Linking GABAergic and Dopaminergic Neurotransmission: Effects on Neural Activity During Human Speech Control

Decades of research were instrumental in identifying the brain function controlling speech production. However, our understanding of the regulation of neuronal excitability via neurotransmission during speaking remains scant as the role of the inhibitory GABAergic system in controlling speech production is unknown. Using PET with [¹¹C]flumazenil radioligand combined with PET with [¹¹C]raclopride and functional MRI in healthy humans, we investigated the GABAergic neurotransmission and its relationship with dopaminergic function and brain activity during speaking and at the resting state. We demonstrate significant associations between neural activity and GABA_A receptor binding during speaking, with positive associations found in the inferior and superior parietal cortices, inferior frontal gyrus, supplementary motor area, superior temporal gyrus, putamen, and negative associations identified in the left inferior and middle frontal gyri. Neural activity was related to the interaction between the GABAergic neurotransmission and nigrostriatal dopamine release in the left associative caudate nucleus and sensorimotor putamen. Conversely, significant correlations between GABAergic neurotransmission and resting-state activity were limited to the primary visual cortex and the cerebellar lobule VI. These data provide the first direct evidence of the specific interactions of GABAergic and dopaminergic transmission with neural activity controlling the production of speech in healthy humans. Our findings suggest that GABAergic modulation of brain activity is exerted at different stages of speech control, from auditory perception to motor production, whereas dopaminergic function is important for maintaining the balance between excitation and inhibition within the speech motor circuitry.