Vahe E. Amassian

Magnetic coil stimulation of straight and bent amphibian and mammalian peripheral nerve in vitro: locus of excitation.

1. According to classical cable theory, a magnetic coil (MC) should excite a linear nerve fibre in a homogeneous medium at the negative‐going first spatial derivative of the induced electric field. This prediction was tested by MC stimulation of mammalian phrenic and amphibian sciatic nerve and branches in vitro, immersed in Ringer solution within a trough, and identifying the sites of excitation by recording responses of similar latency to local electrical stimulation. Subsequently, the identified sites of excitation were compared with measurements of the induced electric field and its calculated first spatial derivative. A special hardware device was used to selectively reverse MC current direction and to generate predominantly monophasic‐ or polyphasic‐induced pulse profiles whose initial phases were identical in polarity, shape and amplitude. When using the amphibian nerve preparation, a complication was excitation at low threshold points related to cut branches. 2. Reversal of monophasic current resulted in latency shifts corresponding approximately to the distance between induced cathode and anode. The location of each site of excitation was at, or very near, the negative‐going first spatial derivative peaks of the induced electric field measured parallel to the straight nerve. Significantly, excitation of the nerve did not occur at the peak of the induced electric field above the centre of the ‘figure of eight’ MC junction. 3. A polyphasic pulse excited the nerve at both sites, by the negative‐going first phase at one location, and approximately 150 microseconds later, by the reversed negative‐going second phase at the other location. Polyphasic and monophasic pulses elicited responses with similar latency when the induced current flowed towards the recording electrode. 4. Straddling a nerve with non‐coding solid lucite cylinders created a localized spatial narrowing and increase in the induced electric field, resulting in a lowered threshold of excitation. The corresponding closer spacing between first spatial derivative peaks was exhibited by a significant reduction in latency shift when MC current direction was reversed. 5. When a nerve is bent and the induced current is directed along the nerve towards the bend, the threshold of excitation is reduced there. Increasing the angle of the bend from 0 deg to more than 90 deg graded the decrease in threshold. 6. In a straight nerve the threshold was lowest when current was directed towards the cut end.(ABSTRACT TRUNCATED AT 400 WORDS)

Modelling magnetic coil excitation of human cerebral cortex with a peripheral nerve immersed in a brain-shaped volume conductor: the significance of fiber bending in excitation

To help elucidate some basic principles of magnetic coil (MC) excitation of cerebral cortex, a model system was devised in which mammalian phrenic nerve, or amphibian sciatic nerve with its branches was suspended in appropriate Ringers solution in a human brain-shaped volume conductor, an inverted plastic skull. The nerve was recorded monophasically out of the volume conductor. The site of nerve excitation by the MC was identified by finding where along the nerve a bipolar electrical stimulus yielded a similar action potential latency. MC excitation of hand-related corticospinal (CT) neurons was modelled by giving the distal end of nerve attached to the lateral skull an initial radial (perpendicular) trajectory, with subsequent bends towards the base and posterior part of the skull; this nerve was optimally excited by a laterally placed figure 8 or round MC when the induced electric field led to outward membrane current at the initial bend. By contrast, nerve given a trajectory modelling CT neurons related to the foot was optimally excited when the coil windings were across the midline, but again when membrane current flowed outward at the first bend. Corticocortical fibers were modelled by placing the nerve in the anteroposterior axis lateral to the midline; with the round MC vertex-tangentially orientated, optimal excitation occurred at the bend nearest the interaural line, i.e., near the peak electric field. The findings emphasize the importance of orientation and direction of current in the MC and fiber bends in determining nerve excitation. The findings in the peripheral nerve-skull model help explain (1) why lateral and vertex-tangentially orientated MCs preferentially excite arm-related CT neurons directly and indirectly (through corticocortical fibers), respectively, and (2) why the MC orientations for optimally exciting directly arm and leg-related CT neurons differ.

Comparison of human transcallosal responses evoked by magnetic coil and electrical stimulation

Human transcallosal responses (TCRs) were elicited by focal magnetic coil (MC) stimulation of homologous sites in contralateral frontal cortex and compared with those to focal anodic stimulation. With MC stimulation, the TCR consisted of an initially positive wave with an onset latency of 8.8-12.2 msec, a duration of 7-15 msec, and an amplitude which reached up to 20 microV, sometimes followed by a broad low amplitude negative wave. With anodic stimulation, a similar response was obtained in which the positive wave was similar in latency and maximum amplitude, but had a greater duration. With anodic stimulation, not only was the TCR threshold below that for contralateral movement, but it reached substantial size at intensities below motor threshold. With MC stimulation, contralateral arm movement and scalp corticomotor potentials were observed when the MC was displaced posteriorly towards the central sulcus. Unlike with anodic stimulation, the MC evoked TCR was usually not preceded by a prominent EMG potential from temporalis muscle and was not associated with subject discomfort. The TCR provides unique information concerning the functional integrity of callosal projection neurons, their axons and transsynaptic processes in recipient cortex. This information may prove useful in the evaluation of intrinsic cerebral mechanisms and in establishing cortical viability.

