Transcript Basal Ganglia, Tremor, Vim-DBS, and the Excitability of Spinal Motor

Basal Ganglia, Tremor, Vim-DBS, and
the Excitability of Spinal Motor Neuron
Pooya Pakarian
Presentation based on:
Pakarian P, Rayegani SM, and Shahzadi S. (2004) Effect of Vim thalamic DBS
in Parkinson's disease on F wave duration. Neurosci Lett. Sep 9;367(3):323-6.
Basal Ganglia
Straitum:
1- Putamen
2- Caudate
3- Nucleus Accumbens (ventral striatum)
Pallidum:
1- Globus Pallidus internus
2- GP externus
3- Substantia Innominata (ventral pallidum)
Other nuclei:
1- Substantia Nigra pars reticulata
2- SN pars compacta
3- SubThalamic Nucleus (STN)
Caudate
Putamen
GPe
GPi
STN
SN (r & c)
Basal Ganglia: 3 circuits
• Sensoriomotor: Putamen to GPi
• Associative: Caudate to SNr
• Limbic: Ventral striatum to ventral pallidum
Sensorimotor circuit
somatosensory
cortices
D1
motor cortices
Putamen
GPe
excitation
D2
GPi
inhibition
Thalamus
D1 & D2
Dopamine
receptors
STN
SNc
Medical Remarks
•
Hypokinetic disorders result from overactivity in the indirect pathway.
example: Decreased level of dopamine supply in nigrostriatal pathway results
in akinesia, bradykinesia, and rigidity in Parkinson’s dieseas (PD).
•
Hyperkinetic disorders result from underactivity in the indirect pathway.
example: Lesions of STN result in Ballism. Damage to the pathway from
Putamen to GPe results in Chorea, both of them are involuntary limb
movements.
•
Lesion-making in STN or GPi are successful therapeutic procedures of PD.
Cognitive Remarks
• Putamen, GPi, and GPe are organized somatotopically. Their
neurons are selectively responsive to the direction of limb
movement. A considerable convergence is also evident along
the cortico-basal ganglio- thalamo- cortical pathway.
• GPi cells have a baseline firing rate of 60-80Hz.
• During a voluntary hand movement, the firing rates of 70% of
the cells in the hand area of GPi increase, while those of the
remaining 30% decrease.
• Focusing theory vs. Scaling theory ( result of
emphasis on somatotopy vs. convergence)
New findings inconsistent with the old model
• Most striatal cells have both D1 and D2 receptors.
• GPe neurons send some axons back to striatum.
• Although the projections from GPe to GPi are inhibitory, the
pattern of activity in GPe replicates that of GPi (the 70-30
distribution of increase/decrease in firing rate).
• STN neurons project strongly back to GPe.
• SNc send dopaminergic projections to GPe, GPi, and STN.
• Intralaminar group of thalamic nuclei, receive projections from GPi
and send projections to Putamen. This is some sort of feedback.
Mechanisms of Tremor in PD
peripheral
tremor
Cerebellum
Cellular
oscil.
central
BG-thal
network
oscil.
Peripheral vs. Central
1- Deafferentation does change the
frequency of tremor, but does not cease it.
2- Novacaine infiltration in a muscle can
cancel stretch reflexes. Rigidity will be
alleviated in this situation but not tremor.
3- Induction of Tonic Vibration Reflex whose
signals are exclusively conveyed in Ia fibres
(which are the afferent fibers of stretch
reflexes) results in tremor cessation.
Cerebellum vs. BG-Thal
1- Vim is a nucleus of thalamus that connects
cerebellum to motor cortices. Lesion-making, as
well as High Frequency Deep Brain Stimulation
(reversible analogous of lesion-making) in Vim
are very successful strategies for alleviation of
tremor in PD, but not in cerebellar tremors.
2- PD patients previously undergone
hemicerebellectomy are not tremorfree in the corresponding side of
their bodies.
Cellular vs. Network Oscillators
1- Both hyperpolarization-induced low threshold calcium spike and other
kinds of bursts have been seen in tremor-locked activity of thalamic cells.
2- Not only thalamic cells, but also cells seated in STN and GP can
demonstrate synchronous oscillatory activity.
Mechanism of rigidity in PD
1- Non- paralyzing doses of novacaine,
concurrently alleviate rigidity and cancel
stretch reflexes.
2- Deafferentation alleviates rigidity.
3- Spinal stretch reflex is normal in
rigidity (confirmed by H-reflex).
4- Supraspinal stretch
hyperexcitable in rigidity.
reflexes
are
5- The peripheral theory of tremor claims
that tremor shares these mechanisms
with rigidity.
F-Wave
F-wave is elicited by antidromic activation of spinal motoneurons and their
consequent backfiring. The duration of F-wave is an index for motoneuron
excitability. Excitability of spinal motoneuron serves as an index for excitability
of long loop reflex pathway.
Tremor or Rigidity?
Milanov 2001: F wave duration was most prolonged in Parkinsonian
tremor patients followed by PD patients with rigidity. In conclusion
increased motoneuron activity participates in generation of both
Parkinsonian tremor and rigidity.
Abbruzzese et al. 1985 ,Naito et al. 1988: excitability of the spinal
motor neurons was enhanced in rigid Parkinsonian patients. It thus
seemed reasonable to assume that the main underlying cause of
rigidity is an excessive supraspinal drive to the spinal motor neurons,
including an increase in motoneuron excitability. No evidence for
contribution of these mechanisms to cause tremor was observed.
Functional Anatomy
Anteriorly located lesions in Vim nucleus tend to be more effective in reducing
rigidity, whereas the lesions more effective in tremor cessation tend to lie more
posteriorly. The location of DBS electrodes also varies in various patients.
Methods
F-waves where recorded from abductor hallucis muscle by stimulation
of tibial nerve. Twenty F-waves were recorded in two DBS conditions of
On & Off from each of the 8 PD patients who participated in our study.
The Implantable Pulse Generator
(IPG) attached to the DBS electrode
can be easily turned on and off by
using the proper electronic device
whose probe is put on the skin
surface.
Medtronic Model 7432 Physician Programmer
Guiot’s method of electrode localization
Analysis
Based on their electrode location, participants where grouped in two 4-member
groups of more anteriorly or more posteriorly electrode located.
Independent variables: 1- two levels group of electrode location (anterior &
posterior), 2- two levels of DBS status (On & Off).
Dependent variable: F wave duration.
Analysis: 2x2 ANOVA on pooled data
Group of electrode location had a significant main effect. F(1,316)= 6.499, P=0.01
DBS status had a significant main effect: F(1,316)= 23.445, P=0.000
They had a significant interaction: F(1,316)= 11.204, P=0.001
Our results does not confirm the idea that tremor and rigidity have
common mechanisms and contradicts the peripheral theory of tremor