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Devices for neural recording and stimulation interact with neural tissues with different degrees of precision and invasiveness. For example, electroencephalography (EEG) is performed noninvasively through the skull and thus offers a low-resolution map of smoothed field potentials associated mainly with the neural activity of the whole cortical surface. Electrocorticography (ECoG), involving devices placed directly on the cortical surface, yields higher temporal and spatial resolution and is routinely used to identify seizure loci in epilepsy patients.

Neural systems exchange information in the form of action potentials?voltage spikes that propagate along neuronal membranes?and fluctuations in local field potentials (LFPs) averaged across a neuronal subnetwork or even an entire structure in the nervous system. Detailed mapping of neural activity is clinically relevant not only in the cortex but also in deep brain regions (e.g., the subthalamic nucleus in Parkinson’s patients), the spinal cord, and peripheral nerves (e.g., in trauma patients or those in chronic pain). Moreover, many neurological disorders are associated with abnormal activity of specific types of neurons, and hence single-neuron resolution is essential to the development of effective therapies. I focus here on penetrating neural recording devices, designed to interface with individual cells in a particular region of the nervous system.

As with neural recording, neural stimulation offers varying degrees of precision and invasiveness. Noninvasive transcranial magnetic stimulation (TMS) allows for interrogation of cortical circuits via initiation of local flows of ions, which are hypothesized to cause changes in LFPs. However, there is currently no strategy for extending this approach to deep brain regions or targeting it to specific neuronal types because of the nonspecific nature and limited penetration depth of the low-frequency magnetic fields used in TMS.

In deep brain stimulation (DBS), an approved treatment for Parkinson’s and essential tremor patients, high-voltage pulses (1?10 V; as compared to membrane voltages, ~30?100 mV, or LFPs, ~1?5 mV) are used to stimulate the neural tissue surrounding the electrodes. But although the DBS therapeutic effect is well documented, its underlying mechanisms remain unclear; both electrically induced excitation and inhibition of neural activity have been proposed. Furthermore, nonspecific interrogation of large tissue volume often yields undesirable side effects such as depression or compulsive behaviors.

Epidural electrical stimulation (in the spinal cord of chronic pain patients) is essentially equivalent to DBS, with the key difference that the electrode leads are placed on top of the dura (the thin barrier that isolates nerves from other tissues) rather than deep in the neural tissue.

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