Influence of pulse sequence, polarity and amplitude on magnetic stimulation of human and porcine peripheral nerve

1 Mammalian phrenic nerve, in a trough filled with saline, was excited by magnetic coil (MC)‐induced stimuli at defined stimulation sites, including the negative‐going first spatial derivative of the induced electric field along a straight nerve, at a bend in the nerve, and at a cut nerve ending. At all such sites, the largest amplitude response for a given stimulator output setting was elicited by an induced damped polyphasic pulse consisting of an initial quarter‐cycle hyperpolarization followed by a half‐cycle depolarization compared with a predominantly ‘monophasic’ quarter‐cycle depolarization. 2 Simulation studies demonstrated that the increased efficacy of the induced quarter‐cycle hyperpolarizing‐half‐cycle depolarizing polyphasic pulse was mainly attributed to the greater duration of the outward membrane current phase, resulting in a greater outward charge transfer afforded by the half‐cycle (i.e. quarter‐cycles 2 and 3). The advantage of a fast rising initial quarter‐cycle depolarization was more than offset by the slower rising, but longer duration depolarizing half‐cycle. 3 Simulation further revealed that the quarter‐cycle hyperpolarization‐half‐cycle depolarization showed only a 2.6 % lowering of peak outward current and a 3.5 % lowering of outward charge transfer at threshold, compared with a half‐cycle depolarization alone. Presumably, this slight increase in efficacy reflects modest reversal of Na+ inactivation by the very brief initial hyperpolarization. 4 In vitro, at low bath temperature, the nerve response to an initial quarter‐cycle depolarization declined in amplitude as the second hyperpolarizing phase progressively increased in amplitude and duration. This ‘pull‐down’ phenomenon nearly disappeared as the bath temperature approached 37 °C. Possibly, at the reduced temperature, delay in generation of the action potential permitted the hyperpolarization phase to reduce excitation. 5 Pull‐down was not observed in the thenar muscle responses to median nerve stimulation in a normal human at normal temperature. However, pull‐down emerged when the median nerve was cooled by placing ice over the forearm. 6 In a nerve at subnormal temperature straddled with non‐conducting inhomogeneities, polyphasic pulses of either polarity elicited the largest responses. This was also seen when stimulating distal median nerve at normal temperature. These results imply excitation by hyperpolarizing‐depolarizing pulse sequences at two separate sites. Similarly, polyphasic pulses elicited the largest responses from nerve roots and motor cortex. 7 The pull‐down phenomenon has a possible clinical application in detecting pathologically slowed activation of Na+ channels. The current direction of the polyphasic waveform may become a significant factor with the increasing use of repetitive magnetic stimulators which, for technical reasons, induce a cosine‐shaped half‐cycle, preceded and followed by quarter‐cycles of opposite polarity.

Neurophysiological mechanisms underlying motor evoked potentials in anesthetized humans.: Part 1. Recovery time of corticospinal tract direct waves elicited by pairs of transcranial electrical stimuli

Direct (D) corticospinal tract discharges were recorded epidurally in patients at anesthetic depths suppressing indirect (I) activity and were elicited by two equal transcranial electrical stimuli. The recovery of amplitude of the second D wave (D2) was a function of the interstimulus interval (ISI) and the stimulus duration. For example, with a 100 micros pulse, there was no response at an ISI of 1.1 ms, but partial recovery occurred with a 500 micros pulse. This indicates a relative refractory component at this ISI. Both D2 amplitude and conduction time recovered completely using a 4 ms ISI, with evidence of increased amplitude and reduced conduction time (supernormality) at longer ISIs. These findings are relevant in explaining high frequency D and I discharges and facilitation of motor responses by two transcranial magnetic pulses. Furthermore, these data help to understand why an ISI of 4 ms would be optimal in eliciting limb muscle responses when a short train of transcranial stimuli elicits only D waves in anesthetized patients (Deletis et al., Clin Neurophysiol 112 (2001) 445).

Neurophysiological mechanisms underlying motor evoked potentials in anesthetized humans. Part 2. Relationship between epidurally and muscle recorded MEPs in man

OBJECTIVE AND METHODS Direct (D) and transynaptic, (i.e. indirect) (I) corticospinal tract (CT) discharges were simultaneously recorded epidurally with muscle motor evoked potentials (MEPs) in patients under different levels of anesthesia. The effects of the one, two or more equal electrical stimuli, applied transcranially or directly to the motor cortex, were studied at different interstimulus intervals (ISIs) to determine the optimal conditions for eliciting I and MEP responses. RESULTS AND CONCLUSION At anesthetic levels permiting large D and I responses to single stimuli, optimal D and I wave facilitation and MEPs occurred with two stimuli at ISIs greater than 4 ms (e.g. at 5.9 and 8 ms). When single electrical stimuli elicit only a D response, optimal MEP responses are determined by the number of stimuli and the recovery of CT fibers excitability (e.g. at an ISI of 4 ms).

