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Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to lay essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.

Animals↗

Electrophysiologic evaluation of the facial nerve in Bell's palsy. A review.

Facial nerve paralysis is the most common mononeuropathy and idiopathic facial paralysis (Bell's palsy) the most common seventh nerve disease electromyographers may be asked to evaluate. The electrophysiologic method of choice to assess the facial nerve is side-to-side evoked amplitude comparison with the affected side expressed as a percentage of the nonaffected side. This examination should be performed on days 3, 5, 7, 9, 11 and 13 after onset of paralysis. If the percentage of surviving axons falls below 10% within the first 14 days, an incomplete recovery is suggested. Electromyography may assist in prognosticating a functional return, determining neural conduction across the site of injury and following reinervation in the recovery period. The persistence or early return of an absent R1 component of the blink reflex may qualitatively suggest a satisfactory functional outcome in facial paralysis. Supramaximally exciting the facial nerve at the stylomastoid foramen and comparing the clinical response on the affected and nonaffected side, maximum stimulation test, can also predict eventual seventh nerve return. Observing a minimal twitch, utilizing the nerve excitability test or measuring the facial nerve latency have yielded poor correlations with functional return and are of limited usefulness in the prognostication of acute facial palsies. Trigeminal somatosensory evoked potentials can be employed to evaluate the status of the trigeminal nerve as approximately 50% of patients with Bell's palsy also have lesions involving the fifth nerve. Side-to-side amplitude comparison and electromyography are the two most valuable electrophysiologic methods of assessing facial nerve functioning.

Action Potentials↗

Predictive value of somatosensory evoked potentials for long-lasting pain relief after spinal cord stimulation: practical use for patient selection.

OBJECTIVE: Spinal cord stimulation (SCS) has been used for more than 30 years in patients with intractable neuropathic pain, and global success rates have varied from 40 to 70%, according to reported series. Patient selection is currently based on a preliminary percutaneous test, which is useful but invasive, increases the risk of infection, and has yielded false-positive and false-negative results. In this study, we evaluated an alternative method of predicting the effectiveness of SCS before deciding whether to implant laminotomy electrodes-specifically, assessment of neural conduction in the dorsal columns with the use of somatosensory evoked potentials (SSEPs). Thus, we examined the value of preoperative central conduction time (CCT) of SSEPs to stimulation at the level of the painful area as a possible predictor of patient outcome after SCS. METHODS: Ninety-five patients were evaluated during a mean follow-up period of 18.8 months. Patients were classified into four categories according to the location of the lesion responsible for pain: 28 patients had lesions of the peripheral nerves, 27 had radicular lesions, 8 had root avulsions, and 32 had cord lesions. The SCS electrode was implanted through an interlaminar opening at the upper part of the painful territory without performing a percutaneous screening test. Clinical and social markers of pain relief (i.e., Visual Analog Scale scores, analgesic drug intake, work status) were evaluated prospectively 2 months after implantation and then annually. RESULTS: The global success rate in our study group, with success defined as at least 50% long-term pain relief, was 54.7% (52 of 95 patients). Statistical analyses showed a clear influence of preoperative CCT on SCS outcome. Thus, the success rate was nil in patients with significantly abnormal CCT, whereas it was 75.4% in patients with normal preoperative SSEPs. Significant differences between the two groups of patients also were observed with regard to medication intake and work status. CONCLUSION: Preoperative SSEPs provide an objective prediction of patient outcome after SCS. We suggest that if a patient's CCT is abolished or significantly altered, the patient should not undergo SCS.

Adult↗

Interaction between conducted vasodilation and sympathetic nerve activation in arterioles of hamster striated muscle.

