Intermediate Physics for Medicine and Biology: Magnetoencephalography: Theory, Instrumentation, and Applications to Noninvasive Studies of the Working Human Brain

Screenshot of the title and abstract of Hämäläinen, Hari, Ilmoniemi, Knuutila, and Lounasmaa, "Magnetoencephalography: Theory, Instrumentation, and Applications to Noninvasive Studies of the Working Human Brain. Rev. Mod. Phys. 65:413-497, 1993.

Hämäläinen et al. (1993).

In Chapter 8 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I cite one of my favorite review papers: “Magnetoencephalography: Theory, Instrumentation, and Applications to Noninvasive Studies of the Working Human Brain,” by Matti Hämäläinen, Rita Hari, Risto Ilmoniemi, Jukka Knuutila and Olli Lounasmaa (Reviews of Modern Physics, Volume 65, Pages 413-497, 1993). The authors worked in the Low Temperature Laboratory at Helsinki University of Technology in Espoo, Finland. Even though this review is over 25 years old, it remains an excellent introduction to recording biomagnetic fields of the brain. According to Google Scholar, this classic 84-page reference has been cited over 4500 times. Below is the abstract.

Magnetoencephalography (MEG) is a noninvasive technique for investigating neuronal activity in the living human brain. The time resolution of the method is better than 1 ms and the spatial discrimination is, under favorable circumstances, 2—3 mm for sources in the cerebral cortex. In MEG studies, the weak 10 fT—1 pT magnetic fields produced by electric currents flowing in neurons are measured with multichannel SQUID (superconducting quantum interference device) gradiometers. The sites in the cerebral cortex that are activated by a stimulus can be found from the detected magnetic-field distribution, provided that appropriate assumptions about the source render the solution of the inverse problem unique. Many interesting properties of the working human brain can be studied, including spontaneous activity and signal processing following external stimuli. For clinical purposes, determination of the locations of epileptic foci is of interest. The authors begin with a general introduction and a short discussion of the neural basis of MEG. The mathematical theory of the method is then explained in detail, followed by a thorough description of MEG instrumentation, data analysis, and practical construction of multi-SQUID devices. Finally, several MEG experiments performed in the authors laboratory are described, covering studies of evoked responses and of spontaneous activity in both healthy and diseased brains. Many MEG studies by other groups are discussed briefly as well.

Russ and I mention this review several times in IPMB. When we want to show typical MEG data, we reproduce their Figure 47, showing the auditory magnetic response evoked by listening to words (our Fig. 8.20). Below is a version of the figure with some color added.

Reproduction of Fig 47 from Hämäläinen et al. (1993), showing an auditory evoked magnetic field from the brain.

Effect of attention on responses evoked by auditorily presented words.
The subject was either ignoring the stimuli by reading (solid trace)
or listening to the sounds during a word categorization task (dotted trace);
the mean duration of the words is given by the bar on the time axis.
The field maps are shown during the N100m deflection and the sustained
field for both conditions. The contours are separated by 20 fT and the dots
illustrate the measurement locations. The origin of the coordinate system,
shown on the schematic head, is 7 cm backwards from the eye corner,
and the x axis forms a 45 angle with the line connecting the ear to the eye.
Adapted from Hämäläinen et al. (1993).

We also refer to the article when discussing SQUID gradiometers, which they discuss in detail. Russ and I have a figure in IPMB showing two types of gradiometers; here I show a color version of this figure adapted from Hämäläinen et al.


Red: a magnetometer. Green: a planer gradiometer. Blue: an axial gradiometer. Purple: a second-order gradiometer. Adapted from Hämäläinen et al. (1993).

In Chapter 11 of IPMB, Russ and I reproduce my favorite figure from Hämäläinen et al.: their Fig. 8, showing the spectrum of several magnetic noise sources. Earlier in our book, Russ and I warn readers to beware of log-log plots in which the distance spanned by a decade is not the same on the vertical and horizontal axes. Below I redraw Hämäläinen et al.’s figure with the same scaling for each axis. The advantage of this version is that you can easily estimate the power law relating noise to frequency from the slope of the curve. The disadvantage is that you get a tall, skinny illustration.

A reproduction of Fig. 1 from Hämäläinen et al. (1993), showing peak amplitudes and spectral densities of fields due to typical biomagnetic and noise sources.

Peak amplitudes (arrows) and spectral densities of
fields due to typical biomagnetic and noise sources.
Adapted from Hämäläinen et al. (1993).

I like many things about Hämäläinen et al.’s the review. They present some lovely pictures of neurons drawn by Ramon Cajal. There’s a detailed discussion of the magnetic inverse problem, and a long analysis of evoked magnetic fields. In IPMB, Russ and I mention using a magnetically shielded room to reduce the noise in MEG data, but don’t give details. Hämäläinen et al. describe their shielded room:

The room is a cube of 2.4-m inner dimensions with three layers of μ-metal, which are effective for shielding at low frequencies of the external magnetic noise spectrum (particularly important for biomagnetic measurements), and three layers of aluminum, which attenuate very well the high-frequency band. The shielding factor is 10³—10⁴ for low-frequency magnetic fields and about 10⁵ for fields of 10 Hz and above.

They show a nice photo of a subject having her MEG measured in this room; I hope she’s not claustrophobic.

The authors were members of a leading biomagnetism group in the 1990s. Matti Hämäläinen is now with the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and is a professor at Harvard. Rita Hari is an emeritus professor at Aalto University (formerly the Helsinki University of Technology). Risto Ilmoniemi is now head of the Department of Neuroscience and Biomedical Engineering at Aalto. Olli Lounasmaa (1930—2002), the leader of this impressive group, was known for his research in low temperature physics. In 2012 the Low Temperature Laboratory at Aalto was renamed the O. V. Lounasmaa Laboratory in his honor.

What do I like best about the Finn’s landmark review? They cite me! In particular, the experiment I performed as a graduate student working with John Wikswo to measure the magnetic field of a single axon.

Wikswo et al. (1980) reported the first measurements of the magnetic field of a peripheral nerve. They used the sciatic nerve in the hip of a frog; the fiber was threaded through a toroid in a saline bath. When action potentials were triggered in the nerve, a biphasic magnetic signal of about 1 ms duration was detected. Later, the magnetic field of an action potential propagating in a single giant crayfish axon was recorded as well (Roth and Wikswo, 1985). The measured transmembrane potential closely resembled that calculated from the observed magnetic field. From these two sets of data, it was possible to determine the intracellular conductivity.

The videos below, presented by several of the authors, augment the discussion of biomagnetism in Intermediate Physics for Medicine and Biology, and provide a short course in magnetoencephalography. Enjoy!