LaDIVA: A neurocomputational model providing laryngeal motor control for speech acquisition and production.

Many voice disorders are the result of intricate neural and/or biomechanical impairments that are poorly understood. The limited knowledge of their etiological and pathophysiological mechanisms hampers effective clinical management. Behavioral studies have been used concurrently with computational models to better understand typical and pathological laryngeal motor control. Thus far, however, a unified computational framework that quantitatively integrates physiologically relevant models of phonation with the neural control of speech has not been developed. Here, we introduce LaDIVA, a novel neurocomputational model with physiologically based laryngeal motor control. We combined the DIVA model (an established neural network model of speech motor control) with the extended body-cover model (a physics-based vocal fold model). The resulting integrated model, LaDIVA, was validated by comparing its model simulations with behavioral responses to perturbations of auditory vocal fundamental frequency (fo) feedback in adults with typical speech. LaDIVA demonstrated capability to simulate different modes of laryngeal motor control, ranging from short-term (i.e., reflexive) and long-term (i.e., adaptive) auditory feedback paradigms, to generating prosodic contours in speech. Simulations showed that LaDIVA's laryngeal motor control displays properties of motor equivalence, i.e., LaDIVA could robustly generate compensatory responses to reflexive vocal fo perturbations with varying initial laryngeal muscle activation levels leading to the same output. The model can also generate prosodic contours for studying laryngeal motor control in running speech. LaDIVA can expand the understanding of the physiology of human phonation to enable, for the first time, the investigation of causal effects of neural motor control in the fine structure of the vocal signal.

Auditory and somatosensory feedback mechanisms of laryngeal and articulatory speech motor control.

PURPOSE: Speech production is a complex motor task involving multiple subsystems. The relationships between these subsystems need to be comprehensively investigated to understand the underlying mechanisms of speech production. The goal of this paper is to examine the differential contributions of 1) auditory and somatosensory feedback control mechanisms, and 2) laryngeal and articulatory speech production subsystems on speech motor control at an individual speaker level using altered auditory and somatosensory feedback paradigms. METHODS: Twenty young adults completed speaking tasks in which sudden and unpredictable auditory and physical perturbations were applied to the laryngeal and articulatory speech production subsystems. Auditory perturbations were applied to laryngeal or articulatory acoustic features of speech. Physical perturbations were applied to the larynx and the jaw. Pearson-product moment correlation coefficients were calculated between 1) auditory and somatosensory reflexive responses to investigate relationships between auditory and somatosensory feedback control mechanisms, and 2) laryngeal and articulatory reflexive responses as well as acuity measures to investigate the relationship between auditory-motor features of laryngeal and articulatory subsystems. RESULTS: No statistically significant correlations were found concerning the relationships between auditory and somatosensory feedback. No statistically significant correlations were found between auditory-motor features in the laryngeal and articulatory control subsystems. CONCLUSION: Results suggest that the laryngeal and articulatory speech production subsystems operate with differential auditory and somatosensory feedback control mechanisms. The outcomes suggest that current models of speech motor control should consider decoupling laryngeal and articulatory domains to better model speech motor control processes.

Physics of phonation offset: Towards understanding relative fundamental frequency observations.

Relative fundamental frequency (RFF) is a promising assessment technique for vocal pathologies. Herein, we explore the underlying laryngeal factors dictating RFF behaviours during phonation offset. To gain physical insights, we analyze a simple impact oscillator model and follow that with a numerical study using the well-established body-cover model of the vocal folds (VFs). Study of the impact oscillator suggests that the observed decrease in fundamental frequency during offset is due, at least in part, to the increase in the neutral gap between the VFs during abduction and the concomitant decrease in collision forces. Moreover, the impact oscillator elucidates a correlation between sharper drops in RFF and increased stiffness of the VFs, supporting experimental RFF studies. The body-cover model study further emphasizes the correlation between the drops in RFF and collision forces. The numerical analysis also illustrates the sensitivity of RFF to abduction initiation time relative to the phase of the phonation cycle, and the abduction period length. In addition, the numerical simulations display the potential role of the cricothyroid muscle to mitigate the RFF reduction. Last, simplified models of phonotraumatic vocal hyperfunction are explored, demonstrating that the observed sharper drops in RFF are associated with increased pre-offset collision forces.