We tested the hypothesis that sympathetic nerve activity can influence the conduction of vasodilation along the arteriolar wall. Arterioles in the superfused cremaster muscle of anesthetized male hamsters (n = 21, 109 +/- 4 g) were studied. Microelectrodes were positioned adjacent to the distal end of primary arterioles to stimulate sympathetic nerves throughout arteriolar networks (perivascular nerve stimulation [PNS]). Microiontophoresis micropipettes (tip outer diameter, 1 to 2 microns) filled with acetylcholine (ACh, 1 mol/L) were positioned adjacent to the wall of second-order (2A) or third-order (3A) arterioles approximately 1 mm distal to their origin to induce local and conducted vasodilation; diameter responses were recorded at the micropipette tip and at vessel origins, respectively. For 2A and 3A arterioles (resting diameters, 15 to 54 and 9 to 30 microns, respectively), vasoconstriction with PNS was frequency dependent (0.5 to 32 Hz); this was attenuated by 65% (P < .05) with alpha-adrenoceptor blockade (phentolamine, 1 mumol/L). Conducted vasodilation was attenuated by > 40% during 16-Hz PNS (P < .05); this effect was reversed by phentolamine. In a reciprocal fashion, conducted vasodilation diminished PNS-induced vasoconstriction by approximately 50% (P < .05). Elevating oxygen (from 0% to 10%) in the superfusion solution induced vasoconstriction similar to that with 16-Hz PNS yet had no effect on conduction. Neural blockade with tetrodotoxin (1 mumol/L) eliminated PNS-induced vasoconstriction and enhanced (P < .05) conducted vasodilation. These findings indicate that perivascular nerves in striated muscle can influence cell-to-cell communication along the arteriolar wall both at rest and during enhanced sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats.

This study was designed to explore the efficacy of a human clone cell line as an alternative neural graft source and to validate the practice of cryopreservation and xenografting as logistical approaches toward conducting neural transplantation. We investigated the biological effects of transplanting cultured human neurons (NT2N cells) derived from a well-characterized embryonal carcinoma cell line into the brains of rats subjected to transient, focal cerebral ischemia induced by embolic occlusion of the middle cerebral artery. At 1 month and extending throughout the 6-month posttransplantation test period, ischemic animals that were transplanted with NT2N cells and treated with an immunosuppressive drug displayed a significant improvement in a passive avoidance task as well as a normalization of asymmetrical motor behavior compared to ischemic animals that received rat fetal cerebellar cell grafts or vehicle alone. Remarkably, cryopreserved NT2N cell grafts compared with fresh NT2N cell grafts, remained viable in the immunosuppressed rat brain and effective in producing behavioral recovery in immunosuppressed ischemic animals. The long-term viability of cryopreserved NT2N cell xenografts in vivo and their sustained effectiveness in promoting behavioral recovery suggest potential utilization of xenografting and cryopreservation as useful protocols for establishing clone cell lines as graft source in neural transplantation therapies for central nervous system disorders.

Animals↗

Co-existence and elimination of convergent motor nerve terminals in reinnervated and paralysed adult rat skeletal muscle.

1. Experiments were carried out to determine whether neuromuscular synapse elimination can occur in skeletal muscle in the complete absence of conducted neural activity, using reinnervation of partially denervated adult muscle as a paradigm. Partially denervated rat lumbrical muscles were paralysed with a nerve conduction block applied to the sciatic nerve during regeneration of injured sural nerve motor axons. Both intact (lateral plantar nerve) and regenerating motor axons converging on the same muscle fibres were therefore inactive. 2. Paralysed muscles expressed prolonged twitch contractions, low tetanus-to-twitch ratios, prolonged synaptic potentials and marked post-tetanic potentiation of frequency of miniature endplate potentials compared with control muscles and neuromuscular junctions. 3. Isometric tension and intracellular recording data suggest that regenerating axons reinnervated more muscle fibres in paralysed muscles than in controls. A greater proportion of muscle fibres was polyneuronally innervated in the paralysed muscles, but significant numbers of muscle fibres acquired a mononeuronal innervation by regenerated, inactive motor nerve terminals. 4. The data suggest that muscle paralysis enhances the regeneration of motor axons when they grow into partially denervated muscles, but activity-independent competition may also be important in the mechanism of synapse elimination at neuromuscular junctions. The data further imply that when nerve endings expressing identical patterns of activity converge on a postsynaptic cell, Hebbian rules may not be sufficient to predict the outcome of the competition, contrary to specific postulates of the neurotrophic theory of development and maintenance of neural connections.

