Respiratory influences on pupil size dynamics and visual recognition memory

Breathing, a fundamental rhythm of life, has traditionally been associated with the exchange of oxygen and carbon dioxide. However, recent research in both animal models and humans has unveiled additional roles of respiration in modulating cortical neuronal activity, influencing sensory, motor, emotional, and cognitive processes. This dissertation aims to explore the impact of respiration on pupil size dynamics and visual recognition memory in humans. In Study I, we synthesized the research conducted on respiratory influences on pupil size dynamics in humans by conducting a systematic literature review. We discovered that the evidence for respiratory influences on pupil size dynamics in humans is less solid and extensive than previously believed. After more than 50 years of research, only 12 studies have directly investigated this topic. Not only was the underlying evidence for an effect of breathing phase, depth, and rate on pupil size dynamics weak, but the influence of breathing route (oral or nasal breathing) had not been investigated at all. In Study II, we conducted an experimental study to answer the outstanding questions identified in Study I. We collected pupil size data from participants during periods of rest while they breathed through their nose and mouth, on separate occasions. We demonstrated small but significant effects of breathing phase on pupil size and a spurious correlation and phase synchronization between the breathing and the pupil signal that is largely driven by breathing rate. After accounting for this spurious correlation and phase synchronization, we show that a small but significant interaction between the breathing and the pupil signal remains. Importantly, we show that, contrary to common belief, pupil size does not increase during inhalation, but rather during exhalation. Furthermore, we did not find any changes in pupil size in the time around inhalation and exhalation, and our results were not affected by the breathing route. In conclusion, we confirmed the influence of breathing on pupil size dynamics, while uncovering a more complex and intricate relationship than previously conceived. In Study III, we investigated the influence of breathing phase and breathing route on performance in a visual recognition memory task with a within-subject design and with stimuli presentation phase-locked to the inhalation or exhalation onset. We show that neither breathing phase nor breathing route affect memory performance. However, we did find an effect of breathing phase on response bias, with participants using a more conservative response bias during exhalation. Furthermore, we found that breathing route and breathing phase shape the Late Parietal Effect (LPE), but not the Frontal Negative Component (FN400), amplitude during encoding. Additionally, during recognition, both the LPE and FN400 component amplitudes were not, or only to a small extent, affected by breathing route and phase. While we demonstrated that breathing does not shape visual recognition memory performance, we also showed that breathing influences brain activity related to memory functions. Therefore, we highlight the importance of further research to elucidate the extent of respiratory influence on perception, cognition, and behavior. In Study IV, we further investigated the impact of breathing on visual memory performance by investigating the effects of nasal breathing phase on memory of repeated images presented in a rapid serial visual presentation (RSVP) task. In two separate, high-powered experiments, we did not find an effect of breathing phase on task performance. An exploratory analysis in the first experiment discovered a potential performance increase for stimuli presented approximately one second after inhalation. However, this was not replicated in the second, larger, and pre-registered study. Thus, we find no effect of breathing phase on performance in this RSVP task and urge for caution regarding the notion that visual memory is broadly affected by the breathing phase. Finally, in Study V, we investigated whether oral hormonal contraceptives (OC) affect chemosensory sensitivity and perception. Whereas previous research focused nearly exclusively on olfaction, we expanded this to also study the taste and trigeminal sense. Making use of Bayesian statistics, we evaluated the performance differences between a group of women taking OC, and a control group of normal cycling women. Our results indicated that the use of OC does not affect odor, trigeminal, or taste detection thresholds. Furthermore, neither odor nor taste perception were affected, with Bayes factors weighing the evidence in favor of the null hypothesis. We therefore conclude it to be unlikely that OC affect chemosensory perception to a degree that is of behavioral relevance. Collectively, this doctoral thesis challenges prevailing myths while paving the way for a more intricate understanding of the relationship between respiration and pupil size, and perceptual and cognitive processes. Importantly, it underscores the importance of implementing rigorous methodological paradigms in future research

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 165, March 1977

This bibliography lists 198 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1977

