# Neuroimaging, neuronal firing and behavior in spike-wave seizures

> **NIH NIH R37** · YALE UNIVERSITY · 2022 · $445,048

## Abstract

PROJECT SUMMARY / ABSTRACT
Absence seizures occur most commonly in children as staring spells lasting 5-10 seconds, with rhythmic
“spike-wave” discharge (SWD) on electroencephalography (EEG). They can occur up to hundreds of times per
day and are not benign, with deficits in attention and psychosocial function in some cases persisting into
adulthood or even after seizure suppression. The mechanisms by which absence seizures impair cognition are
not known. One intriguing but little-studied aspect of absence seizures is the fact that some episodes impair
and others spare behavioral responses even within the same individual. The relationship between variable
absence behavioral severity and neuronal activity may provide fundamental insights into the pathophysiology
of seizures. Prior human studies and animal models have shown widespread EEG and fMRI increases as well
as decreases during absence seizures. We recently found in a large patient sample that absence seizures with
more severely impaired behavior had larger fMRI and EEG amplitude in widespread brain networks. We also
found that abnormally enhanced fMRI synchrony persists between bilateral cortical regions even when
seizures are not present in patients and in animal absence models. The neuronal basis for these changes both
at rest and during SWD is not known, but our recent work in rodent absence models and normal conditions
suggests that the amplitude of fMRI signals is related to changes in the total population activity of neurons.
Therefore our central hypothesis is that the severity of absence seizures is determined by a combination of the
number of neurons involved and their firing pattern in widespread brain networks before and during seizures.
An important limitation of previous work has been anesthetic agents, which markedly alter fMRI responses and
the excitability of neurons. This may explain why most animal models show cortical fMRI increases during
SWD whereas human studies show a predominance of sustained cortical fMRI decreases. Because of this
discrepancy the neuronal basis of physiology changes in absence seizures remains uncertain. We recently
habituated genetic absence epilepsy rats of Strasbourg (GAERS) to allow awake-head fixed experiments.
Initial measurements in this new model show sustained cortical fMRI and CBF decreases during SWD much
more closely resembling humans. We now plan complementary high spatiotemporal resolution experiments in
this awake model including fMRI, electrophysiology and behavior to fully understand the neuronal basis of
variable severity in absence seizures. Our aims are to first image the networks involved at baseline and during
severe versus mild SWD, and to relate the neuroimaging changes to spike and wave amplitude on EEG.
Second, we will use multiunit and neuronal ensemble recordings to determine the neuronal basis of severe
versus mild SWD. Third, we will relate the physiological severity of SWD to behavior through auditory detection
and re...

## Key facts

- **NIH application ID:** 10459627
- **Project number:** 5R37NS100901-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** HAL BLUMENFELD
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $445,048
- **Award type:** 5
- **Project period:** 2017-08-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459627

## Citation

> US National Institutes of Health, RePORTER application 10459627, Neuroimaging, neuronal firing and behavior in spike-wave seizures (5R37NS100901-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10459627. Licensed CC0.

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