Synthetic Vasomotion for Glymphatic Enhancement
Synthetic Vasomotion for Glymphatic Enhancement: A Pilot Study of Intermittent Hypercapniaand Noninvasive Vagus Nerve Stimulation With Continuous Parenchymal Resistance Monitoring inParkinson's Disease and Healthy Older Adults
The goal of this pilot clinical trial is to learn whether a week-long study combining controlled breathing procedures, intermittent exposure to a low-concentration carbon dioxide gas mixture, and noninvasive vagus nerve stimulation can be carried out safely and comfortably in adults with early-stage Parkinson's disease and age-matched healthy adults. The study will also explore how these procedures affect physiological signals related to breathing, cardiovascular and autonomic function, brain activity, and physiological processes thought to be related to fluid movement in and around the brain.
The main questions the study aims to answer are:
- Can participants safely and comfortably complete the study procedures and at-home monitoring?
- Do physiological responses differ when intermittent hypercapnia is paired with active noninvasive vagus nerve stimulation compared with sham stimulation?
- Are changes measured during the intervention visits related to overnight physiological measurements and changes in blood-based biomarkers?
Researchers will compare active and sham noninvasive vagus nerve stimulation within the same participants. Both conditions will be paired with guided breathing and intermittent hypercapnia, in which participants briefly breathe a controlled gas mixture containing 5% carbon dioxide.
Participants will:
- Complete an intake and baseline visit and several nights of at-home physiological monitoring.
- Complete two intervention visits in randomized order, one using active vagus nerve stimulation and one using sham stimulation.
- Complete guided breathing and intermittent hypercapnia procedures while respiratory, cardiovascular, and other physiological signals are monitored.
- Provide blood samples before and after intervention procedures for exploratory biomarker measurements.
This is an exploratory pilot study. It is not intended to diagnose, treat, or prevent Parkinson's disease or any other medical condition.
Studieöversikt
Status
Betingelser
Detaljerad beskrivning
This pilot study will evaluate the feasibility, safety, tolerability, and exploratory physiological effects of a multimodal intervention designed to influence autonomic, cerebrovascular, respiratory, and glymphatic-associated physiology. The study combines guided breathing, intermittent hypercapnia, and noninvasive vagus nerve stimulation (nVNS) with continuous or repeated physiological monitoring and exploratory blood-based biomarker assessment.
The glymphatic system is a brain-wide pathway involved in the exchange of cerebrospinal fluid and interstitial fluid and in the movement of metabolic waste products from brain tissue. Glymphatic-associated fluid transport is influenced by sleep, cerebrovascular pulsatility, vasomotion, respiratory physiology, and autonomic regulation. Parkinson's disease is associated with abnormalities in several of these systems, including autonomic function, sleep, and brainstem noradrenergic signaling. This study therefore examines whether controlled manipulation of respiratory and autonomic physiology produces measurable changes in physiological signals hypothesized to be relevant to glymphatic-associated fluid dynamics.
The study will enroll up to 20 adults, including approximately 10 participants with early-stage Parkinson's disease and 10 age-matched healthy control participants. The target analytic sample is approximately 16 participants after accounting for attrition, incomplete visits, or unusable data. The study is designed as a pilot and is not powered to establish clinical efficacy.
Participants will complete a week-long protocol. Following screening and informed consent, participants will complete an intake and baseline visit that may include health and demographic questionnaires, vital signs, baseline physiological measurements, guided breathing, and training on the Applied Cognition GF Monitor. Participants will then complete overnight at-home monitoring on two baseline nights.
Participants will subsequently complete two in-clinic intervention visits separated by approximately 48 hours. The order of active and sham nVNS will be randomized, and each participant will receive both conditions in a within-participant crossover design. During both intervention visits, nVNS or sham stimulation will be paired with guided breathing and intermittent hypercapnia. For intermittent hypercapnia, participants will breathe through a noninvasive mask connected to a controlled breathing circuit that alternates room air with a gas mixture containing approximately 5% carbon dioxide, 21% oxygen, and balance nitrogen. The hypercapnia procedure consists of three approximately 10-minute exposure blocks according to the study protocol. Respiratory and physiological measures will be monitored throughout the intervention and recovery periods, and participants may pause or discontinue procedures at any time.