Oscillatory architecture of memory circuits

The coordinated activity between remote brain regions underlies cognition and memory function. Although neuronal oscillations have been proposed as a mechanistic substrate for the coordination of information transfer and memory consolidation during sleep, little is known about the mechanisms that support the widespread synchronization of brain regions and the relationship of neuronal dynamics with other bodily rhythms, such as breathing. During exploratory behavior, the hippocampus and the prefrontal cortex are organized by theta oscillations, known to support memory encoding and retrieval, while during sleep the same structures are dominated by slow oscillations that are believed to underlie the consolidation of recent experiences. The expression of conditioned fear and extinction memories relies on the coordinated activity between the mPFC and the basolateral amygdala (BLA), a neuronal structure encoding associative fear memories. However, to date, the mechanisms allowing this long-range network synchronization of neuronal activity between the mPFC and BLA during fear behavior remain virtually unknown. Using a combination of extracellular recordings and open- and closed-loop optogenetic manipulations, we investigated the oscillatory and coding mechanisms mediating the organization and coupling of the limbic circuit in the awake and asleep brain, as well as during memory encoding and retrieval. We found that freezing, a behavioral expression of fear, is tightly associated with an internally generated brain state that manifests in sustained 4Hz oscillatory dynamics in prefrontal-amygdala circuits. 4Hz oscillations accurately predict the onset and termination of the freezing state. These oscillations synchronize prefrontal-amygdala circuits and entrain neuronal activity to dynamically regulate the development of neuronal ensembles. This enables the precise timing of information transfer between the two structures and the expression of fear responses. Optogenetic induction of prefrontal 4Hz oscillations promotes freezing behavior and the formation of long-lasting fear memory, while closed-loop phase specific manipulations bidirectionally modulate fear expression. Our results unravel a physiological signature of fear memory and identify a novel internally generated brain state, characterized by 4Hz oscillations. This oscillation enables the temporal coordination and information transfer in the prefrontal-amygdala circuit via a phase-specific coding mechanism, facilitating the encoding and expression of fear memory. In the search for the origin of this oscillation, we focused our attention on breathing, the most fundamental and ubiquitous rhythmic activity in life. Using large-scale extracellular recordings from a number of structures, including the medial prefrontal cortex, hippocampus, thalamus, amygdala and nucleus accumbens in mice we identified and characterized the entrainment by breathing of a host of network dynamics across the limbic circuit. We established that fear-related 4Hz oscillations are a state-specific manifestation of this cortical entrainment by the respiratory rhythm. We characterized the translaminar and transregional profile of this entrainment and demonstrated a causal role of breathing in synchronizing neuronal activity and network dynamics between these structures in a variety of behavioral scenarios in the awake and sleep state. We further revealed a dual mechanism of respiratory entrainment, in the form of an intracerebral corollary discharge that acts jointly with an olfactory reafference to coordinate limbic network dynamics, such as hippocampal ripples and cortical UP and DOWN states, involved in memory consolidation. Respiration provides a perennial stream of rhythmic input to the brain. In addition to its role as the condicio sine qua non for life, here we provide evidence that breathing rhythm acts as a global pacemaker for the brain, providing a reference signal that enables the integration of exteroceptive and interoceptive inputs with the internally generated dynamics of the hippocampus and the neocortex. Our results highlight breathing, a perennial rhythmic input to the brain, as an oscillatory scaffold for the functional coordination of the limbic circuit, enabling the segregation and integration of information flow across neuronal networks

Nasal respiration is necessary for ketamine-dependent high frequency network oscillations and behavioral hyperactivity in rats

Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130–180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked “fast” theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to “fast” theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were coherent with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. These findings suggest that nasal airflow entrains ketamine-dependent HFO in diverse brain regions, and that the OB plays an important role in the broadcast of this rhythm

Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG)

The International Pharmaco-EEG Society (IPEG) presents updated guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-EEG data in man. Since the publication of the first pharmaco-EEG guidelines in 1982, technical and data processing methods have advanced steadily, thus enhancing data quality and expanding the palette of tools available to investigate the action of drugs on the central nervous system (CNS), determine the pharmacokinetic and pharmacodynamic properties of novel therapeutics and evaluate the CNS penetration or toxicity of compounds. However, a review of the literature reveals inconsistent operating procedures from one study to another. While this fact does not invalidate results per se, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. Moreover, this shortcoming hampers reliable comparisons between outcomes of studies from different laboratories and hence also prevents pooling of data which is a requirement for sufficiently powering the validation of novel analytical algorithms and EEG-based biomarkers. The present updated guidelines reflect the consensus of a global panel of EEG experts and are intended to assist investigators using pharmaco-EEG in clinical research, by providing clear and concise recommendations and thereby enabling standardisation of methodology and facilitating comparability of data across laboratories

