McIntyre, Cameron C., Warren M. Grill, David L. Sherman, and Nitish V. Thakor. Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. J Neurophysiol 91: 1457-1469, 2004. First published December 10, 2003 10.1152/jn.00989.2003. Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders. However, fundamental questions remain about the effects of DBS on neurons surrounding the electrode. Experimental studies have produced apparently contradictory results showing suppression of activity in the stimulated nucleus, but increased inputs to projection nuclei. We hypothesized that cell body firing does not accurately reflect the efferent output of neurons stimulated with high-frequency extracellular pulses, and that this decoupling of somatic and axonal activity explains the paradoxical experimental results. We studied stimulation using the combination of a finite-element model of the clinical DBS electrode and a multicompartment cable model of a thalamocortical (TC) relay neuron. Both the electric potentials generated by the electrode and a distribution of excitatory and inhibitory trans-synaptic inputs induced by stimulation of presynaptic terminals were applied to the TC relay neuron. The response of the neuron to DBS was primarily dependent on the position and orientation of the axon with respect to the electrode and the stimulation parameters. Stimulation subthreshold for direct activation of TC relay neurons caused suppression of intrinsic firing (tonic or burst) activity during the stimulus train mediated by activation of presynaptic terminals. Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon. This independence of firing in the cell body and axon resolves the apparently contradictory experimental results on the effects of DBS. In turn, the results of this study support the hypothesis of stimulation-induced modulation of pathological network activity as a therapeutic mechanism of DBS. Because of the similarity in therapeutic outcomes achieved with DBS and lesions, it has been argued that high-frequency electrical stimulation (HFS) inactivates the structures being stimulated. Recordings made in the stimulated nucleus show inhibition and/or decreased activity during and after the stimulus train (Benazzouz et al. 1995Boraud et al. 1996;Dostrovsky et al. 2000). However, recordings made in efferent nuclei of the stimulated nucleus indicate that the output of the stimulated nucleus is increased during DBS (Anderson et al. 2003;Hashimoto et al. 2003;Maurice et al. 2003;Windels et al. 2000Windels et al. , 2003. These results appear to be contradictory, with the former indicating that DBS inhibits the stimulated nucleus and the latter indicating that DBS excites the nucleus.A significant obstacle in interpreting experimental results of DBS and developing a clear mechanism of action is the lack of quantitative understanding of the influence of HFS on ...

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Several adaptive filter structures are proposed for noise cancellation and arrhythmia detection. The adaptive filter essentially minimizes the mean-squared error between a primary input, which is the noisy ECG, and a reference input, which is either noise that is correlated in some way with the noise in the primary input or a signal that is correlated only with ECG in the primary input. Different filter structures are presented to eliminate the diverse forms of noise: baseline wander, 60 Hz power line interference, muscle noise, and motion artifact. An adaptive recurrent filter structure is proposed for acquiring the impulse response of the normal QRS complex. The primary input of the filter is the ECG signal to be analyzed, while the reference input is an impulse train coincident with the QRS complexes. This method is applied to several arrhythmia detection problems: detection of P-waves, premature ventricular complexes, and recognition of conduction block, atrial fibrillation, and paced rhythm.