Stimulation Of Cerebral Cortex Research Articles

Phantom limb pain: actual concepts of pathophysiology and therapeutic targets

In the review, we present the main pathogenetic mechanisms of the development of phantom limb pain (PLP) after limb amputation, the prevalence of which can reach 87%. The exact mechanism of PLP remains unknown. The involvement of peripheral and central mechanisms of the formation of PLP is assumed. Peripheral mechanisms include increased excitability and the formation of ectopic activity in the amputation neuromas and in the ganglion cells of the dorsal roots of the spinal cord. The central mechanisms are represented by central sensitization in the dorsal horns of the spinal cord with the development of the “wind up” phenomenon, reorganization processes in the thalamus and cortex with thalamic and cortical remapping, and proprioceptive memory. Also significant is the neuromatrix theory, the reduction of feedback from the visual and other sensory systems after deafferentation. PLP therapy methods focused on central mechanisms are: spinal cord stimulation, transcutaneous electrical neurostimulation, deep brain stimulation, non-invasive and invasive methods of cerebral cortex stimulation, mirror therapy, virtual and augmented reality technologies, movement representation and its modification “phantom exercises”. In addition, pharmacologic treatment options based on PLP mechanisms can be used: NMDA receptor antagonists, anticonvulsants, tricyclic antidepressants, opioids.

Effectiveness of Repetitive Transcranial Magnetic Stimulation in Patients With Failed Back Surgery Syndrome: A Double-Blind Randomized Placebo-Controlled Study

BACKGROUND: Failed back surgery syndrome (FBSS) is the term of persistent back and/or leg pain after lumbar surgery. Repetitive transcranial magnetic stimulation (r-TMS) is a technique that allows noninvasive and relatively painless stimulation of cerebral cortex. It can reduce the experience of chronic pain by producing the small electrical currents in the cortex via magnetic field. OBJECTIVES: The aim of this study is to determine the effectiveness of r-TMS treatment on patients with FBSS. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: The Physical Medicine and Rehabilitation Clinic of Istanbul Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey. METHODS: In this double-blinded, randomized, placebo-controlled trial, 20 patients (aged 34–65 years) clinically diagnosed as FBSS who had a history of surgery for lumbar disc herniation with persistent back and leg pain were reviewed. Only patients with no root compression and/or spinal stenosis in postoperative magnetic resonance imaging of lumbar spine were included. Patients were randomly assigned to r-TMS (n:10) and sham (n:10) groups. Patients in the r-TMS group received 5 Hz of r-TMS as a 20-minute (1,000 pulses) daily session, 5 days per week, for a total of 10 sessions. r-TMS was applied with MagVenture device (MagPro X100, Denmark, 2009) and figure 8 coil (MMC 140 parabolic, MagVenture). Control group received sham r-TMS with the same protocol. Each patient was evaluated at baseline, days 5 and 10 of treatment, and 1 and 3 months after treatment. Visual Analog Scale (VAS), DN4 (Douleur Neuropathique en 4 Questions), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI) were used for evaluation. RESULTS: There were no statistically significant differences between the groups for age, gender, number of surgeries, pain duration, working status, and drug usage. Significant improvements were achieved in DN4, ODI, BDI, and PSQI scores in the r-TMS group in comparison to the sham group. Both groups displayed improvements in VAS scores, whereas improvement in the sham group was limited to the first month. Achieved improvements in the r-TMS group in terms of VAS, DN4, ODI, BDI, and PSQI scores were sustained at the third month. LIMITATIONS: The limited number of patients and the short follow-up periods are the main limitations of our study. Further placebo-controlled studies with longer follow-up periods and greater number of cases would be beneficial for examining r-TMS application as a new treatment option in patients with FBSS. CONCLUSIONS: r-TMS might be an effective alternative treatment in patients with FBSS, further studies with larger groups are needed. KEY WORDS: Back pain, repetitive transcranial magnetic stimulation, failed back surgery syndrome, chronic back pain

A Biotechnical Brain Stimulation System for Memory Recovery in Post-stroke Patients

The article presents a biotechnical system for researching the cerebral cortex stimulation through receptor systems by exposure to sound and light of changing color. The system allows simultaneous exposure of both eyes, the difference in the frequencies of stimulation of the left and right eyes being close to brain wave frequencies. It also allows local stimulation of neural fields of the cerebral cortex and hippocampus with modulated magnetic fields. Tests showed that the developed system could be used for rehabilitation and restoration of both long-term and short-term memory in post-stroke patients.

