Transcranial Focused Ultrasound to the Thalamus Is Associated with Reduced Extracellular GABA Levels in Rats

Abstract

Objective: Transcranial focused ultrasound (FUS), with its ability to non-invasively modulate the excitability of region-specific brain areas, is gaining attention as a potential neurotherapeutic modality. The aim of this study was to examine whether or not FUS administered to the brain could alter the extracellular levels of glutamate and γ-aminobutyric acid (GABA), which are representative excitatory and inhibitory amino acid neurotransmitters, respectively. Methods: FUS, delivered in the form of a train of pulses, was applied to the thalamus of Sprague-Dawley rats transcranially. Glutamate and GABA were directly sampled from the frontal lobe of the rat brain via a direct microdialysis technique before, during, and after the sonication. The dialysate concentrations were determined by high-performance liquid chromatography. Results: The individual levels of the neurotransmitters sampled were normalized to the baseline level for each rat. In terms of the changes in extracellular glutamate levels, there was no difference between the FUS-treated group and the unsonicated control group. However, extracellular GABA levels started to decrease upon sonication and remained reduced (approximately 20% below baseline; repeated-measures ANOVA, p < 0.05, adjusted for multiple comparisons) compared to the control group. Conclusion: The ability to modulate region-specific brain activity, along with the present evidence of the ability to modulate neurotransmission, demonstrates the potential utility of FUS as a completely new non-invasive therapeutic modality.

Image-Guided Transcranial Focused Ultrasound Stimulates Human Primary Somatosensory Cortex

“…For example, the FUS-mediated functional modulation of a specific brain area may also be used as a new method for non-invasive functional brain mapping. Based on the evidence of its ability to alter the extracellular level of neurotransmitters in the rodent model2324, FUS may shed light on providing new modes of neurotherapeutics for the treatment of neurotransmitter-mediated psychiatric disorders. Furthermore, when combined conjunctively with FUS functional neurosurgery techniques1920, the presented method may be used to evaluate the function of the targeted surgical area prior to its thermal ablation.…”

“…The ability to reversibly modulate region-specific excitability of the sonicated brain tissue has been demonstrated by the excitation or suppression of neural activity via sonication of the motor and visual areas in rabbits21, the suppression of chemically-induced epilepsy22, and the alteration of extracellular concentrations of neurotransmitters in rats2324. In non-human primates, FUS given to the frontal eye field of macaques modulated their visuomotor behavior25.…”

Estimation of the spatial profile of neuromodulation and the temporal latency in motor responses induced by focused ultrasound brain stimulation

“…When administered in bursts of short pulses, FUS has been shown to reversibly excite or suppress the region-specific brain functions in rabbits 8 and rodents 9. In addition, the administration of this neuromodulatory FUS to the thalamic area of the rodent brain altered the level of extracellular neurotransmitters (γ-aminobutyric acid, dopamine, and serotonin) 10,11 and shortened the emergence time from anesthesia 12. Recently, the stimulation of rodent cranial nerves yielded the potential use of FUS in the functional modulation of the peripheral nervous system 13.…”

Noninvasive Transcranial Stimulation of Rat Abducens Nerve by Focused Ultrasound

“…We have also recently demonstrated that FUS, when applied in short bursts of pulses, modulates neural tissue excitability in the motor and visual cortices of rabbits without changing tissue temperature (Yoo et al 2011). This exciting feature has also been applied to decrease the electrographic seizure activites from chemically-induced epileptic rats (Min et al 2011a), and to modify the extracelluar level of neurotransmitters (Min et al 2011b; Yang et al 2012). Converging evidences from these studies indicate that application of FUS at low acoustic intensity, typically under the FDA-limit for diagnostic imaging (720 mW/cm 2 I spta ; spatial-peak temporal-average intensity) (AIUM Clinical Standards Committee 2004), temporarily and reversibly modified neural function in vivo .…”