October 2026

AY '26-'27 Goals

• Submit a manuscript for publication
  • Meet w/ Nina
  • Identify two journals (plan A and plan B) to submit Brandon's study to. Understand their submission requirements. Write up the introduction for the study in LaTeX, formatted and tailored appropriately for each journal.
• Submit RISE 1 application
  • Narrow down research directions and goals
  • Literature review to refine research aims
  • Identify mentors and institutional resources
• Identify additional funding sources and apply
• Start recruiting a research team

10/2

• E-mailed slides to Nina and followed up on study. It is currently paused due to a bupivacaine shortage.
• Texted Brandon about which journals to submit to. 1st choice: A&A, 2nd choice: Journal for Obstetric Anesthesia
• Does TIVA prevent cancer recurrence? Head of Huntsman anesthesia did a cancer anesthesia fellowship and researched this a bit. Though he's now burned out on research, he's the guy to talk to about what's already been done or not.
• Hamilton and I talked about why ketamine causes lasting changes in the brain long after the drug is gone. Is it a change to a gap junction network? Is it anti-inflammatory circulating EVs?. There are three papers on MedLine related to ketamine and EVs, none of which look (anti-)inflammatory molecules. Do circulating EVs after propofol anesthetic also contain the inflammatory cytokines that are seen after isoflurane?

Mechanisms of Anesthesia

Big picture: understand the temporospatial and mechanistic changes in neural activity induced by various anesthetics. Can we recapitulate those with steerable, low latency, closed-loop non-invasive neuromodulation or use this knowledge to drive discovery of novel drugs?

• High-throughput screen of anesthetics (and anesthetic reversal agents) in C.elegans. I could work in parallel in a different organism (e.g. yeast, jellyfish, hydra, sea anemones, corral, bacteria, plants, neuronal explants).
• Has anyone published behavioral assays for these organisms? Detailed protocols for breeding them? Have they already been anesthetized?

• 2026 A&A paper argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA_AR receptor. Based on 30 years of in vitro studies (n>330), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
• According to this paper, some anesthetics (i.e. ketamine, dexmedetomidine, etomidate, benzos) are fairly selective, but are rarely used as sole anesthetics. Below, I list each of the in vitro binding affinities of these "selective" anesthetics, up until there is a change of one order of magnitude or greater for the next receptor.
  • Ketamine binds to α4β4 nAChR w/ IC₅₀ of 0.144 uM, but has an IC₅₀ for the GluN1/N2C NMDAR of 0.338 uM.
  • Dexmedetomidine binds to α_2A AR w/ K_D of 0.0014 uM and the M₃ mAChR w/ IC₅₀ of 0.001 uM.
  • Etomidate binds to α1β2γ2 GABA_AR w/ an EC₅₀ of 1.08 uM, but to I_K(dr) with an IC₅₀ of 4.59 uM, and the α1 GlyR w/ an IC₅₀ of 5.37 uM.
  • Midazolam binds to α1β2γ2 GABA_AR w/ EC₅₀ of 0.041 uM, Na_V (neuron) IC₅₀ of 0.074 uM, and nAChR (muscle) w/ IC₅₀ of 0.143 uM.
  • Diazepam binds to α1β2γ2 GABA_AR w/ EC₅₀ of 0.07 uM.
  • Sevoflurane binds to K_v1.2 w/ EC₅₀ of 0.0097 mM.

• Are there pharmacological agents with receptor specificity? When given together with "promiscuous" anesthetics, what happens? For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA_AR inhibitor?
• Are there genetic KO/KD or optogenetic tools available for location-specific inducible receptor knockdowns?
• Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.
• Worms natively have a blue-light rhodopsin that triggers an aversion response where they turn around and go the opposite direction.
• Next call 10/14.
• What are the differences in mechanisms for amnesia, hypnosis, immobility, and analgesia?

CLAN

Alpha entrainment analgesia study

• • Successfully entrain alpha. What were we doing wrong? Is there anything in the literature that can guide a protocol modification?
  • Can I incorporate withdrawal thresholds?
  • Make it multi-center
  • Is alpha dropout selective for certain types of pain?
  • Power analysis based on pilot study
  • Systematic review and meta analysis

EEG effects of anesthetic agents

Look at benzos, opioids, precedex, and their respective reversal agents. Also caffeine, methylphenidate, and methohexital. In MedLine, combine each agent with the search term Electroencephalography/ and add limits for Adults, Humans, and English. Which drugs are most target selective? What are their EEG effects?

• Yohimbine = 9
  • Yohimbine stimulates NE release from the locus ceruleus (riba2005journalofneuroscience). It decreases latency of the P200 in ERPs, suggesting a possible improvement in selective attention to environmental stimuli (turetsky2002psychophysiology).
• Naloxone = 28
  • 2021 study looking at 20 health male volunteers showed that the magnitude of nociceptive withdrawal reflexes (NWRs) together with amplitudes and insular source strengths of the corresponding EEG responses were attenuated by opioids. In the cold-pressor test, increases in delta amplitude and decreases in alpha power were reversed by opioids.
  • 2010 study of 12 healthy volunteers demonstrated that tramadol decreased the amplitude of LEPs, whereas placebo left LEPs unchanged. The opioid antagonist naloxone partially reversed the tramadol-induced LEP amplitude decrease.
  • Fentanyl self-administration and passive administration (both 1.5-3 mg/70 kg) have differential EEG effects. Delta EEG peak amplitude increases were greater following fentanyl SA than fentanyl PA, primarily over the central midline region, and were attenuated by naloxone pretreatment in a 2005 study of 8 heroin-dependent, methadone stabilized subjects.
  • EEG average frequency was increased in response to pain from direct 60 Hz thalamic electrical stimulation. The effect was blunted by fentanyl (5 mcg/kg) and augmented by naloxone (3.5 mcg/kg), in a 1998 study of 4 epileptic patients.
  • In a pain-evoked potential paradigm with patients undergoing minor surgical procedures, naloxone (3 mcg/kg) increased the amplitude and area of the small P300 while decreasing its latency, but decreased the amplitude and area of the large P300 peak. There were fewer omissions in an odd-ball task 1984 study of patients undergoing minor surgical procedures.
  • 1980 study of 16 patients failed to demonstrate a significant EEG response in response to 1.2 mg naloxone in patients under GA using inhalation (halothane ± N2O) anesthesia.
  • 1980 study showed painful electrical stimulation of the median nerve decreased SEP amplitude in six volunteers. In the four volunteers who noted that this pain-relief was inhibited by naloxone, the SEP amplitude was also returned to baseline following naloxone administration. Two volunteers had a paradoxical reaction.
  • 1979 study showed 10 or 20 mg of naloxone elicited a significant slowing of the average alpha frequency in healthy male volunteers
  • 1979 study reported that some of the analgesic effects of N2O can be reversed with naloxone 0.4 mg, as evidenced by electrical pain-evoked potentials.
• Methylphenidate = 68
• Methohexital = 80
• Flumazenil = 94
• Caffeine = 138

CO2

• Does permissive hypercapnia improve hemodynamic stability, improve oxygen delivery to tissues, deepen anesthesia, and speed recovery?

Depression

• Do ketamine, TIVA w/ propofol, TIVA w/ remimazolam, psychedelics, or burst suppression modulate the post-operative risk of depression?