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The Neuronal Mechanisms of Consciousness

What consciousness is and how it works has been intensely debated for millenia, but it is now accessible to modern tools of neuroscience. We are contributing to this exciting, new field of research by using a set of visual, tactile, and auditory perceptual behavioral tasks coupled with a series of recording techniques. These include pupillometry, fMRI, intracranial EEG, high-density surface EEG, and machine learning.

These experimental methods offer insights into where and when the human brain is active during conscious perception. This work has important clinical implications, particularly for the diagnosis and treatment of patients who experience abnormal conscious states, including epilepsy, vegetative/minimally conscious states, and psychiatric disorders.

Impaired Consciousness in Childhood Absence Epilepsy: EEG-fMRI and Attention

Absence seizures are brief episodes of staring and unresponsiveness. Seen most commonly in children, they can disrupt school and attention performance. The mechanisms for impaired attention in absence epilepsy are not known. To determine how brain networks are affected by absence seizures, we perform simultaneous fMRI and EEG recordings in children during absence seizures. We also test attention both during seizures and under normal conditions. Our work has revealed abnormal activity in specific brain regions, which may serve as new targets for treatment.

Impaired Consciousness in Focal Seizures

How do focal seizures impair consciousness? Temporal lobe seizures are the most common form of localized epilepsy. We propose a "network inhibition hypothesis" in which temporal lobe seizures inhibit subcortical arousal systems, causing depressed cortical function. In support of this hypothesis, we found sleep-like changes in the cortex with intracranial EEG and SPECT during temporal lobe seizures. We are now using high field (9.4 T, 11.7 T) fMRI, single neuron recordings, neurotransmitter studies, and optogenetic techniques in animal models to reveal both the fundamental mechanisms of these changes and to test novel treatment approaches. These approaches include deep brain stimulation in a NIH-supported clinical trial.

Frontal lobe seizures are the second most common form of focal epilepsy. We recently found that focal frontal lobe seizures with impaired consciousness have larger intracranial EEG signals throughout brain networks than seizures with spared consciousness. This appears to be a distinct mechanism in frontal lobe seizure than what we observed in temporal lobe epilepsy, particularly with important therapeutic value.

Neuronal Activity and Neuroimaging in Generalized Seizures

Are "generalized" seizures truly generalized? Our work using high field (9.4-11.7 T) fMRI and electrophysiology recordings from animal models suggests that so-called generalized absence and tonic-clonic seizures are, in fact, localized to specific bilateral cortical-subcortical networks. These findings may help develop targeted therapies with better efficacy and fewer side effects. Additionally, our direct recordings of neuronal electrical activity improve the interpretation of indirect neuroimaging measurements of brain function.

Virtual Reality Driving and Other Bedside Testing in Epilepsy

One of the most devastating effects of altered consciousness in epilepsy is impaired driving safety. To determine how epileptic seizures affect performance, we use virtual reality driving simulation during video/EEG monitoring while patients are in the hospital. We have also developed a prospective bedside testing battery, the Responsiveness in Epilepsy Scale (RES). These testing methods provide better information to patients and physicians making decisions about driving, and may help to identify brain areas crucial for impaired consciousness in epilepsy.

Technical Advances in Epilepsy Surgery Localization

In some patients, seizures are so severe that they cannot be controlled by medicines. Many of these patients can be cured if we identify a damaged brain region to remove safely and prevent the triggering of their seizures. We have recently developed two novel approaches to target surgery to the correct location in the brain:

  • 3D color movies of the "brainwave" electroencephalogram (EEG) in patients with epilepsy show where the seizures start, making safe and effective surgery much more feasible.
  • Innovative methods using single photon emission computed tomography (SPECT) and positron emission tomography (PET) tracers can pinpoint the region for surgical planning.

Preventing Epilepsy

One crucial goal is the prevention of epilepsy before it even begins. In a genetic form of epilepsy, we found that if we treat rat pups with anti-seizure medication from a very early age (even before seizures started) we greatly reduced their tendency to have seizures as adults. Additionally, we found in a recent review of human studies of the same form of epilepsy that early and effective treatment may improve long-term outcome. This is a paradigm shift from current treatment strategies, which view seizure medications as suppressing the symptoms and not the underlying disease. The findings also raise the hope that as genes are identified and enable epilepsy to be predicted, beneficial treatments may be started even before symptoms begin.