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Principal Investigator: Derek J Doss
Organization: VANDERBILT UNIVERSITY
Fiscal Year: 2024
Award: $27,218
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY/ABSTRACT
Epilepsy is a debilitating neurological disorder that affects 1% of the population worldwide and temporal lobe
epilepsy (TLE) is the most common form. Seizure onset in TLE is typically localized to the mesial temporal lobe,
however, patients can suffer from distant effects such as loss of consciousness during seizures (ictally) and
neurocognitive deficits between seizures (interictally), both of which impair one’s activities of daily living, ability
to work, and quality of life. Prior work investigating these global effects have resulted in the Network Inhibition
Hypothesis, which states that focal seizure activity observed with stereotactic electroencephalography (SEEG)
spreads to subcortical structures responsible for neocortical activation, resulting in ictal loss of consciousness in
focal impaired awareness seizures (FIAS). Studies with functional MRI (fMRI) have provided evidence that the
same anatomical areas have abnormal functional connectivity (FC). It thought that recurrent FIAS lead to chronic
interictal decreases in subcortical to neocortical FC, but this knowledge gap but this knowledge gap has not been
addressed. We aim to relate FC of ictal and interictal states using SEEG (Aim 1). I specifically hypothesize during
FIAS ictal FC will decrease in the same anatomical regions as those implicated in interictal FC abnormalities. In
addition to recurrent seizures, patients can also have devastating interictal neurocognitive deficits. These
widespread neurocognitive deficits suggest that there is a common factor, which is thought to be the subcortical
arousal structures. It has been shown that fMRI FC abnormalities of subcortical to neocortical structures are
associated with neurocognitive deficits, seizure frequency, and can recover after surgery. While general
subcortical to neocortical abnormalities have been outlined, there is a gap in understanding of specific brain
networks associated with neurocognitive deficits. This could be due in part to not adequately controlling for
arousal state. The high vigilance or “sustained attention” state, is a state of cognitive engagement mediated by
subcortical arousal structures which fluctuates at rest. It is associated with subcortical to neocortical FC changes,
associated with extratemporal neurocognitive deficits, the state active during neurocognitive testing, and thought
to be a confounder for resting-state fMRI by some. We aim to link specific subcortical to neocortical network
abnormalities with neurocognitive deficits by controlling for the high vigilance state with fMRI-EEG (Aim 2). I
specifically hypothesize that during high vigilance states, patients will have significantly decreased FC within
subcortical to neocortical networks compared to controls, that the decrease will be associated with extratemporal
neurocognitive deficits, and that the network will recover after successful surgery. This proposed fellowship will
provide research training in a collaborative research atmosphere with expert mentors. Research training will be
conducted in an environment that combines an academic medical center with a level 4 epilepsy center, world
class imaging institute, and engineering all on one campus. Studying multiple modalities to characterize epileptic
networks may lead to improved neuromodulation targets for TLE.
Terms: <21+ years old><Academic Medical Centers><Activities of Daily Living><Activities of everyday life><Acute><Address><Adult><Adult Human><Affect><Anatomic Sites><Anatomic structures><Anatomy><Area><Arousal><Awareness><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><Brain region><Chronic><Cognitive><Cognitive deficits><Conscious><Consciousness><Data><Disabling><Disease><Disorder><Distant><Dysfunction><EEG><Electroencephalogram><Electroencephalography><Electrophysiology><Electrophysiology (science)><Encephalon><Encephalon Diseases><Engineering><Environment><Epilepsy><Epileptic Seizures><Epileptics><Fellowship><Focal Epilepsy><Focal Seizure><Focal Seizure Disorder><Frequencies><Functional MRI><Functional Magnetic Resonance Imaging><Functional disorder><Goals><IQ Deficit><Image><Impairment><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Knowledge><Lead><Link><Localization-Related Epilepsy><Mediating><Memory><Mentors><Modality><Nature><Neocortex><Nervous System Diseases><Nervous System Disorder><Neurocognitive><Neurocognitive Deficit><Neurologic Disorders><Neurological Disorders><Neurophysiology / Electrophysiology><Operative Procedures><Operative Surgical Procedures><Partial Epilepsies><Partial Seizure Disorder><Pathology><Patients><Pb element><Persons><Physiopathology><Population><QOL><Quality of life><Recurrence><Recurrent><Regional Anatomy><Research Training><Rest><Scalp><Scalp structure><Seizure Disorder><Seizures><Structure><Surgical><Surgical Interventions><Surgical Procedure><Temporal Lobe Epilepsy><Unconscious><Unconscious State><Unconsciousness><University Medical Centers><Work><adulthood><atmospheric research><atmospheric sciences><atmospheric studies><cognitive defects><compare to control><comparison control><consciousness loss><daily living function><daily living functionality><electrophysiological><epilepsia><epileptogenic><executive control><executive function><fMRI><fMRI/EEG><functional ability><functional capacity><functional magnetic resonance imaging/electroencephalography><heavy metal Pb><heavy metal lead><homotypical cortex><imaging><improved><intelligence quotient deficit><isocortex><lab atmosphere><laboratory atmosphere><medial temporal area><medial temporal lobe><mesial temporal area><mesial temporal lobe><multi-modality><multimodality><neocortical><neopallium><network dysfunction><neural control><neural regulation><neurocognitive decline><neurocognitive impairment><neurocognitive test><neurological disease><neuromodulation><neuromodulatory><neuroregulation><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><partial seizure><pathophysiology><post-operative recovery><postoperative recovery><processing speed><recovery after surgery><recovery following surgery><research atmosphere><science atmosphere><science oriented atmosphere><scientific atmosphere><surgery><sustained attention><vigilance>