Nerve Terminal Branches Research Articles

Clinical Application of Saphenous Nerve Transfer for Sensory Reconstruction of the Sole After Sciatic Nerve Injury: A Case Series

Sole sensation is essential for standing and walking. Moreover, lack of protective sensation of sole increases the risk of fall-related injuries. In the light of recent developments in nerve transfer, reconstruction of sole sensation can be achieved even in sciatic nerve injuries. Few researchers have addressed the problem of lack of potential donor nerve in proximal sciatic nerve injuries. The saphenous nerve has sufficient sensory fibers and is anatomically feasible to be used as a donor nerve to reconstruct sensation. To outline a new approach to restore the sensation of the sole using terminal branches of the saphenous nerve. In an attempt to restore sole sensation, 4 patients underwent saphenous nerve transfer to medial plantar and calcaneal branches. Highet-Zachary system scoring was used to evaluate sensory recovery in target regions (heel, metatarsal heads, and big toe). Of the study population, heel sensation recovered up to S3 in 1 case, S2 in 2 cases, and S1 in 1 case. Partial recovery of the metatarsal heads and the big toe was achieved in 2 cases. The findings of this study indicate that the saphenous nerve is a suitable and available donor to restore sole sensation in sciatic or posterior tibial nerve injuries.

Preservation of terminal branches of the palmar cutaneous branch of the median nerve in open carpal tunnel release.

Post-operative pain in the palm and scar area is the most common complication after carpal tunnel release and injury to the terminal branches of the palmar cutaneous nerve is generally considered one of the causes for this complication. The Authors performed an intraoperative study preserving the terminal branches of the palmar cutaneous branch of the median nerve and verifying the frequency, location and direction of the branches that cross an interthenar incision. Eighty-five consecutive patients (57 F - 28 M, mean age 66 y) underwent carpal tunnel release between February and June 2021. The cutaneous branches crossing the incision were identified and preserved by careful dissection. Subsequently they were counted and classified by their direction and distance from the proximal border of the transverse carpal ligament. Sensory branches were found in 40 % of cases (34/85) and their origin was observed at an average of 1.05 cm (0-1.8 cm) distal from the proximal border of the carpal tunnel. A total of 44 branches were observed of which 23 branches crossed the incision with a transverse course and 21 with an oblique, generally proximal-distal radio-ulnar course. The subcutaneous layer overlying the distal third of the transverse carpal ligament was found to be devoid of sensory branches, therefore it can be considered a relatively safe area. Isolation and protection of palmar sensory branches is important for improving carpal tunnel release results. This goal can be more easily achieved by locating the skin incision on the distal third of the transverse carpal ligament, where the sensory branches have a lower frequency, possibly associated with a second proximal incision (biportal technique) to better visualize the proximal portion of the ligament and antebrachial fascia.

Neurovascular territories of the canine fossa: Analysis of a South African population

The canine fossa, a depression on the surface of the maxillary bone, is important clinically due to the nexus of the neurovascular elements which occur in this region and supply the superficial and deep structures of the face. While it is known that there is much variation in the neurovascular structures of this region, little is known about sex differences. The aim of this study was to investigate and map the neurovascular branching within the region of the canine fossa of a South African population, with particular reference to any sex differences. Sixty hemifaces (n=30 female; n=30 male) of individuals between the ages of 40 and 100years were dissected. The origin, number of branches, connections between branches, origin of connecting branches and the distribution of the neurovascular structures associated with the mid-facial and canine fossa regions were documented. The data obtained was qualitative and was statistically analysed with SPSS v26 statistical analysis software. Frequency and contingency tables, along with Chi-squared analysis and Fischer's Exact test, were used for quantitative data analysis. While high levels of variation in the neurovascular elements were documented, there was no statistically significant variation between the sexes. A sex variation was only observed for the terminal branches of CN VII with females displaying a lower number of buccal nerve terminal branches than males. While only one sex difference of significance was found in the highly variable neurovascular structures resident in the region of the canine fossa, the variability of the neurovascular elements is of importance to surgeons.