Vocal fold kinematics and relative fundamental frequency as a function of obstruent type and speaker age.

The acoustic measure, relative fundamental frequency (RFF), has been proposed as an objective metric for assessing vocal hyperfunction; however, its underlying physiological mechanisms have not yet been fully characterized. This study aimed to characterize the relationship between RFF and vocal fold kinematics. Simultaneous acoustic and high-speed videoendoscopic (HSV) recordings were collected as younger and older speakers repeated the utterances /ifi/ and /iti/. RFF values at voicing offsets and onsets surrounding the obstruents were estimated from acoustic recordings, whereas glottal angles, durations of voicing offset and onset, and a kinematic estimate of laryngeal stiffness (KS) were obtained from HSV images. No differences were found between younger and older speakers for any measure. RFF did not differ between the two obstruents at voicing offset; however, fricatives necessitated larger glottal angles and longer durations to devoice. RFF values were lower and glottal angles were greater for stops relative to fricatives at voicing onset. KS values were greater in stops relative to fricatives. The less adducted vocal folds with greater KS and lower RFF at voicing onset for stops relative to fricatives in this study were in accordance with prior speculations that decreased vocal fold contact area and increased laryngeal stiffness may decrease RFF.

Oral configurations during vowel nasalization in English.

Speech nasalization is achieved primarily through the opening and closing of the velopharyngeal port. However, the resultant acoustic features can also be influenced by tongue configuration. Although vowel nasalization is not contrastive in English, two previous studies have found possible differences in the oral articulation of nasal and oral vowel productions, albeit with inconsistent results. In an attempt to further understand the conflicting findings, we evaluated the oral kinematics of nasalized and non-nasalized vowels in a cohort of both male and female American English speakers via electromagnetic articulography. Tongue body and lip positions were captured during vowels produced in nasal and oral contexts (e.g., /mɑm/, /bɑb/). Large contrasts were seen in all participants between tongue position of /æ/ in oral and nasal contexts, in which tongue positions were higher and more forward during /mæm/ than /bæb/. Lip aperture was smaller in a nasal context for /æ/. Lip protrusion was not different between vowels in oral and nasal contexts. Smaller contrasts in tongue and lip position were seen for vowels /ɑ, i, u/; this is consistent with biomechanical accounts of vowel production that suggest that /i, u/ are particularly constrained, whereas /æ/ has fewer biomechanical constraints, allowing for more flexibility for articulatory differences in different contexts. Thus we conclude that speakers of American English do indeed use different oral configurations for vowels that are in nasal and oral contexts, despite vowel nasalization being non-contrastive. This effect was consistent across speakers for only one vowel, perhaps accounting for previously-conflicting results.

Refining algorithmic estimation of relative fundamental frequency: Accounting for sample characteristics and fundamental frequency estimation method.

Relative fundamental frequency (RFF) is a promising acoustic measure for evaluating voice disorders. Yet, the accuracy of the current RFF algorithm varies across a broad range of vocal signals. The authors investigated how fundamental frequency (fo) estimation and sample characteristics impact the relationship between manual and semi-automated RFF estimates. Acoustic recordings were collected from 227 individuals with and 256 individuals without voice disorders. Common fo estimation techniques were compared to the autocorrelation method currently implemented in the RFF algorithm. Pitch strength-based categories were constructed using a training set (1158 samples), and algorithm thresholds were tuned to each category. RFF was then computed on an independent test set (291 samples) using category-specific thresholds and compared against manual RFF via mean bias error (MBE) and root-mean-square error (RMSE). Auditory-SWIPE' for fo estimation led to the greatest correspondence with manual RFF and was implemented in concert with category-specific thresholds. Refining fo estimation and accounting for sample characteristics led to increased correspondence with manual RFF [MBE = 0.01 semitones (ST), RMSE = 0.28 ST] compared to the unmodified algorithm (MBE = 0.90 ST, RMSE = 0.34 ST), reducing the MBE and RMSE of semi-automated RFF estimates by 88.4% and 17.3%, respectively.

Relationship Between Laryngeal Sensory Deficits, Aspiration, and Pneumonia in Patients with Dysphagia.

