Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations
Brain. 2005-08-25; 128(10): 2372-2382
DOI: 10.1093/brain/awh616
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Meissner W, Leblois A, Hansel D, Bioulac B, Gross CE, Benazzouz A, Boraud T.
Comment in
Brain. 2006 Dec;129(Pt 12):e59; author reply e60.
High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a
well-established therapeutic approach for the treatment of late-stage Parkinson’s
disease. Although the underlying cause of this illness remains a mystery, changes
in firing rate and synchronized activity in different basal ganglia nuclei have
been related to its symptoms. Here we investigated the impact of STN-HFS on
firing rate as well as correlated and oscillatory activity in the STN network in
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned non-human primates
by using simultaneous extracellular single-unit recordings. STN-HFS reduced (i)
the firing rate of STN neurons, (ii) the oscillatory activity at an individual
STN neuron level as well as (iii) the correlated and oscillatory activity between
pairs of STN neurons, while contralateral rigidity was improved. A detailed
analysis showed that the decrease of mean firing rate resulted from the resetting
of firing probability to virtually zero by the stimulus pulse. Subsequently, STN
neurons resumed their activity after a mean duration of 2.9 +/- 0.1 ms and their
firing probability returned to baseline values approximately 7 ms after the onset
of the stimulus pulse, the recovery of the firing probability being represented
by a sigmoid function. Thus, the overall decrease of the mean firing rate
resulted from the repetition of this dynamical process with a frequency of 130 Hz
(interstimulus interval approximately 7.7 ms), allowing the neuron to fire with
its baseline firing rate only for a very short period. Although the mechanisms
underlying the desynchronization of neuronal activity in the STN network remain
unclear, the resetting of STN neuron firing probability by the electrical
stimulus would rather be expected to increase oscillatory activity at an
individual neuron level as well as correlated and oscillatory activity between
pairs of STN neurons. However, assuming the resetting of firing rate to be the
consequence of a transient GABAergic inhibition through excitation of presynaptic
GABAergic axon terminals, different recovery periods of STN neurons might delay
the appearance of synchronized oscillations, particularly if they are not
generated locally. In conclusion, our study provides new evidence that STN-HFS
decreases oscillatory activity in the STN network. Although the exact relation
between oscillatory activity and Parkinson’s disease symptoms remains to be
determined, the present results suggest that STN-HFS might at least partially
exert its beneficial effects through the reduction of oscillatory activity in the
STN network and consequently in the entire cortex-basal ganglia-cortex network.
DOI: 10.1093/brain/awh616
PMID: 16123144 [Indexed for MEDLINE]