Figure t Introduction Methods References Cortical synchronization controls EEG Trough-max vs EEG Peak-max Funding / Conflicts of Interest Disclosure A B C D E F 50 -100 50 -100 Single PYdr Voltage Zoomed TC→PY AMPA current Single TC Voltage Mean TC→PY AMPA current [μA/cm2] [μA/cm2] [mV] [mV] 1.5 0 1.6 1.40 1 2 Time [sec] 0 0 0 2 2 2 π -π 0 Alpha Amplitude (12 Hz) SWO Phase Bin (1.0 Hz) Un-normalized Modulation Index 30 5 G H I 50 -100 50 -100 Single PYdr Voltage Single PYso Voltage Mean PY→PY AMPA current [μA/cm2] [mV] [mV] 0.03 00 0 0 2 2 2 1 Time [sec] J π -π 0 Alpha Amplitude (12 Hz) SWO Phase Bin (1.0 Hz) PY→PY Comodulogram 0.1 0.03 0 15 Time [sec] 7.5 K Coupling Map 0.5 1 Alpha Frequency 8 10 12 SWO Frequency 1.5 2 2.5 Un-normalized Modulation Index 0.2 0.8 EEG Trough-max Spike Rastergrams EEG Peak-max Spike Rastergrams Austin E. Soplata1,2,3(austin.soplata@gmail.com), Michelle M. McCarthy2,3, Erik Roberts1,2, Emery N. Brown2,4,5,6,7, Patrick L. Purdon2,4,5, Nancy Kopell2,3 Cortical UP/DOWN state synchrony drives propofol phase-amplitude coupling in slow waves 289.18 / D4 1Graduate Program for Neuroscience, 2Cognitive Rhythms Collaborative, and 3Department of Mathematics & Statistics, Boston University, Boston, MA, 4Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, 5Department of Brain and Cognitive Sciences, 6Division of Health Sciences and Technology, and 7Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA Download this poster at: asoplata.com/asoplata-poster.pdf Or scan QR code here: • The anesthetic propofol induces beta (12-20 Hz), alpha (8-12 Hz), and Slow Wave Oscillations (SWO, 0.1-1.5 Hz) on the EEG of human patients [1] • At low propofol, near Loss of Consciousness, alpha amplitude is maximal during the trough of the SWO phase, called "Trough-max" phase- amplitude coupling (PAC) [1] • At high propofol, in deep anesthesia, alpha amplitude is maximal during the peak of the SWO phase, called "Peak-max" PAC [1] • SWOs in natural sleep often begin in the cortex [2], while simulations suggest propofol alpha is generated by the thalamus [3] • Propofol "directly" affects properties of thalamic and cortical cells and synapses such as GABA-A conductance, GABA-A decay time, and H-current conductance [1,3] • Propofol "indirectly" affects thalamic and cortical cells via decreasing cortical acetylcholine (ACh) [4], which affects K(Na)-current conductance, corticocortical, and thalamocortical synaptic strengths [5] • We hypothesized that the direct effects of propofol would produce and control both trough-max and peak-max PAC in a full, thalamocortical model, primarily by modulating thalamic behavior. However, we found that indirect effects from propofol on ACh and changes to the thalamocortical feedback loop could control trough-max vs peak-max changes. •Our simulations modeled 100 cortical dendrite compartments (PYdr), 100 cortical axo-somatic compartments (PYso), 20 cortical interneurons (IN), 20 thalamic reticular neurons (TRN), and 20 thalamocortical neurons (TC) using the biophysical Hodgkin-Huxley formalism [3,5]. Synapses are connected via a nearest-neighbor radius. •Our artificial EEG signal was modeled from the combination of AMPAergic corticocortical (PY→PY) and thalamocortical (TC→PY) synaptic currents onto cortical dendrites •Our PAC analysis was based on the standard Modulation Index coupling measure [6] EEG Trough-max Involves Synaptic Competition • We found that while direct effects were necessary for thalamic propofol alpha, indirect effects were also necessary for SWO expression • EEG signal had two components: thalamocortical and corticocortical synapses onto cortical dendrites • In the thalamocortical synapse case: • Thalamic cells exhibit a persistent alpha oscillation, while target cortical cells exhibit a SWO rhythm • The TC→PY synaptic current produces a Trough-max PAC signal since the alpha amplitude