Communicating Branches of the Facial Nerve: Descriptions and Clinical Considerations.

Major branching patterns of the facial nerve have been extensively studied because damage to branches of the nerve is associated with complications ranging from weakness to paralysis. However, communicating branches of the facial nerve have received far less attention despite being hypothesized as a means of motor recovery following facial nerve injury. The aim of this study was to characterize the frequency of communicating branches of the facial nerve to provide clarity on their anatomy and clinical correlations. Bilateral facial dissections were completed on cadaveric donors (n = 20) to characterize the frequency and location of communicating branches across terminal branches of the facial nerve. Statistical analyses were employed to analyze differences between the location of communications by side and whether the communicating branches were more likely to occur on the left or right side (P < 0.05). Communicating branches were identified among all terminal branches of the facial nerve and their frequencies reported. The highest frequencies of communicating branches were identified between the buccal-to-marginal mandibular and zygomatic-to-buccal branches, at 67.5% (27 comm/40 hemifaces). The second highest frequency was identified between the temporal-to-zygomatic branches in 62.5% (25/40) of donors. The marginal mandibular-to-cervical branches had communicating branches at a frequency of 55% (22/40). Location or sidedness of communicating branches did not significantly differ. Our characterization more accurately defines generalizable areas in which communicating branches are located. These locations of branches, described in relation to nearby landmarks, are fundamental for clinical and surgical settings to improve procedural awareness.

Phonation Threshold Pressure Revisited: Effects of Intrinsic Laryngeal Muscle Activation.

Phonation threshold pressure (Pth ) is the minimum subglottic pressure required to reach phonation onset and is considered a marker for vocal efficiency and health. We investigated the effects of intrinsic laryngeal muscle (ILM) activation on Pth . In vivo animal study. In an in vivo canine phonation model, laryngeal adductor muscles were activated together by stimulation of the recurrent laryngeal nerves (RLNs) and individually via stimulation of respective terminal nerve branches. Cricothyroid (CT) muscles were activated via stimulation of the superior laryngeal nerves. ILMs were activated in a graded manner at various combinations as transglottal airflow was gradually increased. Aerodynamic and glottal posture parameters were measured at phonation onset. Graded RLN stimulation decreased glottal distance and increased Pth . Thyroarytenoid (TA) muscle activation alone increased Pth . Lateral cricoarytenoid (LCA) muscle activation alone had minimal effects. However, graded TA activation as a function of LCA activation level revealed a synergistic relationship between the two muscles in increasing Pth . Effects of CT activation were dependent on adductor stimulation level: CT activation increased Pth at low RLN stimulation levels and decreased Pth at high RLN levels. The effects of ILM activation on Pth were consistent with their expected effects on vocal fold stiffness and tension. TA was the primary adductor controlling Pth . While LCA alone had minimal effects on Pth , it enhanced the role of TA in controlling Pth . TA and CT have antagonistic roles in controlling Pth . These relationships should be considered in clinical efforts to improve ease of phonation and vocal efficiency. NA, basic science Laryngoscope, 132:1427-1432, 2022.

Pudendal Nerve Blocks: An Introduction and How-to Guide

<h3>Study Objective</h3> To provide a stepwise description of the anatomy, evidence, and technique for performing pudendal nerve blocks for the treatment of pudendal neuralgia. <h3>Design</h3> Video demonstration with narrated description. <h3>Setting</h3> Academic tertiary care site. <h3>Patients or Participants</h3> Patients with pudendal neuralgia. <h3>Interventions</h3> Digital transvaginal pudendal nerve blocks and blocks of the terminal peripheral branches of the pudendal nerve, including the perineal and dorsal clitoral branches. <h3>Measurements and Main Results</h3> Pudendal neuralgia can be identified using the Nantes criteria, which includes pain in the distribution of the pudendal nerve, increased pain with sitting, not being awakened by pain, lack of sensory loss, and resolution of pain after pudendal nerve block. Pudendal nerve blocks have been shown to provide relief in over 75% of patients with pudendal neuralgia, with relief potentially lasting from days to months post-procedurally. This video presents both a transvaginal digital approach to pudendal nerve block as well as targeted blocks of the peripheral branches of the pudendal nerve, including the perineal and dorsal clitoral branches. A review of the relevant clinical anatomy, benefits and risks of the procedures, type and toxicity of injectate medications, procedural set up, procedural techniques, and post-procedural follow up care is presented. <h3>Conclusion</h3> Pudendal nerve blocks, when performed through a safe and standardized approach, are a beneficial therapeutic tool for clinicians caring for patients with pudendal neuralgia.