Animals↗

Estrogen reduces the excitability of the female rat medial amygdala afferents from the medial preoptic area but not those from the lateral septum.

Electrical stimulation of the medial amygdala (AMY) elicited antidromic action potentials in neurons in the preoptic area (POA) and the lateral septum (LS) of 36 urethane-anesthetized ovariectomized female rats, which were either treated with estrogen o not treated. The extracellular potentials from the two sites showed similar characteristics, with the exception of the sensitivity to estrogen: they had latencies between 3 and 35 ms. Thresholds were as low as 100 microA. The mean relative refractory period was 2.2 ms. The peak-to-peak amplitudes of the positive-negative biphasic potential ranged from 1.0 mV to 12.0 mV. Estrogen had site-specific effects on parameters of antidromic activation in the POA. Estrogen-treated rats had a significantly higher threshold (937 vs 664 microA) and a longer refractory period (2.5 vs 2.1 ms) than the ovariectomized rats (P < 0.05 for each). The effects were absent in the LS. Selective cutting of the stria terminalis diminished the AMY-induced antidromic responses in the POA and LS. Electrical stimulation of the stria blocked the AMY-induced antidromic potentials by collision. Thus, estrogen-sensitive POA efferents as well as non-estrogen-sensitive LS efferents project to the AMY via the stria terminalis. Reductions in axonal excitability would inhibit neural conduction and transmission. Estrogen may therefore reduce the AMY inputs from the POA, without affecting those from the LS. Such alterations in the neural impulse flow may underlie estrogen-dependent neuroendocrine or behavioral regulation.

Amygdala↗

Transtympanic and surface recordings in the diagnosis of retrocochlear disorders.

A series of patients presenting with subsequently surgically confirmed central tumour involving the auditory pathways were investigated using both transtympanic electrocochleography (TT ECochG) and surface recordings of brainstem evoked responses (BER). While ECochG allows a detailed study of peripheral function, BER allow the investigation of neural conduction up to the level of the inferior colliculus. Valuable information can be obtained from: (1) comparison of the amplitudes of the sensory and neural components of the ECochG; (2) comparison of ECochG, BER and auditory thresholds; (3) time interval measurements between the auditory nerve response (N1 on the ECochG) and the inferior colliculus (wave P4-5 on BER); (4) contralateral comparisons. Similar measurements performed in pure cochlear pathologies, mainly in Meniere's disease, yielded very significant differences.

Audiometry↗

Electrophysiologic evidence for an intersegmental reflex pathway between lumbar paraspinal tissues.

