Brain Cooling Biomarkers

The Effect of Selective Brain Cooling on Electrophysiological and Neuroinflammatory Biomarkers of Cognition and Mood

This research is being done to examine the effects of brain cooling on cognition, electrophysiological brain activity via EEG scans, inflammation of the brain, and mood in healthy subjects. Brain cooling has been shown to cause temporary symptom relief after traumatic brain injury, but its implications for general brain and mental health remain unexplored.

Study Overview

• Status: Completed
• Conditions: Mental Health; Neurological Health
• Intervention / Treatment: Device: Brain Cooling

Detailed Description

This research attempts to address gaps in the current literature about the effect of selective brain cooling (SBC) on cognition, mood, electrophysiological markers of brain health and neuroinflammation in healthy subjects. In this study, the investigators will examine the short-term effect of one session of 30 minutes of brain cooling is on EEG patterns, neuroinflammation, cognition, and mood. The investigators will also examine the effect of a week-long intervention of 30 minutes of brain cooling per day on EEG patterns, neuroinflammation, cognition, mood. The overarching goal of this study is to validate the inclusion of selective brain cooling as an easy and safe addition to general health and clinical practice dedicated to cognitive and mood related neuropsychological health.

A minimum of 24 participants will be recruited for this study. 8 days of consecutive visits will be scheduled based on participant availability. Brain cooling consists of a 30-minute seated period, in a dimly lit, quiet room, while listening to calming natural sounds, during which the participants will wear an Arctic Cooling Cap V1.30, set at a temperature of 33.0 degrees Fahrenheit. Participants will be asked to remain awake, refrain from observing a screen, and relax in a wakeful state to the best of their ability. Participants assigned to the control group will be instructed similarly, but the brain cooling cap will not be functional.

The trial will consist of a 1-week daily intervention period and three major measurement time points: pre-intervention on Day 1, conclusion of Day 1, and post-intervention on Day 8. Day 1 will last approximately 105 minutes and will consist of 6 parts: completion of study consent form (10 min), saliva swab (5 min), administration of questionnaires and cognitive tests (10 min), electroencephalography (EEG) (20 mins), brain cooling or seated rest (30 mins), repeat questionnaires (10 mins), and repeat EEG (20 mins). The intervention period will consist of 7 days of daily administration of either 30 minutes of brain cooling or 30 minutes of seated rest. Day 8 will last approximately 35 minutes and will consist of: saliva swab (5 min), administration of questionnaires (10 min), electroencephalography (EEG) (20 mins).

Questionnaires administered to the participants at T1 and T2 will include: Penn State Worry Questionnaire (PSWQ), Hamilton Anxiety Rating Scale (HAM-A), Beck's Depression Inventory-Fast Screen (BDI-FS), Digit Span Test, Digit Symbol Test, Trail Making Test. All questionnaires and tests will be administered verbally or with paper and pencil.

Cheek swabs will be taken after the completion of the initial questionnaires. The process is as follows: for each subject the tester will use 10 swabs. Five swabs will be used to rub inside the left part of the mouth, and the other five will be used to rub inside the right part of the mouth. The exact area that will be swabbed will include the inside of the cheek, lip, and gums. This will be completed with a little pressure against the mouth and turning the swab slightly during the process. This will last approximately 20 seconds per swab. This cheek swab will allow us to test for levels of neuroinflammatory enzymes present in saliva.

EEG will be administered using a 19-channel EEG cap and analyzed using Neuroguide V2.8. Participants will be asked to maintain a seated position, while the EEG cap is fitted and proper electroconductance of all 19 electrodes is established with the scalp. This is done by injecting electroconduction gel through opening in each electrode using a blunt needle. Next, electrophysiological signal is recorded from the electrode cap for a 3-minute period. EEG in non-invasive and very minimal risk to the participant, with the exception of slight discomfort from adjustments to the cap on sensitive scalps or maintenance of the seated position for up to 20 minutes.

Brain cooling consists of a 30-minute seated period, in a dimly lit, quiet room, while listening to calming natural sounds, during which participants will wear an Arctic Cooling Cap V1.30, set at a temperature of 33.0 degrees Fahrenheit. Participants will be asked to remain awake, refrain from observing a screen, and relax to the best of their ability. Participants assigned to the control group will be instructed similarly, with the exclusion having the cooling cap turned on.

Directly following either the brain cooling or rest period, neuropsychological tests and questionnaires and EEG administration will be repeated prior to the subject leaving.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Recreation Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-24 years old.