Efficacy of Skin, Connective Tissue, Aponeurosis Galea, Loose Areolar Tissue, and Pericranium Acupuncture Techniques in Stroke Patients in Improving Muscle Strength of Motion Limbs

BACKGROUND: Nowadays, more than 650,000 stroke survivors needed further therapy and treatment related to mild or severe relief caused by stroke. Defects that cause stroke lesions require more serious and longer handling and will be very burdensome for patients and health insurance. Acupuncture method in the head skin, connective tissue, aponeurosis galea, loose areolar tissue, and pericranium (SCALP) was known to be related to the function of the cerebral cortex known as Zhu’s scalp acupuncture. Stimulation on this point was believed can open blood vessels, and provides better blood flow so it could improve repair in stroke patient.
 AIM: This research aimed to prove the effectivity of needle sticking on SCALP to strengthen limb muscle in stroke patients.
 MATERIALS AND METHODS: This research used a quasi-experimental design, pre-test-post-test without control group. The subjects of this study were stroke patients who were in the recovery phase (after the critical period had passed) and who had an stroke attack <1 year. Sampling method of this study was consecutive sampling, namely, recovery post-stroke patients who were hospitalized or outpatient of all over hospitals in Palembang, Indonesia. In this study, needle pricking was performed in the cerebral motor cortex which is located in the anterior central sulcus. Stimulation is done 10 times for 2 weeks. Assessment of muscle strength in the upper and lower limbs was performed using manual muscle testing measurement before and after therapy. Analysis of muscle strength before and after cerebral cortex stimulation through needle pricking on the SCALP of the head was analyzed by t-test dependent using SPSS 18. Data were displayed in tabular form, with a significance of p < 0.05.
 RESULTS: Subjects of this study were eight people consisting of four men (50%) and four female patients (50%) who had passed the critical stroke and were in the recovery phase within a period of recovery <1 year after stroke attack. The number of subjects who experienced improvement in joint motion of each joint was much greater than the frequency of the number of subjects who had no improvement. About 90% of the study subjects felt improvement in joint motion of each joint. The improvement in muscle strength score almost doubled after being treated with SCALP acupuncture better than before treatment.
 CONCLUSION: SCALP acupuncture technique was effective in improving muscle strength of motion limbs on stroke patients.

Effectiveness of tonic and burst motor cortex stimulation in chronic neuropathic pain.

Background: Motor cortex stimulation (MCS) is an intracranial, invasive method for treatment of chronic pain. Main indications for MCS are central post stroke pain, neuropathic facial pain, phantom limb pain and brachial plexus or spinal cord injury pain. Spinal cord stimulation (SCS) with burst waveform has been proved to be more effective than tonic mode in chronic pain. Necessity to replace depleted batteries of motor cortex tonic stimulators gave us an opportunity of applying burst stimulation. The objective of the pilot study was to evaluate the effects of burst stimulation applied on motor cortex in patients with chronic pain syndromes as well as comparison to tonic mode.Materials and methods: We have evaluated 6 patients (females N=3, males N=3) belonging to the group of 14 cases (females N=5, males N=9) who had undergone surgical procedure of MCS in years 2005–2017. Selected for the study were 6 patients with thalamic pain N=3, with facial pain N=3 (anaesthesia dolorosa and neuropathic trigeminal neuralgia). The patients were subjected to both modes of stimulation then they chose which one was better in relieving pain: tonic or burst. Pain intensity was assessed with the visual analogue scale (VAS) before the replacement of implanted pulse generator (IPG) and after the stimulation with tonic and burst modes.Results: In the study, 5 out of 6 patients with MCS found burst mode more effective than tonic mode. Baseline VAS score in patients that had at least 3 months depleted battery of tonic IPG was 95 mm. After implantation of a new IPG mean VAS score on tonic stimulation was 72 mm, on burst 53 mm.Conclusions: The most preferred option of MCS in selected group of patients was burst stimulation. This study has shown, that the burst stimulation of cerebral cortex is a promising modality when tonic stimulation is not sufficient in refractory, neuropathic pain.

Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review.

