactions are interesting physiologically, their small size means that they do not lessen the advantages of the multiple-stimulus approach.

Estimating the audiogram using multiple auditory steady-state responses.

Multiple auditory steady-state responses were evoked by eight tonal stimuli (four per ear), with each stimulus simultaneously modulated in both amplitude and frequency. The modulation frequencies varied from 80 to 95 Hz and the carrier frequencies were 500, 1000, 2000, and 4000 Hz. For air conduction, the differences between physiologic thresholds for these mixed-modulation (MM) stimuli and behavioral thresholds for pure tones in 31 adult subjects with a sensorineural hearing impairment and 14 adult subjects with normal hearing were 14+/-11, 5+/-9, 5+/-9, and 9+/-10 dB (correlation coefficients .85, .94, .95, and .95) for the 500-, 1000-, 2000-, and 4000-Hz carrier frequencies, respectively. Similar results were obtained in subjects with simulated conductive hearing losses. Responses to stimuli presented through a forehead bone conductor showed physiologic-behavioral threshold differences of 22+/-8, 14+/-5, 5+/-8, and 5+/-10 dB for the 500-, 1000-, 2000-, and 4000-Hz carrier frequencies, respectively. These responses were attenuated by white noise presented concurrently through the bone conductor.