integrity, thus checking the devolution of a cell’s status from healthy to
cancerous. Many of our hormones act in a similar fashion, where an
increase in the secretion of a protein hormone results in the decrease of the
presence of another protein or ion. Looked at another way, the loss of
inhibition is net stimulation. DeLong was able to demonstrate that the
basal ganglia was a complex set of “independent parallel circuits,” with
separate pathways to and from various areas of the basal ganglia to
specific areas of the cerebral cortex, some with excitatory potentials,
others with inhibitory. And just as surprisingly, the circuits were also
involved in emotion and cognition, not just movement.
The deepest part of the basal ganglia is the subthalamic nucleus, and
DeLong concluded by the late 1980s that this clutch of cells was critical in
PD. While it was obvious that the substantia nigra was the area of
degeneration that triggered abnormal physiological output throughout the
entire system, DeLong’s MTPT animal models showed increased
excitatory impulses from the subthalamic nucleus to other parts of the
basal ganglia. He had an idea: how about intentionally destroying (or
“lesioning”) the subthalamic nucleus?
“It was quite a remarkable result that Mahlon would suggest making a
lesion in this region to restore the balance of activity in Parkinson’s
disease, and lo and behold he got that result. I can’t overemphasize what a
significant leap this was, because the one constant that people had known
for more than fifty years is that if you make a lesion in the subthalamic
nucleus, you produce an abnormal movement disorder, and here Mahlon
proposed treating Parkinson’s disease by putting a lesion just in that region
and in fact got the results he predicted,”^26 observed his former lab
associate. It would be like treating a skin cancer patient with prolonged
sunlight.
Mahlon DeLong published his findings in a 1990 article of Science.^27 In
laboratory monkeys who were suffering from experimental parkinsonism,
lesioning of the subthalamic nucleus reduced all of the “major motor
disturbances in the contralateral limbs, including akinesia, rigidity, and
tremor.”^28 In medicine, our preliminary instincts are often wrong. And
DeLong’s suspicion that causing additional nerve damage in another part
of the brain could ameliorate parkinsonism was the counterintuitive
jackpot.