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Biomedical subjects

R G Bickford

Publications and source records attributed to R G Bickford.

At least 19 recordsLinked to original sources

Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans.

The effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial stimulation (tc-MERs) were studied in five healthy human volunteers. Each subject, in four separate sessions, received intravenous bolus doses of propofol 2 mg.kg-1, etomidate 0.3 mg.kg-1, midazolam 0.05 mg.kg-1, and fentanyl 3 micrograms.kg-1. Electrical tc-MERs (tce-MERs) were elicited with anodal stimuli of 500-700 V. Magnetic tc-MERs (tcmag-MERs) were elicited using a Cadwell MES-10 magnetic stimulator at maximum output. Compound muscle action potentials were recorded from the tibialis anterior muscle. Duplicate tce-MERs and tcmag-MERs were recorded before and up to 30 min after drug injection. Reproducible baseline tce-MERs (amplitude 4.7 +/- 0.43 (SEM) mV, latency 29.4 +/- 0.35 ms) and tcmag-MERs (amplitude 3.7 +/- 0.43 mV, latency 31.1 +/- 0.39 ms) were obtained in all subjects. Pronounced depression of tce-MER amplitude to 2% of baseline values (P less than 0.01) was observed 2 min after injection of propofol. Thirty minutes after injection of propofol, amplitude depression to 44% of baseline (P less than 0.05) was still present, despite an apparent lack of sedation. Midazolam caused significant (P less than 0.01) amplitude depression, e.g., tcmag-MER to 16% of baseline values 5 min after injection. Significant depression persisted throughout the 30-min study period. Fentanyl did not cause any statistically significant amplitude changes in this small population. Etomidate caused significant but transient depression of tc-MER amplitude. However, there was considerable intersubject variability. Latency did not change significantly after any drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Multisite recording of brain field potentials and unit activity in freely moving rats.

A technique has been developed to record from 16 different brain sites of the freely moving rat using subminiature MOSFET preamplifiers. The high input impedance, small size, durability and light weight of the amplifiers and connecting cable allows high quality multisite recording of field potentials and unit activity. In addition, a movable headstage for positioning multiple microelectrodes is described. The compact recording system permits one to construct neocortical EEG maps, instant depth profiles of evoked and spontaneous field data, and to study neuronal synchrony of distant cell populations.

Action Potentials

Seizures during opioid anesthetic induction--are they opioid-induced rigidity?

The tape recorded EEGs of 127 patients anesthetized with large doses of opioids were retrospectively analyzed for evidence of opioid-induced seizures, and in particular, correlated with movements that occurred during induction and could be clinically interpreted as seizures. Bilateral EEG leads in patients receiving fentanyl (20), sufentanil (20), or alfentanil (87) were recorded. Forty-six of these patients from all opioid groups manifested intense rigidity, as assessed both clinically and by EMGs recorded from eight muscles in 69 of the patients receiving alfentanil. This intense rigidity often resembled seizures, in that the phenomenon entailed severe stiffness of both limbs and trunk, with an explosive onset of myoclonic limb movements, and associated vertical nystagmus. Electroencephalographic observations were extensive, entailing 69 h of paper recordings played back from the tapes, at paper speeds of 30 or 60 mm/s, with detailed annotations from the voice track. These paper recordings were examined in detail independently by three of the investigators, who were unaware of the clinical phenomena that had occurred. The only observed EEG activity that could have been interpreted as epileptiform consisted of small sharp waves related to muscle activity or other artifact. The EEG never indicated seizure activity during these drug-induced movements and rigidity. Reports of opioid-induced seizures are reviewed and a set of criteria is offered to help achieve future consistency and credibility in evaluating this phenomenon. The available evidence does not support the existence of opioid-induced seizures in the clinical setting.

Alfentanil

Electric activity in the neocortex of freely moving young and aged rats.

Electroencephalographic activity of the neocortex was evaluated in young (5-7 months) and aged (26-28 months) rats. All animals in the aged group showed behavioral impairment in a spatial task (water maze). A neocortical electroencephalogram was derived simultaneously from 16 different neocortical locations and was subjected to spectral analysis. The frequency of occurrence and duration of high-voltage spindles was determined in two sessions, each involving a total of 30 min alert immobility. Changes in spectral characteristics and high-voltage spindles in response to scopolamine administration were also evaluated. The power of high-frequency activity (8-20 Hz) was significantly reduced in the aged subjects. This was greatest in the temporo-occipital regions, while no significant changes were seen in the mediofrontal region. Scopolamine resulted in a large power increase in all frequency bands, but the increase in the higher-frequency range (8-20 Hz) was significantly less in the aged group. The incidence of high-voltage spindles was 6 times higher and their total duration was 9 times longer in aged rats, with virtually no overlap with the young group. In young rats, scopolamine increased the incidence and total duration of high-voltage spindles, while it decreased both parameters in the aged subjects. Cholinergic neurons in the nucleus basalis appeared shrunken in the aged animals. These findings demonstrate that reliable electroencephalographic changes are present in the neocortex of the aged rat, and that some of the physiological alterations may be due to the pathological changes in the cholinergic nucleus basalis.

