Adrian R. M. Upton

A comparison of algorithms for detection of spikes in the electroencephalogram

Identification of the short transient waveform, called a spike, in the cortical electroencephalogram (EEG) plays an important role during diagnosis of neurological disorders such as epilepsy. It has been suggested that artificial neural networks (ANN) can be employed for spike detection in the EEG, if suitable features are provided as input to an ANN. In this paper, we explore the performance of neural network-based classifiers using features selected by algorithms suggested by four previous investigators. Of these, three algorithms model the spike by mathematical parameters and use them as features for classification while the fourth algorithm uses raw EEG to train the classifier. The objective of this paper is to examine if there is any inherent advantage to any particular set of features, subject to the condition that the same data are used for all feature selection algorithms. Our results suggest that artificial neural networks trained with features selected using any one of the above three algorithms as well as raw EEG directly fed to the ANN will yield similar results.

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.

Transcranial magnetic stimulation for migraine: clinical effects

The objective was to assess the impact of transcranial magnetic stimulation (TMS) on pain and the autonomic nervous system (ANS) in migraine. Fortytwo people [mean age 41.43±11.69 (SD) years, 36 females] were randomised into high vs. low TMS stimulation groups and received 2 brief pulses of TMS. Thirty-three (33/42) individuals had heart-rate variability assessed, before and after stimulation. No group effects were found. Pain decreased by 75%; 32% of people after 1 treatment reported no headache after 24 h. Mean heart rate decreased from 79.05±10.27 to 72.89±11.35 beats/min. The low-frequency (LF) and the high-frequency (HF) areas derived from power spectral analyses increased [mean 6522±1277 to 8315±1009 beats/min2 (LF) (p=0.001) and mean 5600±1568 to 8755±3071 beats/min2 (HF) (p=0.001)]. The LF:HF ratio decreased from mean 1.31±0.51 to 1.13±0.48 (NS). TMS produces immediate, sustained reductions in pain and modification of the ANS.

Abnormal cerebral processing of oesophageal stimuli in patients with noncardiac chest pain (NCCP).

In noncardiac chest pain (NCCP), altered visceral perception may result from abnormal cerebral processing of sensory input rather than abnormalities of afferent pathways. However, the interactions between symptoms, autonomic function and oesophageal stimuli are poorly studied. Oesophageal stimulation elicits reproducible cortical evoked potentials [CEP] and modulates heart rate variability via vagal pathways, as visible on power spectrum analysis of heart rate variability [PS‐HRV]. These methods are increasingly used to study the function of visceral afferent neural pathways in human. The aim of this study was to compare EP and PS‐HRV during oesophageal stimuli in NCCP and controls. Twelve healthy volunteers (one female, 11 male; aged 24–51 years; mean 32 ± 8 years), and eight NCCP patients (three female, five male; age range 26–58, mean 40.5 ± 10 years) were studied. Electrical oesophageal stimulation (EOS; 200 μs, 0.2 Hz, 25 stimuli) was applied to the oesophageal wall 5 cm above the lower oesophageal sphincter (LOS), and perception thresholds (measured in mA) determined. EP responses were recorded using 22 standard electroencephalogram scalp electrodes. Autonomic activity was assessed using PS‐HRV, before, during, and after oesophageal stimulation. Measured PS‐HRV indices included high frequency (HF; 0.15–0.5 Hz) and low frequency (LF; 0.06–0.15 Hz) power, respectively, assessing vagal and sympathetic activity, and the LF/HF ratio. EOS perception occurred at lower thresholds in NCCP than in controls (3.6 ± 1 vs. 7.8 ± 2 mA, P < 0.05). EP amplitude was greater (13 ± 2 vs. 6 ± 1 μV, P < 0.0001), and latency longer in controls vs. NCCP (191 ± 7 ms vs. 219 ± 6 ms, P < 0.001). In NCCP, EOS decreased sympathetic outflow (low frequency peak on PS‐HRV) and increased cardiovagal activity (high frequency peak, P < 0.02) to a significantly higher degree in comparison with controls. During EOS, heart rate decreased in NCCP from 68 vs. 62 beats min–1 (P < 0.003) but not in controls. In NCCP patients, EOS was perceived at lower intensities and was associated with a greater cardiovagal reflex response. EP responses associated with EOS were smaller in NCCP than in controls, suggesting that an increased perception of oesophageal stimuli results from an enhanced cerebral processing of visceral sensory input in NCCP, rather than from hyperalgesic responses in visceral afferent pathways.

Evoked Metabolic Responses in the LimbicStriate 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 ofvaiproic 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.

Neurocardiac Responses to Vagoafferent Electrostimulation in Humans

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 fan 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.

