Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans.

Centre for Addiction and Mental Health8 enrolled

Overview

Findings from this study may demonstrate how the insula contributes to reward pathways involved in addiction. There are three main hypotheses for this trial. The first is that inhibiting the insula using transcranial magnetic stimulation (TMS) will not cause noticeable changes of dopamine release in the striatum. The second is that stimulating the insula with TMS will increase dopamine release in the striatum, and will be visualized on PET imaging as decreased radiotracer binding. The third hypothesis is that the participants will not experience major side effects from TMS on the insula.

This project will take advantage of the recently developed Deep rTMS coil to target the insular cortex. Few studies have examined the possibility of using repetitive Transcranial Magnetic Stimulation (rTMS) for nicotine addiction and none so far have explored the use of a coil that specifically targets the insular region. The objective of this study is to test whether low and high-frequency rTMS of the insula modulates striatal dopamine (DA) release in healthy humans. Positron Emission Tomography (PET) with \[11C\]-(+)-PHNO, a radiotracer which is very sensitive to fluctuations in DA transmission in the human brain, will be used to assess the impact of rTMS on dopamine levels. This project will yield the first data in humans linking the insula to the DA system in vivo. These findings could lead to the identification of optimal parameters for Deep rTMS to use secondarily in a proof of principle clinical study in smokers.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Interventions

repetitive Transcranial Magnetic StimulationDEVICE

Each participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging.

repetitive Transcranial Magnetic Stimulation ShamOTHER

The sham coil is built in the same helmet of the active coil. The sham coil is has a circular shape and placed perpendicular to the scalp within the same helmet. This coil produces a similar sound and scalp sensation as the real coil.

Eligibility

Sex: ALLMin age: 19 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy male or female * Between the ages of 19 and 45 Exclusion Criteria: * Pregnancy. * Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning. * Claustrophobia. * Cardiovascular or cerebrovascular diseases. * Major psychiatric disorders including mood, anxiety or psychotic disorders. * History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor. * Gross structural brain abnormalities as revealed by T1 weighted images. * Current use or use during the previous month of medication that may affect the CNS (e.g. neuroleptics, bupropion). * Learning disability, amnesia or other conditions that impede memory and attention.

Outcomes

Primary Outcomes

Changes in [11C]-(+)-PHNO binding

\[11C\]-(+)-PHNO binding at D2/3 receptors will be measured with PET imaging following rTMS at 1Hz, 10Hz, and sham stimulation. Binding at regions of interest will be compared between trial conditions.

Time frame: Participants will complete all sessions in a period of approximately 4 weeks.