Noninvasive vagus nerve stimulation will be delivered with the gammaCore device. In the active condition, stimulation will be applied to the cervical vagus nerve at a participant-tolerated intensity. In the sham condition, participants will undergo an otherwise similar procedure using a sham device that does not deliver the active electrical stimulation.
Physiological measurements may include transcutaneous or end-tidal carbon dioxide, oxygen saturation, respiratory timing and ventilation, heart rate, heart rate variability-related measures, blood pressure, electroencephalography, photoplethysmography, impedance-based physiological measures, and movement. The Applied Cognition GF Monitor will be used during in-clinic and at-home monitoring to collect multimodal physiological signals, including electrical impedance spectroscopy measurements used to estimate changes in brain parenchymal resistance. Overnight monitoring will also be performed after the first intervention visit to explore whether intervention-associated physiological changes persist into subsequent sleep.
Serial blood samples will be collected around the intervention procedures for exploratory measurement of plasma biomarkers associated with neurodegenerative, neuroinflammatory, and glymphatic-related physiological processes. Planned exploratory biomarkers include alpha-synuclein, neurofilament light chain, glial fibrillary acidic protein, amyloid-beta 1-42, amyloid-beta 1-40, and phosphorylated tau 217.
The primary emphasis of the study is feasibility, safety, tolerability, participant adherence, and successful physiological signal acquisition. Exploratory analyses will compare physiological responses during active nVNS plus intermittent hypercapnia with responses during sham nVNS plus intermittent hypercapnia. Additional exploratory analyses will examine relationships among in-clinic physiological responses, overnight monitoring measures, blood-based biomarker changes, and participant group. The results are intended to provide preliminary effect-size and variance estimates, identify practical and physiological response patterns, and inform the design and parameter selection of future hypothesis-driven trials.
This study is non-therapeutic and exploratory. It is not designed to establish clinical benefit or to diagnose, treat, or prevent Parkinson's disease or another medical condition.
Studietyp
Inskrivning (Beräknad)
Fas
- Inte tillämpbar
Kontakter och platser
Studiekontakt
- Namn: Melissa Do, PhD
- Telefonnummer: 850-202-4462
- E-post: mdo@ihmc.org
Studera Kontakt Backup
- Namn: Toshiya Miyatsu, PhD
- Telefonnummer: 850-202-4462
- E-post: tmiyatsu@ihmc.org
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Beskrivning
Inclusion Criteria
Parkinson's Disease Group
Adults aged 60-80 years at the time of enrollment. Clinical diagnosis of early-stage Parkinson's disease and not currently receiving levodopa or other dopaminergic medication.
Hoehn and Yahr stage I. English-speaking and able to provide informed consent and complete study procedures and questionnaires administered in English.
Cognitively able to participate in study procedures, as determined by investigator assessment and/or optional cognitive screening measures, when administered.
Willing and able to comply with all study visits and procedures. Able to tolerate wearing the Applied Cognition GF Monitor, physiological monitoring equipment, face mask, and noninvasive vagus nerve stimulation (nVNS) device for the duration of study procedures.
Age-Matched Healthy Control Group
Adults aged 60-80 years at the time of enrollment. No known diagnosis of Parkinson's disease or other major neurodegenerative disorder.
English-speaking and able to provide informed consent and complete study procedures and questionnaires administered in English.
Cognitively able to participate in study procedures, as determined by investigator assessment and/or optional cognitive screening measures, when administered.
Willing and able to comply with all study visits and procedures. Able to tolerate wearing the Applied Cognition GF Monitor, physiological monitoring equipment, face mask, and noninvasive vagus nerve stimulation (nVNS) device for the duration of study procedures.
Exclusion Criteria
Diagnosis of moderate-to-severe neurocognitive impairment or dementia. Significant pulmonary disease, including chronic obstructive pulmonary disease (COPD), severe asthma requiring daily rescue therapy, restrictive lung disease, or resting oxygen saturation <92%.
Untreated or poorly controlled hypertension, defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at screening.
Symptomatic hypotension, orthostatic hypotension associated with syncope, or clinically significant autonomic dysfunction.
Peripheral vascular disease, significant upper-extremity injury, or other conditions that may interfere with peripheral perfusion or physiological monitoring measurements.
