title: Pre-frontal control of closed-loop limbic neurostimulation by rodents using a brain-computer interface.
abstract: OBJECTIVE
  There is great interest in closed-loop neurostimulators that sense and respond to a patient's brain state. Such systems may have value for neurological and psychiatric illnesses where symptoms have high intraday variability. Animal models of closed-loop stimulators would aid preclinical testing. We therefore sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI).
  
  
  METHODS
  We trained rats to use an auditory BCI controlled by single units in prefrontal cortex (PFC). The BCI controlled electrical stimulation in the medial forebrain bundle, a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator.
  
  
  RESULTS
  All animals successfully learned to use the BCI and neurostimulator, with closed-loop control of this challenging task demonstrated at 80% of PFC recording locations. Analysis across sessions and animals confirmed statistically robust BCI control and specific, rapid modulation of PFC activity.
  
  
  CONCLUSIONS
  Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in PFC can be used to control a BCI without pre-training on a predicate task. This offers the potential for BCI-based treatments in refractory neurological and mental illness.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. Center for Sensorimotor Neural Engineering, University of Washington, Seattle, WA, USA.
authors.forename: Alik S
authors.initials: AS
authors.lastname: Widge
authors.forename: Chet T
authors.initials: CT
authors.lastname: Moritz
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D062207:Brain-Computer Interfaces; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000379:methods; D005260:Female; D008032:Limbic System / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans