Regional cerebral blood flow in man manipulated by direct vagal stimulation.
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Brain↗
Biomedical subjects
A R Upton
Publications and source records attributed to A R Upton.
Neurocardiac responses to vagoafferent electrostimulation in humans.
UNLABELLED: To determine if cardiac vagal tone is enhanced by vagal electrostimulation (VES), we examined the heart rate autospectrum (HRA) in eight patients with implanted stimulators for complex partial seizures. In four patients the VES was activated at 30 Hz and 500-msec pulse (HiStim group) compared to 2 Hz and 130-msec pulse for the LoStim group (n = 4). Continuous ECG and respiratory waveforms were recorded for 45 minutes every 8 hours (7-8 AM; 3-4 PM 11-12 PM) during resting supine wakeful epochs both before and 15 days after surgical implantation. From the HRA cardiac sympathovagal balance was expressed as the ratio of the low frequency (LF) power to the high frequency (HF) power. RESULTS: There were no presurgical differences between the groups in heart rate, its variance, or the energies contained in any autospectral band. The LoStim group showed no significant change in heart rate (HR), HF peak power, or LF:HF ratios during 2 weeks of VES. Conversely, in the HiStim group, the LF:HF peak power ratio (an expression of sympathetic dominance) decreased from 2.5 +/- 1.5 preimplant to 1.5 +/- 0.49 (P < 0.02) with VES. During VES there was a significantly higher HF power in the HiStim compared to LoStim group. No diurnal variations in HRA values were seen for either group. CONCLUSIONS: (1) A relationship exists between selective vagal nerve electrostimulation and the HRA; and (2) high stimulation frequency of the vagus nerve in man is associated with sustained augmentation of cardiac vagal tone throughout a 24-hour cycle.
Adult↗
Effects of chronic left vagal stimulation on visceral vagal function in man.
We examined the effects of chronic left vagal electrostimulation on afferent and efferent gastrointestinal vagal function in eight patients. Afferent function was assessed using cortical evoked responses to electrical stimulation of the esophagus and to direct vagal stimulation using the implanted left vagal electrode. Efferent gastrointestinal vagal function was measured by examining the basal, maximal, and sham fed stimulated gastric acid output prior to and with chronic left vagal electrostimulation. Esophageal electrostimulation produced a cortical evoked response consisting of three negative and three positive peaks within 400 msec after stimulation. Prior to vagal electrostimulation the mean conduction velocity of the afferent signal was measured at 8.72 +/- 3.39 m/sec, compatible with A-delta fibers involvement. Basal, maximal, and sham fed acid output were 1.11, 21.87, and 9.37 mmol/hour, respectively. The evoked response to esophageal electrical stimulation was not changed with chronic left vagal electrostimulation. Direct vagal stimulation also produced evoked potentials that were comparable to those obtained with esophageal stimulation. The mean conduction velocity was 6.26 +/- 2.72 m/sec (NS) so that there was no evidence of loss of myelinated fibers with chronic stimulation. No differences were detected in basal (1.29 mmol/h), maximal (21.64 mmol/h), or sham fed stimulated (8.03 mmol/h) acid output, showing that vagal electrostimulation has no effect on either total or vagally mediated acid output, an efferent vagal function. In conclusion, chronic left vagal electrostimulation has no significant adverse effect on gastrointestinal vagal function.
Adult↗
Evidence of impaired afferent vagal function in patients with diabetes gastroparesis.
Two patients, a 28-year-old male and a 70-year-old female, with chronic insulin dependent diabetes mellitus and evidence of autonomic neuropathy were studied using cortical evoked responses following esophageal balloon and electrical stimulation. Both patients had symptomatic gastroparesis, poor gastric emptying, and reduced gastroduodenal motility including abnormal results of scintigraphy and manometry. There was slowing of afferent vagal conduction but good evoked potential responses were recorded even though one patient could not feel electrical stimulation of either the proximal or distal esophagus. It is improbable that the gastric symptoms are due to an afferent autonomic neuropathy, but symptoms may well be related to impairment of motor vagal pathways. Nevertheless, afferent vagal pathways are involved in severe diabetes mellitus. The clinical significance of this delay in conduction velocity of afferent pathways remains to be established.
Adult↗
Cognitive motor function after electrical stimulation of the vagus nerve.
Chronic stimulation of the vagus nerve does not seem to produce significant differences between high frequency and low frequency stimulation groups. Individuals within each group show significant changes between preoperative assessment and after 6-month stimulation. Some subjects showed significant improvement and some showed significant slowing of responses. Subjects who showed improvement are still considerably slower than normals, but all patients have a very long history of complex partial seizures and exposure to multiple medications. Larger homogeneous sample sizes are needed to delineate more clearly the correlation between cognitive performance, medication effects, and stimulation effects.
Adult↗
Acute effects of high frequency vagal nerve stimulation on balance and cognitive motor performance in epilepsy: three case study reports.
Quantitative measures of area of sway, total sway, and cognitive function failed to show significant differences in acute (50 minute) "ON-OFF-ON-OFF" studies of high frequency left vagal stimulation in three epileptic patients undergoing treatment for chronic complex partial seizures. Fluctuation in blood levels of anticonvulsants may have been associated with some clinical effects. There were no significant adverse effects of acute left vagal stimulation in these three subjects.
Adult↗
Electrostimulation effects of the vagus nerve on balance in epilepsy.
Preliminary results of selected postural measures in quiet standing indicate that stimulation of the vagus nerve appears not to be producing adverse effects. With this specific sample size, more testing is needed to determine long-term effects and future data analyses will examine correlations between electroencephalogram results, drug levels, and seizure frequency. In the present study three subjects have had old injuries to hips and ankles. Two subjects had normal values for postural control prior to stimulation, while other subjects were severely abnormal. In future, studies should include larger homogeneous sample sizes, as the current subjects show marked variability in age and premorbid health backgrounds. Future work should also control more vigorously for variables such as visual input (i.e., blindfolding subjects instead of simply closing the eyes). Evaluation of postural control mechanisms will be continued to assess stability changes in these patients as seizure frequency continues to subside.
Adult↗
Effect of vagal nerve electrostimulation on the power spectrum of heart rate variability in man.
The power spectrum of heart rate variability contains low frequency (LF = 0.08-0.12 Hz) and high frequency (HF = 0.18-0.30 Hz) components said to represent neurocardiac rhythms. To verify whether such a relationship exists we report a unique study where the heart rate autospectrum was determined in a 28-year-old epileptic male patient with an implanted vagal electrical stimulator. The stimulator was activated at 20 Hz, 300 microseconds pulse, and 1.25 V. Continuous ECG and respiratory waveform records were obtained over 45 minutes every 8 hours (7-8 AM; 3-4 PM; 11-12 PM) with the stimulator ON, then 24 hours OFF and then 24 hours ON again. The overall LF:HF peak ratio increased from 0.64 to 1.99 (P less than 0.001) after the stimulator was turned OFF. There was a dramatic increase in the LF peak power (greater than 60%) and a corresponding decrease in the HF peak power (greater than 65%) when the stimulator was turned OFF. These values were reversed when the stimulator was turned ON again. In the early morning and late evening hours, there was a significant rightward shift in the LF peak power frequency (average 0.057 to 0.075 Hz) whenever the stimulator was ON. Otherwise, there were no significant circadian variations in any of the autospectral components. The results demonstrate an unequivocal relationship between selective vagal nerve electrostimulation and alterations in the heart rate autospectrum.
Adult↗
Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome.
We examined whether patients with irritable bowel syndrome have increased airway responsiveness by measuring forced expiratory volumes in 1 second (FEV1) after inhalation of increasing concentrations of methacholine. Responses obtained in 11 IBS patients were compared with those obtained in 11 normal subjects and in 11 subjects with organic disease of the gut or its related organs. All subjects were selected so that other factors that might contribute to increased airway responsiveness were excluded. The methacholine concentration that caused a 20% fall in the FEV1 (PC20), as well as the reduction in FEV1 induced by each methacholine concentration, were used to assess airway responsiveness. The geometric mean PC20 was 197.6 mg/mL (%SEM, 1.15) for normal subjects, 83.9 mg/mL (%SEM, 1.51) for subjects with organic bowel disease (P = 0.012), and only 12.8 mg/mL (%SEM, 1.74) for IBS patients (P less than 0.0001). The 22.5% +/- 2.5% decrease in FEV1 induced by 64 mg/mL of methacholine in IBS patients was significantly greater than that of 12.3% +/- 1.5% observed in healthy subjects (P = 0.003). In contrast, the 15.7% +/- 2.0% decrease in FEV1 observed in patients with organic disease was not different from that seen in normal subjects (P = 0.189). We conclude that IBS is associated with increased airway responsiveness following challenge with methacholine.
Administration, Inhalation↗
Biostim 1990.
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Electric Stimulation Therapy↗
Autonomic stimulation.
Therapeutic stimulation of the autonomic nervous system has been limited by lack of qualitative or quantitative evaluation of autonomic mechanisms. This article provides an historical review of knowledge about autonomic pathways and critical evaluation of available tests of autonomic function. Recent developments in evaluation of autonomic dysfunction and improvement in techniques of neurostimulation have facilitated the development of a number of clinically useful treatments for bladder control, sexual problems, peripheral vascular disease, angina pectoris, and seizure disorders. Future therapeutic measures may allow specific control of hypertension, pain, cardiac arrhythmias, trophic disorders and balance.
Autonomic Nervous System↗
Neurophysiological effects of left vagal stimulation in man.
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Adult↗
Effects of chronic cerebellar stimulation (CCS) setting on the gait and speech of a spastic cerebral palsy adult.
