Modulating Interhemispheric Connectivity Through Chemogenetic Stimulation: A fMRI-fMRS Study

Interhemispheric communication between homotopic brain regions is essential for coordinated motor and cognitive functions. However, the underlying neurometabolic mechanisms remain poorly understood. This study aimed to investigate the neurochemical changes associated with interhemispheric communication in the motor cortex (MC) of rats, selectively manipulated using excitatory Designer Receptors Activated Only by Designer Drugs (eDREADDs). Functional MRI (fMRI) and functional MRS (fMRS) were used to assess neurochemical and connectivity changes. Excitatory transcallosal neurons were selectively activated using clozapine-N-oxide (CNO). Metabolite concentrations were measured before and after CNO activation. The relationship between metabolite levels, fractional amplitude of low-frequency fluctuations (fALFF), and interhemispheric connectivity (Pearson’s correlation) was analyzed. CNO activation led to a significant decrease in total N-acetylaspartate (tNAA) and an increase in aspartate (Asp) and GABA levels in eDREADD animals. Before CNO activation, tNAA and GABA were negatively correlated with fALFFs. After CNO activation, these correlations shifted to positive, with the GABA-fALFF correlation reaching statistical significance. Changes in Pearson’s correlation coefficients between homotopic motor cortices suggested that CNO activation influenced interhemispheric communication, likely via metabolic alterations. This study provides new insights into the dynamic neurochemical processes supporting interhemispheric coordination. These findings highlight the role of metabolic changes in brain communication and lay the groundwork for future research on neurometabolic regulation in interhemispheric connectivity.