Title: Investigating the Neural and Cerebrovascular Effects of the Wim Hof Breathing Technique: Implications for Glymphatic Function and Brain Waste Clearance

1. Overview

Scientific Rationale and Importance: The Wim Hof breathing technique (WHBT)—characterized by repeated cycles of hyperventilation, breath retention, and focused awareness—has demonstrated effects on autonomic function, inflammation, and stress modulation^1,2. Recent research highlights a potential link between respiratory patterns, cerebral blood flow (CBF), and cerebrospinal fluid (CSF) dynamics, both of which contribute to the glymphatic system, a key mechanism for clearing metabolic waste from the brain^3-6. Disruption in glymphatic clearance has been implicated in neurodegenerative disorders such as Alzheimer’s disease^7-11.

Recent work demonstrates that cerebral blood flow (CBF) and respiration patterns directly influence CSF dynamics^12-14. As such, WHBT may represent a non-invasive behavioral method to enhance glymphatic function, potentially offering neuroprotective effects and improvements in mental health.

This study seeks to establish the link between WHBT, neural activity, glymphatic-associated CSF dynamics, and cerebral perfusion, and to determine how these physiological changes are related to psychological outcomes including depression, anxiety, and subjective well-being.

If successful, this project will:

Elucidate the brain clearance mechanisms modulated by WHBT
Provide a foundation for using breath-based interventions to enhance brain health and emotional regulation
Offer novel insights into non-pharmacological prevention strategies for aging and neuropsychiatric disorders

This study will use multimodal functional magnetic resonance imaging (fMRI) to investigate how WHBT modulates neural and physiological processes underlying glymphatic function. Specifically, we will measure:

Resting-state functional connectivity via BOLD fMRI
Cerebrospinal fluid flow dynamics using CSF-sensitive sequences
Quantitative cerebral blood flow (CBF) and CSF measurements using using Arterial Spin Labeling (ASL) before, during and after WHBT near the lateral and medial ventricles including the choroid plexus.
Changes in resting perfusion and CSF rates relative to baseline, as a direct physiological outcome of the breathing intervention

We hypothesize that WHBT will lead to increased resting cerebral perfusion and altered CSF flow patterns immediately post-intervention, indicating enhanced neurovascular and glymphatic activity. These findings could offer a mechanistic basis for using breathwork as a non-pharmacological intervention for brain health.

This study is the first to apply a multimodal MRI approach to investigate the effects of WHBT on:

Resting-state functional connectivity
Cerebral blood flow (CBF) and CSF using arterial spin labeling (ASL)
CSF dynamics and glymphatic-relevant pathways
Psychological well-being and affective functioning

Key innovative features include:

Use of pre-post intervention ASL scans to quantify changes in resting perfusion, a likely driver of glymphatic flow.
Integration of CSF flow markers and functional connectivity, using ASL fMRI, to assess global brain clearance and network-level effects.
Direct measurement of psychological outcomes (depression, anxiety, well-being) to relate physiological changes to mental health status, bridging basic neuroscience and clinical relevance.

The study will be conducted by Dr. Fadel Zeidan, Professor of Anesthesiology at the University of California San Diego (UCSD), utilizing a 3T MRI scanner with BOLD and diffusion-weighted sequences, arterial spin labeling perfusion fMRI including specialized imaging protocols for CSF dynamics. Institutional Review Board (IRB) approval are currently under review and all participants will provide informed consent in accordance with ethical guidelines for human subjects research.

Estimated Timeline

Months 1–3: Finalize protocol, hire staff, and begin participant recruitment
Months 4–12: Data collection (target N = ~20 healthy adults with and without experience in the WHBT)
Months 13–15: Data preprocessing and quality control
Months 16–19: Statistical and connectivity analyses
Months 20–24: Manuscript preparation and dissemination of results

Data Sharing: In alignment with open science principles, de-identified imaging and behavioral data will be shared via the OpenNeuro platform upon publication. The preprocessed and raw data, along with analysis scripts (e.g., in FSL and Python), will be documented and made accessible to promote reproducibility and secondary analysis.

