Another interesting tidbit pulled off of a web page at Columbia University.
It's a whole new perspective on the symptoms of PD.

                Ron Reiner (49/2)
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Memory of Time May Be Factor in Parkinson's

Bad timing, not nerves, may explain the irregular motions of
Parkinson's Disease patients, research led at Columbia has found.=20

Any body movement involves a timed sequence of motions, and "evidence
is accumulating that a central problem in Parkinson's is memory for
time, a cognitive function in the brain, not a neuromuscular
function," said John Gibbon, professor of psychology at Columbia.
"Even simple movements require complex temporal sequencing."=20

The timing function is analogous to an internal stopwatch. It tells
humans a stop light is broken or that the end of a television
commercial is approaching.=20

Gibbon, who is also director of the department of biopsychology at the
New York State Psychiatric Institute, presented the research at the
recent annual meeting of the American Association for the Advancement
of Science in Baltimore, Md. His work, and that of collaborators, has
shown which parts of the brain allow humans and animals to sense
intervals of time and why that sense is so important.=20

Gibbon, with Chara Malapani, a scientist with the French research
organization INSERM U-289 and the H=F4pital de la Salpetri=E8re in Paris,
discovered that Parkinson's patients have difficulty estimating and
remembering timed intervals. Gibbon and his colleagues hypothesize
that the jerky motions of Parkinson's may result from a patient's
inability to time smooth, fluid movement, like a turn of the head or a
wave of the arm, creating instead a series of separate, stop-and-go
motions.=20

In the research at the H=F4pital de la Salpetri=E8re, which began in 1994
and is ongoing, Parkinson's patients were asked to watch a computer
image of a rectangle that changed color after 8 seconds or after 21
seconds and then reproduce the experience by estimating when the
rectangle would change color again. The patients were unable to
accurately remember the interval, consistently guessing too late on
the short interval and too early on the long one. A control group of
matched-age subjects was quite accurate on both.=20

Parkinson's is a degenerative disease that often manifests itself late
in life and is marked by abrupt motions, muscle tremors and a peculiar
gait. People who suffer from this disease, once thought to be strictly
neuromuscular, lose neurons from a part of the brain called the
substantia nigra that produces the neurotransmitter dopamine, which
helps brain cells communicate with one another. Parkinson's patients
also experience a slowing of some cognitive functions and have
difficulty with complex tasks.=20

Treatment with levodopa, which when metabolized by the body increases
the level of dopamine, is effective in treating motor problems but
less so with cognitive ones, and is less effective as the disease
progresses. In the Paris experiments, patients were tested after
stopping their medication. Putting patients back on the drug restored
their sense of time. The work is the first to indicate that damage to
the basal ganglia, a region of the brain that coordinates voluntary
muscle movements, results in temporal memory deficiencies that may
cause the ill-timed motor sequences of Parkinson's.=20

Gibbon has studied humans' sense of passing time, and how, for
example, we know how long a red light should last or how long to snack
while a television commercial is on. He has found, in both animals and
humans, that if an individual perceives a time interval incorrectly,
i.e., as too long or too short, he or she will perceive other
intervals - whether longer or shorter - in the same way, as too long
or too short, and by the same percentage of the original interval.
Gibbon has named this phenomenon the scalar time sense, and has found
it effective at periods ranging from milliseconds to hours.=20

That sense must be based in a cellular or molecular mechanism that
operates subconsciously and allows memories of timed intervals to be
recorded and later retrieved, the scientists say. The next research
question for interval timing researchers is how people and animals
remember the intervals that their internal stopwatch measures, Gibbon
said.=20

The Columbia biopsychologist is beginning experiments with the Paris
research group to determine whether the impairment in Parkinson's
occurs during storage or retrieval of temporal memory.=20

That work could well give scientists the insights that will give
Parkinson's patients back their sense of time and movement.=20

Gibbon and Malapani, with Warren Meck, associate professor of
experimental psychology at Duke and former associate professor of
psychology at Columbia, are working to isolate nerve
connections--called striato-cortical loops--between the basal ganglia
and the frontal cortex, where time is consciously observed.=20

Scientists believe identifying those connections that serve memory
functions will help pinpoint the neural mechanisms that observe,
record and retrieve memories of timed intervals. Knowing how that
system works might some day allow researchers to design therapies to
overcome these impairments.=20

In related discoveries with animals, also reported at AAAS, Gibbon and
two colleagues described components of the interval timing mechanism,
located in the basal ganglia, that act as the body's stopwatch.=20

Collaborators on the work were Meck and Russell Church, professor of
psychology at Brown.=20

Increasing or decreasing the level of dopamine in the brain speeds up
or slows down an individual's sense of the passage of time, Meck and
Church had found in the early 1980's.=20

The three psychologists hypothesized that the brain must record nerve
impulses facilitated by dopamine; the more such impulses registered,
the more subjective time an individual thinks has passed.=20

They have isolated different components of the timing mechanism,
controlled by different structures in the basal ganglia. Severe damage
to the substantia nigra stops all timing, as it cuts off the dopamine
supply.=20

Damage to the caudate and putamen, major structures in the basal
ganglia, appears to impair communication between the clock mechanism
and the frontal cortex, where time is consciously perceived.=20

But therapeutic lesions to the globus pallidus, a way station in the
striato-cortical loops, sometimes improve dopamine regulation and may
improve interval timing as well.=20

Columbia University Record -- April 5, 1996 -- Vol. 21, No. 22