section number 1207
TAKE A GUIDED TOUR THROUGH THE BRAIN
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Overview
The following list of locations provide a walk through the brain of H.M. Select each panel to see the corresponding location.

Go to Location 1 of 9

Surgery 'scar'
In the hallmark 1952 surgery, Dr. Scoville used a spatula to lift the frontal lobes of the brain to gain access to the hippocampus. In the process, a small area of the frontal lobe was damaged.

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Hippocampus lesion
Dr. Scoville removed much of the hippocampus bilaterally (on both sides of the brain), and in some cases all that remains is a cavity and a small bit of unhealthy tissue in the surrounding area.

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Hippocampus lesion
The hippocampal lesion in the same tissue slice on the other side.

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Dentate gyrus
Regions of the hippocampus spared in the procedure. The example image shows the region of the dentate gyrus.

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Entorhinal cortex
One advantage of tissue staining is that certain regions, such as the entorhinal cortex (difficult to identify on MRI), can be easily spotted by cell features which allows for a more extensive examination into the extent of the lesion.

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White matter
Patient HM also presented with extensive damage in the deep white matter (regions of the brain that contain the pathways which connect nerve cells).

Go to Location 7 of 9

Epilepsy
A main challenge of the examination of patient HM is distinguishing between the pathology present from HM's epilepsy (such as the lesion in the cerebellum pictured here) and that resulting from the surgery.

Go to Location 8 of 9

Multiplanar reconstruction
Radiology images (MRI, T1) are used as a standard tool in clinical neuroscience. They can be tailor-made to pickup tissue properties, are non-invasive, but have low resolution.

Go to Location 9 of 9

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HISTOLOGY

This panel contains digital images representing histological slices that were stained to reveal primarily neuronal cell bodies. The tissue was mounted on glass slides and treated with solvents and alcohols before being immersed in a solution of Thionin in acetate buffer (a solution that has acidity comparable to that of red wine). Thionin is a basic dye that binds to negatively charged DNA and RNA in the nucleus and cytoplasm of the neuron. Thus, the neurons and the base portion of the axon and dendrites stain deep blue. When viewed at higher magnification, it is possible to see nuclear material and the nucleolus. Staining with Thionin, and other basic dyes like Cresyl Violet and aniline, were famously employed by Franz Nissl, a German contemporary of Alois Alzheimer, to study the cells in the cerebral cortex.

Selected slices can be compared with histological slices from normal control brains.

Note: Thionin also stains much smaller supportive brain cells collectively called neuroglia (or glia). There are several types of glia, including cells that make myelin (the insulating sheath that wraps around nerve axons) and others that provide mechanical support. Microglia are specialized immune cells that protect neurons; these are ubiquitous in the white matter brain of H.M. and are concentrated where the tissue is damaged look for small dark circular dots, approximately 5-10 times smaller than grey matter neurons.

ANATOMY

We conducted thorough delineations on the raw blockface images in order to produce an Anatomical Atlas of the brain of patient H.M. The labels were created based on the 3-D dataset produced from the images acquired during the cutting procedure. Each label is associated with a single brain structure. Links to descriptions and ontological relations are contained in the legend. You can move the mouse over the image and read the anatomical label associated with any particular location. Subdivisions were based primarily on the 3rd Edition of The Atlas of the Human Brain by Y. Mai, G. Paxinos, G. T. Voss. (2007).

We provide distances relative to the anterior commissure (AC), a fiber tract that is widely adopted in the field of brain mapping as a standard anatomical landmark (Talairach and Tournoux, 1988). The brain of H.M. was digitally registered to such a standard co-ordinate system so that the images that we created can be compared to data from other patients or any individual whose brain was scanned with MRI.

RADIOLOGY

This panel contains images acquired with MRI from the fixed brain specimen. We wanted to obtain a 3-D dataset using sequences that would reveal damage in the white matter explicitly. In addition, this scan represents the geometry of the brain after all histological preparation steps were completed. The scans were acquired on a 1.5T General Electric 'Signa EXCITE' scanner using a 8-channel transmit-receive head coil. The brain was enclosed in a Plexiglas chamber and was imaged for several hours in order to improve the quality of the images by increasing the signal-to-noise ratio. In the future, we hope to incorporate in this panel other scans that were acquired while patient H.M. was alive and other high-quality postmortem scans conducted in Boston before the brain was dissected at The Brain Observatory.

In order to zoom move the yellow cross-hair over a feature of interest. Use the keyboard shortcut '+' and '-' to zoom-in and out.

3D MODELS

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Use the buttons labeled with individual brain structures to toggle the display of surface models. If the models appear too small, adjust the view using the zoom-in '+' and zoom-out '-' buttons.

The 3-dimensional (3-D) models were created by manual delineation on the series of blockface images acquired during the brain cutting procedure (Amira software, VSG, Burlington, MA). Each region was outlined in consecutive cross-sectional images and surface-based models were obtained a 'marching-cubes algorithm', triangulation, surface simplification, and smoothing. Models were exported using a custom-build triangulated surface exporter that supports a javascript object notation (JSON) surface file format.

The surface viewer (see aerotwist.com/a3) uses HTML5/WebGL technology to render the surfaces in modern web-browsers such as Chrome, Firefox and Safari. A requirement to be able to see the models correctly is a relatively recent graphics card with 'OpenGL shader' support and updated graphics card drivers. Today, these cards are available in most consumer desktop and laptop computers.


Zoomed-in view of a sub-set of the anatomical surface models.

BLOCKFACE IMAGE

These images were captured while the brain was being sliced. They are called 'blockface' images, referring to the process of acquiring snapshots of the cut surface of the tissue block. In the case of H.M., the methodology was extended to create a true tomographic volume composed of an unabridged series of digital images though the entire brain. The contrast in the image is produced by the main tissue types of the brain; that is, white matter and grey matter. The anatomical data set produced by this process is superior to Magnetic Resonance Imaging data both in terms of contrast and resolution. We acquired the images using a full-frame LR digital camera that was mounted directly above the microtome stage. The native in-plane (x-y) size of the images is approximately 3,000x2,700 pixels. The distance between each image in the third dimension (the z plane) is 0.07 mm. Each image represents a single histological slice; these were archived sequentially, in numerical order, on hard drives and in the freezers respectively.

GUIDED TOUR

This section contains a guided tour through the brain of patient H.M. We have selected crucial or simply interesting locations that show different morphological or pathological features that tell the 'story' of the brain. You can create your own preferred sites and share them with your colleagues by using the 'hot spot' function in the HISTOLOGY panel.