2. Introduction

The Wim Hof breathing technique (WHBT) is a voluntary, cyclic breathing practice involving hyperventilation and breath-holding, often combined with cold exposure and meditative focus. While anecdotal evidence and early research suggest that WHBT improves stress resilience and immune function^1,15,16, its neurobiological underpinnings remain unclear. There is a growing interest in how volitional breath control can influence central autonomic pathways, cerebral blood flow (CBF), and potentially the glymphatic system—a CSF-mediated waste clearance system in the brain ^{3,4,6-8,17,18}.

The glymphatic system is tightly regulated by vascular pulsatility, respiration, and arousal states ^3,6,17. Given that WHBT produces substantial changes in respiratory and autonomic tone, it may serve as a behavioral intervention to enhance glymphatic clearance, which is crucial for removing metabolic byproducts like amyloid-β and tau—proteins implicated in Alzheimer's and other neurodegenerative diseases.

Moreover, cerebral perfusion is a known driver of glymphatic flow. Techniques like arterial spin labeling (ASL) MRI allow non-invasive measurement of resting CBF, making it feasible to examine vascular-glymphatic coupling in humans. Psychological benefits of WHBT—such as reduced depression and anxiety and increased well-being—have been observed but whether these effects are linked to physiological changes in brain perfusion and waste clearance remains unknown.

Hypotheses

H1: Wim Hof breathing will increase resting cerebral perfusion (CBF) as measured by arterial spin labeling (ASL), particularly in regions associated with autonomic and cognitive-emotional regulation (e.g., medial prefrontal cortex, anterior insula, thalamus, and brainstem). Increased perfusion is expected to facilitate glymphatic fluid exchange by enhancing perivascular and CSF pulsatility.

H2: Wim Hof breathing will produce measurable changes in CSF dynamics, as indicated by alterations in MRI signal intensity in lateral and medial ventricles, in particular the ventral aspect of the 4th ventricle, and perivascular spaces. These changes will reflect enhanced glymphatic activity, consistent with prior work linking respiration and arousal states to fluid exchange efficiency.

H3: Participants will show acute reductions in depression and anxiety symptoms, and increases in subjective well-being, following the WHBT session. These psychological shifts are hypothesized to reflect autonomic recalibration and increased vagal tone associated with breath retention and focused interoceptive awareness.

H4: Increases in resting CBF and CSF flow post-WHBT will be positively correlated with improvements in affective states (i.e., greater perfusion and waste clearance efficiency will predict greater reductions in negative mood and increased well-being). This relationship is based on evidence linking impaired glymphatic function to affective dysregulation and neuroinflammation.

H5: Wim Hof breathing will alter functional connectivity in networks supporting autonomic control, interoception, and emotional regulation—including the default mode network (DMN), salience network (SN), and brainstem nuclei. These connectivity changes are expected to mediate the relationship between physiological modulation (CBF, CSF) and psychological outcomes.

Impact: This study will be the first to systematically examine how the Wim Hof breathing technique influences cerebral perfusion, glymphatic-relevant physiology, and mental health outcomes in humans using cutting-edge multimodal neuroimaging. The proposed work will:

Clarify the physiological footprint of breath-based interventions, providing mechanistic evidence for their clinical and wellness applications.
Advance understanding of the brain’s waste clearance system, a promising target in aging and neurodegeneration research using a novel breathwork technique.
Bridge neuroscience and integrative health, encouraging cross-disciplinary approaches to preventative brain care.

The findings will define boundaries for how volitional respiration can modulate central nervous system physiology—laying essential groundwork for safe, accessible, non-pharmacological strategies for improving brain and mental health.

3. Methods

Participants/Sample

We aim to recruit 20 healthy adults, aged 18 to 95 years, with varying levels of experience in the Wim Hof breathing technique (WHBT), ranging from beginners to regular practitioners. This inclusive age range will allow exploration of whether age-related differences in vascular and glymphatic function moderate the effects of WHBT.

