Yuri Masaoka

Breathing rhythms and emotions

Respiration is primarily regulated for metabolic and homeostatic purposes in the brainstem. However, breathing can also change in response to changes in emotions, such as sadness, happiness, anxiety or fear. Final respiratory output is influenced by a complex interaction between the brainstem and higher centres, including the limbic system and cortical structures. Respiration is important in maintaining physiological homeostasis and co‐exists with emotions. In this review, we focus on the relationship between respiration and emotions by discussing previous animal and human studies, including studies of olfactory function in relation to respiration and the piriform–amygdala in relation to respiration. In particular, we discuss oscillations of piriform–amygdala complex activity and respiratory rhythm.

The amygdala of patients with Parkinson's disease is silent in response to fearful facial expressions.

We previously found that patients with Parkinsons disease (PD) were impaired with respect to recognition of fear and disgust in facial expressions. To investigate the neural mechanisms that underlie this impairment, we recorded visual event-related potentials (ERPs) in response to the viewing of fearful facial expressions. Ten normal elderly volunteers and nine patients with PD were studied. Fearful, surprised, and neutral facial expressions were presented randomly for 500 ms each, with a probability of 0.1, 0.1, and 0.8, respectively. The locations of the components of the ERPs were analyzed using a scalp-skull-brain/dipole tracing method. The ERPs elicited in response to the facial stimuli consisted of a negative peak (N1), two positive peaks, and a subsequent slow negative shift. For N1, the equivalent current dipoles were concentrated in the fusiform gyrus, right superior temporal gyrus, parahippocampal gyrus, cingulate cortex, and cerebellum, in normal subjects. In response to the fearful stimulus, dipoles were also generated from the amygdala in seven out of 10 normal subjects. In contrast, in patients with PD, N1 was centered bilaterally in the angular gyrus and supramarginal gyrus, and there was no neuronal activity in the amygdala. After N1, dipoles moved toward the frontal region in normal subjects, whereas they remained in the parietal lobes in patients with PD. These results suggest that neither the amygdala nor the temporal visual-associated cortices are involved in responding to fearful expressions in patients with PD. Corticostriatal connections may be variably affected by a lack of dopamine or by pathological changes in the amygdala. Thus, somatosensory recruitment may overcome the mild cognitive emotional deficits that are present in patients with PD owing to a dysfunction of the amygdala.

The effect of anticipatory anxiety on breathing and metabolism in humans

Respiratory patterns are influenced by cortical and limbic factors and generated by a complex interaction between metabolic requirements and their behavioral effects. Our previous results showed that the temporal pole and the amygdala in the limbic system are related to anxiety and associated with an increase of respiratory frequency, especially in high trait anxiety subjects. The purpose of this study was to investigate the relationship between respiratory patterns and metabolic output during the production of anticipatory anxiety. In all subjects, fR increased without changes in V(O(2)), V(CO(2)) and HR; and PET(CO(2)) decreased during anticipatory anxiety. In the subjects with high trait anxiety, the increase of fR and the decrease of TE were larger than those in the subjects with low trait anxiety. These results suggest that an increase in respiratory frequency is not related to metabolic factors and is consistent with a mechanism involving the limbic system modulating respiratory drive.

Inspiratory phase-locked alpha oscillation in human olfaction: source generators estimated by a dipole tracing method

Olfactory perception and related emotions are largely dependent on inspiration. We acquired simultaneous respiration and electroencephalographic recordings during pleasant odour and unpleasant odour stimulation. We sought to identify changes in respiratory pattern, inspiratory‐related potentials and location of dipoles estimated from the potentials. Electroencephalographic recording was triggered by inspiration onset. Respiratory frequency decreased at pleasant odour recognition, and it increased at unpleasant odour detection and recognition. O2 consumption records showed that these changes were not due to metabolic demand. During olfactory stimulation, inspiratory phase‐locked alpha oscillation (I‐α) was found in the averaged potential triggered by inspiration onset. I‐α was observed at both pleasant odour and unpleasant odour detection and recognition, but it was not seen in the inspiration‐triggered potentials of normal air breathing. Electroencephalographic dipole tracing identified the location of dipoles from the I‐α in the limbic area and the cortex; the entorhinal cortex, hippocampus, amygdala, premotor area and centroposterior orbitofrontal cortex subserve odour detection, and the rostromedial orbitofrontal cortex subserves odour recognition. We suggest that the I‐α in our study originated from the olfactory cortex in the forebrain and was phase‐locked to inspiration.

Comparison of source localization of interictal epileptic spike potentials in patients estimated by the dipole tracing method with the focus directly recorded by the depth electrodes

The purpose of the study was to investigate the accuracy of location of equivalent current dipoles estimated by the dipole tracing method (DT) utilizing a realistic 3-shell (scalp-skull-brain) head model (SSB-DT). Three patients with intractable complex partial seizures, diagnosed as having typical temporal seizures were investigated. We recorded the interictal spike potentials with surface electrodes (International 10/20 system) and with intracerebral depth electrodes simultaneously. We compared the location of dipoles of the spikes estimated by the SSB-DT with the focus of the spikes determined by the recording from the depth electrodes. We found that the location of the dipoles estimated by SSB-DT corresponded to the location of the depth electrodes, which could record the epileptic spikes. This finding proved that SSB-DT is reliable and valid for estimating neural activity in deep locations such as the limbic system.