Uncontrolled diabetes mellitus or diabetes-associated complications that may significantly affect autonomic or vascular physiology.
History of significant cardiac disease, including clinically significant arrhythmia, congestive heart failure, unstable angina, myocardial infarction within the prior 12 months, or other conditions judged unsafe for intermittent hypercapnia exposure.
Active implanted electrical or neurostimulation devices, including cardiac pacemakers, implantable cardioverter-defibrillators (ICDs), deep brain stimulators, cochlear implants, or implanted vagus nerve stimulators.
Active carotid artery disease, carotid bruits, history of carotid endarterectomy, or other clinically significant cervical vascular abnormalities that may increase risk during cervical nVNS application.
History of moderate or severe traumatic brain injury, defined as loss of consciousness >30 minutes or post-traumatic amnesia >24 hours.
Active psychiatric condition requiring hospitalization within the prior 12 months.
Current use of medications known to substantially alter cerebrovascular reactivity or carbon dioxide sensitivity, such as acetazolamide or other carbonic anhydrase inhibitors.
Claustrophobia or inability to tolerate mask-based breathing procedures. Pregnancy, suspected pregnancy, or lactation in participants of childbearing potential.
Body mass index (BMI) >40 kg/m² due to potential effects on respiratory physiology, mask fit, and CO₂ tolerance.
Known allergy or sensitivity to latex, adhesives, electrode gels, medical tapes, or study device materials that may interfere with safe participation.
Current acute respiratory infection or other acute illness at the time of study participation.
Any other medical, neurological, psychiatric, or safety-related condition that, in the opinion of the Principal Investigator, would compromise participant safety, interfere with study procedures, or affect data integrity.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Grundläggande vetenskap
- Tilldelning: Randomiserad
- Interventionsmodell: Crossover tilldelning
- Maskning: Enda
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Sequence A: Sham nVNS First
Participants complete the common baseline condition with sham nVNS and sham intermittent hypercapnia, followed by sham nVNS + active intermittent hypercapnia and then active nVNS + active intermittent hypercapnia.
|
Active cervical noninvasive vagus nerve stimulation (nVNS) will be delivered using the gammaCore device.
Participants will receive two consecutive 2-minute stimulation applications, one on each side of the neck.
Stimulation intensity will be adjusted by the participant to a perceptible but comfortable level.
The device delivers 1-ms pulses of 5-kHz sine waves at 25 Hz.
Andra namn:
Participants will undergo the same application procedure and duration as active nVNS using a sham device.
The sham device is similar in appearance to the active device and produces vibration and audible feedback but does not deliver active electrical stimulation.
Andra namn:
Participants will intermittently breathe a controlled hypercapnic gas mixture containing approximately 5% carbon dioxide, 21% oxygen, and balance nitrogen through a noninvasive mask.
The intervention consists of three approximately 10-minute hypercapnia blocks according to the study protocol, with respiratory and physiological monitoring throughout.
Andra namn:
Participants will undergo the same mask-based breathing procedures used for the intermittent hypercapnia condition but will breathe room air rather than the hypercapnic gas mixture.
This condition serves as the baseline/sham hypercapnia condition.
Andra namn:
Participants will complete approximately 10 minutes of guided breathing during study visits.
Breathing will be standardized using verbal instruction from study personnel and/or visual or auditory pacing cues, which may include commercially available applications such as Elite HRV or study-specific pacing aids.
The guided breathing procedure is intended to standardize breathing timing and pacing during physiological monitoring and intervention procedures and is not used for diagnosis, treatment, or medical decision-making.
|
|
Experimentell: Sequence B: Active nVNS First
Participants complete the common baseline condition with sham nVNS and sham intermittent hypercapnia, followed by active nVNS + active intermittent hypercapnia and then sham nVNS + active intermittent hypercapnia.
|
Active cervical noninvasive vagus nerve stimulation (nVNS) will be delivered using the gammaCore device.
Participants will receive two consecutive 2-minute stimulation applications, one on each side of the neck.
Stimulation intensity will be adjusted by the participant to a perceptible but comfortable level.
The device delivers 1-ms pulses of 5-kHz sine waves at 25 Hz.