Aging

Nucleus basalis and thalamic control of neocortical activity in the freely moving rat.

EEG and single-unit techniques have been used to study the EEG correlates of cellular firing in the neocortex, n. reticularis (RT) and "specific" thalamic nuclei, and the cholinergic forebrain area (nucleus basalis, NB). Neuronal firing was related to the ongoing behavior of the rat. In addition, using a 16-channel neocortical recording/mapping system, we studied the effects of ibotenic acid lesion of NB, RT, and other thalamic nuclei on the patterns and spatial distribution of neocortical electrical activity. The majority of neurons in neocortex, NB, and RT increased their firing rates during walking, as compared to during immobility, with concurrent decrease of delta power in the neocortical EEG. During immobility, high-voltage spindles (HVS; greater than 1 mV) were occasionally recorded from the neocortex. Depth profiles of HVS and slow delta waves were different in the neocortex. Neocortical cells decreased their discharge frequency during the positive portion of delta waves recorded in layers V and VI. All cells in the neocortex and specific thalamic nuclei fired rhythmically and phase-locked to the spike component of HVS. RT neurons showed an opposite phase relationship and fired mainly during the wave component of HVS. Half of the NB neurons also showed phasic modulation with HVS. Circumscribed lesion of RT and extensive damage of other thalamic regions, including the intralaminar nuclei, suppressed HVS but had no effect on the neocortical EEG correlates of behavior. In sharp contrast, damage to the NB resulted in a dramatic increase of slow delta waves on the side of the lesion, mimicking the effect of scopolamine administration. We suggest that the NB plays a key role in neocortical arousal by directly activating the neocortex and by suppressing the rhythm generation in the RT-thalamocortical circuitry. We further suggest that the NB system may serve as a structural basis for the concept of the generalized ascending activation of Moruzzi and Magoun (1949).

Animals

Magnetic stimulation of human peripheral nerve and brain: response enhancement by combined magnetoelectrical technique.

The authors describe the technique of magnetic stimulation from a pulsed induction coil (4.0 T) and the enhanced (5-fold) electromyogram response from hyperthenar muscles obtained when electric and magnetic stimuli are applied simultaneously. The enhancement results have been confirmed for central brain vertex stimulation using the Sheffield magnet. Results obtained with slow (1 to 6 seconds) depth electrode stimulation and recording in humans are compared and are used to predict probable developments in the magnetic field. Because magnetic and magnetoelectrical techniques are painless, noninvasive, and noninjurious, it is believed that they are an important advance in both research and clinical applications of instrumental modification of brain circuits and behavior. There are many diagnostic and therapeutic uses at peripheral and central levels, and some ethical problems need consideration.

Electric Stimulation

Selective hemispheric stimulation by unilateral forced nostril breathing.

We have previously demonstrated by the integration of EEG amplitudes, that an ultradian rhythm of alternating cerebral dominance exists in humans. This rhythm is tightly coupled with the nasal cycle, since its lateralization correlates with shifts in airflow through the left and right nostrils, where relatively greater integrated amplitudes in one hemisphere correspond to predominant airflow in the contralateral nostril. The nasal cycle is known to be regulated by the sympathetic and parasympathetic branches of the autonomic nervous system. This dynamic lateralization of alternating activity in the autonomic nervous system exists in other peripheral structures and is also likely to be the mode of regulation of the cortical rhythm. This paper shows that forced nostril breathing in one nostril produces a relative increase in the EEG amplitude in the contralateral hemisphere. This phenomena was demonstrated in 5 out of 5 untrained subjects. These results suggest the possibility of a non-invasive approach in the treatment of states of psychopathology where lateralized cerebral dysfunction have been shown to occur.

Adult

Triphasic waves: a reassessment of their significance.

Electroencephalograms and case histories of 50 patients with triphasic waves were reviewed. EEGs were studied for slowed dominant activity, anteriorly dominant triphasic waves, anterior-posterior lag time and bursts of triphasic waves. Etiologies of triphasic waves were: hepatic (28), azotemia (10), anoxia (10) and hyperosmolarity (2). Sixteen hepatic and two azotemic patients showed all of these characteristic EEG features. Triphasic waves demonstrating all of these features are highly characteristic of but are not pathognomonic for hepatic encephalopathy. Prognosis correlated best with the type of hepatic injury and deteriorating renal function. We postulate that triphasic waves are generated by the same thalamocortical volleys which normally induce spindles.

