Neuromodulation using transcranial focused ultrasonography in neonates with perinatal hypoxic-ischemic encephalopathy

Abstract

Perinatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy, accounting for over half of all cases and the consequences of HIE can be devastating, making it one of the most severe perinatal complications. Therapeutic hypothermia has been shown to offer neuroprotection by reducing metabolic demand and slowing the cascade of injury processes. However, despite its benefits, therapeutic hypothermia has only modestly improved neurodevelopmental outcomes, indicating a major need for additional therapeutic approaches. Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive brain stimulation technique for focally modulating specific brain regions that has recently drawn attention for its potential to modulate brain activity and promote neuroplasticity. The capacity of TUS to induce neuroplasticity through specific sonication parameters has been demonstrated in adult patients. Leveraging TUS to enhance functional connectivity and inhibit GABAergic systems within the injured thalami holds promise for inducing neuroplasticity in neonates with HIE. We hypothesize that enhancing thalamocortical functional connectivity and reducing local GABA levels through the use of TUS could potentially improve neurodevelopmental outcomes in neonates with HIE who have sustained thalamic injury and aim to test this hypothesis. Testing of the hypothesis will be conducted with a comprehensive assessment of safety and feasibility in neonates through a Phase I study, followed by further clinical studies to evaluate efficacy.