Introducing a novel approach of network oriented analysis of ERPs, demonstrated on adult attention deficit hyperactivity disorder.

OBJECTIVE: Introducing a network-oriented analysis method (brain network activation [BNA]) of event related potential (ERP) activities and evaluating its value in the identification and severity-grading of adult ADHD patients. METHODS: Spatio-temporal interrelations and synchronicity of multi-sited ERP activity peaks were extracted in a group of 13 ADHD patients and 13 control subjects for the No-go stimulus in a Go/No-go task. Participants were scored by cross-validation against the most discriminative ensuing group patterns and scores were correlated to neuropsychological evaluation scores. RESULTS: A distinct frontal-central-parietal pattern in the delta frequency range, dominant at the P3 latency, was unraveled in controls, while central activity in the theta and alpha frequency ranges predominated in the ADHD pattern, involving early ERP components (P1-N1-P2-N2). Cross-validation based on this analysis yielded 92% specificity and 84% sensitivity and individual scores correlated well with behavioral assessments. CONCLUSIONS: These results suggest that the ADHD group was more characterized by the process of exerting attention in the early monitoring stages of the No-go signal while the controls were more characterized by the process of inhibiting the response to that signal. SIGNIFICANCE: The BNA method may provide both diagnostic and drug development tools for use in diverse neurological disorders.

Forecasting generalized epileptic seizures from the EEG signal by wavelet analysis and dynamic unsupervised fuzzy clustering.

Dynamic state recognition and event-prediction are fundamental tasks in biomedical signal processing. We present a new, electroencephalogram (EEG)-based, brain-state identification method which could form the basis for forecasting a generalized epileptic seizure. The method relies on the existence in the EEG of a preseizure state, with extractable unique features, a priori undefined. We exposed 25 rats to hyperbaric oxygen until the appearance of a generalized EEG seizure. EEG segments from the preexposure, early exposure, and the period up to and including the seizure were processed by the fast wavelet transform. Features extracted from the wavelet coefficients were imputed to the unsupervised optimal fuzzy clustering (UOFC) algorithm. The UOFC is useful for classifying similar discontinuous temporal patterns in the semistationary EEG to a set of clusters which may represent brain-states. The unsupervised selection of the number of cluster overcomes the a priori unknown and variable number of states. The usually vague brain state transitions are naturally treated by assigning each temporal pattern to one or more fuzzy clusters. The classification succeeded in identifying several, behavior-backed, EEG states such as sleep, resting, alert and active wakefulness, as well as the seizure. In 16 instances a preseizure state, lasting between 0.7 and 4 min was defined. Considerable individual variability in the number and characteristics of the clusters may postpone the realization of an early universal epilepsy warning. University may not be crucial if using a dynamic version of the UOFC which has been taught the individual's normal vocabulary of EEG states and can be expected to detect unspecified new states.

Susceptibility of the injured rat brain to CNS oxygen toxicity.

The possibility of an altered susceptibility of the injured brain to central nervous system (CNS) oxygen toxicity was examined in awake rats. Moderate to severe closed head injury with diffuse axonal damage was produced in anesthetized rats by the fluid percussion method (2-2.5 atm), after which chronic EEG electrodes were implanted. Twenty-four hours later, the rats were exposed to 5 atm abs (506.5 kPa) oxygen and the time to appearance of paroxysmal EEG patterns was noted. The difference between the 19 minute median latency of this group and 16 minute of a control group which underwent a sham operation did not reach statistical significance. Some injured animals convulsed with minimal or no EEG changes. The clinical implication could be that brain injured patients are not at higher risk of CNS oxygen toxicity but the EEG alterations that could potentially be used to forecast incipient convulsions, or be the indication of actual convulsions in the intact brain of a paralyzed patient, may not always be present.

Recovery of the hypoxic ventilatory drive of rats from the toxic effect of hyperbaric oxygen.

