Relationship Between Autonomic Central Nervous System Activation and Atrial Fibrillation Using Functional MRI (fMRI)

The central nervous system (CNS) consists of the brain and spinal cord and serves as the
collection point of nerve impulses. The peripheral nervous system (PNS) includes all nerves
not in the brain or spinal cord and connects all parts of the body to the CNS. The autonomic
nervous system (ANS), which consists mostly motor nerves, controls functions of involuntary
smooth muscles, glands, and cardiac muscles. The ANS is further divided into the sympathetic
and parasympathetic systems. In relation to the heart, the sympathetic system controls
increases in heart rate, blood pressure, and cardiac output. The parasympathetic system
lowers heart activity and operates during normal situations where the body is not under
stress1, 2.

While the influence of the central nervous system on cardiac rhythm and function is well
accepted, the mechanisms of this control are poorly understood. A preponderance of data
implicates the autonomic nervous system in the development of many cases of atrial
fibrillation (AF)3, 4. The importance of investigating the role of the central nervous
system in the control of the heart rhythm can be appreciated when reviewing the prevalence
of cardiac arrhythmias. AF alone affects 2.2 million adults in the United States. With the
growing aged population, this number can be expected to rise to 5.6-10 million by the year
2050. AF contributes to the development of heart failure and stroke and can precipitate
angina in some patients. New therapies are needed since both surgical and minimally invasive
ablative techniques are associated with a substantial failure rate in addition to the
complications of invasive procedures. Understanding the CNS's role promises to direct new
therapies to improve treatment success and reduce complications associated with therapy for
AF and other arrhythmias.

Direct current (DC) cardioversion (DCCV) is a procedure in which a synchronized electrical
shock is delivered through the chest to the heart via electrodes that are applied to the
skin of the chest and back. Most elective cardioversion procedures are performed to treat AF
or atrial flutter (AFL). The shock causes all the heart cells to contract simultaneously,
thereby interrupting and terminating the abnormal electrical rhythm of AF without damaging
the heart. This interruption of the abnormal beat allows the electrical system in the heart
to regain control and restore a normal sinus rhythm (see Figure 1, Appendix A). Since the
shock can be painful, the patient is usually sedated. Once sedated, the physician charges
the defibrillator to a specified energy level and then delivers the shock. Additional shocks
at higher energy levels can be delivered if the first attempt does not restore sinus rhythm.
Typically patients are able to go home about an hour after the procedure. DCCV will restore
normal sinus rhythm in 90% of patients5.

Newer MRI techniques offer the ability to not only image anatomy, but also to assess brain
activation patterns. Functional magnetic resonance imaging (fMRI) was developed in the early
1990s, and is a variation of magnetic resonance imaging (MRI). The primary purpose of fMRI
is to observe brain function under varying stimuli in a non-invasive way. fMRI uses a
conventional MRI scanner. It takes advantage of the magnetic properties of iron in the
blood. Whenever any part of the brain becomes active, the small blood vessels in that
localized region dilate, causing more blood to rush into that region of the brain. The
blood's iron atoms cause small distortions in the magnetic field around them, which causes
the MRI scanner to be able to read and display an image of the brain's activity. When a
region of the brain is activated, a large amount of freshly oxygenated blood pours into that
structure of the brain, thus causing a small change in the magnetic field, and producing an
MRI signal in the active region6.

Prior studies have utilized heart rate variation or galvanic skin response as an independent
measure of autonomic arousal and compared these measures to fMRI to determine regions of the
brain that are active during sympathetic or parasympathetic arousal 7-11. Studies have
typically identified activation within the anterior cingulate region and insular cortex
during sympathetic activation and in the ventral anterior cingulate in parasympathetic
activation12, 13. Moreover, attenuation of the parasympathetic myocardial innervations by
myocardial fat pad or ablation of parasympathetic ganglionic plexi have been shown to
suppress AF in a significant number of patients presenting with this arrhythmia14, 15.
Whether attenuation of the central autonomic pathways plays a role in initiating AF, or if
atrial arrhythmias may lead to this central attenuation is an open question. This study is
aimed at defining the effect of AF on the central autonomic pathways and vise versa.

Our expectation is that at the end of this study, we will have greater insight into the role
of the central nervous system and more specifically the autonomic nervous system in
modulating AF. We expect that understanding the interaction between the central nervous
system and cardiac arrhythmias will lead to the development of novel therapies that preserve
and restore normal sinus rhythm.

This study will serve as a pilot study with the goal of obtaining additional grant funding
and expanding the study once differences in volumes of activation are demonstrated.

Inclusion Criteria:

- AF patients presenting for DCCV

- Right-handed

Exclusion Criteria:

- Any neuropsychiatric illness, including substance abuse.

- Any medical or neurological disease likely to impact the central nervous system.

- Subject has a metal implant, pacemaker or other contraindication for MRI or fMRI.

- Currently being treated with any medication that affects the central nervous system.

- Women currently pregnant, breastfeeding or of childbearing age not currently taking
or not willing to use a reliable form of contraception.