The laryngeal adductor reflex (LAR) is an airway protective reflex that manifests as a brief vocal fold closure in response to laryngeal stimulation. This study examined if the absence of the LAR in response to touch delivered by a laryngoscope is associated with penetration/aspiration or pneumonia in patients with dysphagia. Inpatients at a teaching hospital with clinical symptoms of dysphagia were recruited upon referral to the otolaryngology clinic for a swallowing evaluation. Otolaryngologists observed the status of secretions and touched each arytenoid with the tip of the laryngoscope. The patients were then asked to swallow 3-5 mL grape gelatin and 3-5 mL colored water. All procedures were video-recorded. Two independent raters noted absence/presence of the LAR and penetration/aspiration of pharyngeal secretions, gelatin, and water on the recorded videos. A diagnosis of pneumonia during the patient's entire hospital stay was determined by a review of the hospital's medical records. Statistical analyses were performed using Fisher's exact test. Sixty-one patients were included. Twenty-one patients (34.5%) did not exhibit the LAR. No association was found between the absent LAR and penetration or aspiration. There was, however, a significant association between an absence of the LAR and pneumonia development. Patients with an absent LAR had 6.8 times the odds of developing pneumonia as compared to those with a present LAR (OR 6.75; 95% CI 1.76-25.96; p < 0.01). Using the LAR as a marker of laryngeal sensory function appears to be valuable for identifying patients at high risk of pneumonia.

The relationship between acoustical and perceptual measures of vocal effort.

Excessive vocal effort is a common clinical voice symptom, yet the acoustical manifestation of vocal effort and how that is perceived by speakers and listeners has not been fully elucidated. Here, 26 vocally healthy adults increased vocal effort during the production of the utterance /ifi/, followed by self-ratings of effort on a 100 mm visual analog scale. Twenty inexperienced listeners assessed the speakers' vocal effort using the visual sort-and-rate method. Previously proposed acoustical correlates of vocal effort were calculated, including: mean sound pressure level (SPL), mean fundamental frequency (f o), relative fundamental frequency (RFF) offset cycle 10 and onset cycle 1, harmonics-to-noise ratio (HNR), cepstral peak prominence and its standard deviation (SD), and low-to-high (L/H) spectral ratio and its SD. Two separate mixed-effects regression models yielded mean SPL, L/H ratio, and HNR as significant predictors of both speaker and listener ratings of vocal effort. RFF offset cycle 10 and mean f o were significant predictors of listener ratings only. Therefore, speakers and listeners attended to similar acoustical cues when making judgments of vocal effort, but listeners also used additional time-based information. Further work is needed to determine how vocal effort manifests in the speech signal in speakers with voice disorders.

Surface electromyographic control of a novel phonemic interface for speech synthesis.

Many individuals with minimal movement capabilities use AAC to communicate. These individuals require both an interface with which to construct a message (e.g., a grid of letters) and an input modality with which to select targets. This study evaluated the interaction of two such systems: (a) an input modality using surface electromyography (sEMG) of spared facial musculature, and (b) an onscreen interface from which users select phonemic targets. These systems were evaluated in two experiments: (a) participants without motor impairments used the systems during a series of eight training sessions, and (b) one individual who uses AAC used the systems for two sessions. Both the phonemic interface and the electromyographic cursor show promise for future AAC applications.

Effect of age on human-computer-interface control via neck electromyography.

The purpose of this study was to determine the effect of age on visuomotor tracking using submental and anterior neck surface electromyography (sEMG) to assess feasibility of computer control via neck musculature, which allows people with little remaining motor function to interact with computers. Thirty-two healthy adults participated: sixteen younger adults aged 18 - 29 years and sixteen older adults aged 69 - 85 years. Participants modulated sEMG to achieve targets presented at different amplitudes using real-time visual feedback. Root-mean-squared (RMS) error was used to quantify tracking performance. RMS error was increased for older adults relative to younger adults. Older adults demonstrated more RMS error than younger adults as a function of increasing target amplitude. The differential effects of age found on static tracking performance in anterior neck musculature suggest more difficult translation of human-computer-interfaces controlled using anterior neck musculature for static tasks to older populations.

Associations between laryngeal and cough dysfunction in motor neuron disease with bulbar involvement.

