Dopamine drives left-hemispheric lateralization of neural networks during human speech

Although the concept of left-hemispheric lateralization of neural processes during speech production has been known since the times of Broca, its physiological underpinnings still remain elusive. We sought to assess the modulatory influences of a major neurotransmitter, dopamine, on hemispheric lateralization during real-life speaking using a multimodal analysis of functional MRI, intracranial EEG recordings, and large-scale neural population simulations based on diffusion-weighted MRI. We demonstrate that speech-induced phasic dopamine release into the dorsal striatum and speech motor cortex exerts direct modulation of neuronal activity in these regions and drives left-hemispheric lateralization of speech production network. Dopamine-induced lateralization of functional activity and networks during speaking is not dependent on lateralization of structural nigro-striatal and nigro-motocortical pathways. Our findings provide the first mechanistic explanation for left-hemispheric lateralization of human speech that is due to left-lateralized dopaminergic modulation of brain activity and functional networks.