Inclusion Criteria

Age 18–95 years
Prior experience with the Wim Hof breathing technique (from 2 weeks to regular practice)
Fluent in English (for task instructions and questionnaires)
Ability to comply with breathwork and scanning protocols
No contraindications to MRI (see below)

Exclusion Criteria

History of neurological disorders (e.g., stroke, epilepsy, multiple sclerosis)
History of psychiatric illness (e.g., bipolar disorder, psychosis)
Cardiopulmonary conditions contraindicating breath-holding (e.g., COPD, severe asthma, uncontrolled hypertension)
Active substance abuse
Pregnancy
MRI contraindications, including:
- Presence of metallic implants (e.g., pacemakers, cochlear implants, surgical clips)
- Claustrophobia
- Tattoos containing ferromagnetic ink
- Implanted devices (e.g., insulin pumps, neurostimulators)
- Inability to remain still for up to 60 minutes

Participants will undergo a detailed MRI safety screening and informed consent process before enrollment.

Recruitment Strategy

Participants will be recruited through:

Local and regional Wim Hof community groups (in-person and online)
UCSD’s Research Match clinical trial recruitment service
Social media advertisements targeting individuals interested in breathwork, wellness, and meditation
Flyers at community wellness centers, gyms, yoga studios, and health cooperatives
UCSD participant pools and listservs (with oversampling of older adults via aging research registries)

Screening will be conducted via phone and REDCap surveys to ensure eligibility and collect demographic and WHBT experience level data.

Sample Size Justification and Power Analysis

We propose a sample size of N = 20, which is appropriate for a within-subjects, mechanistic fMRI pilot study.

Based on prior ASL and resting-state fMRI studies of breath-based interventions (e.g., mindfulness, slow breathing), medium to large effect sizes (Cohen’s d ≈ 0.6–0.9) are commonly observed in perfusion and connectivity changes.
Using G*Power for a paired-sample t-test (α = .05, two-tailed):
- A sample of 20 provides >80% power to detect medium-to-large within-subject effects (d = 0.65)
Given the richness of the physiological and imaging data, this sample will provide sufficient power to test primary hypotheses and generate effect sizes for future R01-level studies.

This sample size also reflects feasibility constraints tied to fMRI session costs, individualized WHBT instruction, and imaging time.

Materials and Procedures

Study Design

This is a within-subjects, mechanistic observational study designed to assess how the Wim Hof breathing technique (WHBT) acutely modulates cerebral perfusion, CSF flow (glymphatic-relevant markers) using ASL fMRI, and psychological states using multimodal MRI, standardized questionnaires, and AI-driven analysis to extract multivariate brain signatures. Each participant completes a single ~2.5-hour session involving pre/post imaging and behavioral assessment.

Study Setting

All data will be collected at the UCSD Keck Center for Functional MRI under the supervision of Dr. Fadel Zeidan. The facility includes:

