Friday, April 30, 2010

We spend about one third of our lives asleep. This, if you think about it, is a pretty astounding percentage. Historically, this very important part of our brain’s health has been ignored until the last century. Partly, this because we had no method to really study the phenomenon. The EEG gave us the ability to observe the brain’s electrical activity during sleep, and beginning in the 1950s sleep research became a reality. Now, most major hospitals have sleep laboratories for diagnosing sleep disorders. In addition, neuroscientists have studied the mechanisms by which the brain produces sleep.

There is no single sleep center in the brain. Rather, there are nuclei along the brain stem into the base of the brain (hypothalamus) that are actively involved in producing and maintaining sleep. These centers are also associated with the activating systems that produce wakefulness. An old anatomic name for this arrangement of neurons was the reticular activating system. One of the neurotransmitters in these nuclei is serotonin, synthesized from the amino acid tryptophan. This is perhaps one reason it is common to become sleepy after eating a meal loaded with tryptophan – turkey, pumpkin seeds, cheddar and other cheeses.

Because we are not conscious during sleep we tend to think of the state as equivalent to putting a transmission in neutral, with the foot off the gas. It really is an active process. As we fall asleep the brain waves begin to slow and transition into a state termed Slow Wave Sleep. Subjects may dream during SWS, but the images are ill formed and difficult to recall if the subject is awakened. After about ninety minutes the EEG speeds up and our limb muscles become relative paralyzed, while our eyes begin moving in rapid jerks. This is termed rapid eye movement sleep. If you’ve ever watched a pet dog sleep you may see the eyes moving behind the lids. It is during this period we have our most vivid and easily recalled dreams. REM episodes last approximately 20 minutes before quieting down to SWS. As time passes, the REM periods begin to occur more frequently but last the same duration.

Why do muscles become paralyzed during REM sleep? Scientists don’t know for sure but suspect it may be an evolutionary advantage. It wouldn’t be good news to start moving around while asleep in a tree.

There are problems that can occur if the sleep centers become active during wakefulness. One of the most commonly known is narcolepsy, a sleep disorder characterized by excessive sleepiness. Two major forms happen depending upon the presence or absence of the muscle paralysis that accompanies REM sleep. If an attack of REM occurs during wakefulness, the patient can become extremely weak and even fall. This is known as cataplexy. Without the REM component, patients may just fall asleep at their desk or on an assembly line, which obviously can result in severe workplace accidents. For years this has been treated with stimulants like amphetamine. A newer drug, Nuvigil, has also been introduced.

Another cause of excessive sleepiness is inadequate regular sleep due to airway obstruction. For patients who have anatomical causes – such as overgrown tonsils – surgery may be helpful. Extreme obesity can also cause obstruction. Dickens wrote about an extremely fat person who constantly fell asleep. This is now recognized as Pickwickian syndrome.

The take-home message is that sleep disorders are now easily diagnosed and treated. But they need to be worked up at a comprehensive sleep center.

Tuesday, April 27, 2010

One of my wife’s favorite movies is The English Patient, primarily because she loves Ralph Fiennes, the male lead. I like it because the depiction of amnesia is very realistic. The word comes from Greek and refers to a memory disturbance, and the experience is more global than a person being able to recall who he or she is.

Memory is a complex process that includes recognizing an event, person, or object and then storing it in the brain. But memories are of no value unless they can also be retrieved. Typically, amnesia results from disrupting either the laying down or the retrieval of memory. The causes have traditionally been divided into “organic” or “functional.” Organic causes include damage to the brain through physical injury (like the plane crash in The English Patient), neurological disease such as Alzheimer’s disease, or the use of certain (generally sedative) drugs (my favorite is alcohol). Functional causes are psychological factors such as mental disorder, post-traumatic stress or, in psychoanalytic terms, defense mechanisms.

As we experience things the circuits in our brain are activated and monitored by the process we call consciousness. This is purely an electrical phenomenon served by multiple networks of neurons. The moment our attention turns to something else, so does the firing of the involved neurons. But for several seconds a trace of activity remains, just like the spot that lingers after staring into a bright light and closing your eyes. This is the first hint of memory, because the trace is now of something in the past. If this is not worth saving the signal is overtaken by other experiences. If, however, it’s something we want to remember a chemical reaction begins that takes several hours. Scientists are not exactly sure how memories are stored chemically, but hints suggest it involves a protein. Sleep, particularly slow-wave sleep, probably has a significant role in consolidating memories.

Also poorly understood is how memories are retrieved and brought back to consciousness. Specific brain areas, such as the temporal lobe, are rich in memories, but removal of a temporal lobe does not necessarily result in significant memory loss. However, the destruction of both hippocampi results in the inability to lay down or retrieve memory.