Statistical learning for the analysis of multimodal sleep in older men

Introduction: Sleep is essential for human development and maintaining physical and mental health. Sleep disturbances have long been known to be associated with mental illness, metabolic, neurological or other systems diseases. Knowing what factors are associated with sleep quality and sleep-wake homeostasis is important for the study of sleep disorders and may potentially inform new treatment strategies to preserve patients' normal sleep-wake cycle. The present study aims to identify what actigraphic measures, self-reported sleep variables, and other chronic diseases, medications are related to the percentage of slow-wave sleep and delta power spectra in older men. Method: Categorical variables are summarized using frequencies and percentages. For continuous variables, means and standard deviations are computed, and distributions are displayed in histograms. Possible correlations among variables are examined by a matrix of scatterplots and Pearson correlation coefficients. The LASSO is used for feature selection in multiple linear regression models and multiple imputation used to overcome missing data. Results: The past month sleep hours (β=0.0896, p<0.05), kidney diseases (β=0.161, p<0.05) and oral corticosteroids (β=0.148, p<0.05) are significantly positively associated with percentage of deep sleep, while sleep apnea severity (β=-0.0043, p<0.001), age ( = -0.0042, p<0.01), Benzodiazepine use ( -0.155, p<0.001), NSAIDS use (β=-0.0418, p<0.05), and race(β=-0.0476, p<0.01) are negatively associated when controlling other variables’ effect. Cognitive function (β=0.0015, p<0.001), and oral corticosteroids (β=0.0733, p<0.01) are positively related to delta power, while sleep apnea severity (β=-0.0011, p<0.001), age ( = -0.0013, p<0.05), mean sleep minutes (-0.0002, p<0.001) , BMI (-0.031, p<0.001), Diabetes (β=-0.0404, p<0.001), Benzodiazepine use ( -0.061, p<0.001), and the consumption of alcoholic beverages (β=-0.0125, p<0.05) are negatively related to delta power when controlling other covariates. Conclusions: Our study suggested several factors are either positively or negatively associated with the percentage of deep sleep and delta power. Most of the factors affect the percentage of slow-wave sleep and delta power in the same direction. Public Health Significance: These analyses may provide important messages for future study and potential medical interventions application

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 130, July 1974

This special bibliography lists 291 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1974

A longitudinal study of cortical EEG to olfactory stimulation : involving inter- and intra- subjective responses

This thesis forms the largest and most systematic study of the topographical EEG response to odour. The evolutionary history of the olfactory sense is briefly presented and its relevance to humans in the present day is considered. This thesis examines the information processing that occurs in this sensory system. The type of processing that the olfactory system utilises at each anatomical stage is discussed. The character of olfactory information that may reach neocortical levels in humans is considered in the light of the technology available to detect such information. The neurogenesis of the EEG is considered, together with questions concerning its postulated functional significance. The empirical work carried out uses the most advanced methodology for this type of study. The large number of odourants and subjects, combined with the longitudinal element, make this the most ambitious study of this nature undertaken. The issues surrounding the analysis and interpretation of EEG data arc fully discussed and the impact of Chaos theory is considered. Five major analysis techniques were used on the data collected, but largely negative findings arc reported. The reasons for the failure of this experimental paradigm are discussed and improvements arc suggested for future work. The major contribution of this thesis lies in its exploration of the assumptions of the EEG response to odour. The thesis notes the lack of a conceptual framework that has hindered progress in the area of the "odour" EEG. Recent developments in neural network theory and Chaos theory are highlighted as possible alternative approaches to the modelling and understanding of the olfactory system

Aerospace medicine and biology. A continuing bibliography with indexes, supplement 186

This bibliography lists 159 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System in October 1978