Far-field potentials in circular volumes: evidence to support the leading/trailing dipole model.

The leading/trailing dipole model explains the production of far-field potentials as an asymmetry in the leading and trailing dipole moments of a propagating action potential detected by a referential montage. This investigation documents the production of far-field potentials produced by a pure dipole generator in a circular volume conductor. Multiple equipotential waveforms are recorded in an adjoining circular volume conductor attached to the one in which the dipole generator is located. This finding substantiates the "wick electrode" effect that explains the equipotential and instantaneous distribution of far-field potentials over relatively large distances in volume conductors. The present findings support a number of the leading/trailing dipole model proposals which explain far-field potential generation.     

Far-field potentials

Far-field potentials are produced by neural generators located at a distance from the recording electrodes. These potentials were initially characterized incorrectly as being of positive polarity, widespread distribution, and constant latency; however, recent advances have clearly demonstrated that far-field potentials may be either positive or negative depending upon the location of the electrodes with respect to the orientation of the dipole generator. Additionally, peak latencies in the far-field can vary with alterations in body position and the spatial distribution of far-field potentials, while widespread, is not uniform. Recent studies of far-field potentials suggest how such waveforms are produced when the symmetry of an action potential, as recorded by distant electrodes, is broken by such factors as differing conductivities of volume conductor compartments, direction of action potential propagation, size differentials in adjoining body segments, or the termination of action potential propagation in excitable tissue. Human, animal, and computer experiments support the preceding generalizations. These new explanations are directly applicable to such far-field potentials as the short latency somatosensory-evoked potential. Furthermore, since far-field potentials can also occur in muscle tissue, one should expect that these generalizations will hold with respect to electromyographic potentials. © 1993 John Wiley & Sons, Inc.     

Far-field potentials in cylindrical and rectangular volume conductors

The occurrence of a transient dipole is one method of producing a far-field potential. This investigation qualitatively defines the characteristics of the near-field and far-field electrical potentials produced by a transient dipole in both cylindrical and rectangular volume conductors. Most body segments of electrophysiologic interest such as arms, legs, thorax, and neck are roughly cylindrical in shape. A centrally located dipole generator produces a nonzero equipotential region which is found to occur along the cylindrical wall at a distance from the dipole of approximately 1.4 times the cylinder's radius and 1.9 times the cylinder's radius for the center of the cylinder. This distance to the equipotential zone along the surface wall expands but remains less than 3.0 times the cylindrical radius when the dipole is eccentrically placed. The magnitude of the equipotential region resulting from an asymmetrically placed dipole remains identical to that when the dipole is centrally located. This behavior is found to be very similar in rectangular shallow conducting volumes that model a longitudinal slice of the cylinder, thus allowing a simple experimental model of the cylinder to be utilized. Amplitudes of the equipotential region are inversely proportional to the cylindrical or rectangular volume's cross-sectional area at the location of dipolar imbalance. This study predicts that referential electrode montages, when placed at 3.0 times the radius or greater from a dipolar axially aligned far-field generator in cylindrical homogeneous volume conductors, will record only equipotential far-field effects.     

Far-field potentials in muscle

Far-field potentials have been predicted by computer simulations as well as demonstrated in both animals and humans with respect to the peripheral and central nervous systems. Computer simulations have also predicted far-field potentials originating at the termination of muscle tissue. This investigation demonstrates the occurrence of 2 far-field potentials in the human biceps muscle resulting from action potential termination at the musculotendonous junctions. A monophasic potential is produced at both the muscle's origin and insertion, and the polarity is entirely dependent upon the recording montage. Sequential stimulation of the biceps muscle at 2.5-cm increments resulted in the 2 far-field potentials and their respective latencies changing proportional to the distance between the stimulus site and the 2 musculotendonous junctions. Various stimulation and recording montages are used to investigate the properties of these far-field potentials. The leading/trailing dipole model is utilized to explain the production and polarity of far-field potentials generated by muscle tissue.     