As newer more sophistocated methods are developed that can unravel the physiology of the brain, more of these questions will be answered. This is an exciting time in brain research.

Wednesday, April 21, 2010

The April 20 edition of the online publication of NATURE published a study showing that in more than 11,000 healthy adults between 18 and 50 years of age brain training exercises were of no benefit. The group did the exercises three times a week for 6 weeks. At the end of the study the ones trained actually showed less improvement in cognitive function than control patients.

"A couple of years ago, I reviewed the literature on brain training and was surprised to find that, despite the fact that many millions of people are now involved in these types of activities, there is very little solid peer-reviewed scientific evidence out there to show that it actually works," lead author Adrian M. Owen, MD, from the Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, United Kingdom, told reporters at a telephone press briefing. "This is a multi-million-pound industry, and given that so many people are involved, it is interesting that the scientific evidence was lacking."

Dr. Owen and his colleagues conducted an online study to investigate whether regular brain training leads to any improvement in cognitive function. Participants were randomly assigned to 1 of 3 groups. The first group trained in tasks that emphasized reasoning, planning, and problem-solving. The second group trained in a broader range of cognitive functions, which included tests of short-term memory, attention, visuospatial processing, and mathematics. To continuously challenge the participants' cognitive performance and maximize any benefits of training, the difficulty of the training increased as the participants improved.

The control group surfed the Internet to find answers to general knowledge questions.

At the end of 6 weeks, the participants were reassessed to see whether their cognitive functioning had improved. The researchers found that none of the brain training tasks transferred to other mental or cognitive abilities beyond what had been specifically practiced by each group. The control group also improved in their ability to answer obscure knowledge questions, although the effect size was small.
The study found that the training groups did get much better on the test that they actually practiced. In addition, participants got better the more they trained. However, even people who trained much more than average showed no generalization of training to untrained tasks — even those that were cognitively closely related.

Surf on!

Tuesday, April 20, 2010

The peripheral nervous system is the nerves from the spinal cord to muscles and organs. Nerves to muscles are ones we use to play tennis, type on the computer, or move our eyes to read these words. There is also the autonomic nervous system for controlling organ function such as heart rate, gut motility, and bladder. The Vagus Nerve is one and originates in the brainstem just above the neck. It travels far down into the abdominal cavity, making connections to the heart, lungs, and stomach. Not only does it send impulses to organs, it also relays information back to the brain, making it both afferent and efferent.

In the late 70s it was discovered that pulsing the Vagus Nerve with small electric currents could help reduce seizures in some forms of epilepsy. So, Cyberonics began selling a small device similar to a cardiac pacemaker that could be implanted into patients’ chests – Vagus Nerve Stimulators, or VNS. Many people with seizure disorders do not have seizures adequately controlled with medication, so must rely on alternative treatments.

It was noted that some patients with depression in addition to epilepsy showed an improvement in depression regardless of any improvement in seizure control. Soon, VNS devices were being implanted in patients suffering only from depression.

There is no question this treatment is effective for a small number of patients. The question that still is not understood is why this should be.

Thursday, April 15, 2010

I recently overheard a person authoritatively state, “You know, we only use about ten percent of our brain.” I laughed. This wasn’t the first time I’ve heard this outrageous statement and have always wondered where it started. Like a lot of folklore, it’s not true.

Early Greeks realized that a severe depressed skull fracture, say on the left side, could result in paralysis on the right side of the body. But how or where this cross-connectivity between brain and body occurred wasn’t known. For centuries it wasn’t clear that the brain had anything to do with consciousness or thought. The microscope demonstrated neurons and supportive glial tissue, but how they communicated with each other and the rest of the body remained a mystery until a neuroanatomist, Santiago Ramon Cajal, invented a special dye that could demonstrate individual neurons and fiber tracts.

Prior to the last century brain function was localized by carefully correlating obvious brain damage (usually from strokes) with findings from the pre-death neurologic examination. But this only gave anatomists clues to obvious behavior, like movement or speech. Until the mid 20th century there were no methods to measure “silent” brain activities such as memory or solving math problems. The largest lobe of the human brain is the frontal lobe. For centuries anatomists suspected it was important in personality and behavior but there was no methodology to test these hypotheses. Now, with newer imaging techniques, such as Positron Emission Tomography (PET scans) there are elegant ways to visualize brain activity during many subtle functions.

Although we may not be able to ascribe functional labels to every square millimeter of brain, there really are no “unused” areas.

Monday, April 12, 2010

HM is one of the most famous patients in the history of neurosurgery because of what he taught us about memory.

