R. Andrews, K. Bennet, S-Y. Chang, J. Koehne, K. Lee, M. Meyyappan, E. Rand
NASA Ames Research Center,
Keywords: brain-machine interface, carbon nanofibers, deep brain stimulation, nano electrodes, neurotransmitters
Summary:Purpose: Present-day neuromodulation, e.g. deep brain stimulation (DBS), is limited by inefficient charge transfer from electrodes to brain tissue, lack of brain chemical (neurotransmitter) monitoring, and absence of feedback-guided stimulation. Although DBS using platinum macroelectrodes has proven effective for movement disorders (e.g. Parkinson’s disease), it is much less effective in other conditions, including epilepsy and mood disorders (e.g. severe depression). Methods: Carbon nanotube (CNT) and carbon nanofiber (CNF) electrodes can improve the charge transfer of electrodes interacting with brain tissue. Two major challenges have been (1) how to characterize nanoelectrodes to maximize charge transfer (to maximize signal on recording and to minimize tissue-damaging electrolysis on stimulation), and (2) how to structure nanoelectrodes to improve efficacy for either stimulating or recording (electrical or chemical). Another challenge is a wireless system to allow continuous monitoring of brain electrochemical activity in vivo. Various nanoelectrode characterizations, including conducting polymer coatings (e.g. polypyrrole, polyaniline), have been tested for benefits in brain electrical and chemical recording, and electrical stimulation. Novel fast-scan cyclic voltammetry (FSCV) techniques allow continuous recording of two neurotransmitter levels simultaneously. A Bluetooth wireless system has been fabricated for in vivo remote monitoring of neurotransmitters during DBS in vivo. Nanoelectrodes have been incorporated as 6 individually-addressed 50x20 μm “pads” on an electrode one tenth the diameter of the present DBS electrode (which is > 1 mm dia). Each “pad” can be used either to stimulate or to record electrical activity or to monitor a neurotransmitter level. Results: Conducting polymer coatings on CNF electrodes reduce impedance and increase capacitance orders of magnitude above standard platinum electrodes. This allows precise stimulation and recording of brain tissue (e.g. in hippocampal slice preparations) at current levels below that which can cause electrolysis of brain tissue . CNF electrodes, unlike standard electrodes for FSCV, can detect concentration changes in either of two neurotransmitters, e.g. dopamine (DA) and serotonin (5-hydroxytryptamine or 5-HT), in a solution containing ascorbic acid (AA, which is ubiquitous in brain) . CNF electrodes can also monitor DA and dissolved oxygen in a mixture when paired with individualized FSCV waveforms (“triangle” and “N-shape” FSCV voltage waveforms for DA and oxygen, respectively) when the waveforms are interleaved rather than overlapped . The wireless system can monitor DA levels in the striatum of rats undergoing medial forebrain bundle DBS (similar to DBS for Parkinson’s disease) . It is essential to interleave the FSCV and the DBS using an optical fiber connection. Similar to humans undergoing DBS, the striatal DA release is minimal at a DBS frequency less than 60 Hz. Conclusions: The ability to monitor both electrical activity and multiple neurotransmitter concentrations in vivo with hitherto unavailable spatial and temporal resolution will add significantly to our knowledge of DBS effects on the brain (both electrical and chemical). The information gained from such electrochemical monitoring can guide more efficient (feedback-guided) DBS, and will also increase our knowledge of brain electrochemical environments – knowledge essential both for understanding brain function and for planning more effective neuromodulation techniques.