Combining phase analysis and causal stimulation enables longitudinal mesoscale connectivity mapping

Area of Science:

• Neuroscience
• Computational Neuroscience
• Primate Brain Research

Background:

• Understanding flexible behavior requires mapping neural signal propagation in large-scale brain networks.
• Current methods for measuring causal connectivity are limited in scale and duration, especially in non-human primates.
• Longitudinal tracking of brain network dynamics is crucial for studying complex behaviors.

Purpose of the Study:

• To present a novel stimulation and recording method for longitudinally measuring causal connectivity in centimeter-scale cortical networks in macaques.
• To enable stable, daily measurements over weeks-long periods for tracking brain network evolution.
• To investigate the large-scale circuit dynamics underlying complex behaviors in the primate brain.

Main Methods:

• Combined multi-site optogenetic stimulation with micro-electrocorticography using a semi-chronic implant.
• Applied phase-based spectral analysis to differentiate stimulation-driven and secondary activity related to causal connections.
• Validated the approach by tracking connectivity longitudinally over weeks and assessing stability and behavioral state sensitivity.

Main Results:

• Successfully measured causal connectivity across centimeter-scale cortical networks in macaques over extended periods.
• Demonstrated improved stability of measurements over long durations while maintaining sensitivity to behavioral states (e.g., eyes-open vs. closed).
• Showcased the ability to disentangle local and network-driven neural activity using spectral analysis.

Conclusions:

• The developed platform provides a robust method for longitudinal measurement of causal connectivity in primate brains.
• This technique overcomes limitations of current methods, enabling week-long tracking of network dynamics at centimeter scales.
• The platform facilitates the investigation of neural circuit mechanisms underlying flexible behavior and other complex cognitive functions.