Hyperbaric oxygen (HBO) exposure reduces the hypoxic ventilatory drive (HVD), probably by damaging the carotid bodies. The recovery of the HVD from HBO exposure was studied. The HVD was calculated from whole body plethysmographic recordings of the ventilatory response to greater than 85% and 2% O2 in N2 mixtures. Five groups of rats were exposed to HBO for 9 h at pressures of 1.9, 2.0, 2.1, 2.2, and 2.4 ATA, respectively. Each rat underwent three control measurements on different days prior to HBO exposures and then at various intervals following the exposure. Postexposure HVD was reduced to 28% of control values in the high PO2s. Ninety percent recovery of pre-exposure HVD was evident by 12-48 h although in some animals exposed to relatively low PO2s (1.9 and 2.0 ATA) HVD stabilized at a level lower than 100%. The recovery of the HVD in percent during the first 4 d following exposure can be expressed as an exponential function of the time from the termination of HBO: HVD = 28 + 72(1 - exp-0.053t) (t in hours). This information may be of importance in cases of repeated exposures to HBO where one tries to avoid cumulative damage to the carotid bodies, and in the care of the poorly oxygenated patient after HBO treatment.

Effects of dietary factors on antioxidant enzymes in rats exposed to hyperbaric oxygen.

To delineate the effect of dietary supplementation with vitamin E (Vit E) alone or in combination with riboflavin (Rib) or selenium (Se) or both, on biological oxidative damage in rat brain and lungs we exposed rats to hyperbaric oxygen (HBO) and measured the activities of glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G-6-PD) prior to or 48 h after exposure. Rats fed the dietary supplements, and a control group maintained on an unsupplemented diet, for 30 d, were each divided into 2 subgroups, of which 1 was exposed to 4.5 absolute atmospheres (ATA) of 100% oxygen for 30 min, hereafter referred to as "exposed". The remaining subgroups were left unexposed. Pre-exposure GSSG-R activity in brain was elevated in all experimentally fed groups (ranging from 23 to 84%) compared with the unexposed control, whereas GSH-Px, G-6-PD and SOD activities were unchanged. The lungs showed significant increases in pre-exposure GSSG-R, ranging from 15 to 28%, and GSH-Px, ranging from 13 to 23%, activities in all the groups fed the supplemental nutrients, except those on Vit E alone. Increases in G-6-PD activity were observed only in those fed supplements of Rib. In most cases exposure to oxygen caused an increase in GSSG-R, GSH-Px and G-6-PD activities. However the increases were higher in the supplemented groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of carbamazepine and ethosuximide on hyperoxic seizures.

The main manifestations of CNS oxygen toxicity are generalized tonic-clonic seizures. We tested the protective effect of 2 antiepileptic drugs, carbamazepine and ethosuximide, which are commonly used for the treatment of generalized seizures, on hyperbaric oxygen-induced convulsions. Rats implanted with chronic cortical electrodes for continuous EEG monitoring were injected i.p. with either carbamazepine (5 doses in the range of 1.5-50 mg/kg), ethosuximide (400 mg/kg), or their vehicles (40% propylene glycol and saline, respectively). The rats were exposed to 5 ATA (0.5 MPa) oxygen. The duration of the latency until the appearance of electrical discharges in the EEG was used as an index of toxicity. Ethosuximide did not protect against hyperoxic seizures. In contrast, rats pretreated (30 min) with carbamazepine exhibited a dose-related protective effect against hyperoxically induced seizures. The results of our study suggest that carbamazepine should be considered for prevention of oxygen-induced seizures during hyperbaric oxygen therapy.

Effects of dietary supplementation with vitamin E, riboflavin and selenium on central nervous system oxygen toxicity.

