Transcranial ultrasound neuromodulation induces metabolic and resting-state changes in amygdala

Transcranial ultrasound neuromodulation (TUS) is a fast growing non-invasive brain stimulation method allowing reversible and local perturbation of the neuronal activity in superficial but also deep-brain structures. Although TUS efficiency has been shown at the circuit and behavioral levels, its precise impact on the neuronal tissue remains a subject of ongoing investigation. Using resting-state fMRI (rs-fMRI) and MRI spectroscopy (MRS), we characterized both the functional and metabolic effects of TUS on a subcortical structure, the amygdala.In two anaesthetized non-human primates, We selectively stimulated both amygdala nuclei using two stimulation protocols which differ in the amount of energy transmitted to the targeted brain region (250kHz transducer; stimulation duration : 40s; pulse duration : 100ms; Duty Cycle 5% and 30%). Our findings revealed a TUS-induced shrinkage of functional connectivity patterns of the amygdala with the rest of the brain. Additionally, we observed metabolic changes in key neurotransmitters (γ-aminobutyric acid (GABA), glutamate (Glu)) and in neurotransmitter metabolic pathways (glutamine (Gln)). We observed significant reductions of GABA, Glu and Gln with both protocols. However, our results also showed a difference between the two protocols for the Glu but not for the GABA. Altogether our findings could be explained by a greater sensitivity of inhibitory interneurons to TUS compared to excitatory pyramidal cells. These outcomes contribute to a nuanced understanding of neuromodulation and its underlying mechanisms.