Functional magnetic resonance imaging (fMRI) is a non-invasive brain imaging method that detects changes in local blood flow that are coupled to neuronal activity when a specific task is performed. This is possible because oxygenated and deoxygenated blood has different magnetic properties that can be measured by the fMRI machine. This phenomenon is called the blood oxygen level dependent (BOLD) effect and is used to create maps of brain activity.

fMRI has been widely used to study abnormal patterns of brain connectivity at rest and activation during a variety of tasks in patients with Parkinson’s disease. fMRI studies in Parkinson’s have led to a better understanding of many aspects of the disease, including both motor and non-motor symptoms.

How fMRI works

fMRI does not directly measure neural activity. Nerve cells transmit messages by generating tiny electrical impulses called “action potentials,” which trigger the release of specific chemicals or neurotransmitters at the synapse (a junction where one nerve cell meets another nerve cell or a muscle cell). The neurotransmitters then modulate electrical activity in the next cell, and this forms the basis for nerve-cell communication.

This local neural activity also changes the relative concentration of blood oxygen levels in that area. The ratio of oxygenated to deoxygenated blood is read by the fMRI machine as a measure of blood oxygen level-dependent (BOLD) response.

fMRI generates activation maps of the brain’s neural activity based on task-dependent BOLD responses, which highlight areas of the brain that are involved in carrying out a particular task. Therefore, fMRI can detect the differences in neural activity within different regions of the brain and help define pathology in case of brain-related disorders such as Parkinson’s disease. It also can be used to monitor disease progression and response to therapy.

How fMRI is performed

fMRI is an outpatient test. During the test, the patient lies down on a table. A brace may be used to hold the head in place. Then the patient is slid headfirst into a long cylindrical machine, which uses a strong magnetic field to scan the brain.

During the test, the patient will be asked to perform specific tasks, such as tapping their thumb against their fingers, looking at pictures, or answering questions on a computer screen. These tasks increase oxygenated blood flow into a particular part of the brain. The test can last from a few minutes to an hour or more.

After the scan is done, a specialist interprets the results.

fMRI use in Parkinson’s disease

fMRI has been widely used to study abnormal patterns of brain connectivity at rest and activation during a variety of tasks in patients with Parkinson’s.

The technique has multiple clinical applications, including early disease detection, a better understanding of motor and non-motor symptoms, and predicting changes in clinical status as the disease progresses or as a consequence of medication. It also can be used as a biomarker of alterations in brain physiology related to therapeutic agents and rehabilitative strategies.

Some examples of clinical applications of fMRI:

  • A study analyzing resting-state fMRI (rsfMRI) demonstrated Parkinson’s disease-related changes in neural activity and connectivity, which could be used to differentiate Parkinson’s patients from healthy controls.
  • fMRI studies also have shown that tremor signals originate from an area of the brain called the basal ganglia and then amplify in another area called the cerebellothalamocortical pathway.
  • fMRI analysis demonstrated unique patterns of brain activity in patients with Parkinson disease and other neurological conditions, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). This suggests functional changes between the three different brain-related disorders.
  • Real-time fMRI during brain surgery can be used to determine the clinical outcomes of therapy such as deep brain stimulation (DBS). A clinical trial (NCT01809613) completed in 2017 showed that DBS in patients with Parkinson’s results in significant changes in the motor network compared to the non-motor network.
  • fMRI studies also showed that medications that aim to increase the levels of dopamine in the brain, the cell-signaling molecule lacking in Parkinson’s disease, drive distinct connectivity changes in the brain, some of which are associated with improved motor symptoms.

Clinical trials underway

There are several clinical trials currently underway that are exploring newer clinical applications of fMRI for Parkinson’s patients.

Some of these clinical trials are:

  • The Institut National de la Santé et de la Recherche Médicale, France, is conducting a case-control study (NCT02488395) to evaluate whether light responses in the superior colliculus region of the brain can be used as an early biomarker to identify Parkinson’s disease. The light responses are being evaluated using fMRI imaging. This study, which is still recruiting participants, began in July 2015 and is estimated to be finish in April 2019.
  • The Laboratory for Rehabilitation Neuroscience at the University of Florida, in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS), is conducting a Phase 2 randomized and placebo-controlled clinical trial (NCT02789020) using fMRI and MRI imaging. It will investigate how the brain and motor behaviors change in Parkinson’s patients over time in response to rasagiline, a monoamine oxidase-B(MAO-B) inhibitor. This study began in June 2016 and is scheduled to be completed in December 2020. It is still recruiting participants.
  • A randomized, double-blind clinical trial (NCT03623386) at Yale University is examining the effects of fMRI-based neurofeedback on brain plasticity (the brain’s ability to change or “re-wire” itself) and motor performance in Parkinson’s patients. This study is still recruiting participants and is expected to finish in August 2020.
  • A case-controlled clinical trial (NCT01496599) to screen biomarkers — by comparing brain images of people with Parkinson’s disease and healthy volunteers using various imaging techniques such as fMRI — is currently recruiting participants in Maryland. The goal of this study is to identify biomarkers that can be used to predict Parkinson’s early and then follow these biomarkers to document disease progression over nine years.

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