We attempted to modify the resistance of rats to hyperbaric oxygen (HBO)-induced central nervous system (CNS) toxicity, by increasing the tissue antioxidant potential through dietary factors. Groups of rats were fed excesses of vitamin E (VIT E) alone or in combinations with riboflavin (RIB), selenium (Se) or both, for 30 days. A control group was maintained on an unsupplemented diet. On the 23rd day animals to be exposed were implanted with chronic electrodes for electrocorticographic (ECoG) recording. Later, each group was divided into two subgroups, of which one was exposed to 4.5 atmospheres absolute (ATA) of 100% oxygen (O2) for 30 min., hereafter referred to as "exposed", noting the time of appearance of first electrical discharge (FED) in their ECoG. The remaining subgroups were left unexposed. Forty-eight hours later, all animals were sacrificed and some of their tissues were analyzed for glutathione (GSH). The GSH level in the liver, brain, lungs and blood of all experimental subgroups were significantly higher than in the control unexposed counterparts. Combinations of RIB and/or Se with VIT E failed to show a greater increase in GSH over VIT E alone. This increase was, however, not accompanied by a meaningful delay in the appearance of FED. Forty-eight hours post-exposure, the brain GSH levels of all exposed subgroups were still lower than the respective pre-exposure levels. Yet, in the treated exposed subgroups the GSH levels observed 48 hr after exposure were already higher than in the untreated unexposed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity.

We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated.

Attenuation of hypoxic ventilation by hyperbaric O2: effects of pressure and exposure time.

Hyperoxia affects O2 chemoreception in the highly perfused carotid bodies and causes a reduction of the ventilatory hypoxic drive (HD) as was shown for anesthetized cats and awake rats. We looked for a quantitative description of such an effect on HD as a function of both O2 pressure and exposure duration. Ventilation of rats was measured using the barometric method before and after hyperbaric O2 (HBO) exposure, at either air, 80% O2, or 4% O2. We used three exposure durations: 180, 550 and 900 min. The O2 pressure ranged between 1.2 and 3.0 ATA. At each time duration we used four to five groups of rats at a range of O2 pressures that yielded the full scale of effect on HD but avoided obvious lasting difficulties in breathing. HBO caused a reduction of breathing frequency and elevation of tidal volume in both air and 80% O2 but almost no change in minute ventilation. Hypoxic minute ventilation (4% O2) decreased after HBO, mainly through reduced frequency. HD was described by a power function of O2 pressure for each HBO duration. HD did not decline below 20% of the full control response. Ventilatory HD diminution is pictured as a function of both O2 pressure and HBO duration. The dependency of HD on exposure time and on pressure is similar to other known toxic effects of HBO.

Central nervous system oxygen toxicity in the resting rat: postponement by intermittent oxygen exposure.

Intermittent O2 breathing is a proven means of delaying pulmonary O2 toxicity during exposure to hyperbaric oxygen. The effect of an intermittent exposure in the pressure range toxic to the CNS was studied. Conscious, unrestrained rats, implanted with cortical EEG electrodes were subjected at 5 and 6 ATA to alternating periods of 7 min O2 and 7 or 10 min of either air, normoxic nitrox, or N2O-air (the latter mixture being equinarcotic to pure O2). Altogether, nearly half of the animals survived 90 min of intermittent breathing, with no grossly abnormal EEG patterns. At that time, labored breathing (associated with mild lung pathology) supervened. In the remaining animals, seizure patterns in the EEG appeared after a mean cumulative O2 breathing time of 20 min (compared to 9 min during a continuous exposure). Forty percent were affected while breathing the alternating mixture (low-PO2 seizures), mostly soon after switching of the gas. The nature of the alternating mixture did not affect the outcome of the high-PO2 seizures nor did the length of the interim periods. Normoxic nitrox increased and N2O-air reduced the incidence of low-PO2 seizures. At 5 ATA only 10% of the animals experienced high-PO2 seizures. While swift reversibility of the toxic process is indicated, the low-PO2 seizures with as yet an undetermined mechanism pose a serious obstacle for intermittent exposures at this pressure range.

The glycine-prodrug, milacemide, increases the seizure threshold due to hyperbaric oxygen; prevention by 1-deprenyl.