STUDY DESIGN: Electrophysiologic recordings were obtained from a lumbar paraspinal nerve or muscle in the anesthetized cat while electrically stimulating a paraspinal nerve or facet capsule in an adjacent lumbar segment. A variety of approaches were used to demonstrate the reflex nature of both the nerve and the muscle response. OBJECTIVE: The primary purpose of this study was to seek electrophysiologic evidence for the presence of intersegmental reflexes between adjacent lumbar vertebral segments. A second purpose of this study was to confirm a previous procedure used to evoke paraspinal reflexes. This previous work had shown that electrical stimulation of the L1-L2 facet joint capsule elicits electromyographic activity from multifidus muscle one to two vertebral segments caudal to the stimulated facet in a porcine preparation. SUMMARY OF BACKGROUND DATA: Biomechanical approaches have stressed the need for spinal stability to avoid conditions that could give rise to low back dysfunction. It seems reasonable to believe that reflex interactions between vertebral segments contribute to the sensorimotor integration of lumbar paraspinal tissues. It also seems reasonable to believe that alterations or abnormal elicitation of these reflexes could contribute to biomechanical changes associated with low back pain and paraspinal muscle spasm. METHODS: Experiments were performed on 23 alpha-chloralose anesthetized adult cats. In eight cats the L3, L4, and L5 medial branch from each dorsal ramus was exposed and placed on a bipolar hook electrode. In six cats the L4 medial branch was stimulated and a compound action potential was recorded from the L3 medial branch. In three of the six cats the L5 medial branch was stimulated and a compound action potential was recorded from the L3 medial branch. In one cat the L4 medial branch was stimulated and a compound action potential was recorded from the L5 medial branch. In one cat the L3 medial branch was stimulated and a compound action potential was recorded from the L5 medial branch. At the end of each protocol the medial branch was cut just proximal to the stimulating electrode to confirm that the compound action potential was reflexive in nature and not initiated by volume conduction. In 15 cats three approaches were used to confirm that multifidus electromyographic activity evoked by electrical stimulation of a lumbar facet capsule was reflexive in nature: 1) by anesthetizing the site of the sensory endings, i.e., the facet capsule, 2) by injecting lidocaine intrathecally to block neural conduction centrally, i.e., within the spinal canal, or 3) by cutting the afferent pathway, i.e., the medial branch of the dorsal ramus. RESULTS: Electrical stimulation of the medial branch of the dorsal ramus innervating the medial-most lumbar paraspinal tissues evoked a compound action potential in the medial branch innervating the medial-most paraspinal tissues one and two segments away. Stimulating voltages between 2 and 70 V were necessary to evoke the compound action potential. Each compound action potential was reflexive in nature because cutting the lumbar medial branch proximal to its contact with the stimulating electrode abolished each compound action potential. The conduction velocity of the reflex ranged from 3.5 to 6.1 m/sec. Electrical stimulation of a lumbar facet capsule evoked lumbar multifidus muscle electromyographic activity. However, injecting lidocaine intrathecally or transecting the medial branch of the dorsal ramus had no effect on electromyographic activity. Injecting lidocaine into the facet or into the multifidus muscle around the facet joint (near the stimulating electrode) significantly decreased the magnitude of the multifidus electromyography. CONCLUSION: These results indicate that afferent impulses conveyed by the medial branch of the dorsal ramus reflexly altered efferent activity to an adjacent lumbar segment. This intersegmental paraspinal reflex may span at least one or two vertebral segments. The data suggest that electrical stimulation of the facet joint capsule may not have reflexly elicited multifidus activity because neither chemical interruption (intrathecal lidocaine) nor physical interruption (nerve transection) of the presumed reflex pathway diminished or abolished the electromyographic response. Volume conduction of the stimulating currents likely elicited multifidus activity during electrical stimulation of the facet capsule. When using electrical stimulation of neural paraspinal tissues to evoke reflex muscle activity, appropriate control experiments must be performed to clearly demonstrate the reflexive nature of the response.

Action Potentials↗

The effects of carbamazepine and sodium valproate on SEPs and BAEPs.

SEPs and BAEPs were studied in 36 previously untreated epileptics receiving either carbamazepine (CBZ) or sodium valproate (VPA) monotherapy. CBZ prolonged central conduction times in SEPs and BAEPs. SEP latency prolongation correlated with serum CBZ levels. VPA had minimal effects on evoked potentials. The present study gives evidence of similar effects of carbamazepine and phenytoin on central neural conduction.

Adult↗

Evoked potential abnormalities in postoperative patients with biliary atresia.

The somatosensory evoked potentials from the lower extremities were measured postoperatively in 15 patients with biliary atresia to investigate whether they were free of neurologic dysfunction. Because long-standing cholestasis causes progressive neuropathy due to malabsorption of vitamin E, the serum vitamin E, D, and A levels were also examined to evaluate the fat-soluble vitamin status. The cerebral evoked potentials to posterior tibial nerve stimulation were recorded in all 15 patients as well as in 45 controls, but spinal evoked potentials examined at the level of the cauda equina could not be recorded in five patients more than 8 years of age with long-standing icterus. The remaining 10 patients exhibited spinal evoked potentials as observed in the controls, but the mean neural conduction velocity at the cauda equina was significantly lower than that of the 45 controls (42.0 +/- 5.1 m/s vs 52.3 +/- 6.8 m/s, P = .0002). The serum vitamin E, D, and A levels were within the normal range in 13, 9, and 1 of 15 patients, respectively. These results suggest that the patients with long-term follow-up are still at risk of developing neural disturbances even with normal serum vitamin E status.