Brain

Serotonin depletion prevents electrocortical synchronization following acute midbrain deactivation.

Bilateral midbrain cooling (5-15 degrees C) was performed in cats pretreated with p-chlorophenylalanine (PCPA). This was done in order to examine the possible role of 5-hydroxytryptamine (5-HT) systems in the process of electrocortical synchronization which normally accompanies midbrain reticular deactivation. Prior to treatment with PCPA, midbrain cooling always produced tonic electrocortical synchronization and behavioral unresponsiveness. Cooling following PCPA treatment on the other hand produced behavioral unresponsiveness which was not accompanied by tonic electrocortical synchronization; in that case electrocortical desynchronization persisted in spite of midbrain reticular deactivation. These results lead to the hypothesis that two distinct, tonically active, desynchronizing systems exist. During the acute blockade of the classical midbrain reticular activating system it is proposed that 5-HT systems normally operate to inhibit or otherwise prevent the expression of the second brain stem electrocortical desynchronizing mechanism. It is proposed, therefore, that 5-HT acts indirectly to produce electrocortical synchronization. In the absence of 5-HT, midbrain deactivation is not sufficient to guarantee synchronization is assured only when both desynchronizing systems are inactivated as would be the case in the acute cerveau isolé.

Animals

Alternating cerebral hemispheric activity and the lateralization of autonomic nervous function.

Alternating dominance of cerebral hemispheric activity was demonstrated in humans by use of the electroencephalogram (EEG). Relative changes of electrocortical activity have a direct correlation with changes in the relative nostril dominance, the so-called nasal cycle. The nasal cycle is a phenomenon where efficiency of breathing alternates predominantly through right or left nostril with a periodicity ranging from 25 to greater than 200 minutes. Relatively greater integrated EEG value in one hemisphere correlates with predominant airflow in the contralateral nostril, defining a new interrelationship between cerebral dominance and peripheral autonomic nervous function.

Adult

EEG monitoring of clinical coma: the compressed spectral array.

Twenty-four comatose patients were studied by 16-hour compressed spectral array (CSA), made from four-channel portable EEG recordings. Causes of coma included head injury (15), anoxia (6), and brainstem strokes (3). CSA was classified on the basis of frequency and alternating or nonalternating patterns. Alternating CSA was significantly associated with survival (p less than 0.005) in the head-injured and anoxic group combined, and in the head-injured subgroup (p less than 0.013). The prognostic value of CSA equaled the Glasgow Coma Scale or neurologic examination and occasionally added prognostic information.

Adult

Localizing and prognostic value of auditory evoked responses in coma after closed head injury.

We studied brainstem auditory evoked responses (BAERs) in 26 comatose patients after head injury, and long-latency auditory evoked responses (AERs) in 24 patients. BAERs-AERs were graded for abnormality to evaluate graded outcome. Only six patients had central BAER abnormalities. AERs were abnormal in 21, and all patients with abnormal BAER had abnormal AER, implying that the major site of injury affected the cerebral hemispheres. BAER was abnormal in only 5 of 12 with decerebration, suggesting that decerebration may occur with diffuse hemispheric injury. BAER (p less than 0.01) and AER (p less than 0.01) strongly correlated with outcome. Preservation of AER and normal BAER indicated good quality of survival; absent AER and normal BAER, survival; and absent AER and abnormal BAER, severe disability or death. BAER-AER predicted outcome as accurately as the detailed neurologic examination and occasionally added predictive power.

Adult

Comparison of two types of visual evoked potentials: pattern reversal and eye movement (lambda).

The averaged visual evoked potentials of 10 normal subjects were studied either with eyes fixated while a chequerboard reversed or when they moved their eyes across the stationary chequerboard. The resulting occipital potentials averaged using a computer of averaged transients were discrepant for the 2 conditions. The latency of the P100 component was similar allowing for the difference in latency in the computer triggering system but the resulting wave forms were different. There was a prominent negative component preceding the P100 in the lambda response and a prominent negative component following the P100 for the pattern shift. The possible reasons for the findings are discussed.

Adult

Brain stem auditory evoked potentials: the use of noise estimate.