Far-field potentials in the compound muscle action potential

It has long been believed that the compound muscle action potential (CMAP) in motor-nerve conduction studies (MCSs) records the action potential beneath the active electrode over the muscle belly. However, recent studies have revealed the contribution of the reference electrode to the CMAP, most prominent in the tibial nerve, followed by the ulnar nerve. This “reference electrode potential” is recorded when the conventional reference electrode distal to the muscle belly is connected to a proximal reference. It must be a far-field potential (FFP) considering its distribution, although the precise mechanism of its generation has not been clarified. The conventional theory of termination of the action potential at the muscle-tendon junction is insufficient. Regarding the ulnar CMAP, interosseous muscles mostly contribute to the FFPs. New understanding of CMAP based on the FFP theory may provide new insights into the interpretation of MCSs and related techniques, including motor unit number estimation.     

Far-field and cortical somatosensory evoked potentials in motor neuron disease

We examined median somatosensory evoked potentials (SEPs) in 26 patients with sporadic motor neuron disease (MND). SEPs were recorded with multiple scalp derivations, using both the midfront and the earlobe as references for each subject. Central conduction time (CCT) was abnormal in three patients, but only when using the midfront reference. Moreover, an exclusive alteration of the early prerolandic potentials (absent or delayed P20 and/or P22) was noted using the earlobe reference in amyotrophic lateral sclerosis and in progressive bulbar palsy (54% and 50% of patients, respectively) but not in progressive muscular atrophy. These findings correlated with clinical evidence of upper motor neuron signs and with the severity of the disease. In agreement with recent views regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials.     

Far-field potentials generated by action potentials of isolated frog sciatic nerves in a spherical volume.

Previous results in cylindrical volumes have shown that action potentials generate far-field potentials when experimental conditions are such that quadrupolar components of the action potential are reduced to an equivalent dipole. We now show that the same conclusions are also reached within a spherical volume, again recording far-field potentials from isolated bullfrog nerves. A mathematical proof is given that shows that in a sphere, antipodal electrodes primarily detect far-field potentials from dipole generators and not quadrupole generators. A revised conception of the 'far-field' in evoked responses is discussed which equates far-field recordings with dipole detection.     

Generators of the early and late median thenar premotor potentials

The generator sources of the median thenar premotor potentials (PMPs) have remained elusive despite debate in the literature. By studying the median nerve in the hand with a variety of bipolar and referential recording montages, we systematically examined the possible nearfield and far-field sources that may determine these potentials. The results suggest that the early PMP is a near-field potential recorded by G₁ and generated by the median nerve traversing the distal carpal tunnel. The late PMP represents a far-field potential generated by the median digital nerve fibers as they pass from the palm volume into the thumb volume. Characteristics of the late PMP are explained using the leading/trailing dipole (L/TD) model of far-field potential generation. The diagnostic utility of these PMPs is questionable, since they are recorded from “regions” along the nerve rather than from more clearly defined sites. © 1995 John Wiley & Sons, Inc.     

Subthalamic nucleus deep brain stimulus evoked potentials: physiological and therapeutic implications.

The effect of subthalamic nucleus (STN) stimulation on cortical electroencephalographic activity was examined in 10 patients with Parkinson's disease and 4 patients with epilepsy. Evoked potentials were created by time-locking electroencephalography to the onset of electrical stimulation delivered through the lead implanted in the STN of patients who had previously undergone deep brain stimulation (DBS) surgery. The effect of different patterns of stimulation on the evoked response, including single- and paired-pulse as well as burst stimulation, was explored. Cortical evoked potentials to single pulses were observed with latencies as short as 1 to 2 msec after a single pulse of stimulation, with activity continuing, in some cases, for up to 400 msec. Paired-pulse experiments revealed refractory periods on the order of 0.5 msec, suggesting that stimulation of axons contributed to the generation of at least some portion of the evoked potential waveform. Evoked potentials were also present in response to 100-msec bursts of stimulation, with some evidence that the potential was initiated within the burst artifact. The potential implications of the types of responses observed as well as potential applications are discussed.     