Adolescent↗

A new color vep procedure discloses asymptomatic visual impairments in optic neuritis and glaucoma suspects.

OBJECTIVE: To evaluate the reliability of visual evoked potentials obtained with a set of multiple chromatic and achromatic patterns (C-VEPs) in differentiating asymptomatic perifoveal retinal impairment from central conduction impairment. METHODS: We propose a set of colored pattern stimuli that allows relatively differential activation of the magnocellular and parvocellular pathways. The system runs on a standard Pentium PC with peripherals that present stimuli and collect, analyze and print data. P1 latencies of C-VEPs obtained with achromatic (black/white) and chromatic (blue/black and red/black isocontrast) checkerboards were evaluated in normal subjects and patients with subclinical retinal impairment (glaucoma suspects) or mild neural conduction impairment (optic neuritis), none of whom had subjective visual defects. RESULTS: The procedure evoked robust cortical signals and statistically distinguished the 3 groups of subjects. The achromatic and chromatic stimuli used distinguished controls from glaucoma suspects and patients with optic neuritis. Glaucoma suspects had greater impairment of C-VEPs to blue/black checkerboards whereas patients with optic neuritis had greater impairment of responses to red/black stimuli. CONCLUSIONS: Our data suggest that chromatic patterns (color/ black, red and blue), that may activate the parvocellular and magnocellular systems differentially but not selectively, can distinguish between mild perifoveal or foveal conduction impairment. They have the additional advantage of evoking large, stable responses across all the subjects.

Adult↗

Visual resolution in a patient exhibiting a visual fatigue or saturation-like effect: probable multiple sclerosis.

A rapid visual resolution test conducted on available equipment reveals the presence of rapid falloff in acuity in a case of probable multiple sclerosis. Intense large field illumination was used, and grating acuity was tested using laser red light. The effect is so large that minor anomalies (not subjectively appreciated) or the residuum of earlier minor attacks of retrobulbar optic neuritis can be readily detected. A related "visual fatigue or saturation-like syndrome" was described earlier. In bright environments these patients' vision fades. Briefly closing the eyes restores visual sensitivity. Providing filters or lowering the light level tends to maintain vision. This test must be studied intensively. It offers a noninvasive simple means of showing underlying anomalies in neural conduction of the visual signal. Such anomalies can be prognostic and previously have been revealed only with sophisticated electrophysiological techniques.

Adult↗

Beta-adrenoceptors on duodenal mucosal cells mediate venous serotonin release.

We have previously documented predominant intraluminal release of serotonin (5-HT) following activation of muscarinic receptors on enterochromaffin cells. Gronstad et al. reported that portal venous release of 5-HT in response to vagal stimulation was mediated by beta-adrenergic receptors. The purpose of this study was to determine whether 5-HT release induced by the beta-adrenergic agonist, isoproterenol, is mediated by enteric nerves or is a direct action at the enterochromaffin cell level. We mounted rabbit duodenal mucosal sheets stripped of muscularis in modified Ussing chambers and measured release of 5-HT in response to 10(-5) M isoproterenol, in the presence and absence of the neural conduction blocker tetrotoxin, 10(-6) M. Serotonin was measured in the buffer bathing the mucosal and submucosal surfaces by HPLC. In the presence of isoproterenol, total (mucosal and submucosal) 5-HT release (21.0 +/- 4.9 ng/cm2/45 min) was significantly (P less than 0.05) greater than that in untreated controls (7.8 +/- 2.7 ng/cm2/45 min); release was predominantly toward the submucosal surface. In the presence of tetrodotoxin alone, net 5-HT release was significantly (P less than 0.05) increased to 12.8 +/- 2.8 ng/cm2/45 min. In tetrodotoxin-treated mucosa, isoproterenol increased 5-HT release to 28.6 +/- 5.3 ng/cm2/45 min which was significantly greater (P less than 0.05) than that with tetrodotoxin alone. Since 5-HT release was increased even in the presence of neural blockade, these results suggest that activation of beta-adrenergic receptors on or near enterochromaffin cells induces release of 5-HT predominantly toward the submucosal surface.

