3 years ago

S-Ketamine-Induced NMDA Receptor Blockade During Natural Speech Production and its Implications for Formal Thought Disorder in Schizophrenia: A Pharmaco-fMRI Study

Christian Schales, Tilo Kircher, Andrea Oppel, Maurice Cabanis, Arne Nagels, Andre Kirner-Veselinovic


Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear, whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, cross over, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 minutes each, while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20-second epochs was correlated with BOLD responses. Participants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs. placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri. Similar to a previous fMRI study in schizophrenia patients vs. healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation.

Publisher URL: https://www.nature.com/articles/npp2017270

DOI: 10.1038/npp.2017.270

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