All MRI data will be acquired on a 3T Siemens MAGNETOM Skyra scanner with a 32-channel head coil (Siemens Healthineers AG, Munich, Germany) at the UCSD Keck Center for Functional MRI. Structural MRI: High-resolution structural scans will be acquired using an MP-RAGE sequence [TI= 900 milliseconds (ms); TR= 2300ms; flip angle= 8°; TE= 2.32ms; 1mm isotropic spatial resolution; 192 slices, GRAPPA factor = 2]. Functional MRI: BOLD fMRI will be acquired with echo-planar imaging (TE = 30ms; TR=800ms; 60 x 2.4-mm-thick slices, no gap; 1.5²x3 mm in-plane resolution; flip angle= 52°; 180 reps; 300s. MRI-compatible physiological monitoring equipment (respiratory belt, pulse oximeter). Perfusion fMRI: A pseudo-continuous arterial spin labeling (PCASL) protocol will be employed with labeling durations ranging from 1 to 3 seconds and post-labeling delays spanning 0.5 to 4 seconds. Repetition times will be adjusted according to each label-delay combination, ranging from 4610 to 10,200 ms. To suppress background tissue and CSF signals, two background suppression pulses will be applied. Readout will be conducted using a segmented 3D GRASE sequence with echo times increasing in 261 ms steps (TE = 10 to 1837 ms), a turbo spin echo factor of 200 (first pulse at 180°, subsequent pulses at 160°), and 8 echoes per acquisition. The acquisition matrix will be 64 × 60, reconstructed to 80 × 80, with 28 slices and a voxel size of 3 × 3 × 6 mm³. EPI phase encoding will be in the anterior-posterior direction, with an echo train length of 15 and a slice oversampling factor of 1.8. Each acquisition will be repeated four times and averaged. Additionally, a high-resolution 3D-FFE T₁-weighted anatomical scan will be collected (TR/TE = 9.8/4.6 ms, resolution 0.875 × 0.875 × 1.2 mm³). This protocol will enable precise measurement of blood-to-CSF water transport by leveraging ultra-long echo times to isolate labeled water signals based on their T₂ properties.
Quiet testing and recovery rooms for behavioral assessments and WHBT practice
On-site medical staff trained in breathwork monitoring and emergency procedures

Procedure Overview

1. Screening and Consent

Participants are screened for eligibility, contraindications, and WHBT experience level.
Informed consent is obtained, followed by MRI safety screening.

Baseline psychological measures are administered:

· Pittsburgh Sleep Quality Index (PSQI)

· State-Trait Anxiety Inventory (STAI)

· Cohen Perceived Stress Scale (PSS): This assessment is critical for controlling stress in our analyses as well as a potential predictor in clinical pain improvements

· The Freiburg Mindfulness Inventory (FMI): This is a 14-item standard mindfulness scale to measure potential changes in mindfulness before and after intervention.

· Subjects’ Global Impression of Change (PGIC): This is a self-report assessment recommended to evaluate self-reported perception of improvement over trial/efficacy of treatment.

· Five Facet Mindfulness Questionnaire (FFMQ): This is a 39-item multidimensional measure of trait mindfulness and includes five subscales: non-reactivity, nonjudgement, describing, observing, and acting with awareness.

· The Beck Depression Inventory (BDI): This is a 21-item standard assessment widely used to measure clinical depression.

· Pain Catastrophizing Scale (PCS): This is a 13-item assessment derived from definitions of catastrophizing. The PCS yields a total score and three subscale scores assessing rumination, magnification, and helplessness in study volunteers.

· Profile of Mood States Questionnaire (POMS-short form): This is a 40-item measure of 6 mood states: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment. This assessment is recommended by the IMMPACT group as a core measure of emotional functioning.

· SF-12 Health Survey (SF-12): This is a 12-item version of the SF-36 item Health Survey designed to assess general mental and physical functioning, and overall health-related quality of life.

· Social Connected Scale (SCS): This is a 20-item assessment designed to measure social connectedness, an attribute of the self that reflects cognitions of enduring interpersonal closeness with the social world, in participants.

· Multidimensional Assessment of Interoceptive Awareness (MAIA): This is a 32-item multidimensional instrument that includes 8 scales ranging from 3 to 7 items each. The scales are noticing, not-distracting, not-worrying, attention regulation, emotional awareness, self-regulation, body listening, and trusting.

· Nondual Awareness Dimensional Assessment (NADA): This is a 13-item standardized instrument capable of facilitating quantitative investigation of nondual awareness using two dimensions: bliss and self-transcendence.

· The Compassion Scale (CS-M; Martins, Nicholas, Shaheen, Jones, & Norris, 2013). Martins et al.'s CS-M is a 10-item self-report scale developed to measure five domains of compassion: generosity, hospitality, objectivity, sensitivity, and tolerance across social networks and relationships (strangers, friends, and family) using a 1 (none) to 7 (all) response scale. The aim of the scale was to provide a measure of compassion across domains that could be enhanced through training, as the authors argue that scales like the CLS do not lend themselves well to measuring compassion in a way that can be targeted for education. Items were generated and evaluated by a panel of academic and community experts.

2. Pre-Intervention Baseline Scan

Participants undergo MRI acquisition in the following order:
- Structural T1-weighted scan (MPRAGE; 1 mm³ isotropic)
- Resting-state fMRI (eyes closed, 10 minutes; BOLD EPI, TR = 2000 ms)
- Arterial Spin Labeling (ASL) perfusion scan
- CSF-sensitive fast T2-FLAIR or phase-contrast MRI to assess glymphatic-relevant fluid dynamics (depending on system availability)
Participants are instructed to lie still with their eyes closed and remain relaxed, following MRI safety guidelines.

3. Wim Hof Breathing Intervention

Participants will practice the Wim Hof breathing technique during fMRI acquisition.
- The intervention involves:
  - 30 rapid inhalations (deep breaths, followed by forced exhalations)
  - Breath retention after exhalation for as long as comfortable
  - Recovery breathing once retention is complete
  - Breath Holding
- This cycle is repeated for 3–4 rounds, lasting approximately 15–20 minutes.
Physiological parameters (heart rate, respiratory rate, oxygen saturation) will be monitored throughout using an MRI-compatible pulse oximeter and respiratory belt.

4. Post-Intervention Scan

Immediately following the breathwork session, we will measure changes in resting state BOLD, CBF and CSF to assess glymphatic clearance changes post-Wim Hof breathing.

6. Post-Intervention Psychological Measures

Participants complete the same psychological assessments as in the baseline phase:
Participants are also asked about their subjective experience of the Wim Hof session (e.g., physical sensations, mood).

Planned Analyses

All analyses will be conducted using FSL, Python (Nilearn, Scikit-learn), and R. The plan includes both a priori ROI-based analyses and exploratory whole-brain voxelwise analyses. False Discovery Rate (FDR) or family-wise error correction will be applied to control for multiple comparisons where appropriate.

H1: WHBT will increase resting CBF in specific regions associated with autonomic and emotional regulation

Data Input:

Arterial Spin Labeling (ASL) perfusion maps (pre vs. post)
Normalized to MNI space, smoothed (6 mm FWHM)

Analysis:

Paired t-tests on pre/post ASL CBF maps using SPM or FSL FEAT.
A priori ROIs: medial prefrontal cortex (mPFC), anterior insula, thalamus, brainstem.
- ROI masks will be created using the Harvard-Oxford atlas and brainstem templates (e.g., from SUIT).
Effect size estimates (Cohen’s d) reported for each ROI.
Whole-brain exploratory analysis to detect unanticipated changes.
Covariates: age, sex, WHBT experience level

H2: WHBT will alter CSF dynamics consistent with enhanced glymphatic activity

Data Input:

Fast T2-FLAIR or phase-contrast MRI sequences pre/post (CSF-sensitive)
Signal intensities and flow velocity maps in:
- Lateral and medial ventricles with a focus on the ventral aspect of the 4th ventricle and choroid plexus.
- Perivascular spaces (PVS) of basal ganglia and cortex

Analysis:

Repeated measures ANOVA on CSF signal intensity and flow parameters
ROI-based time series extraction and paired t-tests
For dynamic CSF data (e.g., velocity/flow): compute peak-to-peak amplitude and variance
Exploratory voxelwise nonparametric permutation testing (FSL Randomise)

H3: WHBT will acutely reduce depression/anxiety and increase well-being

Data Input:

Pre/post behavioral scores (BDI-II, STAI, WHO-5)

Analysis:

Paired-samples t-tests for each measure
Wilcoxon signed-rank test if normality assumptions are violated
Effect size: Cohen’s d and percent change
Exploratory moderation analysis: effect of prior WHBT experience on magnitude of change