True vocal fold (TVF) dysfunction may lead to cough ineffectiveness. In individuals with motor neuron disease (MND), cough impairment in the context of dysphagia increases risk for aspiration and respiratory failure. This study characterizes differences and associations between TVF kinematics and airflow during cough in individuals with bulbar MND. Sequential glottal angles associated with TVF movements during volitional cough were analyzed from laryngeal video endoscopy examinations of adults with bulbar MND (n = 12) and healthy controls (n = 12) and compared with simultaneously collected cough-related airflow measures. Significant group differences were observed with airflow and TVF measures: volume acceleration (p ≤ 0.001) and post-compression abduction TVF angle average velocity (p = 0.002) were lower and expiratory phase rise time (p = 0.001) was higher in the MND group. Reductions in maximum TVF angle during post-compression abduction in the MND group approached significance (p = 0.09). All subjects demonstrated complete TVF and supraglottic closure during the compression phase of cough, except for incomplete supraglottic closure in 2/12 MND participants. A strong positive relationship between post-compression maximum TVF abduction angle and peak expiratory cough flow was observed in the MND group, though it was not statistically significant (r = 0.55; p = 0.098). Reductions in the speed and extent of TVF abduction are seen during the expulsion phase of cough in individuals with MND. This may contribute to cough impairment and morbidity.

Comparison of voice relative fundamental frequency estimates derived from an accelerometer signal and low-pass filtered and unprocessed microphone signals.

The relative fundamental frequency (RFF) surrounding the production of a voiceless consonant has previously been estimated using unprocessed and low-pass filtered microphone signals, but it can also be estimated using a neck-placed accelerometer signal that is less affected by vocal tract formants. Determining the effects of signal type on RFF will allow for comparisons across studies and aid in establishing a standard protocol with minimal within-speaker variability. Here RFF was estimated in 12 speakers with healthy voices using unprocessed microphone, low-pass filtered microphone, and unprocessed accelerometer signals. Unprocessed microphone and accelerometer signals were recorded simultaneously using a microphone and neck-placed accelerometer. The unprocessed microphone signal was filtered at 350 Hz to construct the low-pass filtered microphone signal. Analyses of variance showed that signal type and the interaction of vocal cycle × signal type had significant effects on both RFF means and standard deviations, but with small effect sizes. The overall RFF trend was preserved regardless of signal type and the intra-speaker variability of RFF was similar among the signal types. Thus, RFF can be estimated using either a microphone or an accelerometer signal in individuals with healthy voices. Future work extending these findings to individuals with disordered voices is warranted.

Effects of spectral content on Horii Oral-Nasal Coupling scores in children.

A miniature accelerometer and microphone can be used to obtain Horii Oral-Nasal Coupling (HONC) scores to objectively measure nasalization of speech. While this instrumentation compares favorably in terms of size and cost relative to other objective measures of nasality, the metric has not been well characterized in children. Furthermore, the measure is known to be affected by vowel loading, as speech loaded with "high" vowels is consistently scored as more nasal than speech loaded with "low" vowels. Filtering the signals used in computation of the HONC score to better isolate the correlates of nasalization has been shown to reduce vowel-related effects on the metric, but the efficacy of filtering has thus far only been explored in adults. Here, HONC scores for running speech and the vowel portions of consonant-vowel-consonant tokens were calculated for the speech of 26 children, aged 4-9 yrs. Scores were computed using the broadband accelerometer and speech signals, as well as using filtered, low-frequency versions of these signals. HONC scores obtained using both broadband and filtered signals resulted in well-separated scores for nasal and non-nasal speech. HONC scores computed using filtered signals were found to exhibit less within-participant variability.

The Impact of Foreign Language Accent on Expert Listeners' Auditory-Perceptual Evaluations of Dysphonia.

INTRODUCTION: Auditory-perceptual evaluations of dysphonia, though essential for comprehensive voice evaluation, are subject to listener bias. Knowledge of an underlying voice disorder can influence auditory-perceptual ratings. Accented speech results in increased listener effort and delays in word identification. Yet, little is known about the impact of foreign language accents on auditory-perceptual ratings for dysphonic speakers. The purpose of this work was to determine the impact of a foreign language accent on experts' auditory-perceptual ratings of dysphonic speakers. METHODS: Twelve voice-specializing SLPs who spoke with a General American English (GAE) accent rated vocal percepts of 28 speakers with a foreign language accent and 28 with a GAE accent, all of whom had been diagnosed with a voice disorder. Speaker groups were matched based on sex, age, and mean smoothed cepstral peak prominence. Four linear mixed-effects models assessed the impact of a foreign language accent on expert auditory-perceptual ratings of the overall severity of dysphonia, roughness, breathiness, and strain. RESULTS: The twelve raters demonstrated good inter- and intra-rater reliability (ICC[3, k] = .89; mean ICC = .89). The linear mixed-effects models revealed no significant impact of foreign language accent on ratings of overall severity of dysphonia, roughness, breathiness, or strain. CONCLUSION: Despite the possibility of increased listener effort and bias, foreign language accent incongruence had no effect on expert listeners' auditory-perceptual evaluations for dysphonic speakers. Findings support the use of auditory-perceptual evaluations for voice disorders across sociolinguistically diverse populations. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2272-2276, 2024.

