We have a few main research directions. We study the human sense of smell, how smells are represented in the brain, how breathing affects brain activity, how brain activity affects breathing, and how brain oscillations affect cognition.
Human Olfaction and respiratory oscillations:
We use a combination of intracranial electroencephalography (iEEG), functional neuroimaging and psychophysics to study how odors are coded in the human brain. Because olfactory sampling is tightly linked to respiration, a large part of this effort involves measuring and analyzing respiratory oscillations in human olfactory and limbic brain regions. Using iEEG, we study the spectral and temporal properties of local field potential oscillations in response to odor stimuli in human olfactory cortex, orbitofrontal cortex, amygdala, hippocampus and other medial limbic brain regions. Using functional neuroimaging, we use multivariate pattern analyses and ROI-based time series analyses to study the functional and anatomical underpinnings of olfactory processing across the entire brain. Psychophysics allows us to study behavioral responses to smells and relate them to brain activity.
Example of sniff-locked oscillatory power increases recorded from human piriform cortex:
Conscious control of respiration:
Given the strong link between olfaction and breathing, we are interested in understanding the neural mechanisms underlying intentional respiratory control, and how these mechanisms relate to olfactory sampling (sniffing). The autonomic nervous system acts largely unconsciously to regulate bodily functions such as heart rate, digestion, respiratory rate and pupillary response. Unlike most autonomic functions, respiration is highly susceptible to conscious intentional manipulation.
Recent data from our lab indicate a role for the medial human amygdala in control of breathing. We found that local field potential power, measured from depth wires inside the amygdala, is enhanced upon inhalation during natural breathing, and electrical stimulation directed into the amygdala induces apnea. We are using a combination of functional neuroimaging, Diffusion tensor imaging and iEEG methods to better understand how intentional control of breathing is achieved by the human brain.
On the left, spectrograms from human amygdala during natural breathing show increased LFP power during inhalation, only during nasal breathing. On the right, electrical stimulation of the human amygdala induces hypopnea.
Fear related response times across the respiratory cycle:
Based on observed respiratory entrainment of LFPs in human amygdala combined with the amygdala’s role in threat detection and face processing, we looked for respiratory modulations in response to faces expressing fear. We have found that fear-specific respiratory modulations are predictive of individual subjects’ levels of state anxiety.
Sudden unexpected death in epilepsy (SUDEP):
A deeper understanding of human respiratory regulation is important, particularly in relation to patients with epilepsy, given its potential relevance to Sudden unexpected death in epilepsy (SUDEP). SUDEP is the most frequent cause of death in epilepsy patients, with accumulating evidence suggesting respiratory involvement. In 16 SUDEP cases that occurred in epilepsy monitoring units across the world, a consistent sequence of events was observed after each seizure that resulted in SUDEP: rapid breathing followed the generalized tonic-clonic seizure, followed by apnea, followed by increasing bradycardia and postictal generalized electroencephalogram suppression with terminal apnea preceding the terminal asystole. Thus in all recorded cases of SUDEP, the initial pathological symptom consisted of respiratory dysfunction. One possibility is that seizures spreading to brain structures involved in higher order control of brainstem function can lead to SUDEP. The extended amygdala, comprising chiefly of the central amygdala and the bed nucleus of the stria terminalis, is a part of the central autonomic network that is interconnected between higher order cortical areas, brainstem, and hypothalamic networks raising the possibility that it could be the missing link in the mediation of SUDEP. The central amygdala is activated by seizures, and its activation can have powerful effects on heart rate, blood pressure and respiratory function. Furthermore, extended amygdala projections reach areas that are important for control of cardiorespiratory function including the nucleus of the solitary tract and the ventrolateral medulla. Studies from our lab have found that electrical stimulation of the human amygdala induces apnea. We have also recently found that stimulation-induced apnea can be prevented in two ways. First, electrical stimulation delivered during mouth breathing does not induce any apnea. Second, if we directly instruct the patient to take a breath during electrical stimulation, the patient can overcome the apnea and is able to breathe. We hope this research may lead to new avenues of research into the prevention of SUDEP.