PROJECT SUMMARY/ABSTRACT Radiculopathy is a common spinal condition resulting from compression and irritation of the spinal nerve roots, leading to sensory deficits, muscle weakness, and pain. Dermatomal maps are a key component of the clinical exam and provide information on the correspondence between cutaneous sensations and the nervous system. Dermatomal sensory deficits can help localize neurological injury in spinal conditions and guide treatment. Dermatomal maps, however, are limited—they contain uncertainty in the neuroanatomy mapped (spinal nerve, dorsal root ganglion, dorsal horn, or spinal cord (SC) segment), assume left-right symmetry and no sex differences, provide no information on between-subject variability, and remain to be validated. SC functional magnetic resonance imaging (fMRI) permits the non-invasive in vivo spatial mapping of human SC activity. Here we will use SC fMRI to test hypotheses central to dermatomal maps, investigate the effects of neurological injury on SC sensory processing, develop markers of SC sensory activity, and test their diagnostic value in cervical radiculopathy while improving our SC fMRI methods. To accomplish this, we will first enhance our existing SC fMRI methods by building a research-grade 64-channel head-neck coil, testing a novel spatial normalization method that accounts for SC segment location, and exploring the use of surface electromyography to monitor and remove motor-related noise during fMRI experiments. We will compare the improved SC fMRI methods against our currently operational methods while characterizing the SC correlates of sensory stimulus intensity encoding using electrocutaneous sensory stimulation of the third digit of the right hand (C7 dermatome) in 30 healthy volunteers (HV) (20-79 years old, 15 females, 15 males). Then using the enhanced SC fMRI methods, we will quantitatively map the spatial distribution of SC activity in 120 right- handed HVs (20-79 years old, 60 females, 60 males, stratified by age) during electrocutaneous sensory stimulation of the first, third, and fifth digits (C6, C7, and C8 dermatomes, respectively) of the left and right hands. We will develop probabilistic maps of the spatial distribution of SC activity, assess the superior-inferior localization of activity, contrast the activity between left and right stimulation and sexes, and quantify between- subject variability. We will use machine learning algorithms to develop normative SC sensory markers by predicting the stimulation site. Finally, 40 right-handed patients with right-sided C7 cervical radiculopathy (30– 79 years old, 20 females, 20 males) and 40 age- and sex-matched HVs will also undergo the same SC fMRI experiment, and we will investigate group differences in SC activity to uncover the effects of neurological injury on SC sensory processing and then assess the diagnostic value of the SC sensory markers. Completing our aims will improve SC fMRI methods, validate/refute hypotheses central t...