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Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease.

ABSTRACT: Subthalamic deep brain stimulation (DBS) is superior to medical therapy for the motor symptoms of advanced Parkinson's disease (PD), 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 the cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for PD. In 5 subjects (six hemispheres), EEG 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. We found that subthalamic brain stimulation at 20 Hz activates the somatosensory cortex at discrete latencies (mean latencies: 1.0 ± 0.4, 5.7 ± 1.1, and 22.2 ± 1.8 ms, denoted as 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 ms; P < 0.001, Levene's test). We conclude that clinically effective subthalamic brain stimulation in humans with PD activates the cerebral cortex at 1 ms after stimulus onset, most likely by antidromic activation. These findings suggest that alteration of the precise timing of action potentials in cortical neurons with axonal projections to the subthalamic region may be an important component of the therapeutic mechanism of subthalamic brain stimulation.

SUBMITTER: Walker HC

PROVIDER: S-EPMC3636546 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease.

Walker Harrison C HC Huang He H Gonzalez Christopher L CL Bryant James E JE Killen Jeffrey J Cutter Gary R GR Knowlton Robert C RC Montgomery Erwin B EB Guthrie Bart L BL Watts Ray L RL

Movement disorders : official journal of the Movement Disorder Society 20120530 7

Subthalamic deep brain stimulation (DBS) is superior to medical therapy for the motor symptoms of advanced Parkinson's disease (PD), 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 the cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for ...[more]

PMID: 22648508

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Project description:Deep brain stimulation of the subthalamic nucleus for Parkinson's disease is an established advanced therapy that addresses motor symptoms and improves quality of life. However, it has also been associated with neuropsychiatric symptoms such as impulsivity and hypomania. When significant, these symptoms can be distressing, necessitating psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken. We examined this matter in a consecutive sample of 64 persons with Parkinson's disease undertaking subthalamic deep brain stimulation. Participants were assessed with a battery of neuropsychiatric instruments at baseline and at repeated postoperative intervals. A psychiatrist identified patients with emergent, clinically-significant symptoms due to stimulation. The site of the active electrode contact and a simulated volume of activated tissue were evaluated with reference to putative limbic, associative and motor subregions of the subthalamic nucleus. We studied anatomical correlates of longitudinal neuropsychiatric change and delineated specific subthalamic regions associated with neuropsychiatric impairment. We tested the ability of these data to predict clinically-significant symptoms. Subthalamic stimulation within the right associative subregion was associated with inhibitory errors on the Excluded Letter Fluency task at 6-weeks (p = 0.023) and 13-weeks postoperatively (p = 0.0017). A cluster of subthalamic voxels associated with inhibitory errors was identified in the right associative and motor subregions. At 6-weeks, clinically-significant neuropsychiatric symptoms were associated with the distance of the active contact to the right associative subregion (p = 0.0026) and stimulation within the right associative subregion (p = 0.0009). At 13-weeks, clinically-significant symptoms were associated with the distance to the right (p = 0.0027) and left (p = 0.0084) associative subregions and stimulation within the right associative subregion (p = 0.0026). Discrete clusters of subthalamic voxels associated with high and low likelihood of postoperative neuropsychiatric symptoms were identified in ventromedial and dorsolateral zones, respectively. When a classifier was trained on these data, clinically-significant symptoms were predicted with an accuracy of 79%. These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention of these occurrences, improving safety and tolerability.

Project description:BackgroundMonitoring the depth of anesthesia by electroencephalogram (EEG) based on the prefrontal cortex is an important means to achieve accurate regulation of anesthesia for subthalamic nucleus (STN) deep brain stimulation (DBS) under general anesthesia in patients with Parkinson's disease (PD). However, no previous study has conducted an in-depth investigation into this monitoring data. Here, we aimed to analyze the characteristics of prefrontal cortex EEG during DBS with propofol general anesthesia in patients with PD and determine the reference range of parameters derived from the depth of anesthesia monitoring. Additionally, we attempted to explore whether the use of benzodiazepines in the 3 days during hospitalization before surgery impacted the interpretation of the EEG parameters.Materials and methodsWe included the data of 43 patients with PD who received STN DBS treatment and SedLine monitoring during the entire course of general anesthesia with propofol in a single center. Eighteen patients (41.86%) took benzodiazepines during hospitalization. We divided the anesthesia process into three stages: awake state before anesthesia, propofol anesthesia state, and shallow anesthesia state during microelectrode recording (MER). We analyzed the power spectral density (PSD) and derived parameters of the patients' prefrontal EEG, including the patient state index (PSI), spectral edge frequency (SEF) of the left and right sides, and the suppression ratio. The baseline characteristics, preoperative medication, preoperative frontal lobe image characteristics, preoperative motor and non-motor evaluation, intraoperative vital signs, internal environment and anesthetic information, and postoperative complications are listed. We also compared the groups according to whether they took benzodiazepines before surgery during hospitalization.ResultsThe average PSI of the awake state, propofol anesthesia state, and MER state were 89.86 ± 6.89, 48.68 ± 12.65, and 62.46 ± 13.08, respectively. The preoperative administration of benzodiazepines did not significantly affect the PSI or SEF, but did reduce the total time of suppression, maximum suppression ratio, and the PSD of beta and gamma during MER. Regarding the occurrence of postoperative delirium and mini-mental state examination (MMSE) scores, there was no significant difference between the two groups (chi-square test, p = 0.48; Mann-Whitney U test, p = 0.30).ConclusionFor the first time, we demonstrate the reference range of the derived parameters of the depth of anesthesia monitoring and the characteristics of the prefrontal EEG of patients with PD in the awake state, propofol anesthesia state, and shallow anesthesia during MER. Taking benzodiazepines in the 3 days during hospitalization before surgery reduces suppression and the PSD of beta and gamma during MER, but does not significantly affect the observation of anesthesiologists on the depth of anesthesia, nor affect the postoperative delirium and MMSE scores.

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Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease.

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Short latency activation of cortex during clinically effective subthalamic deep brain stimulation for Parkinson's disease.

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