The following was taken from a long article in New Scientist 26/2/00



MIEKO had no quality of life any more, says her surgeon Ali Rezai from
theCleveland Clinic in Ohio. For 15 years, she'd coped with Parkinson's
disease, but then her medication began to fail her, and she found
herselfalternating between the uncontrollable wild movements created by her
drugs and being locked motionless.

For Antonia it was a different story. She had endured agonising pain around
her face for seven years since an operation to relieve the pressure of a
blood vessel against a nerve. Drugs did nothing. Last month, both found
instant relief when Rezai implanted a small electronic pace-maker-like
device deep inside their brains.

Such devices appear to work by interrupting the excessive neuronal firing
that causes chronic pain or by smoothing out the strange rhythmical brain
activity that causes rigidity and tremors, much as a heart pacemaker
flattens the unusual beat rhythms of a fibrillating heart. They aren't a new
way of dealing with pain or Parkinson's disease stimulating the spine
tointerrupt pain signals was first used in the 1960s. But, if a
controversial new theory is correct, surgeons like Rezai may soon be getting
ready to fitthese "pacemakers" in a whole new group of patients with
psychiatric conditions such as obsessive compulsive disorder (OCD) and
depression, or desperately distracting sensations such as ringing in the
ears (tinnitus) or schizophrenic hallucinations.

According to Rodolfo Llinas, a neuro-scientist at the New York
MedicalCenter, and Daniel Jeanmonod, a neurosurgeon at the University
Hospital inZurich, these conditions are united by a common feature. The
researchers believe that they are all characterised by strange, slow rhythms
of neuralactivity originating in a walnut-sized brain region called the
thalamus.

This activity, they say, looks just as though one tiny part of the brain
has fallen asleep. The resulting disruption in the flow of signals to the
rest of the brain would produce the abnormal patterns of activity that
could account for bizarre perceptions and neurological symptoms as
wide-ranging as tinnitus and depression. Until recently, the thalamus was
considered to be no more than a simple relay station sitting at the top of
the brainstem, controlling the flow of information from our senses to the
brain's outer cortex. But interest in the region has grown since
neuroscientists discovered that when we're awake, it is working overtime,
passing on and modifying fast "gamma" rhythms of activity to the cortex that
seem to equate to conscious perception (New Scientist, 30 October 1999, p
28).

It's by no means a one-way flow of information. Within milliseconds of
receiving information from the thalamus, the cortex returns a signal
indicating which information might be worth dealing with. The thalamus
filters out what appears irrelevant and reinforces the relevant by sending
more signals back to the cortex. "You can't think thalamus without cortex,
or vice versa," says Jeanmonod, "It's a recurrent interplay between the
two."

But it is not only the physical connections between the thalamus and cortex
that guide the passage of sensory infomation. The different activity
patterns of sleep or waking states are also important. Llinas describes the
thalamusas a "central switch" for sending the brain to sleep. When we fall
asleep,the thalamus lets very little information through. It becomes less
excitable,lowering its level of activity to a slow, rhythmical pattern
the"theta"and "delta" rhythms and effectively dis- connects us from
theoutside world.

Llinas was one of the first to detect the switch from waking to sleeping
rhythms in individual thalamocortical neurons, back in 1982. He discovered
that the switch could be triggered by altering the chemi- calenvironment
orthe electrical charge of the outer membrane of the cell. More recently, he
wondered what effect switch- ing from fast to slow rhythms would have if it
occurred at the wrong time: "It would be like having one part ofyour
brainasleep," he says. But what would this then do to the cortex? Howmight
thisalter peo- ple's perceptions of the outside world, and theirhealth?
"Itwould be terrible if you got stuck in any one of thesesituations."

One of the first groups of patients Llinas looked at with these ideas
inmindwere people with Parkinson's disease, who were experiencing limb
tremors. He noticed that their muscles were twitching in time to a theta
rhythm between three and six twitches every second. At the same time, he was
able to record electrical activity across the brain using a technique called
magnetoencephalography, or MEG, and found the same rhythmic activity
appearing in the areas of the cortex that were responsible for initiating
and sensing movement. He suspected that the rhythms originatedin theregion
of the thalamus connected to these cortical areas (Neurology^vol 46,p 1359).

This set him wondering whether some- thing similar could occur in partsofthe
thalamus related to other areas of the ner- vous system, such asthevisual,
auditory and emotional areas, and not just in thoseregionsresponsible for
movement.

Meanwhile, Jeanmonod had been recording electrical activity directly
inthebrains of patients with Parkinson's disease and chronic pain who
hadbeenreferred to him for brain surgery because they had failed to
respondtonormal drug treatment.

Like many surgeons, Jeanmonod routinely destroyed small parts of
thethal-amus in order to bring Parkinson's tremors under contro a common
alternative to implanting a pacemaker. This approach was decades old,even
though surgeons had only the vaguest idea of how it could relieve
symptoms.The problem, however, was that some patients suffered severe side
effects,ranging from defects in language and analytical thinking to
paralysis, when surrounding brain tissue was damaged. Jeanmonod hoped that
by recording the activity in the thalamus, using tiny electrodes implanted
during exploratory surgery, he would be able to pinpoint exactly which areas
were abnormal, and so target his surgery more precisely.

He found the sleep-like theta rhythms in the thalamus in patients with
Parkin- son's disease and chronic pain when they were awake. Just as Llinas
had suspected, Jeanmonod managed to pin the rhythms down to two neighbouring
regions of the thalamus, which together are responsible forpassing on
movement and pain sensa- tions. By destroying only the affected part of
thethalamus, Jeanmonod was able to considerably improve the outcome of his
surgery, and has now operated on more than 50 people with Parkinson's,and
more than 100 with chronic pain, using theta rhythms for guidance
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Nigel Cockle
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