But First ...

• Patients are conscious when they undergo the procedure.
• They often are sent home on the same day.
• Anti-anxiety drugs used during HR acceleration (the least comfortable part of the procedure).
• The actual deployment of the stent+valve takes about 5 seconds, so period of accelerated HR is very short.
• Recovery time is relatively short since incisions only involve those used for cathethers.
• Once catheter is for the valve, another for electrical apparatus to electrically stimulate the heart and (I think) for a scope to watch the placement of the valve.
• The stent-new valve goes in right on top of the old valve.
  
• Conventional equipment is kept on hand in case the procedure does not go as planned. 
  

Introduction to Today's Material

Last time we talked about ...
 

The geography of the brain  The brain stem  The cerebellum Cerebrum

Lobes and locations of functions.

 
 

Our "hard wired" sensory input centers.

A bit more on the transduction problem. Last class I mentioned that there were really 2 parts to transduction:

• There's the transducer.
• The transducer converts (in our case) the environmental signal to an electrical signal (a current).
• There is also a second part to the problem: The circuitry that interprets the current and makes it meaningful to the "user".

Here is a meter used to measure the amount of oxygen in water.   The sensor (white piece, at the end of the cord) creates a current that is proportional to the amount of oxygen in the water. The meter measures the current and converts it into oxygen concentration. Together, the sensor and meter are a solution to the transduction problem. Both parts are necessary.

Our receptor cells are like the sensor in this example.

The circuitry in the sense centers and association areas of our brain provide the metering: they make sense of the current inputs.
 

The motor cortex (for directing currents to efferent neurons).

Here is another view of the left sensory (1) and left motor (3b) cortexes.

We talked about association areas. Lower order (right column colors) - associated with specific sensory centers.  Higher order (gray) - can synthesize output from multiple lower order areas or work independently. The human brain has a high percentage of association areas compared to other organisms, which reflects our greater cognitive ability relative to the other creatures on our planet.

Methods to Study Brain Function

Earliest Method: Study How Brain Damage Effects Behavior and Performance
 

Accidental lobotomy of Phineas Gage (1848) Phineas Gage was a railroad worker in the 19th century living in Cavendish, Vermont.  One of his jobs was to set off explosive charges in large rock in order to break them into smaller pieces.  On one of these instances, the detonation occurred prior to his expectations, resulting in a 42 inch long, 1.2 inch wide, metal rod to be blown right up through his skull and out the top.  The rod entered his skull below his left cheek bone and exited after passing through the anterior frontal lobe of his brain.

Remarkably,  Gage never lost consciousness, or quickly regained it (there is still some debate), suffered little to no pain, and was awake and alert when he reached a doctor approximately 45 minutes later.  He had a normal pulse and normal vision, and following a short period of rest, returned to work several days later.
 

Effects: Gage’s personality, reasoning, and capacity to understand and follow social norms had been diminished or destroyed.  He illustrated little to no interest in hobbies or other involvements that at one time he cared for greatly.  Quote about Gage by a contemporary person: "After the accident, Gage became a nasty, vulgar, irresponsible vagrant. His former employer, who regarded him as the most efficient and capable foreman in their employ previous to his injury, refused to rehire him because he was so different."

There have been many other opportunities to study damaged brains to see how the damage effected behavior and performance.
 

Deliberately inflicted damage was the purpose of the "frontal lobotomy" (literally, removal of the frontal lobe).

Injuries to the frontal lobe (including those from lobotomies) showed multiple personality and performance alterations.
 

This table shows specific effects of frontal lobe injuries.

Non or Minimally Invasive Procedures

Electroencephalogram (EEG).
 

The EEG measures the activity of large numbers (populations) of neurons.  First recorded by Hans Berger in 1929.  EEG recordings are noninvasive, painless, do not interfere much with a human subject's ability to move or perceive stimuli, are relatively low-cost.  Electrodes measure voltage-differences at the scalp in the microvolt range.  Voltage-traces are recorded with millisecond resolution - (fMRI and PET don't respond as quickly).

The necessity for nerve activity to be synchronous to get useful information has resulted in focusing on waveforms in brain electrical activity.

Positron Emission Tomography (PET).
 

Watch the first 2 minutes of this video. Injection of mildly radioactive substance (water, glucose, etc.).  Blood (mostly water) and sugar will concentrate where metabolism is greatest.  Regions with greatest gamma emission have highest blood/sugar service and are most active.  Applied to the brain, this allows activated regions to show up. Expensive, resolution not as good a fMRI.  But still widely used because subject can be somewhat active (i.e., reading aloud) without destroying the image (not true for fMRI).

Magnetic Resonance Imagery (MRI). MRI (not fMRI) is based on radio waves produced when a strong magnetic field polarizes hydrogen atoms. The poles of the atoms align. When the magnetic field is removed, the atoms revert to their initial position and emit a radio wave as they change back. The MRI measures and localizes the radio wave production. Since different tissue types have different concentrations of water, it is possible to create images of internal structures based on radio wave production and position.  MRI's are used to make images of structure.

Functional Magnetic Resonance Imagery ( fMRI ).
 

A fMRI works a bit differently.  It's still based on imposing and removing a magnetic field to measure radio wave production and position, BUT ... It is looking specifically at hemoglobin.  The iron component changes slightly as it loses oxygen in it's radio wave producing properties. Areas where this change is occurring the most are the most metabolically active. In the brain, they are the parts that are most active (which require the greatest blood supply. An MRI maps structure. An fMRI maps function (metabolic activity).

