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.