BackgroundNegative symptoms are one of the most difficult areas in the treatment of schizophrenia because antipsychotics are often less effective towards them. Repetitive transcranial magnetic stimulation (rTMS) is a new technique for cerebral cortex stimulation and is believed to be a safe and promising method for the treatment of mental disorders. As the clinical research and new treatment models have increased in recent years, the efficacy towards negative symptoms and safety evaluation of rTMS treatment should also be updated.AimsTo explore the efficacy and safety of rTMS in the treatment of negative symptoms for patients with schizophrenia.MethodsWe searched for relevant controlled clinical trials from the following databases: PubMed, EMBASE, the Cochrane Library, EBSCO, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SINOMED, and Airiti Library. The retrieval time went up to January 2, 2017. The research literature was screened according to the predefined inclusion and exclusion criteria. After data extraction, statistical analysis was conducted by using RevMan 5.3 and Stata 14. Quality evaluation was done on the included research articles. The Cochrane risk of bias assessment tool was adopted for assessing risk of bias. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used as the reference standard.ResultsA total of 3500 articles were retrieved. In the end, there were 29 articles included in the metaanalysis with a total sample size of 1440. After the meta-analysis, it was found that the use of antipsychotic treatment combined with rTMS could improve the negative symptoms of patients (SMD=-0.40, 95% CI= -0.62~-0.18). Based on the bias of the efficacy evaluation assessed by the Cochrane risk of bias assessment tool, there were 6 studies rated as having “high risk of bias” and the rest were rated as “unable to determine”. According to the assessment, development and evaluation criteria of the GRADE classification, the evidence quality for the efficacy evaluation index was “moderate”. The acceptability of rTMS treatment was better (RR= 0.75, 95% CI= 0.49~1.15, based on the 1492 samples from the 28 studies), however, the patients who received the rTMS treatment had a higher rate of mild adverse effects (RR= 2.20, 95% CI= 1.53~ 3.18, based on the 1296 samples from the 23 studies).ConclusionsThe use of the antipsychotic treatment incorporated with rTMS treatment can slightly improve the negative symptoms of patients with schizophrenia and has better acceptability and fewer adverse effects. Nevertheless, there is publication bias in this study and the heterogeneity of the study is relatively high. Therefore, we need to be cautious when interpreting the results

Motor Potentials Evoked by Navigated Transcranial Magnetic Stimulation in Healthy Subjects

Navigated transcranial magnetic stimulation (TMS) is a tool for targeted, noninvasive stimulation of cerebral cortex. Transcranial stimuli can depolarize neurons and evoke measurable effects which are unique in two ways: the effects are caused directly and without a consciousness of the subject, and, the responses from peripheral muscles provide a direct measure for the integrity of the whole motor pathway. The clinical relevance of the method has not always been fully exposed because localizing the optimal stimulation site and determining the optimal stimulation strength have been dependent on time-consuming experimentation and skill. Moreover, in many disorders it has been uncertain, whether the lack of motor responses is the result of true pathophysiological changes or merely because of unoptimal stimulation. We characterized the muscle responses from human primary motor cortex system by navigated TMS to provide normative values for the clinically relevant TMS parameters on 65 healthy volunteers aged 22 to 81 years. We delivered focal TMS pulses on the primary motor area (M1) and recorded muscle responses on thenar and anterior tibial muscles. Motor threshold, latencies and amplitudes of motor-evoked potentials, and silent period duration were measured. The correction of the motor-evoked potential latency for subjects' height is provided. In conclusion, we provide a modified baseline of TMS-related parameters for healthy subjects. Earlier such large-scale baseline material has not been available.

Victor Horsley's Contribution to Jacksonian Epileptology

To describe Victor Horsley's contribution to John Hughlings Jackson's understanding of the mechanisms involved in the generalization of convulsive epileptic seizures. I reviewed Horsley's writings and other relevant late 19th century medical literature. Horsley's combination of strategically sited surgical lesions and cerebral cortex stimulation studies in experimental animals showed that, contrary to Hughlings Jackson's earlier belief, epileptic activity arising in one cerebral hemisphere had to spread to the contralateral hemisphere before bilateral convulsing could occur. On the basis of well-designed experiments, Horsley made a major contribution to the understanding of epileptic seizure propagation mechanisms.

Extracellular ascorbate modulates cortically evoked glutamate dynamics in rat striatum

To determine if extracellular ascorbate, which may increase by several hundred micromolar in striatum during behavioral activation, directly alters glutamate transmission, we monitored striatal glutamate transients evoked by electrical stimulation of cerebral cortex in anesthetized rats tested with varying concentrations of ascorbate (0, 50, 200, and 500 μM) by reverse dialysis. Capillary electrophoresis coupled with laser-induced fluorescence detection was used to analyze dialysates collected at 3-s intervals. Ascorbate elevated striatal glutamate in a concentration-dependent fashion. Addition of 500 μM ascorbate not only more than doubled basal glutamate levels relative to the ascorbate-free condition, but significantly increased both the magnitude of the electrically evoked glutamate response as well as its subsequent return to baseline. In fact, the time required to return to within 10% of the pre-stimulation baseline increased by >100 s. Reverse dialysis of iso-ascorbate, in contrast, had no effect on stimulation-evoked glutamate release arguing against an antioxidant effect. It appears, therefore, that the level of extracellular ascorbate plays a critical role in regulating corticostriatal glutamate transmission.