A great many cases of epilepsy are associated with scarring on the brain surface from a variety of causes – stroke, infection, trauma, etc. One brain area commonly responsible for seizures is the temporal lobe, located on each side directly behind the eye and bone of the temple. In the late 1930s surgery was being developed to remove brain scars as one method of seizure control in an era when there were no effective medications. In cases where seizure-causing scars could be easily approached surgically, the results were quite good.
Patient HM developed seizures as a result of a bike accident at age 9. A New England neurosurgeon diagnosed HM’s seizures as originating from both his right and left temporal lobes. In September, 1953, both of HM’s temporal lobes were removed, rendering him seizure free. However, although he could remember how to do previously learned tasks, he was no longer able to commit new events to long-term memory (termed anterograde amnesia). He also suffered moderate retrograde amnesia, and could not remember most events in the 1-2 year period before surgery, and some events up to 11 years before, meaning that his amnesia was temporally graded. However, his ability to form long-term procedural memories was still intact; thus he could, as an example, learn new motor skills, despite not being able to remember learning them.
Until his death, HM was the subject of numerous psychological studies aimed at learning more about the process of memory. Up until his surgery, it was unclear what parts of the brain are crucial for the various processes involved in laying down, storing, and retrieving memories. Even after his death, HM’s brain continues to teach us about the complex physiology of memory.

Friday, April 9, 2010

A critical component of traumatic brain injury (TBI) is brain swelling. Contents inside of the skull include the brain matter itself, spinal fluid (around the brain and inside ventricles), and the blood in vessels. Because the skull is a rigid container, a change in volume of any one of these three components can dramatically alter intracranial pressure.

Under normal conditions the brain’s blood vessels are partially constricted. Immediately following a blow to the head, the normal control of these vessels is lost. As a result, the vessels dilate, causing an increase in intracranial pressure. The CO2 content of blood affects vessels; high CO2 dilates them whereas low CO2 constricts them. To lower intracranial pressure neurosurgeons hyperventilate the patient; over-breathing quickly lowers the blood’s CO2 content, which constricts the vessels.

Brain tissue has a great deal of water in it. So sucking water out of brain can also lower pressure. This is accomplished by injecting a non-metabolized sugar into the blood stream. The sugar molecules (such as mannitol) are too large to pass from blood into brain tissue, but their presence pulls water from the brain into the blood by osmosis. The water then excreted by the kidneys. For obvious reasons, these sugars are termed osmotic diuretics.

Finally, intracranial pressure can be lowered by carefully draining small amounts of fluid from the chambers in the brain. Severely head injured patients however may have already collapsed these spaces, making this option impossible.

Why is controlling intracranial pressure so important? Because the higher the pressure the harder it is to push blood through the brain. When the pressure inside the skull exceeds arterial pressure blood flow to the brain stops. If this happens, massive brain damage results. To help manage a patient, pressure sensors are commonly placed directly inside the skull.

Wednesday, April 7, 2010

My last post discussed subdural hematomas, so it’s a good time to talk about epidural hematomas. As previously mentioned, the Dura is a fibrous membrane attached to the inner surface of the skull. Like all tissue, it needs a blood supply. The artery feeding it (the Middle Meningeal artery) runs just in front of the ear where the skull is quite thin and easily fractured. When fractured, the bone edge can be quit sharp and cut this artery. Unlike veins that transmit blood at low pressure, arteries carry blood at high pressure. So when the meningeal artery is cut a blood clot forms between the skull and dura; hence the name of epidural hematoma. Because the bleeding is under arterial pressure, the clot can grow large quickly.

As the clot enlarges it pushes brain aside. But since the skull can’t expand the compressed brain becomes squeezed. And just like a tube of toothpaste, the squeezed brain seeks the path of least resistance, which is out the base of the skull – a phenomenon termed herniation. This is considered a surgical emergency.

Epidural hematomas seldom occur in isolation and are usually accompanied by additional forms of traumatic brain injury. For this reason, even with prompt removal, a patient may remain in coma depending upon any other injuries.

Monday, April 5, 2010

Lining the inside of the skull is a tough fibrous tissue called Dura. Between the Dura and brain is a space filled with Cerebrospinal Fluid (CSF). Young people have a very thin subdural space, but as we age and the brain shrinks because of loss of neurons and, as a result, this space grows larger. Blood is supplied to the brain by two carotid and two vertebral arteries that travel up the neck and cross this space. Veins bridge this space along the midline of the head and at the temples, to drain eventually into the Jugular Veins on either side of the neck.

When the head is struck by an object (either deceleration or acceleration) the brain moves within the skull and tugs on these bridging veins. A strong enough tug will tear a vein, causing bleeding into the subdural space. This results in a clot which is called a subdural hematoma. Because older people have smaller, atrophic brains, there is more space for the brain to move on impact, even with relatively minor trauma, such as falls. For this reason, subdural hematomas are more common in seniors.

