Optimizing Deep Brain Stimulation of the Nucleus Accumbens in a Reward Preference Rat Model.
OBJECTIVE
Deep brain stimulation (DBS) has become the preferred therapy for a growing number of treatment-resistant neuropsychiatric conditions, offering the benefit of being amenable to fine-tuning to enhance its efficacy. However, while some DBS parameters are routinely adjusted, the stimulation is almost always delivered in a continuous "tonic" pattern, which may be suboptimal at times. Our overall aim is to investigate the application of differing levels of rewarding DBS to the reconditioning of behavioral "trigger" and "non-trigger" stimuli in impulse-control disorders (including addiction). As a first step, we used a rat model of nucleus accumbens (NAc) DBS to rigorously compare the relative reward values of different stimulation paradigms. We hypothesized that delivering pulses in a more physiological pattern would prove more rewarding than delivering tonic stimulation.


METHODS
We implanted microelectrodes in the left NAc shell and trained rats to initiate and terminate DBS to demonstrate their "preference" between different brain stimulation reward (BSR) paradigms. We tested a range of BSR paradigms, including tonic, intermittent tonic, and burst paradigms. Two paradigms were compared at a time, and paired t-tests were used to determine whether the rats significantly "preferred" one paradigm over another.


RESULTS
The rats significantly preferred intermittent tonic BSR paradigms to continuous and burst paradigms, and generally preferred paradigms that delivered more pulses over the stimulation period.


CONCLUSIONS
These findings highlight that the standard approach of delivering tonic DBS is not optimal under all circumstances. Further research should investigate which DBS paradigms are best for different brain disorders.
Department of Anatomy, Brain Health Research Centre, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Maggie C
MC
Evans
Department of Anatomy, Brain Health Research Centre, School of Medical Sciences, University of Otago, Dunedin, New Zealand.|Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Vincent W
VW
Clark
Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Patrick J
PJ
Manning
Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Dirk
D
De Ridder
Department of Anatomy, Brain Health Research Centre, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
John N J
JN
Reynolds
D000818:Animals; D001703:Biophysics; D003216:Conditioning, Operant / Q000502:physiology; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000628:therapy*; D007839:Functional Laterality; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D011597:Psychomotor Performance; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D012653:Self Stimulation
Deep brain stimulation; nucleus accumbens; operant conditioning; rats