Background Subthalamic deep brain stimulation is superior to medical therapy for the motor symptoms of advanced Parkinson’s disease, and additional evidence suggests that it improves refractory symptoms of essential tremor, primary generalized dystonia, and obsessive-compulsive disorder. Despite this, its therapeutic mechanism is unknown. We hypothesized that subthalamic stimulation activates cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for Parkinson disease. Methods In 5 subjects (6 hemispheres) electroencephalography measured the response of cortex to subthalamic stimulation across a range of stimulation voltages and frequencies. Novel analytical techniques reversed the anode and cathode electrode contacts and summed the resulting pair of event related potentials to suppress the stimulation artifact. Results Subthalamic brain stimulation at 20 Hertz activates somatosensory cortex at discrete latencies (mean latencies 1.0 ± 0.4, 5.7 ± 1.1, and 22.2 ± 1.8 milliseconds, denoted R1, R2, and R3, respectively). The amplitude of the short latency peak (R1) during clinically effective high frequency stimulation is nonlinearly dependent on stimulation voltage (p < 0.001, repeated measures analysis of variance), and its latency is less variable than that of R3 (1.02 versus 19.46 milliseconds, p < 0.001, Levene’s test). Conclusions Clinically effective subthalamic brain stimulation in humans with Parkinson disease activates cerebral cortex at one millisecond after stimulus onset, most likely by antidromic activation. Our findings suggest that alteration of the precise timing of action potentials in cortical neurons with axonal projections to the subthalamic region is an important component of the therapeutic mechanism of subthalamic brain stimulation.

Deep brain stimulation relieves disabling symptoms of neurologic and psychiatric diseases when medical treatments fail, yet its therapeutic mechanism is unknown. We hypothesized that ventral intermediate nucleus stimulation for essential tremor activates cortex at short latencies and that this potential is related to suppression of tremor in the contralateral arm. We measured cortical activity with electroencephalography in 5 subjects (7 brain hemispheres) across a range of stimulator settings, and reversal of the anode and cathode electrode contacts minimized the stimulus artifact, allowing visualization of brain activity. Regression quantified the relationship between stimulation parameters and both the peak of the short latency potential and tremor suppression. Stimulation generated a polyphasic event related potential in ipsilateral sensorimotor cortex with peaks at discrete latencies beginning less than one millisecond after stimulus onset (mean latencies 0.9±0.2, 5.6±0.7, and 13.9±1.4 milliseconds, denoted R1, R2, and R3, respectively). R1 showed more fixed timing than the subsequent peaks in the response (p<0.0001, Levene’s test), and R1 amplitude and frequency were both closely associated with tremor suppression (p<0.0001, respectively). These findings demonstrate that effective ventral intermediate nucleus thalamic stimulation for essential tremor activates cerebral cortex at approximately one millisecond after the stimulus pulse. The association between this short latency potential and tremor suppression suggests that deep brain stimulation may improve tremor by synchronizing the precise timing of discharges in nearby axons, and by extension the distributed motor network, to the stimulation frequency or one of its subharmonics.

Results suggest that horses with a complicated injury of the proximal, middle, or distal portion of the second or fourth metacarpal or metatarsal bone may be successfully treated by means of segmental ostectomy of the abnormal portion of the bone.

An influenza B/Hong Kong viral epidemic was monitored by surveillance of respiratory illness in three different age groups. Prospective viral monitoring of febrile respiratory illness was a useful mirror of the epidemiologic behavior of influenza in the community. Influenza B virus infection in infants and young children was distinguished by high fever and respiratory symptoms and was occasionally associated with otitis media. In older children and young adults, systemic and gastrointestinal complaints were more prominent. Of young children experiencing their first infection, a hemagglutination-inhibiting antibody response was seen in only one-third. Eleven children who received inactivated B/Hong Kong virus vaccine three years earlier were not protected from clinical infection but exhibited an anamnestic serum antibody response.

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