Neural adaptation to responsive stimulation: a comparison of auditory and deep brain stimulation in a rat model of absence epilepsy.
BACKGROUND
Responsive deep brain stimulation (rDBS) has been recently proposed to block epileptic seizures at onset. Yet, long-term stability of brain responses to such kind of stimulation is not known.


OBJECTIVE
To quantify the neural adaptation to repeated rDBS as measured by the changes of anti-epileptic efficacy of bilateral DBS of the substantia nigra pars reticulata (SNr) versus auditory stimulation, in a rat model of spontaneous recurrent absence seizures (GAERS).


METHODS
Local field potentials (LFP) were recorded in freely moving animals during 1 h up to 24 h under automated responsive stimulations (SNr-DBS and auditory). Comparison of seizure features was used to characterise transient (repetition-suppression effect) and long-lasting (stability of anti-epileptic efficacy, i.e. ratio of successfully interrupted seizures) effects of responsive stimulations.


RESULTS
SNr-DBS was more efficient than auditory stimulation in blocking seizures (97% vs. 52% of seizures interrupted, respectively). Sensitivity to minimal interstimulus interval was much stronger for SNr-DBS than for auditory stimulation. Anti-epileptic efficacy of SNr-DBS was remarkably stable during long-term (24 h) recordings.


CONCLUSIONS
In the GAERS model, we demonstrated the superiority of SNr-DBS to suppress seizures, as compared to auditory stimulation. Importantly, we found no long-term habituation to rDBS. However, when seizure recurrence was frequent, rDBS lack anti-epileptic efficacy because responsive stimulations became too close (time interval < 40 s) suggesting the existence of a refractory period. This study thus motivates the use of automated rDBS in patients having transient seizures separated by sufficiently long intervals.
Inserm, U836, Grenoble Institut des Neurosciences, Grenoble, France.
Sandrine
S
Saillet
Sadok
S
Gharbi
Guillaume
G
Charvet
Colin
C
Deransart
Régis
R
Guillemaud
Antoine
A
Depaulis
Olivier
O
David
D000161:Acoustic Stimulation / Q000379:methods*; D000222:Adaptation, Physiological / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D005072:Evoked Potentials, Auditory / Q000502:physiology; D008297:Male; D051381:Rats; D013378:Substantia Nigra / Q000502:physiology*; D013997:Time Factors
D000927:Anticonvulsants