Effects of Left Amygdala Lesions on Respiration, Skin Conductance, Heart Rate, Anxiety, and Activity of the Right Amygdala During Anticipation of Negative Stimulus:

The present study reports the effects of lesions in the left amygdala on anxiety, respiration, skin conductance, heart rate, and electrical potentials in the right amygdala in two patients. Trait and anticipatory-state anxiety were measured before and after left amygdala resection to control medically intractable epilepsy in the patients. Lesions in the left amygdala resulted in decreases of trait and state anxiety, respiratory rate, and activity in the right amygdala in both patients; one patient also showed notable decreases in skin conductance and heart rate. The study also reports that activities in the right amygdala before the lesion were not observed after the lesion. We suggest that the activity of the right amygdala is dominantly activated in anxiety and anxiety-related physiological responses but needs excitatory inputs from the left amygdala.

Impairment of odor recognition in Parkinson's disease caused by weak activations of the orbitofrontal cortex.

Olfactory dysfunction and abnormalities of olfactory brain structures are found in patients with Parkinsons disease (PD), and a number of studies have reported that olfactory dysfunction is caused by abnormalities of the central olfactory systems. We previously analyzed electroencephalograms (EEGs) and respiration simultaneously in normal subjects while testing for detection and recognition of odors. We identified changes in respiration pattern in response to odor stimuli and found inspiratory phase-locked alpha oscillations (I-alpha). The genesis of I-alpha were identified in olfactory-related areas including the entorhinal cortex, hippocampus, amygdale and orbitofrontal cortex with an EEG dipole tracing method. In the present study, we used the same protocol in PD patients and compared results of PD with those of age-matched controls. All PD patients detected odor, but 5 out of 10 showed impaired odor recognition. Changes in breathing pattern associated with emotional changes during exposure to odor stimuli were not observed in PD patients. I-alpha waveforms were not observed; however, positive waves followed by negative waves were identified approximately 100ms after inspiration onset. Dipoles of this component were localized in the entorhinal cortex for odor detection in all patients and in the entorhinal cortex and middle temporal gyrus for PD patients who could discriminate odors. Odor recognition in PD could be subserved by a different neural circuit from that of normal subjects, done through the temporal association cortex as a subsystem for recognizing the odor; however, the system may not be associated with the odor-induced emotions.

Slow Breathing and Emotions Associated with Odor-Induced Autobiographical Memories

An important feature of olfactory perception is its dependence on respiratory activity. By inspiration, olfactory information ascends directly to olfactory-related limbic structures. Therefore, every breath with odor molecules activates these limbic areas associated with emotional experience and memory retrieval. We tested whether odors associated with autobiographical memories can trigger pleasant emotional experiences and whether respiration changes during stimulation with these odors. During presentation of odors related to autobiographical memories and control odors, we measured minute ventilation, tidal volume, respiratory frequency, O2 consumption, and end tidal CO2 concentration. Findings showed that autobiographical memory retrieval was associated with increasing tidal volume and decreasing respiratory frequency more than during presentation of control odors. Subjective feelings such as emotional arousal during retrieval of the memory, arousal level of the memory itself, or pleasantness and familiarity toward the odor evoked by autobiographical memory were more specific emotional responses compared with those related to control odors. In addition, high trait anxiety subjects responded with a stronger feeling of being taken back in time and had high arousal levels with tidal volume increases. We discussed assumptions regarding how deep and slow breathing is related to pleasantness and comfortableness of an autobiographical memory.

Amygdala and emotional breathing in humans

According to many reports the amygdala plays a role in fear, attention and anxiety1. In addition to these emotional roles, the amygdala which is involved in the conditioning process projects to many anatomical areas to elicit physiological responses such as blood pressure elevation, skin conductance response and respiration as well as behavioral responses such as freezing and facial expression of fear. In an awake state, the amygadala evaluates a variety of environmental stimuli to determine whether the stimulation is harmful or safe; if it is harmful, the amygdala immediately elicits emotions of fear and anxiety simultaneously with physiological changes. In other words, measuring physiological responses could be an index to determine the level of emotion occurred in a situation.

Remembering the past with slow breathing associated with activity in the parahippocampus and amygdala

Breathing plays an important role in perception of odors and the experience of emotions. We used the dipole tracing method to analyze brain areas related to odor-induced autobiographical memory and emotions estimated from averaged electroencephalograms triggered by inspiration onset during odor presentation. Odor stimuli were perfumes subjects named that elicited a specific, pleasant and personal memory as well as two pleasant odors for controls. The perfumes induced specific emotional responses during memory retrieval, arousal level of the memory, feelings of pleasantness and a sense of familiarity with the odor. Respiration measurement indicated that tidal volume increased and respiratory frequency decreased during presentation of perfume stimuli, showing a deep and slow breathing pattern. Throughout the olfactory stimulation, electroencephalograms and respiration were simultaneously recorded. In the averaged potentials, low frequency oscillation was phase-locked to inspiration. Dipole analysis showed that perfumes activated more widespread areas of the right parahippocampal cortex and converged in the right amygdala compared to control odors. Slow breathing synchronized with odor-induced autobiographical memory and emotions may be subconsciously stored in the parahippocampal cortex and amygdala.