The opioid use disorder (OUD) is a rapidly expanding health epidemic in the United States with little progress intreatment efficacy. Insufficient sleep represents the most severe and pervasive symptoms of both phases ofwithdrawal and persist despite treatment. Because sleep loss plays a key role in anxiety and daily routine, itsdisruption is a major factor in a patient's relapse evidenced by the higher incidence of relapse in OUD patientswith sleep disorders. Sleep dysfunction in OUD is characterized by significant loss in slow wave sleep (SWS),which are critical components of the benefits of sleep. In patients with severe withdrawal, sleep may consistalmost entirely of brief periods of rapid eye movement (REM) with sparse non-REM (NREM) sleep interruptedby numerous awakenings. Given the prevalence of poor sleep quality in OUD and the association with relapse,treatments enhancing the restful effects of sleep could reduce the rate of relapse. However, commonlyprescribed sleep medications have sedative and hypnotic effects with a risk of dependency too great for patientswith OUD. Thus, new interventions to augment sleep are a critical unmet medical need which could have anoutsized influence on their life. Here, we build off of research in humans and animal models demonstrating thatfocused ultrasound can stimulate brain regions underlying SWS. We will design a wearable device integratingsleep recordings and steerable ultrasound arrays. Ultrasound arrays will target the thalamus, a core SWSstructure, using MRI maps of patient's brains and skulls. We will design custom EEG analytics software fordelivering the stimulus during the rising phase of slow waves to enhance wave amplitude, duration, and beneficialeffects. We will perform a human factors study with OUD patients to assess comfort and usability for redesigningthe wearable. Throughout the project we will interact with the FDA in efforts to gain approval for a phase II studywith OUD patients.
Public Health Relevance Statement: Project narrative
Sleep issues are a primary cause of relapse in opioid use disorder patients. While there are numerous
pharmacological strategies for enhancing sleep, the addictive nature of these compounds poses a significant
threat to patients with addiction proclivity. We will develop an ergonomic wearable device for enhancing sleep
through targeted focused ultrasound stimulation of the brain. The device will use an integrated EEG to identify
and enhance slow wave sleep patterns through stimulation of the thalamus using patient specific brain maps.
We will work with both OUD subjects and the FDA to identify the necessary steps for making the device both
safe and usable for a phase II study and future commercialization.
Project Terms: Withdrawal ; Opioid ; Opiates ; tool ; Nature ; Life ; Difficulty in sleep maintenance ; Difficulty staying asleep ; Fitful sleep ; Interrupted sleep ; Night waking ; Sleep maintenance insomnia ; difficulty maintaining sleep ; sleep maintenance difficulty ; Middle Insomnia ; Investigation ; Dimensions ; Dependence ; drug craving ; success ; neural control ; neural regulation ; neuromodulation ; neuromodulatory ; neuroregulation ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Structure ; novel ; novel technologies ; new technology ; Devices ; sleep diseases ; sleep dysfunction ; sleep illness ; sleep problem ; Sleep Disorders ; Modeling ; theories ; pharmacobehavioral ; behavioral pharmacology ; Intervention Strategies ; interventional strategy ; Intervention ; Magnetic Resonance Imaging Scan ; MRI Scans ; Insomnia ; Insomnia Disorder ; Sleeplessness ; vulnerable group ; Vulnerable Populations ; Brain region ; Thickness ; Thick ; Effectiveness ; Symptoms ; device development ; instrument development ; Device or Instrument Development ; Cognitive ; Development ; developmental ; image registration ; design ; designing ; Sleep Architecture ; non rapid eye movement ; NREM ; non-REM ; non-rapid eye movement ; nonREM ; nonrapid eye movement ; Treatment Efficacy ; intervention efficacy ; therapeutic efficacy ; therapy efficacy ; Population ; Prevalence ; Individual Differences ; imaging Segmentation ; Abstinence ; usability ; addiction ; addictive disorder ; prototype ; commercialization ; treatment strategy ; phase 2 study ; phase II study ; cognitive process ; Focused Ultrasound ; opioid use disorder ; opiate use disorder ; relapse patients ; persistent symptom ; chronic symptom ; wearable device ; wearable electronics ; wearable technology ; sleep quality ; quality of sleep ; human model ; model of human ; sleep pattern ; poor sleep ; Home ; Helping to End Addiction Long-term ; HEAL Initiative ; Helping End Addiction Long-term ; Helping End Addiction Longterm ; Helping to End Addiction Longterm ; Acoustics ; Acoustic ; Affect ; Animals ; Anxiety ; Brain ; Brain Nervous System ; Encephalon ; Clinical Research ; Clinical Study ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Electroencephalography ; EEG ; Elements ; Epidemic ; Future ; Goals ; Health ; Human ; Modern Man ; hypnotic ; Incidence ; Intervention Studies ; intervention research ; interventional research ; interventional study ; interventions research ; Magnetic Resonance Imaging ; MR Imaging ; MR Tomography ; MRI ; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance ; NMR Imaging ; NMR Tomography ; Nuclear Magnetic Resonance Imaging ; Zeugmatography ; Maps ; Memory ; Outpatients ; Out-patients ; Patients ; Pharmacology ; Physicians ; Play ; Quality of life ; QOL ; rapid eye movement ; Relapse ; Research ; Risk ; Rodent ; Rodentia ; Rodents Mammals ; Role ; social role ; Running ; sedative ; cranium ; Skull ; Sleep ; Sleep Deprivation ; deficient sleep ; inadequate sleep ; insufficient sleep ; sleep debt ; sleep deficiency ; sleep deficit ; sleep insufficiency ; sleep loss ; Sleep disturbances ; aberrant sleep ; disrupted sleep ; disturbed sleep ; impaired sleep ; irregular sleep ; sleep disruption ; sleep dysregulation ; Computer software ; Software ; Temporal bone structure ; Temporal Bone ; Thalamic structure ; Thalamus ; thalamic ; Tissues ; Body Tissues ; Transducers ; Translating ; Ultrasonography ; Echography ; Echotomography ; Medical Ultrasound ; Ultrasonic Imaging ; Ultrasonogram ; Ultrasound Diagnosis ; Ultrasound Medical Imaging ; Ultrasound Test ; diagnostic ultrasound ; sonogram ; sonography ; sound measurement ; ultrasound ; ultrasound imaging ; ultrasound scanning ; United States ; Work ; Withdrawal Symptom ; Custom ; base ; improved ; Clinical ; Phase ; Physiological ; Physiologic ; Medical ; Ensure ; Stimulus ; Slow-Wave Sleep ; Delta Wave ; Delta Wave sleep ; Individual ;
