Vagus Nerve Stimulation Synchronized fMRI – VNS/fMRI

Daryl E. Bohning, Ph.D.

Medical University of South Carolina, Charleston, SC

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

June 2000, for 3 years

Funding Amount:

$100,000

Investigator Biographies

Daryl E. Bohning, Ph.D.

Professor of Radiology, Medical University of South Carolina

Hypothesis

Hypothesis:
Studies using combined VNS and fMRI (VNS/fMRI) in patients with implanted generators can map both the location and levels of the brain's response to VNS. Referenced to a known stimulation such as a brief tone, VNS/fMRI would provide a basis for objective comparisons of the brain's response to different VNS patterns. That is, a 7-second period of VNS will have brain effects (neuronal activation associated blood flow changes) that are in regions specific to VNS and different than those associated with hearing a simple tone for 7 seconds, but of comparable but characteristic magnitude and duration.

Goals:
1. To implement VNS synchronized fMRI (VNS/fMRI) on a clinical 1.5T MR scanner and demonstrate its ability to: 1) map the areas of the brain showing significant blood-oxygenation-level-dependent (BOLD) response to VNS, and 2) plot the time course of the BOLD response in crucial areas of cerebral cortex in VNS implant patients with clinical depression.

2. To determine whether VNS at high frequency (30 Hz) causes a different pattern and/or level of brain response than VNS at low frequency (5 Hz); all other settings held constant.

3. To assess whether there are changes over time in VNS-produced brain activity in subjects receiving VNS treatment in a clinical trial for depression, and whether those changes are associated with clinical antidepressant response.

Methods:
VNS Stimulation Synchronization: Before putting subjects into the MR scanner, standard adhesive backed MRI ECG electrodes and ECG leads, as used for cardiac imaging, will be placed on the subject over the place where the implanted VNS leads are attached to the vagus nerve. These electrodes will be connected to an independent physiological filter/amplifier located at the foot of the MR scanner bed via shielded leads, which in turn will be connected to a PowerMac personal computer. Once the subject has been moved into scanning position in the scanner bore, the generator signal will be monitored with the PowerMac via the independent physiological filter/amplifier. Using special custom software, the PowerMac will sample the generator signal for a few minutes to determine the precise timing (phase) of the VNS generator stimulation cycle. Once synchronization has been achieved, the generator monitoring leads and electrodes will be removed and the fMRI data acquisition will commence.

VNS/fMRI interleave pattern: During the MRI scan procedure, a 440 Hz tone was fed through the scanner's sound system and interleaved in 7 second trains of 100 ms long pulses, 100 ms apart, on alternate 58.0 sec epochs of a VNS epoch-TON epoch stimulation cycle. During each cycle, 40 15-slice volumes of BOLD-EPI images were acquired at the rate of one volume every 2.900 seconds. The VNS-TON cycle was repeated 10 times.

fMRI Data Processing: fMRI data processing followed standard practice.

Follow-on Funding: The researchers have contracted with Cyberonic, Inc. to use their VNS synchronized fMRI technique (VNS/fMRI) to study the acute and long-term effects of VNS treatment for anxiety.

Selected Publications

Mu Q., Nahas Z., Bohning D.E., Walker J., Anderson B., Denslow S., Johnson K.A., Lomarev M., Moghadam P., Chae J.H., and George M.S. Acute vagus nerve stimulation using different pulse widths produces varying brain effects. Biol Psychiatry. 2004 Apr 15;55(8):816-25 .

Chae J.H., Nahas Z., Lomarev M., Denslow S., Lorberbaum J.P., Bohning D.E., and George M.S. A review of functional neuroimaging studies of vagus nerve stimulation (VNS). J Psychiatr Res. 2003 Nov-Dec;37(6):443-55 .

George M.S., Nahas Z., Bohning D.E., Kozel F.A., Anderson B., Chae J.H., Lomarev M., Denslow S., Li X., and Mu C. Vagus nerve stimulation therapy: a research update. Neurology. 2002 Sep 24;59(6 Suppl 4):S56-61 .

Lomarev M., Denslow S., Nahas Z., Chae J.H., George M.S., and Bohning D.E. Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects. J Psychiatr Res. 2002 Jul-Aug;36(4):219-27 .

Bohning D.E., Lomarev M.P., Denslow S., Nahas Z., Shastri A., and George M.S. Feasibility of vagus nerve stimulation-synchronized blood oxygenation level-dependent functional MRI. Invest Radiol. 2001 Aug;36(8):470-9 .