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 sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI). Approach 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 (MFB), a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator. Main 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. Significance Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in prefrontal cortex 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.

Repairing neural damage in aC. eleganschemosensory circuit using genetically engineered synapses

“…The notion of creating artificial links to overcome neural circuit damage is proving to be especially effective in brain-machine-brain interfaces (BMBIs) 32 . These electronic devices composed of electrodes and computers, monitor and decode neural signals from one brain region, and then encode and deliver corresponding stimulation to a second region 33 . Such systems appear to be capable of bridging disconnected neural pathways, and thus restoring function after neural damage 34,35 .…”

Closed-loop neuromodulation systems: next-generation treatments for psychiatric illness

“…Our group recently demonstrated platform technology for an alternate approach, where patients directly control the stimulator by thinking about what they want it to do (Widge et al, 2014; Widge & Moritz, 2014). A patient would evaluate whether the current simulation parameters (particularly the intensity of stimulation) match his/her needs, and could then volitionally modulate the stimulation parameters.…”

“…The patient would only receive treatment when they explicitly will it, making this a more personalized treatment compared to more traditional concepts of closed-loop stimulation. In rodent models, we have shown that animals can use this type of intentional control to trigger brain stimulation to the medial forebrain bundle (MFB), a reward center that is also a DBS target for MDD (Widge & Moritz, 2014). There would be much work to translate such a device to the clinic, including identifying a DBS target and stimulation regime that caused noticeable and immediate symptom relief.…”

Closing the Loop in Deep Brain Stimulation for Psychiatric Disorders: Lessons from Motor Neural Prosthetics

“…The patient's signals in the recorded area would then 'tune' the DBS intervention as needed. We recently showed that rodents can learn to use prefrontal cortex signals in precisely this fashion to activate DBS-like stimulation (Widge and Moritz, 2014). Similar strategies may be useful for modulating fear behaviors in anxiety disorders, using fronto-limbic networks as targets (Besnard and Sahay, 2015).…”