Animals↗

[The influence of haemodialysis on hearing organ of children with chronic renal failure].

Haemodialysis applied in terminal phase of chronic renal failure causes considerable metabolic and electrolyte disturbances within a few hours in human organism. The aim of the work was an evaluation of the influence of those disturbances on hearing organ as potential factors being responsible for perceptive hearing loss in considerable number of the patients with chronic renal failure (CRF). Examination was conducted on 20 children with CRF, aged 10-18 years. In each case, before and after dialysis, on the same day, ENT examination, pure tone audiometry, brain auditory evoked potentials (BAEP) and acoustic otoemissions (TEOAE, DPOAE) were performed. Audiometric tests revealed significantly worse hearing in children with CRF in comparison to healthy subjects with not statistically significant improvement after dialysis. Significantly elongated I, III, V peak latencies as well as I-III and I-V interpeak latencies in BAEP of children with CRF before dialysis were considerable shorter after dialysis except III-V but in 2 of them they appeared after dialysis. In 8 CRF cases DPOAE was present after dialysis in the range of frequencies absent before and in 9 CRF cases there was an increase of the response on the level of 10-15 dB for some frequencies. There were no any changes after dialysis in 3 cases with CRF. The results of our studies reflect subclinical disturbances in neural conduction of auditory pathway and its significant improvement after normalisation of blood parameters (uremic toxins, hyperkalaemia). This fact suggests central component of ureic axonopathy in the pathogenesis of hearing impairment in children with CRF. Dynamism of the changes in TEOAE and DPOAE reflects also the influence of those disturbances on auditory cells on the level of the labyrinth.

Adolescent↗

Spinal mechanisms of the analgesic action of electroconvulsive shock.

The present study investigated the spinal systems involved in the analgesic action of electroconvulsive shock (ECS). To identify such systems complete spinal transections and discrete lesions within the dorsal half of the spinal cord were performed. Complete spinal transection eliminated ECS analgesia totally, demonstrating that the observed analgesic effect is attributable to neural conduction. Lesions within the region of the dorsolateral funiculus (DLF) caused a pronounced, but incomplete, attenuation of ECS analgesia. Larger lesions of the dorsal aspects of the spinal cord including both the DLF and the dorsal column area did not result in further attenuation of analgesia. Thus, it appears that within the dorsal cord the area of the DLF contains the fibers mediating the antinociceptive action of ECS. Additional experiments were conducted to determine the neuromediators involved in ECS analgesia. Of a wide range of antagonists injected intraperitoneally (methysergide, phentolamine, haloperidol, diphenhydramine, naloxone, picrotoxin, theophylline and scopolamine), only methysergide produced a significant attenuation of ECS analgesia. In contrast, following intrathecal injections of antagonists a dose-related decrease of analgesia could be seen after the injections of methysergide, phentolamine and naloxone implicating spinal serotonin, noradrenaline and the enkephalins in the analgesic action of ECS. To assess further the interaction between the action of these neurotransmitter systems, we evaluated the effect of drug pair combinations on ECS analgesia. Intrathecal phentolamine + naloxone, methysergide + naloxone and methysergide + phentolamine were injected at doses that caused maximal attenuation of analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

Auditory evoked brain stem potentials in a case of "locked-in" syndrome.

Auditory evoked brain stem potentials were measured in a patient with occlusion of the basilar artery about 7 mm above its origin, resulting in the "locked-in" syndrome due to infarction at the junction of the lower one third and upper two thirds of the pons. The first three waves of the evoked response originating from the acoustic nerve and auditory nuclei in the caudal pons were normal in wave form, peak latency, and voltage level. Waves IV and V, generated in the region of the lateral lemniscus and inferior colliculus in rostral pons and caudal midbrain, demonstrated prolonged peak latency and reduced voltage, indicative of slowed neural conduction in the pons above the level of the superior olivary complex. These findings suggest that auditory evoked potential recordings may have considerable value in the localization of brain stem disorders.

Acoustic Stimulation↗