Role of the calcarine cortex (V1) in perception of visual cues for saccades.

OBJECTIVE: To determine the initial level at which the pathways for cue perception, saccades and antisaccades diverge. METHODS: Two procedures: single pulse transcranial magnetic stimulation (sTMS) over posterior occiput and backward masking were used. A visual cue directed saccades to the left or right, either a pro-saccade (to the side of the cue but beyond it) or an antisaccade, i.e., contraversive saccade. No visual target was presented. RESULTS: Latencies of the two types of saccades did not differ. Focal sTMS applied unilaterally over V1 suppressed both perception of a cue flashed 80-90ms earlier contralaterally (but not ipsilaterally) and the appropriate saccade. Masking at a delay of 100ms abolished the appropriate saccade and cue perception. CONCLUSIONS: V1 is essential for the perception of a flashed cue and for executing appropriate pro- and contraversive saccades. Masking may occur beyond V1, where the pathways for perception and for saccades at least to the next visual processing level start separating. SIGNIFICANCE: VI is needed for rapid, accurate perceptual and motor responses to the crudest (left versus right) cues. It is unlikely that the "where" system can have a major direct input bypassing V1.

Short latency somatosensory evoked potentials in brain dead patients.

Scalp-recorded, short latency somatosensory averaged evoked potentials to median nerve stimulation that arise in the brachial plexus and in central somatosensory afferent pathways were studied in 11 patients who fulfilled the clinical criteria for brain death. These potentials were compared with similar responses that have been recorded in normal subjects. Potentials that arise in central subcortical afferent pathways were recorded in seven of these patients. This suggests that these pathways are able to conduct impulses in some clinically brain dead patients.

Short-latency somatosensory evoked potentials to median nerve stimulation in patients with diffuse neurologic disease.

Short-latency somatosensory evoked potentials were found to be abnormal in 15 of 28 patients with diffuse neurologic disease of varying etiology and severity. These abnormalities often did not directly correlate with the presence or degree of clinical sensory impairment. They were similar to findings in patients with demyelinating and focal lesions of the nervous system. This suggests that the interpretation of these potentials can be done only in the context of the patient's clinical assessment.

Brainstem auditory evoked potentials in Guillain-Barré syndrome.

Brainstem auditory evoked potentials were abnormal in five of six patients with Guillain-Barré syndrome. The abnormalities imply focal demyelination in the extramedullary portion of the auditory nerve.

The spinal evoked response in infants and children.

Summated responses to peroneal nerve stimulation were recorded from surface electrodes placed over the spine of 60 infants and children. These potentials generally were greater in amplitude in infants than in older children. Over the cauda equina and rostral cord, initially positive triphasic potentials were recorded. Over the caudal cord, complex potentials were recorded in children less than three years of age. The conduction velocity of the response from midlumbar to lower cervical recording sites was less in infants than in older children and progressively increased with age, reaching adult values after the fourth year.

Short-latency somatosensory evoked potentials to median and peroneal nerve stimulation: studies in normal subjects and patients with neurologic disease.

SSEPs to median nerve stimulation which arise in the brachial plexus, subcortical and cortical structures can be recorded from the scalp. Abnormalities of these potentials have been found in patients with demyelinating disease and focal or diffuse disease of the nervous system. SSEPs to peroneal nerve stimulation which arise in rostral spinal cord, brainstem, and cerebral structures have also been recorded from the scalp. These methods can be expected to provide useful information in patients with certain neurological disorders.

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.

A sense of movement elicited in paralyzed distal arm by focal magnetic coil stimulation of human motor cortex.

Two magnetic coils (MCs) of special design (Cadwell Laboratories) were used to elicit movements predominantly of one or a few digits by percutaneous stimulation of human motor cortex. When cortically elicited movements were ischemically blocked, the MC still elicited a discrete sense of digit movement; a sense of movement map was constructed by stimulating at different scalp sites. Our findings support the existence of corollary discharge.

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.

Unmasking human visual perception with the magnetic coil and its relationship to hemispheric asymmetry.

Visual suppression by a magnetic coil (MC) pulse delivered over human calcarine cortex after a transient visual stimulus 80-100 ms earlier has been used to suppress the representation of a 'masking' visual stimulus and thus to unmask a 'target' visual stimulus given, e.g., 100 ms before the mask. The resulting target unmasking as a function of the interval between mask and MC pulse is approximately the inverse of the visual suppression curve. Arbitrary visual linear patterns can similarly be unmasked. At the long target-mask interval used, the site of masking is deduced to lie beyond calcarine cortex. In several right-handed subjects tested, powerful MC stimulation of the left (but not right) temporo-parieto-occipital cortex also led to (weaker) unmasking.