The novel glycine-prodrug anticonvulsant, milacemide (2-N-pentylaminoacetamide) (500 mg/kg), significantly increased (greater than 400% the seizure threshold induced by hyperbaric oxygen (4.5 atmosphere). This effect was significantly reduced by the selective inhibition of monoamine oxidase B by 1-deprenyl (2.0 mg/kg). 1-Deprenyl alone hardly affected the seizure threshold. These results suggest that, in the brain, milacemide is oxidized to glycine and that this reaction is mediated primarily by monoamine oxidase B. However, the interaction of milacemide metabolites (glycine amide, pentanoate and glycine) as antagonists of receptors of the glutamate NMDA (N-methyl-D-aspartate) subtype cannot be excluded.

Ventilatory response to transient hypoxia in O2 divers.

This study addresses the question of whether repeated acute exposure to hyperbaric oxygen, such as encountered in O2 diving, affects the peripheral oxygen chemosensors. Groups of nondivers, active O2 divers, and ex-O2 divers, as well as active air scuba divers, were given 1 or both of 2 tests that measure the ventilatory response to transient hypoxia. Results showed that all groups of divers have a mean response similar to or higher than that of nondivers as well as that of normal subjects, as reported in the literature. A repeat test on 10 diving candidates before and after 200 h of accrued O2 diving also did not show an impairment in the hypoxic ventilatory response. Oxygen diving within the established depth and time limits does not seem to cause cumulative damage to the peripheral O2 chemosensors.

Hyperoxic exposure affects the ventilatory response to hypoxia in awake rats.

We tested whether hyperbaric O2 (HBO) has an adverse effect on the hypoxic ventilatory drive. Four groups of rats were exposed for 550 min to O2 at 1.67, 1.90, and 2.15 ATA and to air at 1.90 ATA, respectively. Ventilatory parameters (frequency, tidal volume, and minute ventilation) were measured using whole-body plethysmography, before the hyperbaric exposure, immediately after the exposure, and up to 20 days after the exposure. Resting ventilation was not affected after exposure at 1.90 ATA to air or at 1.67 ATA to O2. HBO at 1.90 and 2.15 ATA caused a reduction of frequency and an elevation of tidal volume at different inspired gases: air, 5% CO2 balance O2, 80% O2, and 4.5% O2. However, minute ventilation on the day after the hyperoxic exposure was not different from the control at either air, 5% CO2, or 80% O2 but was markedly attenuated on the first three breaths at 4.5% O2. The hypoxic ventilation decreased to 48 +/- 13 (SD) and 32 + 11% after 1.90 and 2.15 ATA, respectively. The ventilatory parameters recovered in the days after HBO. We conclude that HBO reversibly depresses the hypoxic ventilatory drive, most probably by a direct effect on the carotid O2 chemoreceptors.

The transportable recompression rescue chamber as an alternative to delayed treatment in serious diving accidents.

This report summarizes experience in the use of a Transportable Recompression Rescue Chamber (TRRC) for one man in the rapid initiation of treatment and evacuation in severe scuba diving accidents. An evacuation system is described which incorporates the centralized management of all diving accidents and standardized TRRCs capable of interlocking under pressure with the stationary medical chamber. Oxygen breathing capability in the TRRC allows the use of up-to-date U.S. Navy oxygen treatment tables. Included are 19 cases of Type II decompression sickness and pulmonary barotrauma with neurological manifestations, most of which occurred at remote diving sites with no nearby walk-in chambers. Case analysis includes distance and means of evacuation, delay in initiating therapy, time spent in TRRC, and initial and final outcome. Together, TRRCs and airborne evacuation to a stationary medical chamber insures a minimal delay between the onset of symptoms and the start of recompression therapy. The use of the TRRC is a prime factor in minimizing delay. No complications associated with the use of TRRCs have been encountered. Ideally, evacuation should be made in a pressurized two-compartment (for a victim and an attendant) chamber. However, if this is not available we strongly advocate the use of one-man pressurized TRRCs over unpressurized evacuation.

Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity.

A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. We conclude that either the sodium valproate inhibition of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures.