Toward Extending Auditory Steady-State Response (ASSR) Testing to Longer-Latency Equivalent Potentials

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1 Department of History of Art and Architecture Toward Extending Auditory Steady-State Response (ASSR) Testing to Longer-Latency Equivalent Potentials John D. Durrant, PhD, CCC-A, FASHA

2 Department of Communication Science and Disorders Acknowledgements: Mini-Interlude:

3 Department of Communication Science and Disorders Associates Pitt Collaborators: Abreena Tlumak (portions from PhD dis & on-going collaboration--va Pittsburgh Healthcare System) J Robert Boston, Dept. of Electrical & Computer Engineering IHS Collaborators: Rafael Delgado; Ed Miskiel

4 Department of Communication Science and Disorders REMINDER of SOME FUNDAMENTALS The brain is well-known to be highly electrically active at all times (EEG). This electrical activity can be synchronized, at least to some extent, to an event. Traditional approach: test the system via a transient stimulus-response paradigm with temporal analysis and peak-peaking as the primary method of evaluation Although spectral and other analyses are not without merit, they have received limited attention and zero clinical acceptance. What is the traditional approach methodologically? -- Roughly a test of the impulse response of the sys tem but without specific knowledge of the system transfer function. Up-shot: Limited relation of response (output) spectrum to stimulus (input) spectrum. Steady-state responses (SSRs) offer another stimulus and analysis approach that is inherently more deterministic It thus lends itself to good use of spectral information (in and out) straight-forward SNR assessment and other advantages. Despite a hilly early history of interest, ASSR has found great research, clinical, and commercial interests in audiology primarily for hearing threshold estimation in uncooperative subjects. Yet, issues remain and there is plenty of room for more work, both in the SSR approach and applications, as well as R&D in related (even traditional) evoked potential technology.

5 Department of Communication Science and Disorders

6 TRADITIONAL APPROACH Auditory Evoked Electric Responses

7 Auditory Evoked Electric Responses

8 Auditory Evoked Electric Responses

9 But, other potentials and/or approaches are possible Hz Plot } - MAGNITUDE (nv) IFR NB filter "raw" LATENCY (ms)

11 Department of Communication Science and Disorders

13 Department of Communication Science and Disorders Clearly there is nothing magical about spectral analysis. Time and spectral analyses simply tell the same story from a different points of view. The problem again with transient AEP stim/analysis is that, unless the response looks like the stimulus and is well preserved, challenging to identify the response in either domain! This is true even if we use a frequency specific stimulus! This in turn challenges the examiner to interpret responses and makes rule-based response detection and assessment difficult to implement. There have been innovative approaches with transient stimulusresponse approach For example, e.g the algorithm used in Algol ABR screener and template analyses, but with varied success for ERA per se.

14 Department of Communication Science and Disorders Knowing exactly what the output signal should look like, or at least where in the frequency domain to look for it--is a really big advantage in semi-/fully automated ERA and toward the goal of truly objective response detection/assessment and toward more uniform tests across clinics and clinicians of varied experience. The Auditory Steady State Response measurement thus empowers the examiner. What changes in the test? Inputting to the ear a virtually steady stimulus (the carrier ) and getting the brain to entrain on it. Thereafter, conceptually, it is largely a matter of analysis Yet (as always), there are practical stimulus-response considerations.

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16 Department of Communication Science and Disorders

17 Department of Communication Science and Disorders

18 Department of Communication Science and Disorders And perhaps, old tricks are still the best tricks, properly adapted.

19 Fundamentals for Moving Forward Current ASSR methods (in clinical applications) have focused largely on ERA applications (responses corresponding essentially to ABR and MLR). There thus have been limited interests in the broader neurological arena... and to applying SSR stimulus-response concepts to longer latency potentials and thus putatively contributions of more corticalward, if not, cortical activity. We sought to explore a SSR approach applicable to a broad range of stimulus repetition rates (or modulation frequency, Fm) for testing ultimately subjects across subject state, age, and clinical population.

20 Aims of Efficacy Study ASSLLR and ASSR Rate Profile Analysis The primary aim was to profile ASSR amplitudes in adults and children over a wide range of repetition rates specifically, those that were expected to represent the general ranges of stimulus repetition rates traditionally utilized in AEP testing. This required first an approach to very low-repetition rate stimulation capable of robust LL-like responses (if not =). This required, in turn, alternative approaches to the analyses and validation. The secondary aim was an exploratory examination of the effect of F m s on response amplitude during natural sleep.

21 METHODS Modeling of the Response

Since the SSRs corresponding to short latency transient responses approach sinusoidal signals and are well known, adapting the longlatency-equivalent range of modulation rates/frequencies indeed was

22 Since the SSRs corresponding to short latency transient responses approach sinusoidal signals and are well known, adapting the longlatency-equivalent range of modulation rates/frequencies indeed was the challenge of this work. Here is a grand-average P1-N1-P2 complex recorded at Cz from the study cohort of 25 college-aged, normal-hearing female subjects, with a 1 khz tone-burst stimulus presented at 70 db SPLpeq.

23 For a quasi-steady-state long-latency response, the timeensemble analysis window is extended 10 s-- & embraces a train of 7 sinusoidal pulses, < 1 Hz (progressively shorter window and longer higher Fm s, e.g. 40 for 40 Hz, 1s analysis in deference to decreased signal)

24 So what should the spectrum look like?

25 But is this a valid representation of the response, especially toward the goal at the lowest Fm to have perfectly parallel parameters between test modes?

26 Resulting predicted nuances of ASSLLR Quasi-line spectra whose spectral envelope follows the spectrum of the transient response (per Fourier 101). Somewhat complex spectrum necessarily results (not surprisingly from an underlying signal looking something like 3 haversinesof of 3 different periods). The possibility of relatively lowspectral power at frequencies near the repetition rate (Fm) is attributable to the low duty cycle of the underlying signal complex. Unlike conventional ASSR (40/80 Hz) AM-ingat such low rates and natural adaptation of the LLR precludes overlapping stimulation (LLR 101). AND WITH INCREASING Fm? Expected progressive change in spectral envelope and number of components as we progress toward strong entrainment of overlapped responses and dominance of the fundamental, at ~40 Hz and above.

27 METHODS Empirical Study

28 Subjects 25 adults (18-35) and 12 children (6-9). Female/tested in RE No personal history of otological/neurological disorders Normal ME function and hearing sensitivity

29 ASSR Recording Parameters

30 Preview another issue measuring magnitude: Fundamental or what?

31 Harmonic Sum

32 Harmonic Sum vs. Fundamental Rate Profile (preview)

34 Hz Adult Awake Legend Response Est. Noise Relative Amplitude Frequency (Hz) Grand-average Fm = 0.75 Hz. BLACK tracing is the response spectrum (summed buffers). RED tracing is the estimated noise floor derived taking the difference between the buffers of the dual-buffered response acquisition process. Tlumak, Durrant, Delgado, & Boston, J.R. (2011) Int. J. Audiol. 50:

35 Adults Est. Legend Response Hz Adult Awake Noise 1.0 Est. Legend 5 Hz Adult Awake Response Noise Hz Adult Awake Est. Legend Noise Hz Adult Awake Legend Hz Adult Awake Hz Adult Awake Relative Relative Amplitude Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Relative Relative Amplitude Amplitude 0.75 Hz Adult Awake Legend 1.25 Hz Adult Awake Legend Response Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Response Est. Response Noise Est. Legend Reponse Noise Legend Est. Response Noise Est. Response Noise Est. Noise

36 Pediatric (6-9 years, N=12) versus adult (18-35 yrs, N=25) grand average transient response. Tlumak, Durrant, Delgado, & Boston (2012) Int. J. Audiol. 51:

37 Relative Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Children Hz Children Hz Children vs. Adult Legend Hz Children Hz Children vs. Adult Legend Est. Response Noise Child 2.5 Hz 2.5 Children Hz Children vs. Adult Est. Legend Response Est. Noise Noise Child Adult 5 Hz Children 5 Hz Children vs. Adult Est. Response Est. Legend Noise Response Noise Adult Child Child Response Est. Noise Child 10 Hz 10 Children Hz Children vs. Adult Est. Legend Response Noise Adult Adult Child Response Est. Est. Noise Adult Noise Child 20 Hz 20 Children Hz Children vs. Adult Adult Est. Legend Response Noise Child Response Adult Child 40 Hz Children vs. Adult Est. Est. Legend Response Noise Adult Response Adult Response Est. Est. Noise Noise Child 80 Hz Children vs. Adult Legend Response Adult Child Response Adult Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz) Est. Noise Child Est. Est. Noise Noise Adult Child Response Est. Noise Adult Adult Response Response Child Adult Response Child

38 ASSR-based stimulus rate profiles compared

39 10 Adult Amplitude (uv) 1 0,1 0, Repetition Rate (Hz)

40 Relative Relative Amplitude Amplitude Relative Amplitude Relative Amplitude Relative Amplitude Relative Relative Amplitude Amplitude Relative Amplitude Adults during sleep 0.75 Hz 0.75 Adult Hz Sleep Adult vs. Sleep Adult Awake Legend 1.25 Hz 1.25 Adult Hz Sleep Adult vs. Sleep Adult Awake Legend Response Est. Noise Sleep 2.5 Hz Adult 2.5 Hz Sleep Adult vs. Sleep Adult Awake Response Est. Legend Noise Awake Sleep 5 Hz Adult 5 Hz Sleep Adult vs. Sleep Adult Awake Est. Response Est. Legend Noise Awake Sleep 10 Hz Adult 10 Hz Sleep Adult vs. Sleep Adult Awake Response Est. Est. Response Legend Noise Noise Awake Awake Sleep Sleep Response Est. Response Noise Awake Sleep 20 Hz Adult 20 Hz Sleep Adult vs. Sleep Adult Awake Est. Legend Noise Awake Sleep Sleep Response Est. Noise Awake Sleep Response Sleep Awake 40 Hz Adult Sleep vs. Adult Awake Est. Legend Noise Sleep Response Awake Est. Noise Sleep Awake Sleep 80 Hz Adult 80 Hz Sleep Adult vs. Sleep Adult Awake Response Est. Legend Noise Response Awake Sleep Sleep Est. Noise Awake Response Response Est. Noise Awake Sleep Response Est. Noise Sleep Sleep Awake Response Response Awake Sleep Response Awake Frequency (Hz) Frequency (Hz) Frequency 20 (Hz) Frequency 40 (Hz) Frequency 40 (Hz) Frequency (Hz) Frequency (Hz) Frequency (Hz)

41 ASSR-based stimulus rate profiles: HS vs. F1 and Dozing vs. Alert Adults 1,8 1,6 1,4 Magnitude 1,2 1 0,8 0,6 0,4 0,2 0 0,75 1,25 2, Frequency Tlumak, Durrant, Delgado, & Boston (2012) Int. J. Audiol. 51:

42 Department of Communication Science and Disorders Conventional vs. SS-mode Acquistion: Parity truly achieved for LLR (alias SVP/other)? magnitude (uv) Rcontra dwnsmpl deconv latency (ms) Grand means: cross-correlation = 0.98

43 --db SPL-- <70 <50 <20 <15 {=VDL of LLR} <0

44 Department of Communication Science and Disorders Time analysis, pulse train (adult, awake)

45 Conclusions The results demonstrate our ASSR approach to low-repetition rates to be efficacious in adult and pediatric subjects alike, including (we predict) still younger subjects. The rate-profile results are encouraging as they (1) mimic overall a similar function constructed from data largely on the more traditional transient response (suggesting internal validity), (2) reflect nevertheless some differences from transient-responsebased results, that could be interesting to explore, and (3) were obtained without possible confounds of peak identification and while controlling substantially for background noise. (4) are well accessible in in-attentive subjects and likely during sleep, but remains to be evaluated in young and/or sedated subjects. Issues of use of ASSLLR for use in ERA and other technical issues currently are under investigation/planned. Initial results for ERA applications, per se, are encouraging.

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THRESHOLD PREDICTION USING THE ASSR AND THE TONE BURST CONFIGURATIONS

THRESHOLD PREDICTION USING THE ASSR AND THE TONE BURST ABR IN DIFFERENT AUDIOMETRIC CONFIGURATIONS INTRODUCTION INTRODUCTION Evoked potential testing is critical in the determination of audiologic thresholds