Andra namn:
Participants will undergo the same application procedure and duration as active nVNS using a sham device.
The sham device is similar in appearance to the active device and produces vibration and audible feedback but does not deliver active electrical stimulation.
Andra namn:
Participants will intermittently breathe a controlled hypercapnic gas mixture containing approximately 5% carbon dioxide, 21% oxygen, and balance nitrogen through a noninvasive mask.
The intervention consists of three approximately 10-minute hypercapnia blocks according to the study protocol, with respiratory and physiological monitoring throughout.
Andra namn:
Participants will undergo the same mask-based breathing procedures used for the intermittent hypercapnia condition but will breathe room air rather than the hypercapnic gas mixture.
This condition serves as the baseline/sham hypercapnia condition.
Andra namn:
Participants will complete approximately 10 minutes of guided breathing during study visits.
Breathing will be standardized using verbal instruction from study personnel and/or visual or auditory pacing cues, which may include commercially available applications such as Elite HRV or study-specific pacing aids.
The guided breathing procedure is intended to standardize breathing timing and pacing during physiological monitoring and intervention procedures and is not used for diagnosis, treatment, or medical decision-making.
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Feasibility of Completing the Multimodal Study Protocol
Tidsram: From enrollment through completion of the approximately 1-week study protocol
|
Feasibility will be assessed as the number and proportion of enrolled participants who complete the planned in-clinic visits, intervention procedures, and scheduled at-home Applied Cognition GF Monitor recordings.
Reasons for incomplete procedures or study withdrawal will also be documented.
|
From enrollment through completion of the approximately 1-week study protocol
|
|
Incidence of Study-Related Adverse Events
Tidsram: From initiation of study procedures through completion of the approximately 1-week protocol
|
Safety will be assessed by the number and proportion of participants experiencing adverse events during or following study procedures.
Adverse events will be documented with respect to type, severity, timing, and relationship to intermittent hypercapnia, guided breathing, nVNS, physiological monitoring, or blood collection.
|
From initiation of study procedures through completion of the approximately 1-week protocol
|
|
Change in Participant-Reported Tolerability During Intervention Procedures
Tidsram: During intervention visits on Days 3 and 5, before and after each 10-minute hypercapnia block and immediately after the overall hypercapnia protocol, up to 1 week
|
Participants will rate dizziness, stress/anxiety, and overall discomfort on 1-to-10 numeric rating scales before and after each 10-minute intermittent hypercapnia block and following completion of the overall hypercapnia protocol.
Additional symptoms and tolerability concerns will also be recorded.
|
During intervention visits on Days 3 and 5, before and after each 10-minute hypercapnia block and immediately after the overall hypercapnia protocol, up to 1 week
|
|
Proportion of Planned Physiological Recordings With Usable Data
Tidsram: From baseline through completion of scheduled intervention, recovery, and overnight monitoring periods, up to 1 week
|
The proportion of planned physiological recording sessions that yield usable data will be assessed across the Applied Cognition GF Monitor and respiratory, cardiovascular, and autonomic monitoring systems.
Device failures, incomplete recordings, and technical problems resulting in unavailable or unusable data will be documented.
|
From baseline through completion of scheduled intervention, recovery, and overnight monitoring periods, up to 1 week
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Change in EIS-Derived Brain Parenchymal Resistance During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through the post-intervention recovery period, approximately 1.5-2 hours
|
Electrical impedance spectroscopy (EIS) obtained with the Applied Cognition GF Monitor will be used to quantify changes in brain parenchymal resistance across baseline, intervention, and recovery periods.
Within-participant responses will be compared across the study intervention conditions.
|
During each intervention visit, from pre-intervention baseline through the post-intervention recovery period, approximately 1.5-2 hours
|
|
Change in Overnight EIS-Derived Brain Parenchymal Resistance Following Intervention
Tidsram: Baseline Nights 1 and 2 compared with the overnight recording following the first intervention visit, within approximately 3 days
|
Overnight EIS-derived brain parenchymal resistance measured following the first intervention visit will be compared with measurements obtained during the baseline overnight monitoring nights to explore intervention-associated changes in overnight physiology.