Fatigue-related changes in motor unit action potentials of adult cats.

The purpose of this study was to quantify the changes in motor-unit action potentials (MUAP) and force during a standard motor-unit fatigue test. MUAP waveforms were characterized by the measurement of amplitude, duration, area, and shape (as reflected in a coefficient of proportionality). Fatigue-resistant motor units exhibited small, but statistically significant, changes in MUAP amplitude and area during the fatigue test, whereas fatigable motor units displayed variable changes in MUAP amplitude, duration, and area. For all motor-unit types, the coefficient of proportionality did not change, and hence the change in MUAP area was proportional to the combined changes in amplitude and duration. The between- and within-train changes in MUAP were also distinct for the fatigue-resistant and fatigable motor units. Although several mechanisms could be responsible for the changes in the MUAP as the fatigue test proceeded, the dissociation of the time courses for MUAP and force indicated that these MUAP changes were not the principal reason for the decline in force under these conditions.     

Barbiturate reduction of calcium-dependent action potentials: Correlation with anesthetic action

Calcium-dependent action potentials were recorded from mouse spinal cord neurons in primary dissociated cell culture following addition of the potassium channel blockers tetraethylammonium ion and 3-aminopyridine. The pharmacologically active barbiturates, pentobarbital and phenobarbital, but not the pharmacologically inactive barbiturate, barbituric acid, produced reversible, dose-dependent reduction of action potential duration at sedative-hypnotic and anesthetic concentrations. Pentobarbital reduced action potential duration at concentrations from 25 to 600 μM (50% reduction at 170 μM) while phenobarbital reduced action potential duration at concentrations from 100 to 5000 μM (50% reduction at 900 μM). The barbiturate concentrations which reduced calcium-dependent action potential duration in this study correlate with reduction of neurotransmitter release from other neuronal preparations and with reduction of calcium uptake by synaptosomes. The results suggest that barbiturates may produce anesthesia in part by reduction ofpresynaptic calcium entry and consequent reduction of neurotransmitter release in addition topostsynaptic increase of membrane chloride ion conductance. Barbiturate anticonvulsant actions are probably due topostsynaptic augmentation of GABA-mediated inhibition and depression of excitatory synaptic transmission. The major difference between anticonvulsant (phenobarbital) and anesthetic (pentobarbital) barbiturates was the dose-dependency of these actions. Phenobarbital produced postsynaptic modulation of neurotransmitter responses at low concentrations and decreased calcium-dependent action potential duration and increased chloride ion conductance at high concentrations. In contrast, pentobarbital produced all actions at low concentrations. Thus for phenobarbital there would be a large therapeutic index for anticonvulsant activity compared to anesthetic activity but for pentobarbital there would be a small therapeutic index.     

The diagnostic significance of large action potentials in myopathy

Electromyographic and histopathological studies were performed on 112 skeletal muscles in 101 subjects with myopathy. The diagnostic significance of large action potentials (LAPs) in myopathy was studied. LAPs were defined as those action potentials with a duration of over 13 ms and an amplitude of over 3 mV (peak to peak). The following results were obtained: Most muscles with LAPs showed the grouped atrophy of small fibers of neuropathic change in addition to myopathic findings. Even in myopathy most LAPs reflected neuropathic change, except in thyrotoxic myopathy. LAPs were not related to an increase of connective tissue increasing the impedance in volume conduction of the action potentials. LAPs were frequently seen in: progressive muscular dystrophy of limb-girdle type; scapuloperoneal dystrophy; distal myopathy; oculopharyngeal dystrophy; myotonic dystrophy; polymyositis; and thyrotoxic myopathy. Other types of myopathy had few LAPs. There were two types of progressive muscular dystrophy. One had LAPs frequently and the other, rarely. In myotonic dystrophy the muscles with LAPs showed scattered small angular fibers, possibly indicating neurogenic changes. Interstitial myositis had LAPs more frequently than parenchymatous polymyositis. The chronic phase of polymyositis had LAPs more frequently than the acute or subacute phases. In thyrotoxic myopathy the muscles with LAPs rarely showed definite neuropathic change histopathologically. Therefore, LAPs in thyrotoxic myopathy may not indicate denervation.     

