Development of the Brain Modulation Model Using Focused Ultrasound : a Novel Non-Invasive Brain Lesion Research( I )

A fundamental question in neuroscience is to understand the neuronal substrate of mental processing. The causality between neuronal activity and behavior is first established in lesion studies by observing the loss of function in lesioned brains in patients with stroke and animals received brain ablation. Later on, reversible brain lesion is achieved by administrating agents that suppresses cortical activities, by brain cooling, or by repetitive transcranial stimulation (rTMS). However, the technique of rTMS could be limited by the relatively weak suppression magnitude, the lack of high spatial acuity, the short lasting effect, its inability to deliver to brain areas away from scalp surface and inability to modulate nerve tracks in white matter. In the present study, we propose a revolutionary method that can deliver noninvasive and reversible brain modulation dubbed as brain modulation induced by focused ultrasound (BMFU). With co-administration of focused ultrasound that enhanced local permeability across blood-brain barrier and intravenous cortical modulation agents, we could selectively modulate brain activities at arbitrary cortical or subcortical sites. BMFU could present cortical modulation at multiple cortical areas simultaneously and at deep brain or skull base structures (such as thalamus and infratemporal cortex) at which rTMS could not reach. Also, we hypothesize that BMFU could have facilitation, inhibition, or other effects according to the modulation agents we select; analogously, the effects could be short-term or long-term. These properties will fit the need for a variety of neurophysiological experiments. To this end, we will establish the first demonstration of BMFU model by suppressing a rat hemisphere and observe the decreased of somatosensory evoked potentials. Later on, we will systematically survey the proper brain modulation agents and the dose that could fulfill our modulation goal. Finally, we will observe the change of task performance in behaving monkeys following BMFU to unilateral thalamus to demonstrate the correspondence of BMFU and functional change. The long-term objective of the present project is to establish a pioneering “(1) non-invasive” and “(2) localized” brain modulation method that is capable of modulating brain activity at (3) deep brain structure and (4) at either single or multiple brain areas.

Project ID:PC10109-0151
External Project ID:NSC101-2321-B182-012