Measurement of information processing delays in human visual cortex with repetitive magnetic coil stimulation.

Previous work disclosed that single magnetic coil (MC) pulses applied over human calcarine cortex could suppress perception of letters briefly presented, e.g. 80-100 ms earlier. Although individual MC stimuli presented 0-60 ms, or more than 140 ms after the visual stimulus were apparently ineffective, combinations of 2 or 3 MC pulses at such intervals temporarily depressed visual perception. Thus, progressing of such language information could be slowed, without being abolished. By contrast, when the first MC pulse was delivered 120 ms or later, a second MC pulse 40 ms later had no detectable effect, implying that calcarine cortex had already transmitted the information. Perceptual recovery of 5-character words initially occurred no earlier than that of random letters, nor or random letters vs. arbitrary linear patterns, implying that the processing delays in calcarine cortex were similar.

Intracranial stimulation of facial nerve in humans with the magnetic coil

Using ourselves as subjects, maximal compound motor action potentials (CMAPs) were evoked in ipsilateral nasal and orbicularis oculi muscles (onset latency 4.9-5.4 msec) by a magnetic coil (MC) tangentially oriented over parieto-occipital scalp. The facial nerve was also electrically stimulated sequentially at the posterior tragus near the stylomastoid foramen, anterior tragus and 3 cm more distally. Onset latency of the CMAP elicited at posterior tragus ranged from 1.0 to 1.3 msec less than that elicited by the MC over scalp. Because the measured distal facial nerve motor conduction velocity was 50-60 m/sec, the locus of impulse generation induced by magnetic coil stimulation was estimated to be approximately 6.5 cm proximal to the site of electrical stimulation at the posterior tragus, i.e., closer to the exit of the facial nerve from the brain-stem than to its entrance into the internal auditory meatus. This non-invasive technique should be useful in evaluating patients with peripheral facial nerve disorders including Bells palsy.

Focal stimulation of human peripheral nerve with the magnetic coil: A comparison with electrical stimulation

The hypothenar compound motor action potential (CMAP) response to ulnar nerve stimulation at the elbow was used as a test system in the human to compare excitations by a round magnetic coil (MC), 92 mm in outer diameter, and by electrical bipolar or tripolar stimulation. Optimal focality of excitation was obtained with the MC at 90 degrees to the extended arm and its plane parallel to the arm, i.e., an orthogonal-longitudinal orientation. Tangential orientation of the MC on the arm, i.e., laying it flat on the arm, powerfully excited additional structures. As expected from classical axonology, orthogonal-transverse orientations were the least effective. With orthogonal-longitudinal orientation and submaximal stimulation, the spread of excitation lateral to the median nerve at the wrist was of the order of 10-15 mm, the thickness of the MC being 12 mm. With the same orientation, the site of origin of the distally propagating impulse was estimated by comparing CMAP latencies to bipolar electrical (with cathode distal) and MC stimulation. Tripolar stimulation (with cathode intermediate) had no advantage over bipolar stimulation. The impulse originated 13-22 mm from the midpoint of the contacting edge. Rotating the MC through 180 degrees and thus reversing the field polarity did not significantly change the CMAP latency, indicating that the effective cathode and anode lay within a few mm of each other. Stimulating with a tilted MC resulted in a maximum CMAP when the orthogonal-longitudinal orientation failed to do so. A simple volume conductor model yielded a potential gradient of the right order of magnitude (35 mV/mm) when the MC stimulator output was 25% of maximum, i.e., a little above threshold for exciting ulnar motor axons.

Cerebral function revealed by transcranial magnetic stimulation

Although transcranial magnetic stimulation (TMS) has been introduced only recently, it is safe and provides a painless, inexpensive noninvasive method for the evaluation of brain function. Determining central motor conduction time (CMCT) permits assessment of the corticospinal pathways. Mapping the central representation of muscles provides a method for investigating the cortical reorganization that follows training, amputation and injury to the central nervous system. Such studies of human plasticity may have important implications for neurorehabilitation. TMS also provides a method whereby cortical excitability can be noninvasively evaluated, which is likely to have important implications in the study of epilepsy, movement disorders and related conditions. TMS is useful in tracking the flow of information from one brain region to another and in investigations of cognition and functional localization, thereby complementing information obtained using functional imaging techniques, which have superior spatial but inferior temporal resolution. Finally, TMS is currently being investigated as a method for establishing cerebral dominance and as a therapeutic tool in the treatment of depression. Investigations for treatment of other neurologic and psychiatric conditions are likely to be undertaken.