Platinized graphene fiber electrodes uncover direct spleen-vagus communication

Neural interfacing nerve fascicles along the splenic neurovascular plexus (SNVP) is needed to better understand the spleen physiology, and for selective neuromodulation of this major organ. However, their small size and anatomical location have proven to be a significant challenge. Here, we use a reduced liquid crystalline graphene oxide (rGO) fiber coated with platinum (Pt) as a super-flexible suture-like electrode to interface multiple SNVP. The Pt-rGO fibers work as a handover knot electrodes over the small SNVP, allowing sensitive recording from four splenic nerve terminal branches (SN 1–4), to uncover differential activity and axon composition among them. Here, the asymmetric defasciculation of the SN branches is revealed by electron microscopy, and the functional compartmentalization in spleen innervation is evidenced in response to hypoxia and pharmacological modulation of mean arterial pressure. We demonstrate that electrical stimulation of cervical and sub-diaphragmatic vagus nerve (VN), evokes activity in a subset of SN terminal branches, providing evidence for a direct VN control over the spleen. This notion is supported by adenoviral tract-tracing of SN branches, revealing an unconventional direct brain-spleen projection. High-performance Pt-rGO fiber electrodes, may be used for the fine neural modulation of other small neurovascular plexus at the point of entry of major organs as a bioelectronic medical alternative.

Iatrogenic Damage to Neurovascular and Soft Tissue Structures During Lateral Release of Hallux Valgus: A Comparative Anatomical Study of Minimally Invasive Versus Open Surgical Techniques

Lateral release is often an integral step in surgical correction of hallux valgus and can be performed using open or minimally invasive techniques. We investigated whether these techniques cause iatrogenic damage to arteries, nerves, tendons, or joint capsules. In this cadaver study, lateral release was performed on 9 pairs of specimens by a specialized foot surgeon. The specimens were randomly assigned to each group. The operations were followed by anatomical preparation, data collection, photo documentation, and statistical analysis. Iatrogenic damage to arteries, nerves, tendons, or joint capsules was rare, regardless of the surgical technique used. However, with the minimally invasive technique, the tendon of the extensor hallucis longus muscle and the sensitive terminal branches of the fibular nerve were at risk due to their anatomical proximity to the access portal. The deep transverse metatarsal ligament was potentially at risk if the adductor hallucis muscle was completely detached from the lateral sesamoid. When the deep transverse metatarsal ligament was transected there was risk of damaging the underlying plantar neurovascular structures. Both surgical techniques are safe in terms of the risk of injury to neighboring neurovascular and soft tissue structures.

Branching Pattern of Terminal Branches of the Facial Nerve

Background: For a successful facial surgery, it is vital to have a good knowledge of the distribution of the facial nerve in the face. The aim of this study was to highlight the pattern in the branching of the end part of the facial nerve in adults and fetuses and to look for any anastomoses between them. The branching pattern in the two groups is compared for any significant association. Methodology: Cross sectional study done in cadavers and stillborn fetuses. Subjects and Methods: Done in 100 facial halves. Statistical Analysis Used: Chi square test is used to look for any significant association between the branching pattern and gender &amp; side of the face. Results: The branching pattern was classified into six types as per Davis et al. classification in the two study groups – adults and fetuses. The frequencies of occurrence in the first group were Type I – 1%, Type II – 7%, Type III – 18%, Type IV – 17%, Type V – 4%, and Type VI – 3% and in the second group were Type I – 1%, Type II – 8%, Type III – 20%, Type IV – 15%, Type V – 5%, and Type VI – 1%. No significant association was found in the branching pattern with respect to gender and side of the face in the two groups of study. Conclusions: There are multiple anastomotic communications among the end branches of the facial nerve. More the anatomical knowledge of these communications, lesser will be any unwanted facial nerve injury.