One of the main difficulties with the interpretation of evoked potential data is the question of how much noise is contained within the average. This question is crucial in deciding whether any particular peak component is a genuine signal, or whether it is a random occurrence due to noise. This is particularly crucial in abnormal cases, and with stimuli near sensory threshold. A simple method is described which allows on-line objective statistical determination of the presence of significant non-random peak components. It is shown that high signal-to-noise (S/N) estimates are seen with 'clean' and reproducible BAEPs and low S/N estimates are seen with poorly reproducible BAEPs. This provides an objective measure to judge the acceptability of any single BAEP, or to indicate that further averaging is required. The effect of noise on wave shape and peak latency is discussed. This can be quite marked, with gross distrotion of morphology and latency as a result. The technique lends itself to evoked response audiometry (ERA) and sensory threshold determination. Further, it can be applied to evoked potentials from other stimulus modalities.

Acoustic Stimulation

The relationship of head size to alpha frequency with implications to a brain wave model.

Analogies between brain waves and waves in physical systems suggest that EEG frequency may be partly determined by cortical surface area. Since a number of other physiological and anatomical parameters probably influence EEG frequency, only a weak correlation is to be expected. A study was made of 159 subjects, some of whom had either very large or very small heads. A single number representing head size was determined as the cube root of three linear measurements. Several characteristic EEG frequencies were determined for each subject by means of Fourier analysis. The data indicate that alpha frequency is significantly correlated with head size: larger heads tend to produce slower alpha rhythms. It was also shown that alpha frequency tends to be lower in all subjects above roughly age 60. Subjects above produced significantly less alpha rhythm than the younger group. It is suggested that analogies between brain waves and physical waves may explain a number of phenomena which are typical of EEG.

Adolescent

Effect of flurazepam on sleep spindles and K-complexes.

In this research, a quantitative study of the EEG from 5 subjects permitted a detailed analysis of the effect of 30 mg of flurazepam administered over 7 nights. Four placebo baseline nights and 3 placebo withdrawal nights were also recorded. For 4 of the subjects, a nondrug and nonplacebo follow-up record was obtained 4 to 6 weeks later. The subjects were 4 females, 1 male, age range 23-42. All complained of either sleep onset greater than 45 min, sleep length of less than 6 h, or two or more sleep awakenings. Compressed spectral analysis yielded a computer-generated somnogram on each of the 15 nights of sleep, and an automated spindle detector was used to count and measure the duration of spindle bursts with frequencies of 12.25-15.5 c/sec on baseline nights 3 and 4, drug nights 1, 2, 3 and 7, on the 3rd withdrawal night, and on the 4-6 week followup record. K-complexes were scored visually on the 4th baseline and 7th drug nights. There were no significant differences in spindle rate per minute among baseline nights and the follow-up record. By the 2nd drug night, spindle rate had significantly increased over the baseline rate. Linear contrast analysis indicated there was a significant increase of spindle rate over drug nights. All 5 subjects showed this pattern of increase. In contrast to the increase in spindle activity, the rate per minute of K-complexes significantly decreased during drug administration.

Adult

Visual and auditory evoked responses during penicillin-induced generalized spike-and-wave activity in cats.

In 13 healthy adult cats chronically implanted with parasagittal electrodes applied to the dural surface, curarization was performed and baseline recordings of the visual evoked response (VER), auditory evoked response (AER), and brainstem auditory evoked response (BAER) were made. Following the procedure of Prince and Farrell (1969), the animals were then given intramuscular doses of 300,000 to 500,000 U/kg of penicillin with the subsequent development of diffuse, bilaterally symmetrical, photosensitive spike-and-wave discharges in the EEG from 1 to 1 1/2 hr later and concomitant facial myoclonus, arrest of movement, and "absence-like" staring in non-curarized animals. The VER, AER, and BAER were monitored at 15-min intervals for several hours during which time the VER consistently decreased in amplitude up to the time at which the first spike-and wave bursts could be elicited by photic stimulation, approximately 1 hr after injection, after which all early components (0-200 msec) of the VER were progressively increased from 150 to 300% until spontaneous spike-and-wave bursts were consistently recorded (1 1/2-2 hr). Coincident with this change, a marked increase in late components (200-500 msec) was also observed. Both th early diminution and later augmentation of the VER were equally observable in visual and nonvisual cortex. Changes in the AER were also recorded with the development of this model, and were similar to those of the VER but of a lesser degree. The amplitudes of waves I through V of the BAER were found to increase from 28 to 88% maximal at 1 1/2 hr following penicillin injection. These data and the similarity of this model to human petit mal epilepsy argue against increased inhibitory impulses to the visual system during the ictal discharge being responsible for the subjective loss of visual information during petit mal absence. If the amplitude of the evoked response is directly related to the functional integrity of a sensory system, this suggests that the impairment of sensory input, or absence, during spike-and-wave paroxysm is due to interference with sensory processing rostral to the brainstem ascending auditory pathway, and probably does not occur in primary sensory cortex but rather in cortical or subcortical association tracts.

Animals