The biphasic morphology of voluntary and spontaneous single muscle fiber action potentials

The extracellular morphology of single muscle fiber action potentials (SMFAPs) is anticipated by volume conductor theory to be triphasic. Single muscle fiber action potentials recorded during single muscle fiber studies (500 Hz to 20 kHz) usually appear triphasic; however, when recorded with an open bandwidth (1 Hz to 20 kHz) they are found to be biphasic. Fibrillation potentials recorded with a single fiber electrode and open bandwidth have identical biphasic morphologies as volitional SMFAPs. Computer simulations suggest that the intracellular action potential models currently used to derive simulated extracellularly recorded SMFAPs must have the repolarization phase considerably prolonged to yield the clinically recorded potentials. This implies that either the models presently used require significant modification, or there is some distortion of the transmembrane source current induced in needle recording studies such that biphasic and not triphasic potentials are detected. © 1994 John Wiley & Sons, Inc.     

Kinetics and distribution volumes for tracers of different sizes in the brain plasma space

Regional brain and plasma concentrations were determined for a series of radiotracers that differ in molecular weight and size in pentobarbital-anesthetized rats at 1, 5 and 30 min after i.v. injection. The tracers, [3H]inulin (mol. wt. 5000 Da, radius 1.5 nm), 5 [3H]dextrans (10,000-200,000 Da, 2.3-9.5 nm) and [51Cr]transferrin (79,000 Da, 3.8 nm), are not taken up into erythrocytes and do not measurably cross the blood-brain barrier in 30 min. Results were expressed as a brain distribution volume, defined as (dpm/g brain)/(dpm/ml plasma). Within 1 min after injection, all tracers attained an initial distribution volume which varied regionally from 0.4 to 1.6 X 10(-2) ml/g. The volumes remained constant between 1 and 30 min for tracers with radii greater than or equal to 3.8 nm, whereas the volumes increased up to 90% for tracers with radii less than or equal to 3.1 nm. Rates of equilibration for tracers with radii less than or equal to 3.1 nm were size dependent with smaller tracers equilibrating before larger tracers. These results indicate that the brain distribution volume for plasma tracers consists of two compartments: one which is quickly filled (less than or equal to 1 min) by all tracers and comprises approximately 60% of the total volume, and one which allows only tracers with radii less than or equal to 3.1 nm and comprises 40% of the total volume. The inverse relation between the rate of equilibration in the second compartment and molecular size may indicate a diffusion limitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Membrane depolarization and prolongation of calcium-dependent action potentials of mouse neurons in cell culture by two convulsants: Bicuculline and penicillin

The convulsant compounds bicuculline (BICUC) and penicillin (PCN) are antagonists of GABA-mediated synaptic inhibition. In addition, we have shown that BICUC and PCN produced membrane depolarization of mouse spinal cord neurons in primary dissociated cell culture by blocking a potassium conductance, a non-synaptic direct effect. Both compounds also prolonged calcium-dependent action potentials of mouse dorsal root ganglion and spinal cord neurons in cell culture. Thus, BICUC and PCN had both synaptic and non-synaptic actions. The possibility that both synaptic and non-synaptic actions of BICUC and PCN are involved in their convulsant mechanism of action is discussed.     