Oculomotor nerve guidance and terminal branching requires interactions with differentiating extraocular muscles

Muscle function is dependent on innervation by the correct motor nerves. Motor nerves are composed of motor axons which extend through peripheral tissues as a compact bundle, then diverge to create terminal nerve branches to specific muscle targets. As motor nerves approach their targets, they undergo a transition where the fasciculated nerve halts further growth then after a pause, the nerve later initiates branching to muscles. This transition point is potentially an intermediate target or guidepost to present specific cellular and molecular signals for navigation. Here we describe the navigation of the oculomotor nerve and its association with developing muscles in mouse embryos. We found that the oculomotor nerve initially grew to the eye three days prior to the appearance of any extraocular muscles. The oculomotor axons spread to form a plexus within a mass of cells, which included precursors of extraocular muscles and other orbital tissues and expressed the transcription factor Pitx2. The nerve growth paused in the plexus for more than two days, persisting during primary extraocular myogenesis, with a subsequent phase in which the nerve branched out to specific muscles. To test the functional significance of the nerve contact with Pitx2+ cells in the plexus, we used two strategies to genetically ablate Pitx2+ cells or muscle precursors early in nerve development. The first strategy used Myf5-Cre-mediated expression of diphtheria toxin A to ablate muscle precursors, leading to loss of extraocular muscles. The oculomotor axons navigated to the eye to form the main nerve, but subsequently largely failed to initiate terminal branches. The second strategy studied Pitx2 homozygous mutants, which have early apoptosis of Pitx2-expressing precursor cells, including precursors for extraocular muscles and other orbital tissues. Oculomotor nerve fibers also grew to the eye, but failed to stop to form the plexus, instead grew long ectopic projections. These results show that neither Pitx2 function nor Myf5-expressing cells are required for oculomotor nerve navigation to the eye. However, Pitx2 function is required for oculomotor axons to pause growth in the plexus, while Myf5-expressing cells are required for terminal branch initiation.

Anatomical study of the innervation of different parts of the posterior ligamentous region of the sacroiliac joint

Background and objectivesThe periarticular sacroiliac joint (SIJ) technique has become an important area of focus, and the quartering of the SIJ posterior ligamentous region has been proposed as a way...

Imaging of the hand : What should be considered regarding the nerves?

Peripheral nerve disorders of the hand and wrist are most commonly caused by entrapment neuropathies, while traumatic nerve injuries and neoplasms are less common. The indication for additional imaging methods and different imaging options, especially in patients with atypical symptoms or remaining unclear etiology of symptoms after completion of standard diagnostics, are presented. The imaging methods magnetic resonance (MR) neurography and neurosonography are introduced, and typical findings as well as diagnostic pitfalls are presented. The diagnostic gold standard, which comprises apast medical history, neurologic examination and electrophysiology, can often establish the diagnosis. Imaging methods, especially MR neurography and neurosonography, are gaining increasing importance in the diagnostic workup of atypical neuropathies, as well as in the determination of the exact lesion location and spatial lesion extension, especially for surgical planning. Recent technical advances allow high-resolution depiction of small distal terminal nerve branches. MR neurography allows for the high-resolution depiction of peripheral nerves of the hand and wrist. It can confirm the diagnosis of neuropathy, identify the exact lesion location, and rule out any differential diagnoses. Neurosonography is atime- and cost-efficient alternative diagnostic method.

Antidromic Spike Propagation and Dissimilar Expression of P2X, 5-HT, and TRPV1 Channels in Peripheral vs. Central Sensory Axons in Meninges.