A single (N = 1) spastic cerebral palsy adult who had experienced Chronic Cerebellar Stimulation (CCS) for 9 years without any change in the stimulator settings was assessed at six different stimulator settings. These voltage settings varied from 0 volts to 40 volts and frequencies of stimulation from 0 to 200 Hz. Stimulation was with bipolar rectangular pulses with less than 0.2 C/mm2 charge per phase. Responses measured at each setting were quantitative gait, speech, and somatosensory evoked potential measurements. Additional clinical assessments were done by a neurologist and speech therapist. Alteration in stimulator settings occurred 1 week apart to allow for stabilization and all assessments were completed in the same sequence each day. None of the individual stimulator settings were known to any of the assessors or to the patient. The results showed consistently that the patient's gait and speech were poorest when the stimulator was switched off completely. Switching on the stimulator caused improved function according to all assessments. There was consistent improvement in gait and speech when the rate of the cerebellar stimuli was high (for voltages between 0 and 40 V). Changing the voltage (within the range 0 to 40 V), while keeping the frequency of stimulation constant, did not appear to have as much effect. This preliminary evaluation suggests that the technique of CCS is safe and can improve function in a measurable manner.
Adult↗
Biostim 1988.
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Electric Stimulation Therapy↗
Statistical pattern classification of clinical brainstem auditory evoked potentials.
The brainstem auditory evoked potentials (BAEPs) recorded in the neurological clinic were classified using the Bayes classifier (BC) and Fisher's linear discriminant function (FLD). The latencies of initial five peaks, interpeak intervals were examined for optimum features to develop classifiers. The accuracy of classification was 85.3% when absolute latencies of peaks III, IV and V were used as features. The BC gave better performance than FLD, indicating that second order statistics of BAEPs for normal and pathological classes are different. The results of this study indicate that latencies alone give enough information for recognizing normal from pathological BAEPs, using physician's evaluation of BAEPs as the reference.
Adult↗
Patterns of cerebral glucose metabolism using 18FDG and positron tomography in the neurologic investigation of the full term newborn infant.
18F fluorodeoxyglucose (18FDG) and positron tomography (PT) were used in 20 full term babies with seizures or hypotonia to describe regional cerebral glucose metabolism. Among babies with seizures, birth asphyxia was the most common cause. PT was performed at age 6-17 days. One hour before PT, 18FDG (50-100 microCi/kg) was injected intravenously. Ten or more PT sections were obtained in each infant. The areas of the brain that were metabolically the most active were the cortex and the thalami. Six cortical areas and a white matter reference area were selected for analysis of relative rates of glucose metabolism as indicated by relative rates of fluorine-18 activity. Cortical fluorine-18 activity was highest in the pericentral (sensorimotor) regions and lowest in the frontal regions. The overall cortex/white matter ratio for fluorine-18 activity averaged 1.78 +/- 0.44 (SD). Four patterns of regional cerebral glucose metabolism were distinguished: 1) bilateral symmetry, 2) loss of metabolic definition, 3) hemispheral asymmetry, 4) focal hyper- or hypometabolism. Patterns 1) and 2) correlated with a history of birth asphyxia, a diagnosis of hypoxic-ischemic encephalopathy and the absence of focal echoes on cranial ultrasound. Hypodense areas on CT could be associated with either high or low fluorine-18 relative activity on PT. The prognostic significance of the presently reported patterns of cerebral glucose metabolism remains to be determined.
Brain↗
Power spectral analysis of normal and pathological brainstem auditory evoked potentials.
The brainstem auditory evoked potential (BAEP) recording has become a powerful investigational tool in neurological diagnosis. The BAEPs of patients have different latencies and morphologies when compared to those of normals. In this paper the power spectra (PS) of BAEPs of 21 normals, 17 patients with multiple sclerosis (MS) and 12 patients with head injury (HI) computed by Blackman-Tukey (BT) and Maximum Entropy (ME) methods are examined for their frequency composition. Three major peaks appear at approximately 170 Hz, 520 Hz and 950 Hz in PS of normal BAEPs. The average power contained in the frequency bands spread around these frequency bands for BAEPs of patients differed significantly (P less than 0.05) from those of normal BAEPs. The peaks observed in ME spectra were found to match those computed using BT method. The model order for representing both normal and patient BAEPs is greater than 40 and data compression afforded by modelling the BAEPs is of the order of 5:1.
Adolescent↗
Evoked metabolic responses in the limbic-striate system produced by stimulation of anterior thalamic nucleus in man.
Six human subjects (5 male, 1 female, age 23.7 + 5.7 years) with incapacitating partial seizure disorders intractable to medical therapy have been treated by ongoing pulsed electrical stimulation of anterior nucleus of the thalamus. Four of the six patients have demonstrated statistically significant clinical control of the seizure disorder. One patient (D.L.) has been seizure-free for the last two years. In two of these six patients, it was possible to study not only electrophysiological activity of the brain, but also regional cerebral glucose metabolism by the (18F) 2-fluoro-2-deoxy-D-glucose method, blood cortisol levels, and blood levels of valproic acid, diphenylhydantoin, and carbamazepine. Significant changes were seen during periods of stimulation compared with control periods without stimulation. These results imply that stimulation of the principal thalamic relay nucleus of the limbic system causes clinical, behavioral, cerebral metabolic, electroencephalographic, endocrinologic, and pharmacokinetic responses.
Adult↗