1 Département de psychologie, Université de Montréal, Québec, Canada.
2 Mcgill University, Montréal, Canada.
3 Department of Psychology, Carleton University, Ottawa, Canada.
4 Center for Studies in Behavioral Neurobiology and Perform Center, Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC, Canada; Research Center, Institut Universitaire de Gériatrie de Montréal, Montréal, Qc, Canada.
5 Département de psychologie, Université de Montréal, Québec, Canada; Centre de recherche du Centre Hospitalier Universitaire de l'Hôpital Sainte-Justine, Montréal, Québec, Canada. Electronic address: hugo.theoret@umontreal.ca.

TMS and H1-MRS measures of excitation and inhibition following lorazepam administration.

Neuroscience. 2020 Nov 24; :

Authors: Ferland MC, Therrien-Blanchet JM, Proulx S, Klees-Themens G, Bacon BA, Vu TTD, Théoret H

Abstract

This study aimed at better understanding the neurochemistry underlying TMS and MRS measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate+glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABAA-receptor mediated motor cortex inhibition (SICI). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

PMID: 33246064 [PubMed - as supplied by publisher]