This Project Grant award from the National Institute of Mental Health (NIMH), under the Mental Health Research Grants program (CFDA 93.242), provides $215,343 to the Laureate Institute for Brain Research, LLC in Tulsa, Oklahoma to study the dose-dependent effects of low-intensity focused ultrasound (LIFU) on functional connectivity within deep brain white matter tracts. The grant aims to determine the relationship between LIFU dose and the intensity of target engagement, as measured by decreased...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Drug Abuse and Addiction Research Programs (CFDA 93.279), provides $2,505,537 to The Leland Stanford Junior University to develop a focused ultrasound (FUS) device for noninvasive, peripheral nerve blockade to manage acute pain. The goal is to provide an alternative to opioids and current peripheral nerve block techniques, which have significant limitations in acute pain management. The...
This Project Grant award, issued under the National Institutes of Health's Research and Training in Complementary and Integrative Health program (CFDA 93.213), provides $721,428 to the University of Pittsburgh to conduct a mechanistic neuroimaging study on the effects of auricular stimulation and auriculotherapy in healthy volunteers and chronic low back pain patients. The key objectives are to: 1) Evaluate the neural responses to non-therapeutic touch stimulation of different ear points in...
The National Institute on Drug Abuse (NIDA) awarded a $399,739 project grant under the Drug Use and Addiction Research Programs (CFDA 93.279) to Attune Neurosciences, Inc., a for-profit company specializing in advanced neurotechnology. The funding supports the development of a head-worn low-intensity focused ultrasound (LIFU) device to enhance sleep in individuals with substance use disorder, particularly opioid use disorder. The key objectives of the project are to reconfigure Attune's existing...
This $514,178 Project Grant from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242) will fund a study to investigate the mechanistic relationship between brain circuit function and negative valence system behaviors in treatment-resistant depression. The project aims to use low-intensity focused ultrasound (LIFU) neuromodulation to determine how connectivity between the thalamus and prefrontal cortical regions (orbitofrontal and anterior...
The U.S. National Institute of Neurological Disorders and Stroke (NINDS) awarded a $1,643,228 Cooperative Agreement grant under the Drug Abuse and Addiction Research Programs (CFDA 93.279) to Worcester Polytechnic Institute (WPI) to develop an Integrative Mindfulness-Based Predictive Approach for Chronic Low Back Pain Treatment (IMPACT). The key objectives of this 2-year IMPACT project are to: 1) Initiate a clinical trial of Mindfulness-Based Stress Reduction (MBSR) for chronic low back pain...
The National Institute on Drug Abuse (NIDA) awarded a $319,278 Project Grant under the Drug Use and Addiction Research Programs (CFDA 93.279) to Photopharmics, Inc. to develop a novel, non-pharmacological whole body vibration (WBV) device to treat anxiety, craving, and opioid use associated with opioid use disorder (OUD). The project aims to improve the technical aspects of the WBV device, evaluate physiological indices of anxiety, and implement telemetry to control and record from the device....
This Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $159,711 to the University of California, Los Angeles (UCLA) to conduct research on the electrophysiological dynamics of acute opioid use in human reward, affect, and pain pathways. The project aims to uncover how acute opioid administration impacts neural connectivity by directly recording neuronal signals from brain regions associated with opioid...
This $1,523,422 federal Project Grant awarded by the National Institute on Drug Abuse (CFDA 93.279 - Drug Use and Addiction Research Programs) to Virginia Commonwealth University (VCU) will fund a 5-year study investigating the role of the orexin system in the treatment of opioid use disorder (OUD) and insomnia. The key objectives are to: 1) Examine the effects of the dual orexin receptor antagonist lemborexant on sleep among individuals with OUD receiving buprenorphine treatment (Aim 1); 2)...
The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $6,522,833 Project Grant to The Leland Stanford Junior University to conduct a mechanistic randomized clinical trial investigating the central and peripheral nervous system mechanisms of pain relief induced by peripheral nerve stimulation (PNS) for the treatment of refractory chronic neuropathic pain. The 3-year study, funded under the NIH HEAL Initiative's CFDA 93.279 Drug Abuse and Addiction Research Programs, aims...
TOWARDS TREATMENT FOR THE COMPLEX PATIENT: INVESTIGATIONS OF LOW-INTENSITY FOCUSED ULTRASOUND. - OPIOID USE DISORDER WITH CO-MORBID CHRONIC PAIN AND ANXIETY (OCPA) IS A CLINICAL TRIAD ASSOCIATED WITH THE HIGHEST RISK OF OPIATE OVERDOSE DEATHS. CO-OCCURRENCE OF THESE THREE DISORDERS AMPLIFIES SYMPTOMS OF EACH AND RESULTS IN POORER TREATMENT OUTCOMES. THERE ARE SHARED NEUROBIOLOGICAL SUBSTRATES FOR THESE DISORDERS SUCH AS REWARD PROCESSING AND STRESS RESPONSE. THE ANTERIOR INSULA (AI) IS A BRAIN REGION INVOLVED IN THESE PROCESSES AS WELL AS IN CLINICAL DISORDER OF PAIN, ADDICTION, AND ANXIETY. THE AI IS UPREGULATED IN PAIN, ADDICTION AND ANXIETY DISORDERS AND IS THEREFORE A POTENTIAL THERAPEUTIC TARGET FOR NEUROMODULATION. LOW-INTENSITY FOCUSED ULTRASOUND (LIFU) IS A NONINVASIVE METHOD TO INHIBIT CORTICAL AND DEEP BRAIN REGIONS. LIFU CAN REACH DEEP BRAIN REGIONS SUCH AS THE AI WITH SPATIAL SPECIFICITY, UNLIKE TRADITIONAL NONINVASIVE NEUROMODULATION METHODS WHICH LACK SPATIAL SPECIFICITY AND DEPTH PENETRATION. LIFU CAN SELECTIVELY TARGET THE INSULA AND ITS SUBREGIONS AND PROVIDES A POTENTIALLY TRANSFORMATIVE METHOD TO REDUCE SYMPTOMS OF PAIN, OPIATE CRAVING, AND ANXIETY IN A COMPLEX PATIENT POPULATION SUCH AS OCPA. IN THE UG3 PHASE OF THIS STUDY, WE WILL ADMINISTER ONE SESSION OF INHIBITORY LIFU TO THE AI IN INDIVIDUALS WITH OCPA [OPIATE USE DISORDER, CHRONIC BACK PAIN, AND ANXIETY DISORDERS (GENERALIZED ANXIETY DISORDER, POST-TRAUMATIC STRESS DISORDER, OR SOCIAL ANXIETY DISORDER)]. THE AIM OF THIS PHASE OF THE STUDY IS TO ESTABLISH THAT LIFU VS SHAM LIFU TO AI IS SAFE AND WELL TOLERATED AS MEASURED BY ADVERSE EVENTS, CLINICAL EVALUATION AND REPEATED STRUCTURAL BRAIN MAGNETIC RESONANCE IMAGING SCANS. WE WILL ALSO GATHER PRELIMINARY DATA ON THE EFFECT OF LIFU TO AI ON OPIATE CUE-INDUCED CRAVING AND LABORATORY MEASURES OF CENTRAL SENSITIZATION(CS) WHICH OCCURS WITH PAIN CHRONICITY SUCH AS TEMPORAL SUMMATION OF PAIN AND CONDITIONED PAIN MODULATION. IN THE SECOND PHASE OF THIS PROJECT (UH3), WE WILL EXAMINE THE EFFICACY, IN A LARGER SAMPLE OF INDIVIDUALS WITH OCPA, OF REPEATED LIFU DELIVERY ON MEASURES OF PAIN AND OPIATE CUE-INDUCED CRAVING, ANXIETY SYMPTOMS, INTEROCEPTION AND AUTONOMIC REACTIVITY AS THESE OUTCOMES ARE DYSREGULATED IN OCPA AND ARE MEDIATED BY THE AI. LIFU WILL BE DELIVERED FOR 10 MINUTES EACH HOUR FOR 4 HOURS ON A SINGLE DAY. WE HYPOTHESIZE THAT REPEATED SESSIONS OF LIFU WILL REDUCE MEASURES OF CS, OPIATE CUE-INDUCED CRAVING, STATE ANXIETY SYMPTOMS, INCREASE HEART RATE VARIABILITY AND NORMALIZE MEASURES OF INTEROCEPTION. WE WILL EXAMINE THE DURABILITY AND EFFECT OF 1 VS 2 SESSIONS OF REPEATED LIFU ON THESE OUTCOME MEASURES. REPEATED SESSIONS OF OTHER FORMS OF NEUROMODULATION RESULT IN INCREASED MAGNITUDE AND LONGER LASTING EFFECTS. WE HYPOTHESIZE THAT 2 SESSIONS VS 1 OF REPEATED LIFU WILL RESULT IN GREATER MAGNITUDE OF CHANGE IN THE OUTCOME MEASURES. LASTLY, WE WILL EXAMINE THE SAFETY AND TOLERABILITY OF REPEATED LIFU SESSIONS. THERE IS A NEED FOR IMPROVED TREATMENTS FOR COMPLEX PATIENTS SUCH AS OCPA BEYOND COMBINING TREATMENTS FOR EACH DISORDER. LIFU PROVIDES AN ABILITY TO TRANSIENTLY AND SELECTIVELY INHIBIT AI TO DETERMINE ITS CAUSAL ROLE IN OCPA SYMPTOMS WHICH THEN MAY LEAD TO IMPROVED TREATMENTS FOR THIS CLINICAL TRIAD WHICH IS ASSOCIATED WITH POOR TREATMENT OUTCOMES.