Neuroelectronics and Biooptics: Closed-Loop Technologies in Neurological Disorders

Abstract

Brain-implanted devices are no longer a futuristic idea. Traditionally, therapies for most neurological disorders are adjusted based on changes in clinical symptoms and diagnostic measures observed over time. These therapies are commonly pharmacological or surgical, requiring continuous or irreversible treatment regimens that cannot respond rapidly to fluctuations of symptoms or isolated episodes of dysfunction. In contrast, closed-loop systems provide intervention only when needed by detecting abnormal neurological signals and modulating them with instantaneous feedback. Closed-loop systems have been applied to several neurological conditions (most notably epilepsy and movement disorders), but widespread use is limited by conceptual and technical challenges. Herein, we discuss how advances in experimental closed-loop systems hold promise for improved clinical benefit in patients with neurological disorders.

Figure. Closed-Loop Intervention to Inhibit Spontaneous Seizures

A, In contrast to traditional therapeutic approaches (black lines), which are applied in a constant or scheduled manner without regard to brain states or the actual occurrence of pathologic events such as seizures, on-demand intervention is designed to align intervention (blue arrowheads) with events that require intervention (eg, seizures [red]). B, Such closed-loop approaches use information about ongoing brain activity to determine when to provide intervention. Brain activity is recorded (step 1 [gray]) and processed in real time (step 2 [upper rectangle]) to detect events online (red exclamation point). Detection triggers immediate intervention (step 3 [blue]), altering brain activity and closing the loop. C, Closed-loop optogenetic system used to detect spontaneous temporal lobe seizures based on various properties of the signal, including power, spiking, and frequency components. D, On-demand optogenetic inhibition of excitatory cells reduced seizure duration. The top trace shows a spontaneous seizure without intervention, and the bottom trace shows a spontaneous seizure with light intervention. E, Closed-loop transcranial electrical stimulation intervention system used to inhibit absence seizures in rats (described in detail in the Effectors and Actuators section in the main text). CSD indicates current source density. F, On-demand transcranial electrical stimulation intervention shortens absence seizures. The top trace shows a spontaneous seizure recorded without intervention, and the bottom trace shows a spontaneous seizure detected online (red exclamation point), triggering transcranial electrical stimulation intervention (the period of intervention is denoted by a blue bar [the large amplitude signal is a transcranial electrical stimulation–induced artifact and has been truncated]). Scale bars are 500 ms and 0.5 mV (D) and 5 s and 100 μV (F). C and D are modified with permission and in accord with the Creative Commons license (http://creativecommons.org/licenses/by/3.0/) from Krook-Magnuson et al. E and F are modified with permission from Berényi et al.