Chronic pain, that is, pain that persists or recurs for 3 months or more, affects 20 % of adults in the United States and contributes to an annual economic cost of greater than $600 billion and is more prevalent among Veterans compared to non-Veterans with significantly higher rates of chronic pain in women veterans. Noninvasive neuromodulation holds promise as a therapeutic approach to treat chronic pain conditions, but current noninvasive neuromodulation techniques lack spatial specificity and are unable to modulate deep neural structures. Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions and has spatial specificity. For chronic pain, one promising brain target for treatment is the insular cortex, a brain structure whose function is linked to pain processing. The insula is a critical brain region which is activated in the response to painful stimuli and in chronic pain states, underlying central sensitization(CS) which occurs in chronic pain syndromes. Our recent pilot data in healthy controls demonstrates that LIFU can target with spatial specificity subregions of the insula; LIFU to the posterior insula (PI) reduces contact heat evoked potentials as well as temporal summation of pain(TSP) and conditioned pain modulation (CPM) which are laboratory measures of somatosensory pain processing that are altered in CS. LIFU can selectively target the insula and its subregions and provides a potentially transformative method to reduce pain and the processes in chronic pain states that constitute CS which amplify chronic pain disorders. We will administer inhibitory LIFU to the PI in individuals with chronic back pain(CBP) with symptoms of widespread pain, a population that demonstrates symptoms of CS. We will inhibit the PI to determine whether there is a causal role for this brain region in altered processes of CS as measured by heat pain thresholds, TSP, and CPM all of which are hallmark features of chronic pain syndromes with CS. As an LIFU control condition we will use sham LIFU with auditory masking to the insula; the sham condition has been shown to be indistinguishable from active LIFU. We also propose to examine the effects of LIFU to PI compared to sham on patterns of blood level oxygen dependent (BOLD) activity during evoked thermal pain and resting state. Specifically, we will examine the effect of LIFU to PI compared to sham on the 1) BOLD response to thermal stimuli in the Neurologic Pain Signature(NPS)which is a multivariate outcome whose magnitude predicts clinical pain intensity and 2) resting state functional connectivity during tonic pain in the Tonic Pain Signature (ToPS) which also predicts clinical pain intensity. Both the NPS and ToPS are sensitive to and specific for physical pain and have been replicated in studies of chronic pain patients. We hypothesize, given our pilot data, that inhibitory LIFU to PI will increase pain thresholds, re...