H4: Increases in CBF and CSF flow will predict improvements in psychological state

Data Input:

ΔCBF and ΔCSF metrics (difference scores or % change)
ΔBDI, ΔSTAI, ΔWHO-5 scores

Analysis:

Pearson correlations between physiological and behavioral changes
Multiple linear regression models predicting ΔPsychological Score from ΔCBF and ΔCSF metrics, controlling for age, sex, baseline scores, and WHBT experience.
Variance explained (R²) and predictive accuracy reported

H5: WHBT will modulate functional connectivity in DMN, SN, and brainstem—mediating psychophysiological effects

Data Input:

Pre/post resting-state fMRI
ICA- and ROI-based functional connectivity (FC) measures

Analysis:

Preprocessing using fMRIPrep, followed by denoising (CompCor), band-pass filtering (0.01–0.1 Hz)
Dual regression to extract time series from networks (DMN, SN, brainstem)
Paired t-tests on Fisher z-transformed connectivity matrices
Seed-to-voxel FC from:
- vmPFC and PCC (DMN)
- anterior insula and dACC (SN)
- PAG and nucleus of the solitary tract (brainstem)

Mediation Modeling:

Path analysis (e.g., PROCESS in SPSS or lavaan in R)
- ΔCBF/CSF → ΔFC → ΔMood/Well-being
- Test indirect effects via bootstrapped confidence intervals

Exploratory Multivariate Brain Signature and Predictive Modeling

Data Input:

Whole-brain changes in fMRI (BOLD), ASL, and CSF dynamics
Behavioral outcomes (ΔBDI, ΔSTAI, ΔWHO-5)

Analysis:

Train machine learning classifiers (e.g., SVMs, random forest, or elastic net regression) to:
- Predict responder status (binary: high vs. low change)
- Identify multivariate neural signatures associated with physiological and affective improvements
Use nested cross-validation and report metrics:
- AUC, accuracy, and permutation testing
Feature importance maps (e.g., weight maps from classifiers) visualized and interpreted relative to known networks

Ethics and Data Management

UCSD IRB Approval will be obtained before any data collection.

A. Repository where scientific data and metadata will be archived: All data will be deposited to the delineated data archive depositories after data collection is completed and after study team has been unblinded to data.

B. How scientific data will be findable and identifiable: Data will be findable for the research community through the NDA Collection that will be established when this application is funded. For all publications, an NDA study will be created. Each of those studies is assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow researchers easy access to the exact data used.

C. When and how long the scientific data will be made available: Researchers will have access to data when the award ends. Separate studies will properly created and labeled to reflect data used for every publication. Those studies will be shared when the pre-print is available. For all publications, an NDA study will be created. Each of those studies is assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. NDA will make decisions about how long to preserve the data, but that data archive has not deleted any depository.

Access, Distribution, or Reuse Considerations

A. Factors affecting subsequent access, distribution, or reuse of scientific data: All research participants will be consented for broad data sharing.

B. Whether access to scientific data will be controlled: Public Use Data: All deidentified study data that are not designated as restricted use will be made available as public use data to the research community via the Data Sharing for Demographic Research. Users of the public use data must register and agree to the Terms of Use, which are designed to protect study participants by limiting data use to scientific research and to aggregate statistical reporting. Data users will also need to agree not to share or redistribute any data downloads. Restricted Access Data: Data that are determined to be potentially identifying through indirect or deductive disclosure are provided under restricted data contract to users who demonstrate a valid research need and meet conditions of use. These restricted data will include separate files with geospatial indicators below the level of state, such as county, census tract, block-group, and block for all years. To request access of the data, researchers will use the standard processes at NDA, and the NDA Data Access Committee will decide which requests to grant. The standard NDA data access process allows access for one year and is renewable.

