title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Po Song
authors.initials: PS
authors.lastname: Yang
authors.forename: Hyungmin
authors.initials: H
authors.lastname: Kim
authors.forename: Wonhye
authors.initials: W
authors.lastname: Lee
authors.forename: Mark
authors.initials: M
authors.lastname: Bohlke
authors.forename: Shinsuk
authors.initials: S
authors.lastname: Park
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
authors.forename: Seung-Schik
authors.initials: SS
authors.lastname: Yoo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D045604:Extracellular Fluid / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000000981:diagnostic imaging* / Q000378:metabolism*; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial / Q000295:instrumentation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid