Roger Q. Cracco

Suppression of visual perception by magnetic coil stimulation of human occipital cortex

Magnetic coil (MC) stimulation percutaneously of human occipital cortex was tested on perception of 3 briefly presented, randomly generated alphabetical characters. When the visual stimulus-MC pulse interval was less than 40-60 msec, or more than 120-140 msec, letters were correctly reported; at test intervals of 80-100 msec, a blur or nothing was seen. Shifting the MC location in the transverse and rostro-caudal axes had effects consistent with the topographical representation in visual cortex, but incompatible with an effect on attention or suppression from an eyeblink. The MC pulse probably acts by eliciting IPSPs in visual cortex. The neural activity subserving letter recognition is probably transmitted from visual cortex within 140 msec of the visual stimulus.

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.

Focal stimulation of human cerebral cortex with the magnetic coil : a comparison with electrical stimulation

Percutaneous stimulation of human motor cortex electrically (focal anode) and with magnetic coils (MCs) of various designs is compared. The theoretical prediction was confirmed that positioning the standard round MC laterally and orientating it more towards the vertical induces an electric field appropriate for directly exciting corticospinal neurons (cf., the conventional tangential orientation at the vertex). Thus, during voluntary contraction, minimal latency compound motor action potentials (CMAPs) in contralateral arm were elicited both by focal anodic and appropriately orientated MC stimulation. Conduction time from motor cortex to motoneuron was estimated by subtracting peripheral conduction time and monosynaptic delay at the motoneuron from the overall CMAP latency, yielding an estimated corticospinal conduction velocity as high as 66 m/sec. Discontinuous latency variations observed in population CMAPs or individual motor units approximated mono- or polysynaptic cortical synaptic delays and, therefore, are attributed to the intervals between direct and early, or late indirect corticospinal discharges. A TV computer system was used to track movements of individual digits and the hand following MC stimulation. An appropriately orientated MC readily elicited movements predominantly of a single digit, implying focal activation of motor cortex. A double square and a small pointed MC proved especially convenient for eliciting reproducibly single digit movements. Stronger stimulation revealed a topographical gradient in the responses of the different digits. Responses to a given MC stimulus a little above threshold were variable in amplitude, which could not be explained by the relationship of stimulus to phase of the cardiac or respiratory cycle. Overall, our findings indicate the importance of appropriately orientating a standard round MC and using a specially designed MC to obtain the various types of motor response to stimulation of cerebral cortex.

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.

TRANSCRANIAL MAGNETIC STIMULATION IN STUDY OF THE VISUAL PATHWAY

The authors critically reviewed experiments in which transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) of the higher visual pathway were used. Topics include basic mechanisms of neural excitation by TMS and their relevance to the visual pathway (excitatory and inhibitory effects), TMS and rTMS of calcarine cortex (suppression, unmasking, and phosphenes), TMS of V5 (suppression), TMS and rTMS of higher level temporoparietooccipital areas (perceptual errors, unmasking, and inattention), the role of frontal lobe output in visual perception, and vocalization of perceived visual stimuli (role of consciousness of linguistic symbols).

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.

Intravenous Magnesium Sulfate Rapidly Alleviates Headaches of Various Types

Background.—Circumstantial evidence points to the possible role of magnesium deficiency in the pathogenesis of headaches and has raised questions about the clinical utility of magnesium as a therapeutic regimen in some headaches. Methods.—We evaluated the efficacy of intravenous infusion of I gram of magnesium sulfate (MgSO4) for the treatment of patients with headaches and attempted to correlate clinical responses to the basal serum ionized magnesium (IMg2+) level. We also determined if patients with certain headache types exhibit low serum IMg2+ as opposed to total serum magnesium. Using a case‐control comparison at an outpatient headache clinic, a consecutive sample of patients presenting with a moderate or severe headache of any type were included in the study. Of the 40 patients in the study (mean age 38.2 ± 9.4 years; range 14 to 55; 11 men [39.2 ± 7.3 years] and 29 women [37.8 ± 10.2 years]), 16 patients had migraines without aura, 9 patients had cluster headaches, 4 patients had chronic tension‐type headaches, and 11 had chronic migrainous headaches. Total serum magnesium was measured with atomic absorption spectroscopy and a Kodak Ektachem DT‐60. Sensitive ion selective electrodes were utilized to measure serum IMg2+ and ionized calcium (ICa2+); ICa2+/IMg2+ ratios were calculated. Results.—Complete elimination of pain was observed in 80% of the patients within 15 minutes of infusion of MgSO4. No recurrence or worsening of pain was observed within 24 hours in 56% of the patients. Patients treated with MgSO4 observed complete elimination of migraine‐associated symptoms such as photophobia and phonophobia as well as nausea Correlation was noted between immediate and 24‐hour responses with the serum IMg2+ levels. Immediate pain relief was observed in 32 (80%) of 40 patients (P <0.001). In 18 of the 32 patients, pain relief persisted for at least 24 hours (P<0.005) Of these 18 patients, 16 (89%) had a low serum IMg2+ level Total magnesium levels in contrast in all subjects were within normal range (0.70‐0.99 mmol/L). No side effects were observed, except for a brief flushed feeling. Of the 8 patients with no relief, only 37.5% had a low IMg2+ level. Patients demonstrating no return of headache or associated symptoms within 24 hours of intravenous MgSO4 exhibited the lowess initial basal levels of IMg2+. Non‐responders exhibited significantly elevated total magnesium levels compared to responders. Although most subcategories of headache types investigated (ie, migraine, cluster, chronic migrainous) exhibited low serum IMg2+ during headache and prior to intravenous MgSO4 the patients with cluster headaches exhibited the lowest basal levels of IMg2+ (P<0.01). All headache subjects except for the chronic tension group exhibited rather high serum ICa2+/IMg2+ ratios (P<0.01, compared to controls). Conclusions.—Intravenous infusion of 1 gram of MgSO4 results in rapid relief of headache pain in patients with low serum IMg2+ levels. Measurement of serum IMg2+ levels may have a practical application in many types of headache patients. Low serum and brain tissue ionized magnesium levels may precipitate headache symptoms in susceptible patients.

