The dynamics of GABA and Glutamate in semantic control: a combined 7T fMRS and fMRI study

1007 

Abstract Submission 

JeYoung Jung¹, Adam Berrington²

¹University of Nottingham, Nottingham, Nottingham, ²University of Nottingham, Nottingham, Please Select

JeYoung Jung  
University of Nottingham
Nottingham, Nottingham

Adam Berrington  
University of Nottingham
Nottingham, Please Select

Semantic control involves the adaptable skill of entering and handling meaningful information, allowing individuals to concentrate on the pertinent facets of a concept in accordance with a given context or objective (Jefferies, 2013; Lambon Ralph et al., 2016). This encompasses the ability to enhance less prominent features or uncommon meanings of a word while suppressing more prominent but unrelated attributes. Additionally, it includes the aptitude to transition between tasks effortlessly and address conflicting meanings or uncertainties. While the inferior frontal gyrus (IFG) has been associated with semantic control (Thompson-Schill et al., 1997; Wagner et al., 2001), the neurochemical mechanism underlying this process remains unclear.
Proton magnetic resonance spectroscopy (MRS) is a non-invasive, in vivo technique that measures neurometabolite levels in the brain, including the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate. Functional MRS (fMRS) acquires multiple spectra during a task, providing a dynamic measurement of neurometabolites changes in response to stimuli (Stanley and Raz, 2018). While the existing literature on fMRS is limited, there is evidence indicating remarkable sensitivity in detecting task-related dynamic changes in glutamate and GABA within functionally relevant areas of the brain (Stanley and Raz, 2018). Here, we employed a combination of 7T fMRS and fMRI to examine the dynamic changes in GABA and glutamate within the left IFG during semantic control processing.

Sixteen healthy English speakers (4 males, mean age = 23yrs old) participated in this study. Participants performed a semantic categorization task at two different difficulty levels (easy [ES] and hard [HS]) during fMRS and a semantic categorization task and a picture matching task as a control task during fMRI (Fig. 1A). fMRS started with the fixation (2mins) followed by a semantic task (6mins) and ended with the fixation (3mins) (Fig. 1A). During fMRS, we measured GABA and glutamate in the left IFG (Fig. 1B).

Results showed that participants performed better in the easy task compared to the hard task, with higher accuracy and faster reaction times (Fig. 1C). We found that the levels of GABA and glutamate exhibited distinct patterns of changes corresponding to task difficulty. During the easy task, GABA concentrations in the IFG seemed to be stable, whereas during the demanding semantic control processing of the hard task, GABA levels increased (Fig. 2 Top). Contrary to GABA, glutamate was increased during the easy task and did not show any changes during the hard task (Fig. 2 Top). fMRI revealed increased regional activity in the IFG during the hard semantic task compared to the easy task (Fig.2 Bottom). Importantly, the task-modulated GABA changes were significantly correlated with task-induced regional activity in the IFG during the hard semantic task (Fig.2 Bottom). Furthermore, individual GABA levels were positively correlated with hard semantic task performance.

Our data suggests that semantic control processing modulates regional GABA and glutamate levels as well as fMRI activation in the IFG. GABAergic inhibition in the IFG seems to be important to shape task-induced regional activity and semantic control acuity.

Language Comprehension and Semantics ¹

Long-Term Memory (Episodic and Semantic) ²

Activation (eg. BOLD task-fMRI)

Other Methods

Transmitter Systems

FUNCTIONAL MRI

GABA

Glutamate

Language

Memory

MR SPECTROSCOPY

Neurotransmitter