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.

Evaluation of conduction in central motor pathways: techniques, pathophysiology, and clinical interpretation.

This communication summarizes the highlights of this symposium and reviews our current understanding of the clinical neurophysiology of conduction in central motor pathways produced by transcranial or direct brain stimulation. Direct (D wave) and indirect (I wave) volleys of descending impulses in the pyramidal system result from motor cortex stimulation and determine the measured responses. The advantages and disadvantages of the electrical and the magnetic stimulating modalities are assessed. The increased latency produced by magnetic as opposed to electrical stimulation is considered. Present clinical applications are discussed. The safety record is encouraging, but has aspects that must be addressed. Potential problems of the interpretation of motor evoked potentials in patients with central nervous system disease are emphasized in light of the pathophysiological mechanism underlying these potentials.

Human cerebral cortical responses to contralateral transcranial stimulation.

We wished to develop a noninvasive electrophysiological measure of functioning of human cerebral cortex. The response chosen was that elicited by a corticocortical afferent input, specifically the transcallosal response (TCR). We used ourselves as subjects. The large shock artifacts associated with passing large currents through the head were reduced by: stimulating percutaneously with a focal anode (5 cm2) situated midway between F4 and C4 (i.e., frontal region, standard 10-20 nomenclature) and a medially located, semicircular grounded cathode (26 cm2) no closer than 3 to 4 cm away; and recording with the focal scalp electrode over homologous left frontal cortex vs. two or more reference electrodes interconnected through variable resistors and at least 6 cm away. Transcranial stimulation with pulses of 80 to 140 mA and lasting 100 microseconds elicited a brief diphasic deflection (latency, 2 to 4 ms), followed by an initially positive, often bifid wave with a latency of 9 to 14 ms, lasting 18 to 44 ms and reaching 5 to 10 microV. The initial diphasic deflection greatly increased when the stimulating anode was moved laterally over temporalis muscle, indicating an electromyographic (EMG) origin. The EMG, but not the positive wave, was elicited when the interpolar distance was reduced to 1 cm, which greatly reduced the fraction of current traversing the cortex (epicranial stimulation); furthermore, occluding the circulation to the scalp for 30 minutes by rubber tubing above the zygomas and brows dulled sensation, reduced the EMG, but did not alter the latency or rising phase of the positive wave. Early somatosensory components, if present, were small compared with the positive wave.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxic substances in spinal cord injury.

Several investigators have implicated norepinephrine and other toxic substances released in the region of a spinal cord injury in the genesis of the progressive pathological and clinical changes that follow spinal trauma. To test this hypothesis, we subjected cats to T-10 to T-12 laminectomy and monitored epidural spinal evoked potentials from sciatic nerve stimulation. The spinal subarachnoid space was perfused with normal saline, with norepinephrine solution, or with heparinized autologous blood or the pial surface of the spinal cord was exposed to macerated gray matter taken from the upper cervical cord. During 1- to 2-hour exposure periods, we noted no significant changes in the base line spinal evoked potentials. In another series of cats, we have shown that norepinephrine perfused over the spinal cord in this manner diffuses rapidly into the subpial white matter. Therefore, its failure to affect spinal evoked potentials does not represent a failure to penetrate the spinal cord. Putative toxins must originate either in extravasated blood or damaged neural tissue in the region of the spinal cord injury. The failure of ascending spinal tracts to react to blood or cord tissue in our experiment suggests that toxins are not involved in the spinal cord dysfunction that occurs soon after injury.

Stimulation of the human nervous system using the magnetic coil.

The magnetic coil (MC) is a unique probe that can be used to elucidate basic neurophysiological mechanisms in humans. Either by excitation or inhibition of responding neural elements, we have been able to investigate: (1) the distribution of the electric field induced within isotropic and anisotropic volume conductors by round and figure-eight MCs; (2) the theoretical relationship between electric field distribution and excitation of distal peripheral nerve, nerve root, cranial nerve, and motor cortex; (3) the effect of focal MC stimulation of motor and visual systems; (4) perturbation of sequential digit movements by MC stimulation of human premotor cortex; (5) activation of frontal motor areas related to speech; (6) elicitation of a sense of movement in an ischemic paralyzed limb by focal MC cortical stimulation; and (7) the effect of stimulation of the human visual system to (a) suppress and unmask visual perception using single MC stimuli and (b) prolong visual suppression using short trains of MC stimuli. In the future, prolongation of MC action by using repetitive stimuli should be useful in further investigating functions concerned with language, speech, and cognition.

