In Parkinson's disease, the dopamine-secreting cells in the Substantia Nigra
pars compacta (SNpc) region of the brain degenerate. This leads to
alterations in the activity of the neural circuits within the parts of the
brain that regulate movement.
Pathophysiology of PD (taken with permission from a proposal by
a neuroscientist, University of Pittsburgh, May 2010): All information
passing through the Basal Ganglia (BG) is directed through one of two
pathways: a direct pathway that facilitates movement by inhibiting Globus
Pallidus interna (GPi) and activating thalamus and cortex, or an indirect
pathway that inhibits movement by activating GPi and inhibiting thalamus and
cortex. Dopamine (DA) is known to activate the direct pathway and inhibit
the indirect pathway, thereby stimulating movement. Thus, the striatal DA
loss observed in PD was thought to cause parkinsonian motor signs by
over-activating the indirect pathway and underactivating the direct pathway,
with a net result of increased GPi activity, and reduced thalamic and motor
cortical activity [3,4,5,6]. This simplified model of PD pathophysiology has
been challenged by studies showing only modest changes of firing rate in the
parkinsonian GP, and instead suggesting that abnormal activity patterns,
such as oscillations [2,7,8,9,10,11], bursts [8,9,10,12,13,14], synchrony
[2,15,126.96.36.199], and reduced selectivity of neuronal activity [2,20,21]
might play a more important role in the pathophysiology of PD. Emerging
evidence also suggests that functional de-segregation in the
BG-thalamocortical system plays a role in the pathophysiology of PD
Currently, there are two primary treatment approaches to PD: medical
and surgical. Dopamine replacement therapy (DRT), the first line
approach, effectively reduces PD motor signs initially, but can cause
debilitating abnormal movements (dyskinesias) with prolonged use.
Deep Brain Stimulation (DBS) is the treatment of choice for
DRT-resistant PD. DBS requires neurosurgical placement of a
macroelectrode into the motor region of GPi, or more commonly the
subthalamic nucleus (STN). After the stereotaxic location of an
implantation target is identified, typically by combined structural
imaging and microelectrode recording, the DBS electrode is implanted,
and connected to a stimulator implanted under the patient's skin.
High frequency (greater than 100-Hz) electrical stimulation through
the macroelectrode reduces parkinsonian signs rapidly and stably as
long as stimulation continues. DBS significantly reduces PD signs,
dyskinesias, and improves quality of life . However, the
mechanism of DBS remains unknown, largely due to the poor
understanding of DBS-related changes in neuronal activity. Although
it is common to record neuronal activity from the GPi or STN of human
patients during microelectrode-guided localization of implantation
sites, it is seldom possible to study single unit activity in patients
following DBS electrode implantation. DBS can be more easily studied
in macaques, as neuronal recordings can be obtained from multiple
brain regions across multiple recording sessions, before and during
DBS. Even in macaques, however, electrical artifacts from stimulation
can occlude neuronal activity recordings, making DBS-induced neuronal
responses difficult to study unless the artifact can be subtracted
without altering data.
Although it is not known precisely what triggers a spike, it appears
that normal nervous functions correlate with certain spike frequencies
and patterns or codes whereas abnormal nervous functions
correlate with different patterns as shown in the following figure:
where the top chart shows patterns in a normal brain and the bottom chart
shows patterns in the brain of an epilectic. See  for details.
Study of these patterns has resulted in significant progress in
treating Parkinson's disease, for example, by introducing electrical
stimuli that control neuron firing. See
for a video showing a Parkinson's disease sufferer trying to get
through a doorway and see
for a video showing the result of deep brain neuron spike stimulation.
Here is a video
showing the result of deep brain stimulation.
 W.H. Calvin.
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