Sex Differences in the Speech of Persons With and Without Parkinson's Disease.

BACKGROUND: Sex differences are apparent in the prevalence and the clinical presentation of Parkinson's disease (PD), but their effects on speech have been less studied. METHOD: Speech acoustics of persons with (34 females and 34 males) and without (age- and sex-matched) PD were examined, assessing the effects of PD diagnosis and sex on ratings of dysarthria severity and acoustic measures of phonation (fundamental frequency standard deviation, smoothed cepstral peak prominence), speech rate (net syllables per second, percent pause ratio), and articulation (articulatory-acoustic vowel space, release burst precision). RESULTS: Most measures were affected by PD (dysarthria severity, fundamental frequency standard deviation) and sex (smoothed cepstral peak prominence, net syllables per second, percent pause ratio, articulatory-acoustic vowel space), but without interactions between them. Release burst precision was differentially affected by sex in PD. Relative to those without PD, persons with PD produced fewer plosives with a single burst: females more frequently produced multiple bursts, whereas males more frequently produced no burst at all. CONCLUSIONS: Most metrics did not indicate that speech production is differentially affected by sex in PD. Sex was, however, associated with disparate effects on release burst precision in PD, which deserves further study. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24388666.

Test-Retest Reliability of Behavioral Assays of Feedforward and Feedback Auditory-Motor Control of Voice and Articulation.

PURPOSE: Behavioral assays of feedforward and feedback auditory-motor control of voice and articulation frequently are used to make inferences about underlying neural mechanisms and to study speech development and disorders. However, no studies have examined the test-retest reliability of such measures, which is critical for rigorous study of auditory-motor control. Thus, the purpose of the present study was to assess the reliability of assays of feedforward and feedback control in voice versus articulation domains. METHOD: Twenty-eight participants (14 cisgender women, 12 cisgender men, one transgender man, one transmasculine/nonbinary) who denied any history of speech, hearing, or neurological impairment were measured for responses to predictable versus unexpected auditory feedback perturbations of vocal (fundamental frequency, fo) and articulatory (first formant, F1) acoustic parameters twice, with 3-6 weeks between sessions. Reliability was measured with intraclass correlations. RESULTS: Opposite patterns of reliability were observed for fo and F1; fo reflexive responses showed good reliability and fo adaptive responses showed poor reliability, whereas F1 reflexive responses showed poor reliability and F1 adaptive responses showed moderate reliability. However, a criterion-referenced categorical measurement of fo adaptive responses as typical versus atypical showed substantial test-retest agreement. CONCLUSIONS: Individual responses to some behavioral assays of auditory-motor control of speech should be interpreted with caution, which has implications for several fields of research. Additional research is needed to establish reliable criterion-referenced measures of F1 adaptive responses as well as fo and F1 reflexive responses. Furthermore, the opposite patterns of test-retest reliability observed for voice versus articulation add to growing evidence for differences in underlying neural control mechanisms.

Effects of a Concurrent Working Memory Task on Speech Acoustics in Parkinson's Disease.

PURPOSE: The purpose of this study was to determine the effect of a concurrent working memory task on acoustic measures of speech in individuals with Parkinson's disease (PD). METHOD: Individuals with PD and age- and sex-matched controls performed a speaking task with and without a Stroop-like concurrent working memory task. Cepstral peak prominence, low-to-high spectral energy ratio, fundamental frequency (fo) standard deviation, articulation rate, pause duration, articulatory-acoustic vowel space, relative fo, mean voice onset time (VOT), and VOT variability were calculated for each condition. Mixed-model analyses of variance were performed to determine the effects of group, condition (presence of the concurrent working memory task), and their interaction on the acoustic measures. RESULTS: All measures except for VOT variability, mean pause duration, and relative fo offset differed between people with and without PD. Cepstral peak prominence, articulation rate, and relative fo offset differed as a function of condition. However, no measures indicated disparate effects of condition as a function of group. CONCLUSION: Although differentially impactful on limb motor function in PD, here a concurrent working memory task was not found to be differentially disruptive to speech acoustics in PD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24759648.

Controlling Pitch for Prosody: Sensorimotor Adaptation in Linguistically Meaningful Contexts.

PURPOSE: This study examined how speakers adapt to fundamental frequency (fo) errors that affect the use of prosody to convey linguistic meaning, whether fo adaptation in that context relates to adaptation in linguistically neutral sustained vowels, and whether cue trading is reflected in responses in the prosodic cues of fo and amplitude. METHOD: Twenty-four speakers said vowels and sentences while fo was digitally altered to induce predictable errors. Shifts in fo (±200 cents) were applied to the entire sustained vowel and one word (emphasized or unemphasized) in sentences. Two prosodic cues-fo and amplitude-were extracted. The effects of fo shifts, shift direction, and emphasis on fo response magnitude were evaluated with repeated-measures analyses of variance. Relationships between adaptive fo responses in sentences and vowels and between adaptive fo and amplitude responses were evaluated with Spearman correlations. RESULTS: Speakers adapted to fo errors in both linguistically meaningful sentences and linguistically neutral vowels. Adaptive fo responses of unemphasized words were smaller than those of emphasized words when fo was shifted upward. There was no relationship between adaptive fo responses in vowels and emphasized words, but adaptive fo and amplitude responses were strongly, positively correlated. CONCLUSIONS: Sensorimotor adaptation occurs in response to fo errors regardless of how disruptive the error is to linguistic meaning. Adaptation to fo errors during sustained vowels may not involve the exact same mechanisms as sensorimotor adaptation as it occurs in meaningful speech. The relationship between adaptive responses in fo and amplitude supports an integrated model of prosody. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25008908.

Acoustic correlate of vocal effort in spasmodic dysphonia.

OBJECTIVES: This study characterized the relationship between relative fundamental frequency (RFF) and listeners' perceptions of vocal effort and overall spasmodic dysphonia severity in the voices of 19 individuals with adductor spasmodic dysphonia. METHODS: Twenty inexperienced listeners evaluated the vocal effort and overall severity of voices using visual analog scales. The squared correlation coefficients (R2) between average vocal effort and overall severity and RFF measures were calculated as a function of the number of acoustic instances used for the RFF estimate (from 1 to 9, of a total of 9 voiced-voiceless-voiced instances). RESULTS: Increases in the number of acoustic instances used for the RFF average led to increases in the variance predicted by the RFF at the first cycle of voicing onset (onset RFF) in the perceptual measures; the use of 6 or more instances resulted in a stable estimate. The variance predicted by the onset RFF for vocal effort (R2 range, 0.06 to 0.43) was higher than that for overall severity (R2 range, 0.06 to 0.35). The offset RFF was not related to the perceptual measures, irrespective of the sample size. CONCLUSIONS: This study indicates that onset RFF measures are related to perceived vocal effort in patients with adductor spasmodic dysphonia. These results have implications for measuring outcomes in this population.

Relative fundamental frequency during vocal onset and offset in older speakers with and without Parkinson's disease.

The relative fundamental frequency (RFF) surrounding production of a voiceless consonant has previously been shown to be lower in speakers with hypokinetic dysarthria and Parkinson's disease (PD) relative to age/sex matched controls. Here RFF was calculated in 32 speakers with PD without overt hypokinetic dysarthria and 32 age and sex matched controls to better understand the relationships between RFF and PD progression, medication status, and sex. Results showed that RFF was statistically significantly lower in individuals with PD compared with healthy age-matched controls and was statistically significantly lower in individuals diagnosed at least 5 yrs prior to experimentation relative to individuals recorded less than 5 yrs past diagnosis. Contrary to previous trends, no effect of medication was found. However, a statistically significant effect of sex on offset RFF was shown, with lower values in males relative to females. Future work examining the physiological bases of RFF is warranted.