Exclusion Criteria:

• Not currently recovering from neurological injury or illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brain Cooling Treatment; Brain cooling consists of a 30-minute seated period, in a dimly lit, quiet room, while listening to calming natural sounds, during which they will wear an Arctic Cooling Cap V1.30, set at a temperature of 33.0 degrees Fahrenheit. Participants will be asked to remain awake, refrain from observing a screen, and relax to the best of their ability. This brain cooling treatment will occur on 7 consecutive days.	Device: Brain Cooling; Brain cooling consists of a 30-minute seated period, in a dimly lit, quiet room, while listening to calming natural sounds, during which they will wear an Arctic Cooling Cap V1.30, set at a temperature of 33.0 degrees Fahrenheit. Participants will be asked to remain awake, refrain from observing a screen, and relax to the best of their ability. This brain cooling treatment will occur on 7 consecutive days.; Other Names: Selective brain cooling; Cooling cap
No Intervention: Control; The control arm consists of a 30-minute seated period, in a dimly lit, quiet room, while listening to calming natural sounds. Participants will be asked to remain awake, refrain from observing a screen, and relax to the best of their ability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trail Making Test	The Trail Making Test asks participants to trace a line connecting numbers and letters in logical order around a page. They are timed. It tests cognition and processing speed.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
Digit Span Test	The Digit Span test ask participants to repeat strings of digits in either normal or reverse order to test cognition and working memory.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
Beck's Depression Inventory-Fast Screen	The Beck's Depression Inventory-Fast Screen is a 13-item subjective report of depression symptoms.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
HAM-A	the HAM-A is a 14-item subjective report of anxiety symptoms.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
Digit Symbol Test	The Digit Symbol Test is a 90 second test that requires subjects to continually match numbers 1-9 with corresponding symbols. This test measures processing speed, inhibition, and general cognition.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
Neuroinflammatory Cytokines	We will use the saliva acquired from cheek swabs to assess degree of circulating neuroinflammatory serum biomarkers. Specifically, we will examine the cytokines CRP and IL-6 which have been shown to be associated with neurological trauma and brain health.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
The Penn State Worry Questionnaire	The Penn State Worry Questionnaire is a 16-item subjective report of perceived worry.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).
EEG Pattern	The investigators will use the data acquired from EEG to measure specific electrophysiological metrics (electrical field potential from brain activity). Specifically, we will isolate whole-brain relative alpha-power and relative beta-power.	The metrics will be assessed pre-intervention (beginning of Day 1), after the acute effect of brain cooling (at the end of Day 1), and after the chronic effect of brain cooling (Day 8).

Collaborators and Investigators

• Sponsor: Penn State University

Publications and helpful links

General Publications

• Congeni J, Murray T, Kline P, Bouhenni R, Morgan D, Liebig C, Lesak A, McNinch NL. Preliminary Safety and Efficacy of Head and Neck Cooling Therapy After Concussion in Adolescent Athletes: A Randomized Pilot Trial. Clin J Sport Med. 2022 Jul 1;32(4):341-347. doi: 10.1097/JSM.0000000000000916. Epub 2021 Mar 10.
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• Deng H, Han HS, Cheng D, Sun GH, Yenari MA. Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke. 2003 Oct;34(10):2495-501. doi: 10.1161/01.STR.0000091269.67384.E7. Epub 2003 Sep 11.
• Walter A, Finelli K, Bai X, Johnson B, Neuberger T, Seidenberg P, Bream T, Hallett M, Slobounov S. Neurobiological effect of selective brain cooling after concussive injury. Brain Imaging Behav. 2018 Jun;12(3):891-900. doi: 10.1007/s11682-017-9755-2.
• Tan XR, Stephenson MC, Alhadad SB, Loh KWZ, Soong TW, Lee JKW, Low ICC. Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function. J Sport Health Sci. 2024 Mar;13(2):233-244. doi: 10.1016/j.jshs.2023.09.001. Epub 2023 Sep 9.
• Westermaier T, Nickl R, Koehler S, Fricke P, Stetter C, Rueckriegel SM, Ernestus RI. Selective Brain Cooling after Traumatic Brain Injury: Effects of Three Different Cooling Methods-Case Report. J Neurol Surg A Cent Eur Neurosurg. 2017 Jul;78(4):397-402. doi: 10.1055/s-0036-1596057. Epub 2016 Dec 30.
• Leung LY, Cardiff K, Yang X, Srambical Wilfred B, Gilsdorf J, Shear D. Selective Brain Cooling Reduces Motor Deficits Induced by Combined Traumatic Brain Injury, Hypoxemia and Hemorrhagic Shock. Front Neurol. 2018 Aug 3;9:612. doi: 10.3389/fneur.2018.00612. eCollection 2018.

Helpful Links

• publication from the Journal of Cerebral Blood Flow Metabolism describing use of this product in the methods
• Aspen Cooling Systems (product designer)

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Actual): March 1, 2025
• Study Completion (Actual): March 1, 2025

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Neuroinflammation; Cytokines; Mental health; Electroencephalography (EEG); Brain cooling
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: Brain Cooling Biomarkers

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No