Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Epilepsy Control by Transcranial Electrical Stimulation



Science 10 August 2012:  Vol. 337 no. 6095 pp. 735-737

Closed-Loop Control of Epilepsy by Transcranial Electrical Stimulation

Antal Berényi, Mariano Belluscio, Dun Mao, György Buzsáki

1Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA.

2Neuroscience Institute, School of Medicine, New York University, New York, NY 10016, USA.

3Department of Physiology, University of Szeged, Szeged, H-6720, Hungary.


Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients.

A successful, although not well-understood, therapy in drug-resistant cases of Parkinson’s disease and depression is deep brain stimulation, in which high-frequency stimulation is applied continuously. In many diseases, such as epilepsies, events recur unpredictably and often are separated by long interictal intervals. In such instances, a closed-loop, transient feedback control could abort seizure episodes without inducing detrimental side effects of continuous stimulation. We attempted to achieve seizure control by means of closed-loop transcranial electrical stimulation (TES) in a rodent model of generalized (“petit mal”) epilepsy because previous experiments have shown that even very weak TES can reliably entrain neurons in widespread cortical areas.

We first demonstrated the effect of TES on cortical excitability. Local field potentials (LFPs) and multiple-unit activity (MUA) were recorded by chronically implanted tripolar electrodes and placed in the deep and superficial layers of the frontal and parietal cortical areas. TES was applied either between the left and right temporal electrodes, placed directly on the skull, or between these bitemporal electrodes, against a frontal midline electrode. TES sinusoid trains at 1 Hz induced significant rate modulation of multiple unit firing patterns both in the absence and presence of spike-and-wave (SW) episodes. In addition to affecting the firing rates of neurons, TES at 1 Hz also strongly modulated the spike amplitude of SW patterns but had no effect on the duration of SW episodes. Additional control experiments demonstrated that TES, at the intensities used, neither induced arousal effects when applied during sleep nor affected overt behavior during waking.

These findings show that brain pattern–triggered feedback TES of cortical neurons can interfere with thalamocortical reverberation during SW episodes and effectively reduce their duration. SW patterns—the hallmark of generalized petit mal epilepsy—arise from complex interactions between thalamic and neocortical neurons.

Successful clinical application of closed-loop TES has two fundamental requirements. The first is the recording and identifying of causal pathophysiological network patterns. In generalized SW and focal cortical epilepsies, subdural or epidural electrodes, or even electrodes inserted into the skull, may be sufficient. In complex partial seizures, which make up the largest fraction of drug-resistent epilepsies, deep-electrode recordings are required for accurate detection of abnormal patterns. The second requirement is closed-loop feedback stimulation of the target circuits, whose activation can interfere with the emerging pathological pattern. Intra-skull plate electrodes may ideally diffuse the applied currents to affect sufficiently large groups of neurons. Alternatively, multiple and appropriately placed plates may be used to achieve more focal concentration of current. In contrast to transcranial magnetic stimulation, which requires large and heavy coils, TES electrodes implanted in the skull and powered by ultralight electrical circuits are a cosmetically acceptable solution for long-term clinical applications. Noninvasive, closed-loop TES stimulation may also prove useful for improving mental and mood states.

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