An analysis of peripheral motor nerve stimulation in humans using the magnetic coil

We compared conventional electrical and magnetic coil (MC) stimulation of distal median nerve in 10 normal subjects and 1 patient. Orthogonal (90 degrees to volar forearm)-longitudinal (the plane of the MC aligned with the long axis of nerve or wire), tilted (to 45 degrees) longitudinal, and tangential edge orientations elicited maximal or near maximal compound motor axon potentials (CMAPs) without simultaneous co-activation of ulnar nerve. Transverse and symmetrical tangential orientations were inefficient. A simulation study of an ideal volume conductor confirmed these findings by predicting that the maximum current density was near the outer edge of the MC and not at the center where the magnetic flux intensity is maximal. An orthogonal-longitudinal MC induces a current in the adjacent volume conductor (for example elbow or wrist), which flows in the same circular direction as in the MC. This differs from a tangentially orientated MC which classically elicits current flow in the volume conductor opposite in circular direction to that in the MC. Amplitude and latency of the CMAP were both altered, but not identically, by changing the intensity of MC and cathodal stimuli. Rotating an orthogonal-longitudinal MC through 180 degrees, thus reversing the direction of current flow, elicited single fiber muscle action potentials whose peak latencies differed at most by 100 microseconds. Thus, the (virtual) cathode and anode are significantly closer (i.e., 5-6 mm) with MC than with electrical stimulation where they are at least 20 mm apart. A disadvantage of MC stimulation is the imprecision in defining exactly where the distally propagating nerve impulse originates. In different subjects, using maximum output and orthogonal or tilted (to 45 degrees) longitudinal orientations, the calculated site of excitation in the median nerve varied 2-15 mm distal to the midpoint of the contacting edge of the MC. This limits the usefulness of the MC in its current configuration for determining distal motor latencies. Future advances in MC design may overcome these difficulties.

Low levels of serum ionized magnesium are found in patients early after stroke which result in rapid elevation in cytosolic free calcium and spasm in cerebral vascular muscle cells

Ninety-eight patients admitted to the emergency rooms of three urban hospitals with a diagnosis of either ischemic stroke or hemorrhagic stroke exhibited early and significant deficits in serum ionized Mg2+ (IMg2+), but not total Mg, as measured with a unique Mg2+-sensitive ion-selective electrode. Twenty-five percent of these stroke patients exhibited >65% reductions in the mean serum IMg2+ found in normal healthy human volunteers or patients admitted for minor bruises, cuts or deep lacerations. The stroke patients also demonstrated significant elevation in the serum ionized Ca2+ (ICa2+)/IMg2+ ratio, a sign of increased vascular tone and cerebrovasospasm. Exposure of primary cultured canine cerebral vascular smooth muscle cells to the low concentrations of IMg2+ found in the stroke patients, e.g. 0.30-0.48 mM, resulted in rapid and marked elevations in cytosolic free calcium ions ([Ca2+]i) as measured with the fluorescent probe, fura-2, and digital image analysis. Coincident with the rise in [Ca2+]i, many of the cerebral vascular cells went into spasm. Reintroduction of normal extracellular Mg2+ ion concentrations failed to either lower the [Ca2+]i overload or reverse the rounding-up of the cerebral vascular cells. These results suggest that changes in Mg2+ metabolism play important roles in stroke syndromes and in the etiology of cerebrovasospasm associated with cerebral hemorrhage.