Document text
Principal Investigator: Diany Paola Calderon
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2024
Award: $487,477
Funding agency: National Institute of Neurological Disorders and Stroke
Project Summary
Monitoring the transition to wakefulness is critical during restoration to consciousness after brain injury,
anesthesia, and in those COVID-19 survivors that have altered consciousness. However, we have an imprecise
understanding of neural dynamics linked to behavioral changes as subjects awaken. Our previous work
discovered that stimulating the anterior nucleus gigantocellularis (aNGC) promotes arousal from a coma-like
state. We proposed recruiting multiple arousal pathways through aNGC as an avenue to triggering widespread
activation resulting in wakefulness. Notably, aNGC activation increased frontal-motor cortical activity and
restored full mobility through modulation of an aNGC-to-frontal-motor-cortex pathway despite high anesthetic
concentration exposure. We also showed that animals emerging from diverse coma-like states share a common
dynamic process of cortical and motor arousal that can be consistently sequenced from deep to high arousal
levels. We identified five cortical periods that tracked restored motor behavior in a hypoglycemic coma and a
range of anesthetics, whether inhaled or injected, alongside conventional righting reflex assays. Based on these
findings, we postulate that restoring waking is a common progressive process in which cortical patterns contain
metrics of consciousness that distinguish reflexive from purposeful movements. We hypothesize that cortical
measurements that link neural responsiveness to defined behaviors are an applicable method that can
extend the analysis of the recovery of consciousness beyond monitoring reflexive movements.
Our proposal deepens our understanding of the contribution of cortical neural subtypes, the neuronal pathways
underlying aNGC-induced changes in frontal-motor cortical activity, and the temporal dynamics that distinguish
reflexive from the initiation of voluntary behaviors in our rodent-low arousal models. In addition, we will establish
the cortical patterns that unpack these behavioral transitions. Since pathological states of unconsciousness are
vastly heterogeneous, having a clear understanding of ordinary recovery serves to better appreciate the
variability imposed by the injury to cortical activity and behavior. Thus, we will identify how damaged neural
circuits affect established cortical activity pathways and dynamics that underlie behavior recovery. The proposed
studies are thus significant because they will establish the mechanistic correspondence, examining activation of
neural pathways and their dynamics linked to habitual and intentional behaviors that reveal novel, medically
relevant biomarkers that promote a robust inference of arousal states during emergence from anesthesia and
after brain injury.
Terms: <Acquired brain injury><Affect><Anesthesia><Anesthesia procedures><Anesthestic Drugs><Anesthetic Agents><Anesthetic Drugs><Anesthetics><Animals><Anterior><Area><Arousal><Assay><Auditory><Automobile Driving><Awareness><Behavior><Behavioral><Bioassay><Biological Assay><Biological Markers><Brain><Brain Injuries><Brain Nervous System><Brain Stem><Brainstem><COVID survivors><COVID-19 infection survivors><COVID-19 survivors><Cell Communication and Signaling><Cell Nucleus><Cell Signaling><Coma><Coma hyperglycemic><Comatose><Conscious><Consciousness><Consciousness Disorders><Cues><Decerebration procedure><Deglutition><Diabetic Coma><Doppler Ultrasound><Echography><Echotomography><Encephalon><Exhibits><Face><Fore-Brain><Forebrain><Goals><Head><Hour><Hydrogen Oxide><Image><Individual><Inhalation><Inhaling><Injury><Intracellular Communication and Signaling><Knowledge><Learning><Link><Lip><Lip structure><Locomotor Activity><Maps><Measurement><Measures><Mediating><Medical><Medical Ultrasound><Methods><Mice><Mice Mammals><Modeling><Monitor><Motor><Motor Activity><Motor Cortex><Movement><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neural Pathways><Neurocyte><Neurons><Nucleus><Pathologic><Pathway interactions><Patients><Pattern><Persons><Population><Population Dynamics><Preparation><Process><Prognosis><Prosencephalon><Public Health><QOL><Quality of life><Recovery><Reflex><Reflex action><Reporting><Rodent><Rodentia><Rodents Mammals><SARS-CoV-2 survivors><Si element><Signal Transduction><Signal Transduction Systems><Signaling><Silicon><Stimulus><Swallowing><System><Techniques><Time><Touch><Touch sensation><Ultrasonic Imaging><Ultrasonogram><Ultrasonography><Ultrasound Diagnosis><Ultrasound Medical Imaging><Ultrasound Test><Unconscious><Unconscious State><Unconsciousness><Wakefulness><Water><Work><auditory stimulus><basal forebrain><behavior response><behavioral response><bio-markers><biologic marker><biological signal transduction><biomarker><body movement><brain damage><brain-injured><consciousness loss><decerebration><deep learning><deep learning method><deep learning strategy><density><diagnostic ultrasound><driving><experiment><experimental research><experimental study><experiments><extracellular><faces><facial><frontal cortex><frontal lobe><goal oriented behavior><hypoglycemic coma><imaging><imaging system><improved><injuries><innovate><innovation><innovative><kinematic model><kinematics><motor behavior><neural><neural circuit><neural circuitry><neural mechanism><neurocircuitry><neuromechanism><neuronal><novel><optogenetics><pathway><perceptual stimulus><physicochemical phenomena related to the senses><preparations><recruit><response><restoration><sensory stimulus><sonogram><sonography><sound><sound measurement><survive COVID-19><survive SARS-CoV-2><synaptic circuit><synaptic circuitry><tactile sensation><temporal measurement><temporal resolution><time measurement><tongue base><tongue root><ultrasound imaging><ultrasound scanning>