We use a combination of intracranial electroencephalography (iEEG), surface EEG, functional neuroimaging and psychophysics to study how odors are coded in the human brain. Using iEEG, we study the spectral properties of local field potential (LFP) responses to odor stimuli in human olfactory cortex, orbitofrontal cortex, amygdala, hippocampus and other medial limbic brain regions. Using neuroimaging, we can study odor responses across the entire brain. Psychophysics allows us to study behavioral responses to smells and relate them to brain activity.
Auditory Cortex: Olfactory Cortex:
Spectrograms computed using iEEG data from seven subjects who participated in an olfactory target search task are shown above. Targets were auditory cues delivered prior to any odor delivery (CUE), and sniffs of odor occurred 5 to 10 seconds later (SNIFF). Trials could be aligned to the cue or the sniff. On the left, data from auditory cortex shows a robust response to the auditory cue, with no clear response to the odor. On the right, data from olfactory cortex shows a theta range response to the auditory cue prior to the presence of any odor, and a robust odor related response following sniffing. Phase locking was evident in the theta band between olfactory and auditory cortices following cue presentation.
Conscious control of respiration:
Given the strong link between olfaction and breathing, we are interested in understanding the neural mechanisms underlying intentional respiratory control. 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. While we have a good understanding of the neural mechanisms underlying autonomic respiratory control, very little is known about conscious control of breathing in humans.
Recent data from our lab indicate a role for the 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 understand how intentional control of breathing is achieved by the human brain.
Fear related response times across the respiratory cycle:
In addition to respiratory-related changes in amygdala activity and amygdala stimulation-induced apnea, experiments from our lab have found that fearful faces are recognized more quickly when encountered during inhalation compared to exhalation. The importance of the amygdala in fear processing combined with its potential role in breathing combine to suggest the possibility for fear-related changes in breathing. Preliminary evidence suggests that individuals with high anxiety scores have a different pattern of breathing than those with low anxiety scores following presentation of fearful faces compared to surprised faces. We found that when fearful faces are presented to anxious individuals when they are inhaling, the subsequent exhale is shallower compared to their typical exhales. We also found that when fearful faces are presented to anxious individuals when they are exhaling, the subsequent inhale is deeper compared to their typical inhales. Overall, When grouping subjects by anxiety scores, we found that faster fearful response times during inhalation are only evident in subjects with “low anxiety”. The effect diminishes in subjects with higher anxiety scores. We are conducting a number of psychophysical experiments to probe these effects. Our findings can potentially be used as a simple biomarker for anxiety and support the idea that respiratory phase may influence how stimuli are processed and reacted to.
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 are working to develop a SUDEP alarm device that can prevent respiratory arrest in patients who are at high risk of SUDEP, based on these data.
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