|
Baseline Nights 1 and 2 compared with the overnight recording following the first intervention visit, within approximately 3 days
|
|
Change in Carbon Dioxide Levels During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Transcutaneous carbon dioxide and/or end-tidal carbon dioxide will be measured continuously or repeatedly during baseline, intermittent hypercapnia, and recovery to characterize the physiological response to controlled carbon dioxide exposure.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Peripheral Oxygen Saturation During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Peripheral oxygen saturation (SpO2) will be monitored during baseline, intervention, and recovery periods to characterize respiratory responses and support participant safety monitoring.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Respiratory Rate During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Respiratory rate will be measured during baseline, guided breathing, intermittent hypercapnia, and recovery periods to characterize intervention-associated respiratory responses.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Tidal Volume During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Tidal volume will be measured when available using respiratory monitoring equipment during baseline, intervention, and recovery periods.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Minute Ventilation During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Minute ventilation will be measured when available during baseline, guided breathing, intermittent hypercapnia, and recovery periods to characterize intervention-associated respiratory responses.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Heart Rate During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Heart rate will be measured continuously or repeatedly during baseline, guided breathing, nVNS, intermittent hypercapnia, and recovery periods to characterize intervention-associated cardiovascular and autonomic responses.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Heart Rate Variability During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Heart rate variability-related measures derived from ECG or heart-rate monitoring will be evaluated across baseline, guided breathing, nVNS, intermittent hypercapnia, and recovery periods to characterize autonomic responses.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Blood Pressure During Intervention
Tidsram: During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
Systolic and diastolic blood pressure will be assessed at predefined timepoints during study procedures to characterize cardiovascular responses and support participant safety monitoring.
|
During each intervention visit, from pre-intervention baseline through post-intervention recovery, approximately 1.5-2 hours
|
|
Change in Plasma Neurodegenerative and Glymphatic-Associated Biomarkers
Tidsram: Approximately t=0, t=45 minutes, and t=60 minutes relative to the intervention period during each intervention visit
|
Serial blood samples will be analyzed for plasma alpha-synuclein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid-beta 1-42 (Aβ1-42), amyloid-beta 1-40 (Aβ1-40), and phosphorylated tau 217 (pTau217).
Changes in biomarker concentrations across sampling timepoints will be evaluated within participants and across intervention conditions.
|
Approximately t=0, t=45 minutes, and t=60 minutes relative to the intervention period during each intervention visit
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Consensus Sleep Diary Total Sleep Time
Tidsram: Each morning following scheduled study nights, up to 1 week
|
Total sleep time will be derived from the Consensus Sleep Diary based on participant-reported sleep and wake times for the previous night.
|
Each morning following scheduled study nights, up to 1 week
|
|
Consensus Sleep Diary Sleep Onset Latency
Tidsram: Each morning following scheduled study nights, up to 1 week
|
Sleep onset latency will be derived from the Consensus Sleep Diary as the participant-reported time from attempting to fall asleep to sleep onset.
|
Each morning following scheduled study nights, up to 1 week
|
|
Consensus Sleep Diary Wake After Sleep Onset
Tidsram: Each morning following scheduled study nights, up to 1 week
|
Wake after sleep onset will be derived from the Consensus Sleep Diary based on participant-reported nighttime awakenings after initial sleep onset.
|
Each morning following scheduled study nights, up to 1 week
|
|
Consensus Sleep Diary Sleep Efficiency
Tidsram: Each morning following scheduled study nights, up to 1 week
|
Sleep efficiency will be derived from the Consensus Sleep Diary as the percentage of time in bed spent asleep.
|
Each morning following scheduled study nights, up to 1 week
|
|
Groningen Sleep Quality Scale Score
Tidsram: Following scheduled overnight study periods during the approximately 1-week protocol
|
Subjective sleep quality will be assessed using the Groningen Sleep Quality Scale (GSQS).
