Periodic Reporting for period 1 - ConscBreathDynamics (Breathing dynamics in health and disease: how consciousness shape respiratory patterns)
Periodo di rendicontazione: 2020-03-01 al 2022-02-28
Breathing is a vital physiological process essential to human survival, and as expected from such an important function it occurs automatically without the requirement of conscious control. Nonetheless, breathing automatisms can be consciously modified, and is regularly modulated by our conscious experience and consciousness state. However, it remains unclear how consciousness shapes our breathing. In this research project, we employ an interdisciplinary approach, combining basic and clinical neuroscience in order to tackle this fundamental question.
Breathing, despite its deceptive simplicity, is a highly complex behaviour influenced by a variety of external and internal factors. For example, sniff volume decreases after encountering a skunk and increases when smelling fresh bread; Inhalation/Exhalation ratio is altered during speech production, and when playing a wind instrument; Breath magnitude is modified by a melancholy sigh, a scream of fear or a yawn. Respiratory patterns are also highly influenced by consciousness state, presenting an erratic structure during rapid eye movement (REM) sleep and a more regular form in deep non-rapid eye movement (NREM) sleep. This versatile respiratory repertoire results from a combination of conscious and unconscious processes regulating breathing, and is enabled by a dual neural control involving a constant interplay between subcortical and cortical networks. Unconscious automatic breathing is controlled by well-characterized subcortical brainstem respiratory centers. Conscious regulation of breathing, however, and the interaction between involuntary and voluntary respiration control remains unclear. The goal of our research is to characterize the interaction between breathing dynamics and consciousness, and to elucidate the brain mechanism underlying conscious regulation of breathing.
Disorders of consciousness (DoC) offer a unique model to investigate conscious regulation of breathing. DoC resulting from severe brain injury can range from no signs of awareness in vegetative state (VS), also known as unresponsive wakefulness syndrome (UWS), to inconsistent but purposeful and reproducible evidence of conscious awareness in a minimally conscious state (MCS). Notably, DoC can be a chronic condition lasting for many years or an acute reversible state in which patients can gain partial or full consciousness. Thus, DoC offer a rare opportunity to track breathing dynamics during recovery of consciousness and between consciousness states.
Additionally, evidence for conscious control of breathing could be highly beneficial for awareness detection in DoC. Detection of awareness in DoC patients remains one of the most challenging clinical tasks. Misdiagnosis between UWS and MCS has significant therapeutic, ethical and financial implications, and influences end-of-life decisions. We hypothesized that breathing dynamics governed by both autonomic and voluntary control may offer a meaningful indicator for conscious awareness in DoC patients. The specific aims of the proposed research are to:
1) Characterize the relationship between breathing dynamics and consciousness state.
2) Elucidate the neural mechanism underlying conscious control of breathing dynamics.
3) Investigate whether breathing dynamics can be used as an indicator for awareness in DoC patients.
Breathing, despite its deceptive simplicity, is a highly complex behaviour influenced by a variety of external and internal factors. For example, sniff volume decreases after encountering a skunk and increases when smelling fresh bread; Inhalation/Exhalation ratio is altered during speech production, and when playing a wind instrument; Breath magnitude is modified by a melancholy sigh, a scream of fear or a yawn. Respiratory patterns are also highly influenced by consciousness state, presenting an erratic structure during rapid eye movement (REM) sleep and a more regular form in deep non-rapid eye movement (NREM) sleep. This versatile respiratory repertoire results from a combination of conscious and unconscious processes regulating breathing, and is enabled by a dual neural control involving a constant interplay between subcortical and cortical networks. Unconscious automatic breathing is controlled by well-characterized subcortical brainstem respiratory centers. Conscious regulation of breathing, however, and the interaction between involuntary and voluntary respiration control remains unclear. The goal of our research is to characterize the interaction between breathing dynamics and consciousness, and to elucidate the brain mechanism underlying conscious regulation of breathing.
Disorders of consciousness (DoC) offer a unique model to investigate conscious regulation of breathing. DoC resulting from severe brain injury can range from no signs of awareness in vegetative state (VS), also known as unresponsive wakefulness syndrome (UWS), to inconsistent but purposeful and reproducible evidence of conscious awareness in a minimally conscious state (MCS). Notably, DoC can be a chronic condition lasting for many years or an acute reversible state in which patients can gain partial or full consciousness. Thus, DoC offer a rare opportunity to track breathing dynamics during recovery of consciousness and between consciousness states.
Additionally, evidence for conscious control of breathing could be highly beneficial for awareness detection in DoC. Detection of awareness in DoC patients remains one of the most challenging clinical tasks. Misdiagnosis between UWS and MCS has significant therapeutic, ethical and financial implications, and influences end-of-life decisions. We hypothesized that breathing dynamics governed by both autonomic and voluntary control may offer a meaningful indicator for conscious awareness in DoC patients. The specific aims of the proposed research are to:
1) Characterize the relationship between breathing dynamics and consciousness state.
2) Elucidate the neural mechanism underlying conscious control of breathing dynamics.
3) Investigate whether breathing dynamics can be used as an indicator for awareness in DoC patients.
