The purpose of this study is to determine the effects of pain on facilitating long-term
auditory memory in the presence and absence of distinct intravenous anesthetics. The ability
to identify previously presented words from a list will asses the degree of memory formation.
In a subset of subjects, functional magnetic resonance imaging will be used to identify the
neural correlates of memory inhibition or facilitation by the combination of pain and
anesthetic used. The primary hypothesis is that pain will enhance memory formation, and that
this will be mediated by additional neural pathways compared to those used to encode words
not paired with pain. The study will occur over 4-5 visits and involves no long-term follow
This study will add specific details to the current incomplete body of knowledge examining
the effect of pain on memory formation under the influence of anesthetic agents. Pain is
common during surgery, and preventing memory during such procedures is a fundamental goal of
anesthetic care, as awareness under anesthesia can cause life-long psychiatric disturbance.
However, currently available monitors cannot always detect when a patient is at risk for
awareness or memory under anesthesia. This is largely due to an incomplete description of the
circumstances that favor memory formation versus those that effectively inhibit it.
Pain and anesthetic agents will be administered as experimental variables in this study.
Healthy adult subjects will be played repeated lists of words and perform several
decision-making tasks that encourage memory encoding. Some words will be consistently paired
with painful electric shock, and this is anticipated to improve subsequent memory performance
specifically for those items. The same experiment will be repeated in all subjects during the
administration of two agents that reduce memory formation: dexmedetomidine, a predominantly
sedative agent, and midazolam, a well-known amnestic agent. The extent to which pain
modulates the sedative and amnestic effects of the anesthetic agents will be the primary
outcome of interest. Psychometric testing for stress, anxiety, depression, and sleepiness
will be performed in the subjects, and regression analysis will be used to determine which of
these may explain the commonly observed inter-individual response variability to
pharmacologic sedation and amnesia.
Further, a subset of the subjects will perform the same experimental procedures while
undergoing functional magnetic resonance imaging, which will continuously reflect neuronal
activity throughout the brain. Classic memory areas are predicted to be activated by the
auditory processing task, but how these neural circuits change under the two anesthetic
agents with the concomitant experience of pain will be of interest. It is anticipated that
pain will recruit a parallel memory pathway using limbic structures, known for their
involvement in fear conditioning. Additionally, stronger and more diffuse cortical processing
will likely occur with concomitant pain, as level of sedation will be reduced by this strong
stimulus. Discovering the anatomic correlates specific to each experimental variable (pain
and anesthetic), and their interplay, will refine the investigators' model of brain function
during the dynamics of surgery and may someday allow more predictive monitoring.
- Healthy adult volunteers, with normal memory and hearing, whose native language is
- significant memory or hearing loss
- sleep apnea
- chronic pain
- metal or electronic implants
- Currently taking: antidepressants, anti-psychotics, antihistamines, anti-anxiety
medication, stimulants, sleep-aids, or pain medication