Interhemispheric resting-state functional connectivity correlates with spontaneous neural interactions.

Area of Science:

• Neuroscience
• Systems Neuroscience
• Functional Neuroimaging

Background:

• Functional connectivity (FC) using resting-state (RS) functional MRI (fMRI) maps brain networks but lacks understanding of causal mechanisms, especially for strong interhemispheric connections.
• Investigating the neural basis of RS FC is crucial for understanding brain network organization and function.

Purpose of the Study:

• To investigate the neural basis of resting-state functional connectivity (FC) in mice.
• To differentiate the causal mechanisms underlying spontaneous FC from evoked neural activity.

Main Methods:

• Utilized fMRI in mice combined with anatomically defined patterned optogenetic activation and inhibition of excitatory neurons in six cortical regions.
• Employed optogenetic silencing to suppress spontaneous neural activity, allowing fMRI to track functional connections without excitation-induced perturbations.
• Modeled synaptic path length-dependent connectivity based on structural connectivity (SC).

Main Results:

• Optogenetic activation primarily induced ipsilateral cortical and subcortical responses.
• Optogenetic silencing elicited stronger intra- and interhemispheric cortical responses, mirroring RS FC patterns.
• Spontaneous functional connections are explained by polysynaptic propagation, while evoked activity relies on monosynaptic pathways.

Conclusions:

• Polysynaptic pathways play a critical role in shaping spontaneous connectivity.
• Resting-state functional connectivity arises from causal interactions of spontaneous neural activity, not just direct monosynaptic connections.