Physiological Motion Compensation for Neuroscience Research Based on Electrical Bio-Impedance Sensing

Researchers have developed a large number of methods to study the brain’s function. One of the most effective techniques is in vivo whole-cell patch-clamp recording which allows the recording of intracellular neuronal activity. A major issue that drastically reduces the efficiency of in vivo patch clamping is the excessive movement of the brain primarily caused by heartbeat and breathing, which can be larger than the size of the neurons under investigation. Motion compensation techniques are complicated due to the lack of sensors to reliably measure local physiologically-induced motion. This work proposes the use of electrical bio-impedance (EBI) to the existing patch electrodes in the patching pipette as a proximity sensor. The study further develops an extended Kalman filter (EKF) to estimate overall motion and then establishes a motion compensation algorithm for the patch pipette. The proposed method was developed on a custom laboratory benchtop setup and validated during actual in vivo experiments. The results of the laboratory experiments show a real-time compensatory performance exceeding 80%. The in vivo experiments achieved a performance of over 75%, confirming the ability to compensate for real physiologically induced motion. Moreover, the method demonstrated dynamic continuous motion compensation while the electrode was advanced to a neuron, contacting the neuron membrane without damage illustrating the ability to improve neuronal patch clamping. As far as the authors are aware this is the first time that physiologically induced motion can be compensated for this application and this solely relies on EBI.

I. Introduction

Profound knowledge of brain function at the cellular level is important for understanding sensory systems [1] and other higher brain functions. It is also important for the development of medicines for neurological disorders such as Parkinson’s and Alzheimer’s disease [2]. The brain processes a large amount of information through billions of interconnected neurons. To understand neural processing, it is necessary to electrophysiologically measure the internal activity of individual neurons in their natural environment. This requires techniques that allow in vivo intracellular recordings [3]. Patch clamp is originally an in vitro technique developed in the late 1970s that allows simultaneous recording of neuronal input and output signals with excellent temporal and spatial resolution [4]. Since the 2000s, this technique has been adopted for in vivo measurements in living organisms [5]. During the whole-cell patch-clamping procedure, a glass micropipette filled with a conductive solution is inserted into the brain and advanced to a neuron of interest. Then, the pipette is brought into contact with the neuronal membrane after which it is locally aspirated to make electrical internal contact [6], called a “patch.” However, making an in vivo patch is a huge challenge with limited success due to the small size of neurons (~10 ) [7], the lack of visualization [8], and especially the inherent physiologically induced motion by heartbeat and breathing [9]. The latter involves the risk of an uncontrolled penetration of the neuron. If this happens the whole procedure needs to be repeated with a new micropipette [10].