Lisa T. Fry, PhD Marshall University. Joseph C. Stemple, PhD University of Kentucky

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1 Lisa T. Fry, PhD Marshall University Joseph C. Stemple, PhD University of Kentucky

2 Muscular Components of Voice Disorders

3 Resonance Requires balance among the 3 Phonation Disruption in 1 may perturb the other 2 Respiration

4 Learned patterns of muscle misuse Laryngeal pathology affecting the glottal margin Neuromuscular impairment Age-related impairment These have the potential to disturb the balance and trigger a compensatory muscle response further complicating the pathological sequela.

5 Involves 13 intrinsic muscles that must maintain a relative functional balance for normal voice production Some therapy approaches claim to strengthen and balance these muscles Do these muscles fatigue? Do these muscles weaken? Can they actually be strengthened? Or is the problem simply one of balance? Phonation

6 Prevalence 6% of working age population; 29% of those over age 65 Significant proportion of these disorders contains an element of muscular dysfunction Muscle tension dysphonia Functional dysphonia / aphonia (hyper and hypoadduction) Compensatory hyperfunctional response to vocal fold paralysis and bowed vocal folds Vocal fatigue

7

8 36 year old female Sudden onset of hoarseness following the birth of her child Voice quality: persistent strained hoarseness Chief complaints: Difficult to talk to others Can t be heard in noise Talking causes fatigue

9 Parameter Result Units Mean SPL db Mean Pitch Hz Mean Peak Air Pressure cm H2O Mean Airflow During Voicing 0.17 Lit/Sec Aerodynamic Resistance cm H2O/(l/s)

10 56 year old male Hx sudden onset of hoarseness persistent for three months Chief complaints Chronic hoarseness Effort to talk Voice fatigue

11 Parameter Result Units Mean SPL db Mean Pitch Hz Mean Peak Air Pressure cm H2O Mean Airflow During Voicing 0.24 Lit/Sec Aerodynamic Resistance cm H2O/(l/s)

12 73 year old male Active lecturer Dx: Presbylaryngeus Voice Quality: Mild to mod dysphonia, weak raspy hoarseness Chief complaints: Voice fatigue Laryngeal ache Progressive hoarseness Lack of clarity in voice Inability to project voice

13 Mean Airflow 0.68 Lit/sec Mean Peak Air Pressure 6.37 cm/h2o Aerodynamic Resistance 8.82 cm H2O/(l/s) Vital Capacity 3.1 Liters

14 Vocal Function Exercises 2x each, 2x per day Airflow volume 3100 ml Goal 3100/80 40 sec 2-25 (Baseline MPT) 26.3 sec sec sec sec sec

15 Pre-test Mean Airflow 0.68 Lit/sec Mean Peak Air Pressure 6.37 cm/h2o Aerodynamic Resistance 8.82 cm H2O/(l/s) Post-test Mean Airflow 0.20 Lit/sec Mean Peak Air Pressure 7.16 cm/h2o Aerodynamic Resistance cm H2O/(l/s)

16 Normal voice quality No voice fatigue Ability to project voice Questions: Did his laryngeal muscles strengthen to aid closure? Did the laryngeal muscles rebalance? Did they do both?

17 70 year old female Hx: 18 month history of hoarseness and weak voice Dx: Idiopathic LTVF Paralysis Voice Quality: moderate dysphonia, high pitch, breathy hoarseness Chief Complaints: Hoarseness Inability to project Mild aspiration

18 Parameter Result Units Mean SPL db Mean Pitch Hz Expiratory Airflow Duration 0.38 Sec Mean Peak Air Pressure 7.71 cm H2O Mean Airflow During Voicing 0.58 Lit/Sec Aerodynamic Resistance cm H2O/(l/s)

19 Vocal Function Exercises 2x each, 2x per day Airflow Volume 2000 ml / 80 = 25 sec 7-26 Baseline MPT 6.8 sec sec sec sec sec

20 Pre-test Mean Airflow 0.58 Lit/sec Mean Peak Air Pressure 7.71 cm/h2o Aerodynamic Resistance cm H2O/(l/s) Post-test Mean Airflow 0.16 Lit/sec Mean Peak Air Pressure 5.90 cm/h2o Aerodynamic Resistance cm H2O/(l/s)

21 Mild dysphonia with occasional pitch breaks Ability to project No dysphagia Did her laryngeal muscles strengthen to aid closure? Did the laryngeal muscles rebalance? Did they do both?

22 The Application of Exercise-Based Therapies: Historical Use & Current Questions

23 Various behavioral voice therapies have attempted to restore normal patterns of intrinsic laryngeal muscle (ILM) activity during voicing Froeschels 1940 s ( pushing ) Boone 1970 s Most recently, physiologic voice therapies have emerged with the goal of improving / restoring muscle function

24 From skeletal muscle literature Basic Sciences, PT, Exercise Physiology Assumptions: Exercise programs can improve muscle mass, strength, endurance The ILM are characteristic of the larger class of skeletal muscle Yet, recent work demonstrates that the ILM are distinct from limb skeletal muscle Above assumptions may not be met

