Magnetoencephalography Opens a Window into Brain Connectivity Across Diverse Neuropsychiatric Conditions

By Patricia Klaas, PhD, and John C. Mosher, PhD

Magnetoencephalography (MEG) is useful for identifying pathways of connectivity in the brain in various patient populations so we can better understand what happens — and why — when connectivity goes awry.

Cleveland Clinic has one of the most clinically prolific MEG laboratories in the United States and is researching MEG’s use for a number of applications. This post reviews MEG’s emerging utility for examining brain connectivity across various neuropsychiatric conditions.

Making sense of the brain’s weak magnetic fields

Unlike functional MRI, which uses strong magnetic fields, MEG instead measures the extraordinarily weak magnetic fields generated by brain functions. Using no radiation or magnetic fields, sensors in a helmet (gradiometers and/or magnetometers) pick up the magnetic fields generated by the brain’s electrochemical activity. Because the generated magnetic field is quite small — about 1 billion times smaller than the earth’s magnetic field — its acquisition requires specialized electronics and a magnetically shielded room.

Advantages over other modalities

MEG offers advantages over electroencephalography (EE G) in that it provides for easy acquisition of very-high density (approximately 100-300 channels) wideband (DC – 2000 Hz) recordings of currents within the brain and with high dynamic range. Magnetic fields, in contrast to scalp potentials, suffer minimal attenuation and distortion from the various tissues that the electrical currents have to cross to reach the scalp surface. Whereas more frequently used functional imaging modalities (fMRI, SPECT and PET) have poor temporal resolution, MEG records activity in real time with excellent temporal resolution (< 1 ms). Single focal sources can be localized with good resolution (1-5 mm).

How MEG is used

MEG is frequently used to help localize seizures in patients with intractable epilepsy as well as to examine neurophysiologic responses (evoked magnetic fields) to visual, auditory and tactile stimuli.

After a MEG study has been obtained, the information is processed to allow determination of dipoles that indicate the area in which the activity (or the highest amount of activity) is occurring. The analyst uses coregistration software to localize the dipole on the patient’s MRI. The result is an image that identifies the areas (in the case of epilepsy) where spikes or asynchronous activity were observed during MEG acquisition (Figure 1).

The MEG lab at Cleveland Clinic has obtained MEG studies from more than 700 patients since its inception in 2008. Our ongoing research involving MEG includes the following:

• Examination of language lateralization
• Use of MEG with neurosurgical mapping techniques to localize epileptogenic zones in patients with medically intractable epilepsy
• Development of algorithms to improve the information obtained

Neurophysiologicresponses to stimuli

In the case of neurophysiologic responses to stimuli, many studies have examined the median nerve response to electrical stimulation. This research has determined that different patient populations may respond more slowly than control subjects due to changes in conductivity caused by the disease process.

Other studies have determined that age is a significant mediating factor to be considered when analyzing MEG results. Other factors to consider when using MEG include medications the subject is taking and, in some cases, the subject’s height, as taller individuals have longer latencies to median nerve stimulation due to the necessarily longer path to the cortex.

Figure 2 depicts the median nerve response, as determined by MEG after processing of the evoked magnetic field, in the pre- and postcentral cortex at 36 ms. Patients with intractable epilepsy show a great deal of variability in their response to this stimulation.

Psychiatric applications

Other research has used MEG to assess pre-attentive dysfunction in bipolar disorder and has determined that at the pre-attentive level, information processing is impaired in patients with bipolar disorder.

MEG also enables analysis of temporal correlations or coherence within a number of populations. Clinical research has examined neural coherence in dementia and bandwidth differences in patients with schizophrenia, and other studies have sought to develop a neural marker in patients with depression to help distinguish them from patients with bipolar disorder.

Patients with autism have been studied to determine whether MEG can help identify a neural marker or if differences exist in connectivity.

Studies in connectivity, like the recent investigation by Hinkley et al, have examined the role of corpus callosum development “in integrating information and mediating complex behaviors.”

Utility continues to grow

MEG is an extremely useful technique that is being employed more frequently in research examining brain connectivity in populations with depression, Alzheimer disease, Parkinson disease, schizophrenia, leukemia, multiple sclerosis and many other diseases. Its high temporal and spatial resolution allows for examination of changes in brain activity with greater temporal resolution than fMRI and greater spatial resolution than EEG.

Dr. Klaas is an associate staff member in Cleveland Clinic’s Center for Behavioral Health and Department of Psychiatry and Psychology. She also has appointments in Cleveland Clinic Lou Ruvo Center for Brain Health, the Epilepsy Center and the Department of Neurosciences.

Dr. Mosher is a staff member in Cleveland Clinic’s Epilepsy Center

Figure 1 (on the left). MEG-enabled dipole localization on MRI demonstrating epileptogenicity (yellow markers).

Figure 2 (on the right). Activity in the pre- and postcentral cortex, as determined by MEG after processing of the evoked magnetic field, following median nerve stimulation.