Higher scores indicate poorer perceived sleep quality.
|
Following scheduled overnight study periods during the approximately 1-week protocol
|
|
Karolinska Sleepiness Scale Score
Tidsram: At predefined study assessment timepoints during the approximately 1-week protocol
|
Momentary subjective sleepiness will be assessed using the Karolinska Sleepiness Scale, ranging from 1 (extremely alert) to 9 (very sleepy, fighting sleep).
|
At predefined study assessment timepoints during the approximately 1-week protocol
|
|
System Usability Scale Score
Tidsram: At completion of study device use, within the approximately 1-week protocol
|
Usability of study devices and procedures will be assessed using the 10-item System Usability Scale (SUS), which provides an overall measure of perceived system usability.
|
At completion of study device use, within the approximately 1-week protocol
|
|
Participant-Reported Applied Cognition Device Tolerability
Tidsram: During device use and at completion of scheduled monitoring periods, within approximately 1 week
|
Participants will report discomfort, irritation, technical difficulties, and other issues associated with use of the Applied Cognition GF Monitor and other study devices.
|
During device use and at completion of scheduled monitoring periods, within approximately 1 week
|
|
Composite Autonomic Symptom Score-31
Tidsram: During the study intake/baseline assessment
|
Autonomic symptom burden may be characterized using the Composite Autonomic Symptom Score-31 (COMPASS-31), including orthostatic, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
|
During the study intake/baseline assessment
|
|
Subjective Overnight Sleep Parameters
Tidsram: Each morning following scheduled study nights during the approximately 1-week protocol
|
Consensus Sleep Diary measures may include total sleep time, sleep onset latency, wake after sleep onset, number and duration of awakenings, sleep efficiency, and perceived sleep quality.
|
Each morning following scheduled study nights during the approximately 1-week protocol
|
Samarbetspartners och utredare
Samarbetspartners
Utredare
- Huvudutredare: Toshiya Miyatsu, PhD, Florida Institute for Human & Machine Cognition
Publikationer och användbara länkar
Allmänna publikationer
- Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 2014 Nov-Dec;7(6):871-7. doi: 10.1016/j.brs.2014.07.031. Epub 2014 Jul 16.
- Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012 Aug 15;4(147):147ra111. doi: 10.1126/scitranslmed.3003748.
- Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR, Lewis LD. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science. 2019 Nov 1;366(6465):628-631. doi: 10.1126/science.aax5440.
- van Veluw SJ, Hou SS, Calvo-Rodriguez M, Arbel-Ornath M, Snyder AC, Frosch MP, Greenberg SM, Bacskai BJ. Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain. Neuron. 2020 Feb 5;105(3):549-561.e5. doi: 10.1016/j.neuron.2019.10.033. Epub 2019 Dec 3.
- Ryman SG, Vakhtin AA, Mayer AR, van der Horn HJ, Shaff NA, Nitschke SR, Julio KR, Tarawneh RM, Rosenberg GA, Diaz SV, Pirio Richardson SE, Lin HC. Abnormal Cerebrovascular Activity, Perfusion, and Glymphatic Clearance in Lewy Body Diseases. Mov Disord. 2024 Aug;39(8):1258-1268. doi: 10.1002/mds.29867. Epub 2024 May 30.
- Hauglund NL, Andersen M, Tokarska K, Radovanovic T, Kjaerby C, Sorensen FL, Bojarowska Z, Untiet V, Ballestero SB, Kolmos MG, Weikop P, Hirase H, Nedergaard M. Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep. Cell. 2025 Feb 6;188(3):606-622.e17. doi: 10.1016/j.cell.2024.11.027. Epub 2025 Jan 8.
- Dagum P, Giovangrandi L, Levendovszky SR, Winebaum JJ, Singh T, Cho Y, Kaplan RM, Jaffee MS, Lim MM, Vandeweerd C, Iliff JJ. A wireless device for continuous measurement of brain parenchymal resistance tracks glymphatic function in humans. Nat Biomed Eng. 2025 Oct;9(10):1656-1676. doi: 10.1038/s41551-025-01394-9. Epub 2025 May 27.
- Erhardt EB, Mayer AR, Lin HC, Pirio Richardson SE, Shaff NA, Vakhtin AA, Caprihan A, van der Horn HJ, Hoffman N, Phillips JP, Grigg-Damberger M, Wang CH, Gough J, Hobson S, Deligtisch A, Suarez Cedeno G, Sugar D, Ryman SG. The influence of intermittent hypercapnia on cerebrospinal fluid flow and clearance in Parkinson's disease and healthy older adults. NPJ Parkinsons Dis. 2025 Nov 21;11(1):334. doi: 10.1038/s41531-025-01179-6.
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Studieregistreringsdatum
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