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.

Schizophrenia is often characterized by dysconnections in the brain, which can be estimated via functional connectivity analyses. Commonly measured using resting-state functional magnetic resonance imaging (fMRI) in order to characterize the intrinsic or baseline function of the brain, fMRI functional connectivity has significantly contributed to the understanding of schizophrenia. However, these measures may not capture the full extent of functional connectivity abnormalities in schizophrenia as fMRI is temporally limited by the hemodynamic response. In order to extend fMRI functional connectivity findings, the complementary modality of magnetoencephalography (MEG) can be utilized to capture electrophysiological functional connectivity abnormalities in schizophrenia that are not obtainable with fMRI. Therefore, we implemented a multimodal functional connectivity analysis using resting-state 7 Tesla fMRI and MEG data in a sample of first-episode patients with schizophrenia ( n = 19) and healthy controls ( n = 24). fMRI and MEG data were decomposed into components reflecting resting state networks using a group spatial independent component analysis. Functional connectivity between resting-state networks was computed and group differences were observed. In fMRI, patients demonstrated hyperconnectivity between subcortical and auditory networks, as well as hypoconnectivity between interhemispheric homotopic sensorimotor network components. In MEG, patients demonstrated hypoconnectivity between sensorimotor and task positive networks in the delta frequency band. Results not only support the dysconnectivity hypothesis of schizophrenia, but also suggest the importance of jointly examining multimodal neuroimaging data as critical disorder-related information may not be detectable in a single modality alone.

We have here characterized the MEG saccadic artifact in both the spatial and the frequency domains for saccades of different directions. This could be important in ruling in or ruling out artifact in MEG recordings.

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