Protections for privacy, rights, and confidentiality of human research participants: The NDA global unique identifier tool allows researchers to aggregate data from the same research participant without different laboratories having to share personally identifiable information about that research participant. The NDA data dictionaries do not

Oversight of Data Management and Sharing: The Office of Sponsored Programs at University of California San Diego that will be administering this award has created a data management and sharing plan compliance system as part of their process for submitting the annual NIH progress report. That Office is collecting information related to the number of research participants that are deposited each reporting year. The Office of Sponsored Programs will also look for the NDA data DOIs from NDA Studies and will include that information in the annual progress report.

4. Budget

* Dr. Zeidan will provide 10% effort to supervise all study procedures, ethics approvals, analyses and manuscript preparation = ($35,000/year) = Two years = $70, 000

* Each participant will be paid $300 for study completion. $300 X 24 = $7200

* Each scan will cost $800. $800 X 24 = $19, 200.

* A post-doctoral fellow will perform all study coordination, data collection and analyze the data. Two-year post-doctoral fellow ($90,000/year) = Two years = $180,000.

Total costs = $276, 000 for a two -year fMRI and psychological study.

5. References

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2. Ketelhut, S., et al. The effectiveness of the Wim Hof method on cardiac autonomic function, blood pressure, arterial compliance, and different psychological parameters. Sci Rep 13, 17517 (2023).

3. Hablitz, L.M. & Nedergaard, M. The glymphatic system. Curr Biol 31, R1371-R1375 (2021).

4. Bohr, T., et al. The glymphatic system: Current understanding and modeling. iScience 25, 104987 (2022).

5. Lohela, T.J., Lilius, T.O. & Nedergaard, M. The glymphatic system: implications for drugs for central nervous system diseases. Nat Rev Drug Discov 21, 763-779 (2022).

6. Ghanizada, H. & Nedergaard, M. The glymphatic system. Handb Clin Neurol 209, 161-170 (2025).

7. Mestre, H., et al. Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension. Nat Commun 9, 4878 (2018).

8. Rasmussen, M.K., Mestre, H. & Nedergaard, M. The glymphatic pathway in neurological disorders. Lancet Neurol 17, 1016-1024 (2018).

9. Nedergaard, M. & Goldman, S.A. Glymphatic failure as a final common pathway to dementia. Science 370, 50-56 (2020).

10. Hablitz, L.M. & Nedergaard, M. The Glymphatic System: A Novel Component of Fundamental Neurobiology. J Neurosci 41, 7698-7711 (2021).

11. Kritsilis, M., et al. Loss of glymphatic homeostasis in heart failure. Brain 148, 985-1000 (2025).

12. Kastrup, A., Kruger, G., Glover, G.H., Neumann-Haefelin, T. & Moseley, M.E. Regional variability of cerebral blood oxygenation response to hypercapnia. Neuroimage 10, 675-681 (1999).

13. Kastrup, A., Li, T.Q., Glover, G.H. & Moseley, M.E. Cerebral blood flow-related signal changes during breath-holding. AJNR Am J Neuroradiol 20, 1233-1238 (1999).

14. Isaev, G., Murphy, K., Guz, A. & Adams, L. Areas of the brain concerned with ventilatory load compensation in awake man. J Physiol 539, 935-945 (2002).

15. Muzik, O., Reilly, K.T. & Diwadkar, V.A. "Brain over body"-A study on the willful regulation of autonomic function during cold exposure. Neuroimage 172, 632-641 (2018).

16. Petraskova Touskova, T., et al. A novel Wim Hof psychophysiological training program to reduce stress responses during an Antarctic expedition. J Int Med Res 50, 3000605221089883 (2022).

17. Hablitz, L.M., et al. Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun 11, 4411 (2020).

18. Mestre, H., Mori, Y. & Nedergaard, M. The Brain's Glymphatic System: Current Controversies. Trends Neurosci 43, 458-466 (2020).

Funding

Funding

Title: Investigating the Neural and Cerebrovascular Effects of the Wim Hof Breathing Technique: Implications for Glymphatic Function and Brain Waste Clearance

Funding Progress

Nonprofit Recipient

Funders

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