Closed-Loop Neuroscience and Non-Invasive Brain Stimulation: A Tale of Two Loops

Abstract

Closed-loop neuroscience is receiving increasing attention with recent technological advances that enable complex feedback loops to be implemented with millisecond resolution on commodity hardware. We summarize emerging conceptual and methodological frameworks that are available to experimenters investigating a "brain in the loop" using non-invasive brain stimulation and briefly review the experimental and therapeutic implications. We take the view that closed-loop neuroscience in fact deals with two conceptually quite different loops: a "brain-state dynamics" loop, used to couple with and modulate the trajectory of neuronal activity patterns, and a "task dynamics" loop, that is the bidirectional motor-sensory interaction between brain and (simulated) environment, and which enables goal-directed behavioral tasks to be incorporated. Both loops need to be considered and combined to realize the full experimental and therapeutic potential of closed-loop neuroscience.

Keywords: EEG; NIBS; TMS; closed-loop; non-invasive brain stimulation.

Figure 1

A family of different closed-loop designs to couple with brain state dynamics. (A) Traditional “black box” experiment where there is no environment that the brain can act on: the stimulation is predetermined by the experimenter, the experimental observable is the output from the brain. (B) The feedback loop triggers a stimulus based on a spontaneously occurring instantaneous brain state; here, the environment is static and without state. (C) This loop represents an agent-environment interaction where the environment has its own internal dynamics, consisting of state (which is fully observable) and the equations of motion (the laws that govern the behavior of the environment). The combined result is an interacting complex system. Areas shaded red indicate parts of the set-up under experimental control, white areas show the “observable behavior”. (D) Shows the relationship between “true” brain state trajectories and the projection onto the measured electroencephalogram (EEG) signal as well as the effect that a transcranial magnetic stimulation (TMS) pulse has shifting state to a new position (figure taken from Mutanen et al., 2013) (E). An experimental closed-loop EEG-TMS set-up configured to couple with cortical dynamics during a simultaneously executed motor-sensory task. Two conceptually different feedback loops can be distinguished, a “brain-state dynamics” loop that is designed to influence the trajectory of the brain state and a “task dynamics” loop that enables active interaction with a (real or computer simulated) environment through the motor and sensory system and the respective encoding stages.

Figure 2

Preliminary results from a millisecond latency EEG-TMS set-up. (A) Simplified implementation of a closed-loop brain-state dependent brain-stimulation set-up consisting of EEG stage, real-time digital signal processing stage, and a triggered stimulation stage. (B) Raw EEG traces recorded from electrode C3 in the period before a TMS 100 Hz triplet pulse that is triggered by a real-time system based on the preceding 300 ms of EEG data. The system can be configured to trigger the stimulation either at the trough (top trace) or at the peak (bottom trace) of spontaneous alpha activity recorded by EEG over motor cortex.