The pressure a subdural hematoma exerts on the brain may cause weakness on the opposite side of the body. However, the mass may not cause enough symptoms for the patient to seek medical evaluation. Over time, the center of the clot liquefies while the outer layers form a tough fibrous capsule of scar tissue and the clot changes from an acute, to sub-acute, to a chronic subdural hematoma.

CT or MRI scans easily show the mass.

The treatment is surgical removal. But this can become problematic in chronic cases where the membranes are well formed and rich in small blood vessels, thus potentially causing more problems than leaving them undisturbed.

Sunday, April 4, 2010


Because my previous blog dealt with concussion I thought I’d continue talking about traumatic brain injury (TBI). A brain stem contusion is just one more step in the continuum of TBI. As with a concussion, the kinetic forces of impact are channeled down and out the base of the skull and thus travel through the brain stem. But unlike concussions, which temporarily disrupts neurons from functioning without causing damage to the tissue itself, these forces are strong enough to rupture the small blood vessels that nourish the brain stem, and this results in small (called petechial) hemorrhages. The location of each hemorrhage determines the symptoms it produces. Because the brain stem contains so many pathways for the control of the eyes, movement and coordination, consciousness, and other senses, the damage can cause numerous combinations of neurologic problems involving coma, double vision, paralysis, loss of hearing, and others.

In addition to producing hemorrhages, the shock wave causes a massive release of brainstem synapses, flooding the area with neurotransmitters which can compound the cause of unconsciousness.

Usually these hemorrhages are too small to be seen on a routine MRI or CT scan, so the diagnosis is based on the clinical exam. Treatment is supportive, giving the brain time to recover. Often, however, some symptoms, such as double vision or lethargy may linger for years.

Saturday, April 3, 2010


I was channel surfing the other day when I came across a boxing match. I watched for a few moments out of amazement rather than interest. Boxing appears to be a sport with one purpose only – to inflict brain damage on one’s opponent. There may be a lot of body blows in a round, but what boxers are really trying to do is get a good shot at their opponent’s head for a knock down, or better yet, a knock out. How sick is that?

The past decade has seen a redefinition of what constitutes a concussion. Used to be it was a head injury characterized by a brief loss of consciousness. The requirement for loss of consciousness has been removed, leaving only the symptoms of temporary confusion and amnesia after a blow to the head.

When a force impacts the skull a shock wave of energy is transmitted to the brain. Like electricity, the shock wave travels the route of least resistance, which is out the base of the skull into the spinal canal. This route includes the brainstem, an area crucial to consciousness. If the force is great enough, the neurons supporting consciousness are temporarily disrupted, possibly resulting in a period of unconsciousness. But this period may be extremely short or never even occur. Nevertheless, brainstem circuits are temporarily disrupted, leaving symptoms of confusion, amnesia, headache, dizziness, ringing in the ears, nausea or vomiting, slurred speech, and fatigue. These symptoms may not appear until hours after the injury.

A common misperception is that concussions are trivial, leaving no residual. Actually repetitive concussions have a cumulative effect on brain function. A good example is the “punch drunk” retired boxer who may show slowed movement, Parkinson like tremors, and elements of dementia. For this reason professional neurosurgical organizations have spent a great deal of effort to encourage the use of protective helmets for sports that place the athlete at risk for head injury.

Thursday, April 1, 2010


What’s the difference between encephalitis and meningitis? As most of you know, attaching -itis to a word indicates inflammation. The word encepha – refers to the brain itself. So encephalitis is a condition in which brain tissue is inflamed. The causes of inflammation may be numerous and include bacterial or viral infections. The meninges are three separate layers of tissue that surround the brain and spinal cord (the dura, the arachnoid, the pia). So the term meningitis refers to inflammation of the meninges, also without indicating the cause, which can include bacterial or viral infections.

Many cases of meningitis are transmitted from the environment (from another individual) into the person through the air. The nerves for smell (olfactory nerve), located in the roof of the nose, provides a common direct route for bacteria to reach the brain and meninges. Often, the cause of the infection is unknown.

Meningitis and encephalitis are potentially life threatening diseases that require prompt diagnosis and treatment. Signs of meningitis include sleepiness, nausea, vomiting, headache, fever, and a stiff neck. Because the brain is bathed in spinal fluid (CSF), obtaining a sample of fluid through a “spinal tap” is the most accurate method of diagnosis. Normally CSF has no cells in it and contains protein and sugar. If the meninges are infected the CSF shows white cells, bacteria, and abnormal amounts of protein and glucose. Cases of encephalitis may show only an increase in cells. MRI and/or CT scans are usually also required as part of the evaluation.