Brain stimulation revisited.

The results of the following selected studies using magnetic coil (MC) stimulation are presented: (1) evidence for focality of MC stimulation, (2) MC stimulation of frontal areas related to speech, (3) transcallosal responses evoked by MC stimulation, and (4) suppression of visual perception with MC stimulation over occipital cortex. The authors served as subjects, and in most studies a standard Cadwell stimulator and round MC were used. Using a more vertical, rather than tangential, MC orientation and threshold stimulation, nearly isolated movements of individual digits were elicited implying focal cortical excitation. MC stimulation of frontal areas of either hemisphere elicited electromyography in contralateral laryngeal muscles. The shortest latency responses that were often accompanied by arm movement were thought to be elicited from intermediate areas of precentral gyrus and longer latency responses, from near Broca's area, extreme lateral precentral gyrus, and the supplementary motor area. MC stimulation over the occipital cortex resulted in suppression of visual perception of letters briefly flashed on a screen. The topography of suppression implicated the geniculocalcarine system as the site of MC effect. Focal MC stimulation of posterior frontal cerebral cortex elicited a transcallosal response from contralateral homologous cortex with a latency similar to that obtained with focal anodic stimulation but with considerably less excitation of cranial muscles.

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).

Spinal evoked response in the cat.

Summated evoked potentials to sciatic nerve stimulation were recorded from surface electrodes placed over the spine of cats. The response progressively increased in latency rostrally. It was largest and most complex in configuration in leads placed over the caudal spinal cord where sciatic nerve roots enter and begin to ascend the cord. The conduction velocity of the response was about 90 m/sec from rostral sacral to cervical regions. A comparison of surface-recorded evoked responses to stimulation of the sural nerve, the nerve to the medial head of the gastrocnemius muscle and the sciatic nerve suggest that the peripheral nerve fibers that mediate the response to sciatic nerve stimulation are primarily muscle nerve afferents. In surface, lamina, and dural recordings made over similar segmental levels, the response to sciatic nerve stimulation progressively increased in amplitude, duration, and wave form complexity from surface to depth. Failure of transmission across complete cord transections was demonstrated. Results in preparations with partial cord sections suggest that the surface-recorded response is mediated by multiple spinal cord afferent pathways which are situated primarily ipsilateral to the stimulated peripheral nerve. The data indicate that summated evoked responses arising in spinal cord afferent pathways can be recorded from surface-recording electrodes in cats. They suggest that this animal model may prove useful in the study of certain aspects of spinal cord pathology.

Some positive effects of transcranial magnetic stimulation.

It is hoped that this survey conveys a sense of the many positive uses of focal and nonfocal MC stimulation already manifest within a decade of its introduction. As with other techniques of investigating brain function, MC stimulation has its relative advantages and disadvantages. The precision of defining the site of MC effects currently is inferior to that achieved with PET scanning, but the precision of timing of effects is superior, being on the order of milliseconds. Perhaps the special value of MC stimulation is in moving closer to specifying cause-effect relationships, through interference or facilitatory effects, than when techniques yielding more circumstantial evidence are used. However, it is the testing and cross-validation of the conclusions from the different modes of neuroscientific inquiry that we look to in synthesizing explanations of brain function.

Serum ionized magnesium in premature and term infants.

Magnesium is the element with the second highest concentration in the body and is found almost entirely in the intracellular compartment. The small serum component gives a poor representation of the active, physiologic state of the metal. This state is assessed much better by measuring ionized magnesium in the serum, which can now be performed with a sensitive ion-selective electrode. This study was undertaken to establish the normal serum ionized magnesium levels in newborn infants and to define normal serum ionized calcium/ionized magnesium ratios. Ninety-seven infants were investigated. Six were born before 32 weeks gestation, 28 between 33 and 37 weeks gestation, and 63 were term. Ionized magnesium levels were 0.69 +/- 0.14 mmol/L, 0.63 +/- 0.10 mmol/L, and 0.57 +/- 0.07 mmol/L in each group, respectively. These findings demonstrate a significant decline in serum ionized magnesium with increasing maturity. This decrease may relate to a greater need for magnesium uptake during earlier gestation, more magnesium-induced vasodilation to maintain adequate blood flow to developing tissues and organs, or immature parathormone function earlier in pregnancy. The progressive rise in serum ionized calcium/ionized magnesium ratios found herein supports the latter hypothesis.