1) Respiration dynamics at rest:
We collected and analysed nasal respiration recording from DoC patients. Specifically, we analysed a short nasal respiration of DoC patients’ dataset (146 sessions of ~30 minutes each) previously collected, a long nasal respiration DoC patients’ dataset (86 sessions of up to 24 hours) we collected and long nasal respiration healthy participants’ dataset (33 sessions of up to 24 hours) previously collected. The 24-hour data recordings were done using a small portable device including a nasal cannula connected to a pressure sensor. The analysis of the above-mentioned datasets revealed differences in breathing dynamics between:
a) DoC patients and healthy participants.
b) Conscious (MCS) and unconscious (UWS/VS) DoC patients.
c) Unconscious patients (UWS/VS) who remain unconscious and recovered consciousness.
d) DoC patients who deceased and DoC patients who survived.
2) Elucidate the neural mechanism underlying conscious control of breathing dynamics: We designed an experimental procedure intended to modulate respiration using multimodal paradigms: i) An olfactory passive task, which does not require conscious awareness to the stimuli, included the presentation of a pleasant and an unpleasant odors and clear air. ii) A visual-auditory task, which requires conscious awareness to the stimuli but not to the respiration modulation itself, included short engaging video clips. Simultaneous EEG, respiration, EKG and eye-tracking data was collected from healthy participants during the visual-audio paradigm, and the olfactory paradigm. Preliminary results of the olfactory passive task identify a few olfactory discriminatory respiratory modulation patterns of either increased or decreased inhalation volume relative to baseline. Preliminary results of the visual-audio task identify specific video clips with higher probability to modulate respiration. Currently, in parallel to the respiration analysis we investigate the EEG activity in response to respiration modulation. Data collection in DoC patients will be based on the findings in healthy participants.
3) Breathing dynamics as an indicator for awareness in DoC patients:
We collected longitudinal data from 18 DoC patients in multiple sessions (range 2 to 17). The number of sessions per patient depended on the patient’s medical condition and availability. Preliminary results suggest an evolution in the olfactory-induced respiratory response during consciousness recovery. We observed an initial increase in variably, followed by a non-discriminatory response, followed by a discriminatory response.
Exploitation and dissemination:
These results have been presented in multiple international and local meetings. In addition, these results are currently being prepared into two manuscripts which will be submitted to peer reviewed Open Access journals.
We collected and analysed nasal respiration recording from DoC patients. Specifically, we analysed a short nasal respiration of DoC patients’ dataset (146 sessions of ~30 minutes each) previously collected, a long nasal respiration DoC patients’ dataset (86 sessions of up to 24 hours) we collected and long nasal respiration healthy participants’ dataset (33 sessions of up to 24 hours) previously collected. The 24-hour data recordings were done using a small portable device including a nasal cannula connected to a pressure sensor. The analysis of the above-mentioned datasets revealed differences in breathing dynamics between:
a) DoC patients and healthy participants.
b) Conscious (MCS) and unconscious (UWS/VS) DoC patients.
c) Unconscious patients (UWS/VS) who remain unconscious and recovered consciousness.
d) DoC patients who deceased and DoC patients who survived.
2) Elucidate the neural mechanism underlying conscious control of breathing dynamics: We designed an experimental procedure intended to modulate respiration using multimodal paradigms: i) An olfactory passive task, which does not require conscious awareness to the stimuli, included the presentation of a pleasant and an unpleasant odors and clear air. ii) A visual-auditory task, which requires conscious awareness to the stimuli but not to the respiration modulation itself, included short engaging video clips. Simultaneous EEG, respiration, EKG and eye-tracking data was collected from healthy participants during the visual-audio paradigm, and the olfactory paradigm. Preliminary results of the olfactory passive task identify a few olfactory discriminatory respiratory modulation patterns of either increased or decreased inhalation volume relative to baseline. Preliminary results of the visual-audio task identify specific video clips with higher probability to modulate respiration. Currently, in parallel to the respiration analysis we investigate the EEG activity in response to respiration modulation. Data collection in DoC patients will be based on the findings in healthy participants.
3) Breathing dynamics as an indicator for awareness in DoC patients:
We collected longitudinal data from 18 DoC patients in multiple sessions (range 2 to 17). The number of sessions per patient depended on the patient’s medical condition and availability. Preliminary results suggest an evolution in the olfactory-induced respiratory response during consciousness recovery. We observed an initial increase in variably, followed by a non-discriminatory response, followed by a discriminatory response.
Exploitation and dissemination:
These results have been presented in multiple international and local meetings. In addition, these results are currently being prepared into two manuscripts which will be submitted to peer reviewed Open Access journals.
We combined state-of-the-art methods including neuroimaging, physiology and behaviour analyses to uncover the links between breathing dynamics and consciousness state. The results of this work suggest that respiratory patterns may signal consciousness state, recovery of consciousness and survival in DoC patients and could provide a bedside tool to improve diagnosis and prognosis following severe brain injury.
Additionally, our research topic can be used to support societal discussion on ethical aspects of end-of-life decision, and well-being of patients and their caregivers.
The project has provided extensive training opportunities for the researcher, and enabled further funding opportunities for the researcher and the host lab. Progress thanks to the project: two manuscripts are in the process of being written and submitted to top peer reviewed Open Access journals.
Additionally, our research topic can be used to support societal discussion on ethical aspects of end-of-life decision, and well-being of patients and their caregivers.
The project has provided extensive training opportunities for the researcher, and enabled further funding opportunities for the researcher and the host lab. Progress thanks to the project: two manuscripts are in the process of being written and submitted to top peer reviewed Open Access journals.