Background: The terminal branches of the trigeminal nerve in meninges are supposed to be the origin site of migraine pain. The main function of these peripheral sensory axons is the initiation and propagation of spikes in the orthodromic direction to the second order neurons in the brainstem. The stimulation of the trigeminal ganglion induces the release of the neuropeptide CGRP in meninges suggesting the antidromic propagation of excitation in these fibers. However, the direct evidence on antidromic spike traveling in meningeal afferents is missing.Methods: By recording of spikes from peripheral or central parts of the trigeminal nerve in rat meninges, we explored their functional activity and tested the expression of ATP-, serotonin-, and capsaicin-gated receptors in the distal vs. proximal parts of these nerves.Results: We show the significant antidromic propagation of spontaneous spikes in meningeal nerves which was, however, less intense than the orthodromic nociceptive traffic due to higher number of active fibers in the latter. Application of ATP, serotonin and capsaicin induced a high frequency nociceptive firing in peripheral processes while, in central parts, only ATP and capsaicin were effective. Disconnection of nerve from trigeminal ganglion dramatically reduced the tonic antidromic activity and attenuated the excitatory action of ATP.Conclusion: Our data indicate the bidirectional nociceptive traffic and dissimilar expression of P2X, 5-HT and TRPV1 receptors in proximal vs. distal parts of meningeal afferents, which is important for understanding the peripheral mechanisms of migraine pain.

Reconstruction of Digital Nerve Defects with Posterior Interosseous Nerve Terminal Joint Branch

Abstract Objective: The aim of our study is to retrospectively evaluate the patients who had digital nerve defective injuries of the hand which was reconstructed with the terminal branch of posterior interosseous nerve (PIN) for treatment. Methods: Twenty-three patients with digital nerve defective injuries, who applied late and were treated with PIN terminal branch grafting were included in the study. The mean age of the patients was 36.4 ± 8.1 years and the mean follow-up duration was 17.3 ± 3.2 months. The mean interval between the injury and the surgery was 5 (2-8) months, and the average gap in defective site was 19.7 ± 3.8 mm. Clinical assessment of the nerve healing was made with Semmes – Weinstein Monofilament (SWM) test and Static 2 Point Discrimination (S2PD) test and, the results were classified according to the British Medical Research Council (BMRC) scoring system. Results: The mean SMW test result was determined as 2.8 (2.8-20) grams, and the mean S2PD test result as 6 (4-20) mm at the sensory area of reconstructed nerve. Accordingly, BMRC scoring system revealed that sensory improvement was S4 level in 15 (65.2%) patients, S3 + in 4 (17.4%), S3 in 3 (13%) patients, and S2 level in 1 (4.3%) patient. Neuroma was not detected at any of the patients within the donor site. Scar formation was detected at 6 (26.1%) patients. Conclusion: PIN terminal branch is an appropriate substitute for digital nerve reconstruction with minimum morbidity and acceptable efficiency.

Innervation of the distal part of the vastus medialis muscle is endangered by splitting its muscle fibers during total knee replacement: an anatomical study using modified Sihler’s technique

Background and purpose — The distal part of the vastus medialis muscle is an important stabilizer for the patella. Thus, knowledge of the intramuscular nerve course and branching pattern is important to estimate whether the muscle’s innervation is at risk if splitting the muscle. We determined the intramuscular course of the nerve branches supplying the distal part of the vastus medialis muscle to identify the surgical approach that best preserves its innervation. Material and methods — 8 vastus medialis muscles from embalmed anatomic specimens underwent Sihler’s procedure to make soft tissue translucent while staining the nerves to study their intramuscular course. After dissection under transillumination using magnification glasses all nerve branches were evaluated. Results — The terminal nerve branches were located in different layers of the muscle and ran mostly parallel but also transverse to the muscle fibers. In half of the cases, the latter formed 1 to 3 anastomoses and coursed close to the myotendinous junction. Additionally, most of the branches extended into the ventromedial part of the knee joint capsule. Interpretation — To preserve the innervation of the distal part of the vastus medialis muscle, any split of the muscle during surgical approaches to the knee joint should be avoided.

