Program Director

Principal Investigator

John A
Awardee Organization

University Of Wisconsin-Madison
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Treatment of Functional Deficits IN tongue muscles induced by radiation and chemoradiation treatment

Radiotherapy and chemoradiation for head and neck cancer treatment exposes normal tissues to radiation, which has many devastating effects and often results in difficulty with communication and swallowing. While muscle weakness and fibrosis are possible etiologies for disruptions in critical communicative and deglutition functions following radiation, very little research has been performed on underlying biological changes within muscles of the head and neck following radiation, or possible treatments for these lasting negative effects. Skeletal muscles can adapt at multiple levels of structure and function to changing demands. Exercise training of the tongue, or enhanced muscle contraction via neuromuscular electrical stimulation (NMES) may be beneficial for preventing or reversing muscle tissue damage. However, controlled research examining these putative benefits has not been performed and optimal treatment modalities have not been established. Our hypothesis is that radiotherapy and chemoradiation-induced decline in speech and swallowing function is largely due to alterations in tongue muscle structure and function. Further, we hypothesize that tongue exercise or NMES will result in phenotypic changes in extrinsic tongue muscles that will improve tongue muscle function. To examine these clinically-relevant issues, we will use a rat model to test two different tongue treatment paradigms (tongue exercise; NMES) for remediation of radiotherapy and chemoradiationinduced muscle damage. The proposed research has two specific aims: 1) To determine how treatment modality affects morphological, biochemical, and physiological changes in radiotherapy and chemoradiationinduced muscle damage of the tongue, 2) To discover how tongue exercise and/or NMES treatment affects functional measures of deglutition following radiotherapy/chemoradiation. This work is innovative and significant because the mechanisms by which tongue exercise or NMES can prevent or treat the effects of radiation- or chemoradiation-induced communication and swallowing dysfunction is largely unexplored. Our animal model and treatments are analogs to treatments used in human patients and follow the Institute of Medicine guidelines for increasing probability of translation. Further, this work is highly significant in providing a basis for understanding the mechanisms underlying the potential of therapeutic interventions for radiation- and chemoradiation-induced cranial impairments. Translation of findings will assist with increasing the effectiveness of treatments for radiation- and chemoradiation-induced tongue muscle impairments that are so prevalent in patients with head and neck cancer.


  • Cullins MJ, Wenninger JM, Cullen JS, Russell JA, Kleim JA, Connor NP. Tongue Force Training Induces Plasticity of the Lingual Motor Cortex in Young Adult and Aged Rats. Frontiers in neuroscience. 2019 Dec 19;13:1355. doi: 10.3389/fnins.2019.01355. eCollection 2019. PMID: 31920514
  • Kletzien H, Cullins MJ, Connor NP. Age-related alterations in swallowing biomechanics. Experimental gerontology. 2019 Apr;118:45-50. Epub 2019 Jan 8. PMID: 30633957
  • Kletzien H, Kelm-Nelson CA, Wang S, Suzuki M, Connor NP. Myogenic marker expression as a function of age and exercise-based therapy in the tongue. Experimental gerontology. 2020 Dec;142:111104. Epub 2020 Oct 2. PMID: 33017670
  • Krekeler BN, Rowe LM, Connor NP. Dose in Exercise-Based Dysphagia Therapies: A Scoping Review. Dysphagia. 2021 Feb;36(1):1-32. Epub 2020 Mar 5. PMID: 32140905
  • Cullins MJ, Russell JA, Booth ZE, Connor NP. Central activation deficits contribute to post stroke lingual weakness in a rat model. Journal of applied physiology (Bethesda, Md. : 1985). 2021 Apr 1;130(4):964-975. Epub 2021 Feb 18. PMID: 33600285
  • Rowe LM, Connor NP, Russell JA. Respiratory-swallow coordination in a rat model of chemoradiation. Head & neck. 2021 Oct;43(10):2954-2966. Epub 2021 Jun 23. PMID: 34160109
  • Glass TJ, Figueroa JE, Russell JA, Krekeler BN, Connor NP. Progressive Protrusive Tongue Exercise Does Not Alter Aging Effects in Retrusive Tongue Muscles. Frontiers in physiology. 2021 Oct 21;12:740876. doi: 10.3389/fphys.2021.740876. eCollection 2021. PMID: 34744782
  • Setzke C, Broytman O, Russell JA, Morel N, Sonsalla M, Lamming DW, Connor NP, Teodorescu M. Effects of inhaled fluticasone propionate on extrinsic tongue muscles in rats. Journal of applied physiology (Bethesda, Md. : 1985). 2020 Mar 1;128(3):576-585. Epub 2020 Jan 16. PMID: 31944881
  • Krekeler BN, Weycker JM, Connor NP. Effects of Tongue Exercise Frequency on Tongue Muscle Biology and Swallowing Physiology in a Rat Model. Dysphagia. 2020 Dec;35(6):918-934. Epub 2020 Mar 4. PMID: 32130514
  • Kletzien H, Russell JA, Leverson G, Connor NP. Effect of neuromuscular electrical stimulation frequency on muscles of the tongue. Muscle & nerve. 2018 Sep;58(3):441-448. Epub 2018 Aug 23. PMID: 29797723
  • Cullins MJ, Connor NP. Reduced tongue force and functional swallowing changes in a rat model of post stroke dysphagia. Brain research. 2019 Aug 15;1717:160-166. Epub 2019 Apr 22. PMID: 31022397