Efficacy of kTMP, a novel non-invasive brain stimulation method, for the treatment of anhedonia patients.

/Abstract The discovery of more effective treatments for Major Depressive Disorder (MDD) is a pressing clinical demand. Non-invasive brain stimulation (NIBS) offers a promising treatment for many neurological and psychiatric disorders. However, to date, the clinical efficacy has proven highly variable. This is likely because current NIBS approaches cannot precisely modulate patterns of brain activity at intensity levels sufficient to produce physiological and behavioral change that is clinically relevant. The goal of this proposal is to test and validate a novel first-in-class non-invasive approach to engage the brain reward circuitry for treating anhedonia, a core symptom of MDD. We have developed a kilohertz Transcranial Magnetic Perturbation (kTMP) device, which allows modulating neural activity non-invasively – with no patient discomfort – at and beyond stimulation intensities associated with significant physiological and behavioral change, something that is difficult to achieve with existing NIBS methods. The three-year funding period will be used to assess proof-of-mechanism for the efficacy of kTMP in improving anhedonia in patients suffering from MDD. We will apply kTMP over the dorsal prefrontal cortex (DLPFC) to engage deep structures within the reward circuitry that are connected to the DLPFC. Specifically, our goal is to influence the ventral striatum, a key structure that is associated with anhedonia. Using a novel fMRI-based neuronavigation approach, we will personalize the precise location within DLPFC to optimize the engagement of the reward network. We will assess whether kTMP leads to an increase in ventral striatal activation during reward anticipation (Aim 1) and evaluate if these physiological changes are associated with reduced anhedonia symptoms (Aim 2). If our expectations are confirmed, our novel NIBS system holds the promise of revolutionizing the treatment landscape for patients with debilitating anhedonia symptoms, paving the way for a new era of enhanced recovery and improved quality of life. Project Number: 1R44MH142142-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Ludovica Labruna | Institution: MAGNETIC TIDES, INC., EL CERRITO, CA | Award Amount: $1,651,499 | Activity Code: R44 | Study Section: Special Emphasis Panel[ZMH1 ERB-S (05)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11252829