Resolution is better with fMRI than with PET.  Subject must remain still.

Combined MRI / fMRI

Some Results from PET and fMRI Work
 
 

PET and fMRI scans can show fairly clearly where specific activities occur in the brain.

Pet scans pertaining to language.
 

In image to right, frontal lobe (reasoning) is left, occipital (vision) is right, and temporal lobe (auditory and memory) extends from right to lower left.  Passive viewing activates vision center and vision center association areas.  Speaking words involves Broca's area (organizes motor commands for verbalization) and the motor cortex (exports appropriate currents to efferent neurons). Listening involves auditory center, wiernicke's area (assigning meaning to the sound) and ). Generating verbs - subject is shown a picture of something and then asked to think of a verb that is associated with the picture. Picture of a car - subject thinks of "driving" or "traveling". Involves memory (temporal lobe) and thinking (in frontal lobe).

What does it mean to be in a "vegetative state"?  At least some of the brain centers involved with listening a functioning.

Imagining activity: Subject imagined self hitting a tennis ball.  What lit up?

Second study on a vegetative state woman.

Why does learning hurt?  A great deal of effort (mental work) is required to learn something new.  Most effort in the thought and memory areas. Once learned, thought and memory become less important and doing the task becomes predominate. The task shown at right is one that can be mastered and, as a result, no longer requires thought. Notice the reduction of the activity of the frontal lobe. "Thinking" about the task becomes unnecessary.

The game Minesweeper provides an example of how the need for thought can be replaced by pattern recognition (no thought).  "nb" (no brainer) operations require little or no reasoning: they are one step. The left nb has a "1" that only touches the corner block. We know a mine is there. The right nb's have a "2" that only touches 2 blocks. We know that mines must be there. These are single step operations. Multi step operations require 2 or more reasoning steps. Pattern recognition reduces the operation to a single step once the pattern is recognized. The blocks having known values after the player is "trained" are indicated by a "T". In the leftmost image, 2 steps are required to get each of the T's. The 3 adjacent T's in the rightmost image are also known because of a 2 step operation.  The mines at the 2 nb's are known from the leftmost "2".  Since those 2 mines correspond to the rightmost 2 as well, the 3 T's must contain no mines. The lower T is the rightmost image requires 3 steps. There are 2 mines because of the "2".  There is 1 mine because of the "1". Hence the T must be a mine. The difference between a beginner and a player with a little experience would likely resemble the difference observed in the "unpracticed" and "practiced" subjects in the illustration, above.

There are many activities that we carry out without having to think much about them. In many cases, they required intense effort to learn them but, once learned, they become skills that we can apply without significant effort.

You all probably remember learning to ride a bike. Once the skill was developed, you could ride without very much thought. While learning, however, you had to work very hard.

• First you wobbled and fell.
• Then you wobbled but fell less frequently.
• Then you just wobbled.
• Then you could ride.

There was a similar huge project that you undertook that you probably don't recall: learning to walk.
 

My grandson, Trey, began the process last summer (when he was approaching 1 year old). Here we see him working hard at getting up on two feet and taking a couple of steps with the support of the wall.  He's got some of the neural circuitry complete, but there is more to build. (double click on the video to make it run)

Here we see him taking his first two steps (several weeks later).  He's managing all the sensory input and using it to send coordinated electrical currents to a variety of muscle groups. This is the difficult control and balancing act that we call walking.  The prototype circuitry is mostly working, but needs refinement. (I don't know how to get rid of the controls in this video; anyone know how to do this?)

Here we see him about a month after the last video.  He has grown the electrical circuits that allow him to be a proficient walker!  Well, almost.  Soon he'll walk without conciously thinking about it.

Activities that always require conciously using sensory input and carefully controlling muscle output
 

There are other activities that always require thought and concentration. These are activities that we frequently associate with our professional lives.  They always require care and attentiveness. The image at right is of an amateur and a professional violinist. What we see indicated in the fMRI at right is what happens following years of intensive practice. The neural circuits used appear to be more well defined. Refinement of the neural circuitry in the professional is much more pronounced and is the result of years of practice!

Learning does not happen with one reading or even a night of cramming.  The video at right does NOT show us the way learning happens.  There is no substitute for the intellectual heavy lifting that builds circuits in our brains.

Glial Cells

In addition to neurons, glial cells are important functional entities in the brain. They are also very numerous (making up nearly 90% of the brain's cells).
 

There are 3 different types of glial cells. The most numerouse and important are astrocytes.

It's been known for some years that: Glial cells nourish and protect neurons. They appear to be able to create and deactivate synapses.  They alter their functions to respond to brain injury.  They can signal precapillary sphincters to open capillary beds to increase circulation of blood when neurons in a particular area become active. This is why we can use functional MRI imaging to follow brain activity.

• They are not able to depolarize/repolarize (so they cannot conduct electrical currents).
• But they can release neurotransmitting substances (e.g., glutamate).
• So they may be able to initiate or inhibit intracellular currents in neurons.
• The cytosols of adjacent glial cells are directly connected with each other via “gap junctions” through which they can pass various metabolites.
• It is through these junctions that astrocytes evacuate to the capillaries the excess extracellular potassium generated by intense neuronal activity.
• This network of intercommunicating astrocytes behaves like a single inter-connected entity.
• The astrocytic extensions surrounding the synapses might thus exert a broader control over the concentration of ions and the volume of water in the synaptic gaps.
• "The network of astrocytes may constitute a non-synaptic transmission system superimposed on the neuronal system to play a major role in modulating neuronal activities." (source of quote and preceding several ideas).