Introduction

Seventy percent of head and neck cancer - the sixth most common malignancy -  patients have oropharyngeal cancer (OPC), caused most commonly from human papillomavirus (HPV) infection (most common HPV-related malignancy in the U.S.). Radiation, the mainstay OPC treatment, can induce neuropathy along the lower cranial nerves (the glossopharyngeal and hypoglossal nerves) with a ~10-48% incidence, resulting in tongue motor and sensory deficits. RICN results in dysphonia, dysphagia, loss of taste, tongue fibrosis and atrophy (causing loss of motor control). Thus, patients’ quality of life is impaired and it can even result in mortality due to aspiration. Although clinical trials show that steroids (NCT04151082) and gabapentin (NCT03747562) temporarily reduce pain, their adverse effects compromise treatment tolerance and adherence. Thus, we need new treatments.

Here we show the strengthening of motor and sensory networks that regulate swallowing and tongue motor sensory control (TMSC) through our individualized fMRI neuromodulation, termed iNM (U.S. Patent No.16/954,256). fMRI measures the magnitude and spatial extent of the ratio of oxygenated (O₂) to deoxygenated hemoglobin [Hb]. (1) iNM is a non-invasive, precision-medicine intervention that can strengthen primary motor and sensory areas that regulate TMSC in the brain with 1mm precision without interfering with other treatments or medications (2) iNM targets each patient’s unique anatomical and functional circuitry that regulate swallowing and TMSC. (3) iNM is guided by reinforcing or inhibiting the HbO2 intensity and extent of each patient’s unique brain network, as opposed to the self-regulation of the HbO2 intensity. Here we targeted a patient’s individualized network that regulates TMSC and provided longitudinal neurofeedback training with the immediate future goal to treat RICN.

Methods

Our patient participated in 10 iNM sessions during which she was asked to move and stabilize the tongue for 30-secs in four directions (up; down; left; right) interleaved with 10-secs dedicated to swallowing and baseline-tongue-at-rest. We looked at the evolution of this patient’s spatial patterns and the HbO2 magnitude, as a function iNM training by binning the treatment scans. 

Results

iNM is characterized by an increase in somato-sensory and -motor (inferior parietal, cingulate, cerebellum), prefrontal (pars opercularis, and pars triangularis), and proprioceptive awareness (insula, anterior limb of internal capsule) bilateral networks. These areas are significantly activated during iNM as shown by the AUCs: i. 16% increase for bin-1 sessions; ii. 82.4% increase for bin-2 sessions; and iii. 58.3% for bin-3 sessions. A significant decrease in the variances in bin-2 (85%) and bin-3 (77%) sessions under iNM compared to the control is observed. Speech intelligibility improved by 13% and neuropathic symptoms decreased by 18%.

Conclusion

Our findings are clinically meaningful in the context of RICN, as they show that iNM decreased the variance and increased the intensity of the HbO2 magnitude. This means that strengthening the efferent motor (BA3/1/2 to the medulla’s nuclei of CNIX and CNXII, travelling down to these nerves’ endings) and afferent sensory (CNIX pathways that regulate TMSC) can decrease pain and increase speech intelligibility.