Behavioural disinhibition is a common feature of frontotemporal lobar degeneration (FTLD) syndromes. Impulsive behaviour in several neuropsychiatric diseases and FTLD have been linked with reduced levels of the neurotransmitters, glutamate and GABA. This study aimed to investigate, through a transdiagnostic approach, whether prefrontal glutamate and GABA levels are reduced by FTLD and if these deficits are associated with impaired response inhibition. Participants (33 patients with FTLD syndromes, 20 control participants) completed an ultra-high field (7 T) magnetic resonance spectroscopy and a response inhibition task. Glutamate and GABA levels were measured using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus (IFG; response inhibition region) and the primary visual cortex (control region). FTLD patients had impaired response inhibition as well as reduced GABA concentration in the right IFG compared with controls. Glutamate concentrations did not differ between groups. Results also indicated that greater impulsivity was associated with reduced glutamate and GABA concentrations in the IFG. Glutamatergic and GABAergic deficits in the frontal lobe may be potential targets for symptomatic drug treatments for FTLD syndromes.

Murley, A. G., Rouse, M. A., Jones, P. S., Ye, R., Hezemans, F. H., O’callaghan, C., Frangou, P., Kourtzi, Z., Rua, C., Carpenter, T. A., Rodgers, C. T., & Rowe, J. B. (2020). GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition. BRAIN, 143, 3449–3462. https://doi.org/10.1093/brain/awaa305