25 Parameter Difference Literature Morphogenesis Myosin Heavy Chains Mitochondrial Content Regenerative Capacity Innervation Patterns Response to Disease From most rostral somites with branchial arch completion; hybrid Possess high % of fast MHC; MHCeo in some species High mitochondrial content; high oxidative capacity Continual regeneration of uninjured muscle fibers Small # of fibers per neuron; similar to extraocular (est ) Not affected by dystrophin deficiency Noden & Francis West, 2006 (review) DelGaudio et al., 1995; Lucas et al., 1995; Shiotani et al., 1999 Andrade et al., 2003 Goding et al., 1995 McLoon et al., 2007 Bendiksen et al., 1981; Perie et al., 1997; Marques et al., 2007 Thomas et al., 2008 & in press

26 Considered effects of dystrophin deficiency on TA and PCA of mdx mice ( ) Findings: TA and PCA retain normal structure in the absence of the protein dystrophin Spared in dystrophin deficiency Thomas, L.B., Joseph, G., Adkins, T., Andrade, F., & Stemple, J.C. (2008). Laryngeal muscles are spared in the dystrophin-deficient mdx mouse. Journal of Speech, Language, Hearing Research, 51,

27

28 Follow-up study to consider effects of dystrophin deficiency on CT and IA Findings: CT and IA also retain normal structure in the absence of dystrophin Thomas Fry, L., Stemple, J.C., Harrison, A.L., Andreatta, R.A., & Andrade, F.H. (in press). Effect of dystrophin deficiency on selected intrinsic laryngeal muscles of the mdx mouse. Journal of Speech-Language-Hearing Research.

29

30 Principles of exercise drawn from the study of limb skeletal muscle may not apply to the highly specialized ILM Questions: Can the speed of ILM be improved with exercise? Can the mass of the ILM be increased with exercise? Can the ILM become more fatigue-resistant with exercise?

31 Answering Questions of Laryngeal Muscle Response to Treatment

32 Challenges Human Models Can achieve consistent use of an exercise program Unable to biopsy human vocal folds to assess morphological change Animal Models Able to biopsy for analysis Unable to achieve consistent voicing Unable to engage in a routine program of ILM (ie, vocal) exercise

33 Animal model (rat) Potential Solution Chronic Electrical Stimulation as a Model of Exercise Rodent ILM gross anatomy strikingly similar to human Chronic electrical stimulation of the RLN Elicit contraction of the TA Carry out a structured exercise program

34 Thomas, L.B., Stemple, J.C., Andreatta, R.A., & Andrade, F.H. (2009). Establishing a New Animal Model for the Study of Laryngeal Biology and Disease: An Anatomic Study of the Mouse Larynx. Journal of Speech-Language-Hearing Research, 52,

35 Thomas, L.B., Stemple, J.C., Andreatta, R.A., & Andrade, F.H. (2009). Establishing a New Animal Model for the Study of Laryngeal Bio Thomas, L.B., Stemple, J.C., Andreatta, R.A., & Andrade, F.H. (2009). Establishing a New Animal Model for the Study of Laryngeal Bio Thomas, L.B., Stemple, J.C., Andreatta, R.A., & Andrade, F.H. (2009). Establishing a New Animal Model for the Study of Laryngeal Biology and Disease: An Anatomic Study of the Mouse Larynx. Journal of Speech-Language-Hearing Research, 52,

36 Thomas, L.B., Stemple, J.C., Andreatta, R.A., & Andrade, F.H. (2009). Establishing a New Animal Model for the Study of Laryngeal Biology and Disease: An Anatomic Study of the Mouse Larynx. Journal of Speech-Language-Hearing Research, 52,

37 Thomas, L.B., Stemple, J.C., Andreatta, R.A., & Andrade, F.H. (2009). Establishing a New Animal Model for the Study of Laryngeal Biology and Disease: An Anatomic Study of the Mouse Larynx. Journal of Speech-Language-Hearing Research, 52,

38 RLN of anesthetized rats (N = 32) were fitted with custom-made nerve cuff electrodes

39 Experimental group (n = 16) Stimulation twice daily for 7 days Stimulation twice daily for 14 days Control group (n = 16) No stimulation for 7 days No stimulation for 14 days

40 Animals tolerated well 1 animal lost sick upon arrival 1 animal lost during surgery Animal model of ILM exercise established

41 1 day post last training session, rats anesthetized and killed TA muscle dissected and fixed for analysis Performed histologic & biochemical assays

42 The right (stimulated) side was significantly smaller than the left (unstimulated) side (true change vs. normal variability) This suggests that nerve stimulation may simulate endurance training which decreases muscle size. M = , SD = M = ; SD = Left Right

43 Increased # of NMJs with exercise LEFT RIGHT M = 49.8; SD = M = 55; SD = 28.60

44 Possible increase in mitochondria with exercise Nerve Stimulation Left Nerve Stimulation Right Control Left Control Right

45 Complete analysis from this pilot study Repeat aspects of the study with additional assays Consider other intrinsic laryngeal muscles Vary the exercise program frequency, duration, stimulation rate, etc Potential for exercise to affect diseased, paralytic, or aged vocal folds

46 Tim Butterfield, PhD Colleen McMullen, MS Maria Dietrich, PhD Francisco Andrade, PhD Members of the UK Vocal Dynamics Lab

47 American Speech-Language-Hearing Association Advancing Academic-Researcher Careers (AARC) Award University of Kentucky Research Support Grant

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