Commentary on: Distribution of the Laterally Supplying Facial Nerve to the Orbicularis Oculi Muscle.

Recently, there has been a growing interest on the terminal branches of the VII nerve that preside to the fine movements of the orbital, pre-septal, and pre-tarsal components of the orbicularis oculi muscle (OOM) and their implications for surgery. The authors of this article are to be commended for identifying the intra-orbicularis nerve fibers that form the lateral route of distribution of the facial nerve.1 Their methodology is sound and is based on the utilization of microscopic surgical dissection on 43 samples, with 3 years of research time to enhance the accuracy and reliability of their anatomical study. Their results, derived mainly by dissecting Asian specimens, were also confirmed in Caucasian specimens, attesting the reproducibility of their findings in at least these 2 racial variations. Although the excellent level of their anatomical demonstration prevents any technical comment, the clinical implications derived and presented in the discussion are flawed by...

Peripheral Occipital Nerve Decompression Surgery in Migraine Headache.

Background:Migraine headache in the occipital region is characterized by a recurrent pain of moderate to severe intensity. However, the diagnosis can be difficult because of the multitude of symptoms overlapping with similar disorders and a pathophysiology that is not well-understood. For this reason, the medical management is often complex and ineffective.Methods:A literature search according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted to evaluate the surgical treatment of occipital migraines. Inclusion criteria were: English language, diagnosis of migraine, occipital neuralgia, or tension headache in compliance with the classification of the International Headache Society, follow-up at minimum 3 months, and adult age. The treatment had to consist of peripheral occipital nerve surgery.Results:323 records were identified after duplicates were removed, 30 full text articles were assessed for eligibility, and 9 records were selected for inclusion. A total of 1046 patients were included in the review. General positive response after surgery (>50% reduction in occipital migraine headaches) ranged from 80.0% to 94.9%. However, many differences in the selection of patients, target of decompression surgery, and measurement outcome were described.Conclusion:Despite the decennial proven effectiveness and safeness of surgical therapy for chronic occipital migraine headaches, more significant proof is needed to definitively confirm its use as a standard therapy.

Ultrasound Imaging of the Deep Peroneal Nerve.

Ultrasound is considered an excellent imaging modality to evaluate the nerves of the limbs. The deep peroneal nerve (DPN) is one of the terminal branches of the common peroneal nerve. The DPN may be affected by various disorders, which may be clinically challenging to show. This Pictorial Essay reviews the normal ultrasound anatomy of the DPN and presents disorders that may involve the nerve and its main branches along its course, from proximal to distal.

Branching Patterns of Mental Nerve in Newborns.

In classical textbooks of Anatomy, the mental nerve is considered to be the terminal or main branch of the inferior alveolar nerve, especially trifurcate with no designated names as soon as it emerges from the mental foramen. The textbooks define the innervation area of the mental nerve regionally without naming its terminal branches. Nomina Anatomica designates 3 terminal branches of mental nerve as "labial, gingival, and mental branch" but offers no description about their distribution on the mandible. In the present study, bilateral dissections were performed on the lower lip specimens of 20 newborns for 40 mental nerves to determine the branching types of mental nerve. Although anatomy textbooks indicate that mental nerve divides into 3 branches, the authors noted that mental nerve branched into 1, 2, or 3 branches at or right after its exit from the mental foramen. Branching patterns were typed in 13 different subclasses under 3 main groups (Form I-II-III). Moreover, the branching patterns that could not be included in one of these 3 main groups were defined as "Complex Form." The most common type of branching that the authors observed was Form II, which had 2 terminal branches with an incidence of 41.9% (16 specimens). The next frequently encountered type was Form III, having 3 terminal branches, and it was detected in 32.0% of patients (12 specimens). The least common form was Form I, which had 1 terminal branch with a frequency of 15.8% (6 specimens). The unclassified group, Complex Form, was found 10.5% (4 specimens).

The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release.

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.