Auditory evoked transient and sustained potentials in the human EEG: I. Effects of expectation of stimuli

The characteristics of auditory evoked transient and sustained potentials were recorded using trains of four-tone stimuli of 1-second duration (interstimulus interval = 1 second) presented once every minute. The subject either attentively expected the stimuli or ignored them while reading. The electroencephalogram was recorded from derivations Cz-Al and Fz-Al. Expectation of the stimuli was associated with increased amplitudes of the transient responses both at the first stimulus of the train and during stimulus repetition. In contrast, the sustained potential at the first stimulus of the train was unchanged or smaller when the subject expected the stimuli. During stimulus repetition, however, the amplitude of the potential was enhanced by expectation of the stimuli. The results support the hypothesis of two sustained potential components and stress the importance of stimulus repetition rate when sustained potentials are studied.     

Encoding of point of view during action observation in the local field potentials of macaque area F5

The discovery of mirror neurons compellingly shows that the monkey premotor area F5 is active not only during the execution but also during the observation of goal‐directed motor acts. Previous studies have addressed the functioning of the mirror‐neuron system at the single‐unit level. Here, we tackled this research question at the network level by analysing local field potentials in area F5 while the monkey was presented with goal‐directed actions executed by a human or monkey actor and observed either from a first‐person or third‐person perspective. Our analysis showed that rhythmic responses are not only present in area F5 during action observation, but are also modulated by the point of view. Observing an action from a subjective point of view produced significantly higher power in the low‐frequency band (2–10 Hz) than observing the same action from a frontal view. Interestingly, an increase in power in the 2–10 Hz band was also produced by the execution of goal‐directed motor acts. Independently of the point of view, action observation also produced a significant decrease in power in the 15–40 Hz band and an increase in the 60–100 Hz band. These results suggest that, depending on the point of view, action observation might activate different processes in area F5. Furthermore, they may provide information about the functional architecture of action perception in primates.     

Dorsal root potentials in the cat: effects of bicuculline

Bicuculline (0.2 1 mg/kg) administered intravenously depressed dorsal root potentials (DRPs) evoked by stimulation of mixed, pure muscle or pure cutaneous nerves which was clearly concurrent with enhanced background potentials in intact cat. Administration of sodium pentobarbitone (15-30 mg/kg i.v.) reduced the ability of bicuculline to enhance background potentials and to depress evoked DRPs. In spinalized preparations, bicuculline depression of evoked DRPs by bicuculline in intact cat may not result from its action at axo-axonic GABAergic synapses alone and occlusion may also play a part. However, the role of gamma-aminobutyric acid (GABA) in primary afferent depolarization is confirmed in the spinalized preparations.     

Nimodipine decreases calcium action potentials in rabbit hippocampal CA1 neurons in an age-dependent and concentration-dependent manner

Intracellular recordings were made from rabbit hippocampal CA1 neurons in vitro using slices from aging and young adult rabbits. Calcium action potentials were studied in the presence of 4 μm tetrodotoxin using electrodes filled with 2M CsCl. Increasing concentrations of the dihydropyridine L-type calcium channel antagonist nimodipine were tested on the amplitude and time course of calcium action potentials. The calcium action potential (AP) consisted of two components: an initial fast phase followed by a slower plateau phase. No difference in the peak amplitude of the initial fast phase was observed between age groups. The amplitude and duration of the slower plateau phase of the calcium AP was significantly larger in aging neurons. Switching to a zero Ca²⁺ medium in the presence of 200 μm CdCl₂ completely blocked the calcium AP. Nimodipine decreased the plateau phase of the calcium AP at concentrations as low as 100 nm in aging neurons and 10 μm in young neurons. Switching to higher concentrations of nimodipine did not reveal any substantially increased block of the calcium AP plateau phase. These data suggest that enhanced calcium influx through L-type calcium channels is largely responsible for the enhanced calcium action potentials observed in aging CA1 neurons. The action of nimodipine in reducing the plateau phase of the calcium action potential may underlie the drug's notable ability to improve learning in hippocampally dependent tasks in aging animals.