Chronic Cerebellar Stimulation (CCS) and Deep Brain Stimulation (DBS) in Involuntary Movement Disorders

Motor disorders of disinhibition may be modified by prosthetic mobilization of CNS inhibitory mechanisms by chronic electrical stimulation of the cerebellar cortex (CCS) and by deep brain stimulation of the thalamus and internal capsule (DBS). Reduction in spasticity, abnormal movements, intractable epilepsy and aggressive behavior has been reported after CCS, although negative results in human and animal studies have been published. No adverse neurologic, psychologic or intellectual effects of stimulation have occurred after 7 years of CCS, although subclinical histological changes may occur in the cerebellar cortex under the electrodes. CCS has been shown to produce physiological changes in evoked potentials, motoneurone excitability, epileptic discharges in the EEG and quantitative changes in movement. Surface and deep thalamic recordings have shown reduced amplitudes of somatosensory responses after CCS. Over the last 2 years we have employed chronic deep brain stimulation (DBS) in 49 patients with clinically useful results in half the patients. The technique allows reversible modification of movement disorders, and the technique can be used on the second side after a previous thalamectomy. Physiological testing, direct thalamic recordings and quantitative analysis of movement have allowed assessment of optimal rate and voltage of stimulation. For some intractable movement disorders DBS has effected significant therapeutic results when all other therapeutic techniques have failed.

Neuromuscular function in weight-trainers

Electrophysiologic measurements were made on the median-innervated thenar muscles and triceps surae in 17 weight-trainers (bodybuilders and weight-lifters) and in control subjects. In the median-innervated thenar muscles, the weight-trainers presented normal values for motor unit counts, reflex potentiation, and twitch contractile properties; however, the weight-trainers possessed a significantly greater (8%) median motor nerve conduction velocity. In the triceps surae, the weight-trainers exhibited significantly greater reflex potentiation (70%), which was interpreted as an increased ability to activate motor units during maximal voluntary contractions. Peak twitch tension (16%) and twitch contraction time (20%) of the triceps surae were significantly greater in the weight-trainers, whereas their twitch half-relaxation time and soleus motor unit counts were not significantly different from control values. The observed difference may reflect a combination of genetic endowment and the effects of training.

Neurocardiac and cerebral responses evoked by esophageal vago-afferent stimulation in humans: effect of varying intensities.

OBJECTIVE This study was designed to determine whether esophageal vago-afferent electrostimulation, over a wide range of stimulus intensities, can sustain a cardiac vago-efferent effect by way of central nervous system processing. METHODS Studies were performed in ten healthy male subjects (23.9 +/- 6.3 years). Esophageal electrostimulation was carried out using a stimulating electrode placed in the distal esophagus. Stimulation of esophageal vago-afferent fibres was employed using electrical impulses (200 microseconds at 0.2 Hz x 128 s) varying from 2.7 to 20 mA. Respiratory frequencies, beat-to-beat heart rate autospectra and cerebral evoked potentials were recorded at baseline and at each stimulus intensity in random order. RESULTS With esophageal electrical stimulation, we observed a small non-significant decrease in heart rate. There was a dramatic shift of the instantaneous heart rate power spectra towards enhanced cardiac vagal modulation with intensities as low as 5 mA. This effect was sustained throughout all intensities with no further change in either the low frequency or high frequency power. Conversely, there was a linear dose response relationship between cerebral evoked potential amplitude and stimulus intensity mainly occurring above perception threshold (10 mA). Esophageal stimulation had no significant effect on heart rate or respiratory frequency at any stimulus intensity. CONCLUSIONS These results indicate that electrical stimulation of the distal esophagus across a wide range of current intensities elicits a reproducible shift in the heart rate power spectrum towards enhanced vagal modulation. The data suggest a closed loop afferent/efferent circuitry wherein tonic visceral afferent impulses appear to elicit a phasic or modulatory vago-efferent cardiac response in healthy subjects.

Cortical Evoked Responses Following Esophageal Balloon Distension and Electrical Stimulation in Healthy Volunteers

Recording of evoked potential responsesrepresents an objective and quantifiable method to studyvisceral afferent sensory pathways in humans. Weexamined the evoked responses to mechanical distension(balloon) and electrical stimulation of the proximal anddistal esophagus. A standard manometric catheter with alatex balloon and an additional electrode attached toits body was placed in the lower esophagus in 15 healthy young volunteers. Repeatednonpainful balloon distension stimuli above theindividual sensation threshold (0.17 Hz, 12-20 ml) orshort electrical impulses (0.2 Hz, 12-16 mA) weredelivered in an alternate fashion at 23 and 33 cm from thenares. Evoked potential responses (EP) were recordedthrough 22 scalp surface electrodes using the standard10/20 International EEG system of electrode placement. Balloon distension produced a reproducibletriphasic response at both sites. Peak latencies ofthree negative EP peaks were 92 ± 17, 229± 40, and 339 ± 36 msec with proximalstimulation versus 154 ± 24, 275 ± 24, and384 ± 30 msec obtained with distal stimulation (P< 0.001). Electrical stimulation produced a triphasicresponse with significantly shorter peak latencies atboth sites when compared to mechanical stimulation (P <0.001). Peak latencies were 74 ± 12, 137 ±11, and 245 ± 27 msec proximal versus 83 ±12, 148 ± 32, and 247 ± 51 msec withdistal stimulation (P < 0.01). The calculated conduction velocities forboth modes of stimulation (balloon: 1.73 ± 0.9m/sec vs electrical: 10.1 ± 3.4 m/sec) arecompatible with conduction through C fibers and Adeltafibers, respectively. Both modes of stimulation producecharacteristic brain responses that are conveyed throughdifferent types of afferent fibers. The respectivecontributions of both types of fibers to esophageal function and symptomatology can be specificallyaddressed using this approach in both normal andpathologic conditions.