Glucose and Non-Invasive Brain Stimulation

Modulation of Motor Cortex Excitability by Glucose Administration

Purpose: In this study, the investigators will delineate how brain network dynamics are modulated by experimentally induced elevated blood glucose levels and examine how glucose levels gate neuronal excitability measured by the response to TMS.

Participants: Participants must be between the ages of 18 and 65 with no known diabetes, no known adverse reaction to finger prick blood draw, and no known neurological or psychiatric illness. Participants must have a body-mass index less than 30.

Procedures: Participants will consume either a drink that contains 75 g of glucose or a placebo, and their response to TMS will be measured to examine the effect of glucose on motor cortex excitability.

Study Overview

• Status: Terminated
• Conditions: Glucose Metabolism Disorders
• Intervention / Treatment: Device: Single-pulse TMS

Detailed Description

This study will be a placebo-controlled study that investigates brain function with both electroencephalography (EEG) and TMS. On each study visit, a drink (either glucose drink or water) is administered after baseline assessment of fasting glucose. Changes in brain activity and excitability will be measured with resting-state EEG. Periodic high-density EEG of resting-state brain activity and activity during a working memory task will be performed before the administration of the drink, immediately after the administration of the drink, as well as 30 minutes, 60 minutes, 120 minutes, 150 minutes, and 180 minutes after the administration of the drink. The spectral content of the EEG signal will be investigated to identify the relative presence of cortical oscillations. Primarily, there will be a focus on theta (4-8 Hz) and alpha (8-12 Hz) oscillations.

Previous literature indicates that theta and alpha oscillations represent an engaged and disengaged cortical state, respectively [1]. Alpha and theta oscillations are implicated in cognitive function and are altered in depression. Therefore, this study aims to identify a decrease in frontal theta oscillations and an increase in left frontal alpha oscillations, two defining features of impaired top-down control and mood regulation, in response to the glucose drink contrasted with the response to the placebo.

The study will also examine how glucose levels gate neuronal excitability measured by the response to TMS. Cortical excitability will be measured by applying TMS pulses to the motor cortex and measuring the response in the form of a motor evoked potential by electromyography (EMG). TMS will be applied before the administration of the drink, immediately after the administration of the drink, as well as 30 minutes, 60 minutes, 120 minutes, 150 minutes, and 180 minutes after the administration of the drink. Changes in blood glucose will be monitored over this time interval as well.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Medical School Wing C

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Right-handed
• BMI <30
• Free of major neurological conditions and diabetes

Exclusion Criteria:

• Diabetes
• Adverse reaction to finger prick blood draw
• Known neurological or psychiatric illness
• Prior brain surgery
• Any brain devices/implants, including cochlear implants and aneurysm clips
• Cardiac pacemaker
• Any other implanted electronic device
• History of current traumatic brain injury
• Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glucose drink followed by placebo; Participants will consume the glucose drink at session 1, then they will consume the placebo (water) at session 2.	Device: Single-pulse TMS; Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG).; Other Names: MagPro X100
Experimental: Placebo followed by glucose drink; Participants will consume the placebo (water) at session 1, then they will consume the glucose drink at session 2.	Device: Single-pulse TMS; Single-pulse transcranial magnetic stimulation (TMS) on the motor cortex will lead to a twitch in the target muscle and evoke a motor-evoked potential (MEP) measured by electromyography (EMG).; Other Names: MagPro X100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Evoked Potential (MEP)	Change in MEP over time to indicate changes in motor cortex excitability	Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
TMS Evoked Potential (TEP)	The TMS Evoked Potential (TEP) is the difference in microvolts from 25 milliseconds after a TMS pulse versus pre-TMS such that greater values indicate greater motor cortex excitability. The measure of the change in TEP over time since either glucose or water was consumed approximates a z-distribution with a range of -20 to 20 with central distribution measures of zero. TEPs were source localized and reported using a pseudo-neural activity index (PNAI) expressing source activation in relation to pre-TMS pulse trial baseline. The difference in the source peaks corresponding to the early P25 component have been reported as differences from baseline. Higher values indicate greater cortical excitation, consistent with the study hypothesis.	Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG Measure of Alpha Asymmetry Oscillations	Electroencephalography will be used to measure the change in lateralized alpha asymmetry (10-12 Hz electrical activity) over time	Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
EEG Measure of Frontal Midline Theta Oscillations	Electroencephalography will be used to measure the change in frontal midline theta power (5-8 Hz electrical activity) over time	Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.
Working Memory Task Accuracy	This outcome will analyze the change in accuracy in a computerized working memory task over time. During the task, subjects will be presented with an array of colored squares. Then, they will need to hold this array in mind during a delay period. Finally, participants will be tested on their memory of the array by responding whether a presented color is the same or different as the corresponding square in the first array. Participants' accuracy will be expressed as the percentage of correct responses (from 0% correct responses to 100% correct responses). An accuracy rate of 50% indicates that the participant is performing at the same accuracy level as random chance.	Measurements will be taken before the administration of the drink, as well as 0, 30, 60, 120, and 180 minutes after the administration of the drink.

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Flavio Frohlich, Carolina Center for Neurostimulation

Publications and helpful links

General Publications

• Stitt I, Zhou ZC, Radtke-Schuller S, Frohlich F. Arousal dependent modulation of thalamo-cortical functional interaction. Nat Commun. 2018 Jun 25;9(1):2455. doi: 10.1038/s41467-018-04785-6.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2019
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: July 18, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders
• Other Study ID Numbers: 19-1451

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication.
• IPD Sharing Access Criteria: IRB, IEC, or REB approval, as applicable, and execution of a data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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