Our lab investigates the neural circuit mechanisms underlying memory, sleep, and epilepsy. We combine invasive electrophysiology in human epilepsy surgery patients with chemogenetic and optogenetic approaches in mouse models. Below are our major active research programs.

Human Spatial Recognition Memory

NIH R01 — PI: Nigel Pedersen

How does the brain generate the feeling of familiarity? When you recognize a place you have been before, what neural processes produce that subjective sense of “I’ve been here” — and how does this differ from the richer experience of true recollection?

We use stereoelectroencephalography (SEEG) — depth electrodes implanted in epilepsy surgery patients — to record directly from the human hippocampus and surrounding structures during memory tasks. This gives us a rare window into the real-time neural dynamics of recognition memory at a spatial and temporal resolution that non-invasive methods cannot achieve.

A distinctive feature of this project is its interdisciplinary approach: we collaborate with philosopher Joseph Neisser to develop a rigorous conceptual framework for understanding metamemory experience — the subjective “what it’s like” of remembering — drawing on philosophy of mind to inform how we design experiments and interpret neural data.

Key questions:

  • What are the distinct neural signatures of familiarity versus recollection?
  • How do hippocampal and parahippocampal circuits interact to generate subjective memory experiences?
  • Can we predict the phenomenological quality of a memory from its neural signature?

Sleep Enhancement in Epilepsy

NIH R01 — PI: Nigel Pedersen | Co-I: Christelle Anaclet

Sleep disruption is one of the most common and debilitating problems in epilepsy. Poor sleep worsens seizures, and seizures disrupt sleep — creating a vicious cycle that compounds cognitive impairment and reduces quality of life.

We are testing whether enhancing sleep through targeted activation of brainstem sleep-promoting circuits can break this cycle. Using chemogenetic (DREADD) approaches in mouse models of epilepsy, we selectively activate GABAergic neurons in the parafacial zone of the parvicellular reticular formation — a key node in the brain’s sleep-generating network — to boost slow-wave sleep.

Key questions:

  • Does enhancing slow-wave sleep reduce seizure burden in epilepsy models?
  • Can sleep enhancement rescue the cognitive deficits associated with chronic epilepsy?
  • What are the circuit mechanisms linking sleep quality to seizure susceptibility?

Sleep Circuitry

In collaboration with Christelle Anaclet

Building on our long-standing work on sleep-wake circuitry, we continue to investigate the brainstem and basal forebrain circuits that control transitions between sleep and wakefulness. This work has contributed to our understanding of how the brain switches between states and has implications for sleep disorders, anesthesia, and disorders of consciousness.

Selected foundational work: