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
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
Virtual Reality Driving and Other Bedside Testing 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.
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.