Excitatory aminoacids and epileptic seizures in immature brain

Data on convulsant and anticonvulsant action of drugs influencing excitatory amino acid receptors in developing rats are reviewed. Agonists of NMDA type of receptors NMDA and homocysteic acid, elicited an age-related seizure pattern--flexion, emprosthotonic seizures--in the first three postnatal weeks of rats. Generalized clonic-tonic seizures appeared only after a longer latency. Kainic acid administration resulted in epileptic automatisms and later in minimal, clonic seizures followed by generalized tonic-clonic seizures. A decrease of sensitivity to convulsant action with age is a general rule for all agonists tested. Different anticonvulsant action of NMDA and nonNMDA antagonists was demonstrated in a model of generalized tonic-clonic seizures induced by pentetrazol, whereas their action against epileptic afterdischarges elicited by electrical stimulation of cerebral cortex was similar. Again, higher efficacy in younger animals was a rule. As far as metabotropic glutamate receptors are concerned, agonists of groups II and III were shown to protect against convulsant action of homocysteic acid in immature rats and an antagonist of group I receptors MPEP suppressed the tonic phase of generalized tonic-clonic seizures induced by pentetrazol more efficiently in younger than in more mature rat pups. Unfortunately, a higher sensitivity to the action of antagonists of ionotropic glutamate receptors was demonstrated also for unwanted side effects (motor functions were compromized). In contrast, glutamate metabotropic receptor antagonist MPEP did not exhibit any serious side effects in rat pups.

中枢性とう痛に対する電気刺激療法

Central pain due to stroke, spinal cord injury and surgical or traumatic brain injury is frequently refractory, and therefore, electrical stimulation therapy including stimulation of the spinal cord, thalamus and cerebral cortex is indicated. In this report, we discuss a strategy for dealing with central pain. Spinal cord stimulation has been thought to be ineffective as a treatment for central pain. However, it is a less invasive therapy and is sometimes effective even on the post-stroke pain of extremities. On the other hand, cerebral cortex stimulation has recently been more popular as a treatment for post-stroke pain, and successful cases of treatment have also been documented following spinal cord injury. At the present time, it is difficult to conclude whether cerebral cortex or thalamic stimulation is more effective in the treatment of spinal cord pain. We discuss our strategy for central pain. Medication and observation for at least one year is needed before surgical therapy is considered. If medication is not effective, spinal cord stimulation should be considered. Next, cerebral cortex stimulation is recommended, and depending on the patient's condition, thalamic stimulation may also be indicated.

Dopamine D 1-stimulated adenylyl cyclase activity in cerebral cortex of autopsied human brain

Although the cerebral cortical dopamine D 1 receptor is considered to play a role in normal and abnormal brain function, little information is available on its characteristics in human brain. We compared dopamine-stimulated adenylyl cyclase (AC) activity in homogenates of cerebral cortex (frontal, temporal, parietal, occipital and cingulate cortex) of autopsied brain of neurologically normal subjects to that in striatum. Cerebral cortical AC activity was modestly and dose-dependently stimulated by dopamine (maximal 20–30%) with low μM EC50s and such stimulation was inhibited by the selective dopamine D 1 receptor antagonist SCH23390. The magnitude of the maximal stimulation by dopamine was similar in autopsied and biopsied cerebral cortex. The extent of maximal stimulation was similar to that in dopamine-rich striatum (caudate, putamen and nucleus accumbens), despite much lower density of dopamine D 1 receptors in cerebral cortex vs. striatum. The EC50 for dopamine stimulation in cerebral cortex (∼1 μM) was lower than that for caudate and putamen (∼3 μM). No detectable dopamine stimulation was observed in cerebellar cortex, thalamus or hippocampus. Dopamine stimulation in both cerebral cortex and striatum was independent of calcium activation. We conclude that dopamine stimulated AC can be measured in cerebral cortex of human brain allowing for the possibility that this process can be examined in human brain disorders in which dopaminergic abnormalities are suspected.

Deconvolution of transcranial magnetic stimulation (TMS) maps

Transcranial magnetic stimulation (TMS) is a noninvasive method for local stimulation of cerebral cortex using a small coil's pulsed magnetic field. TMS response maps consist of measured responses to stimulations at points on a scalp-referenced grid and are used to study the topography of the brain's inhibitory and excitatory response. Because the magnetic field distributions of stimulation coils are 1-2 centimeters wide and 2-3 centimeters long, and the induced electric fields are even broader, the resolution of TMS maps is limited and the actual region of cortical stimulation is poorly defined. To better characterize the activation pattern, a practical mathematical procedure was developed for deconvolving a spherical model approximation of the coil's induced electric field distribution (here measured in a phantom) from the TMS response maps. This procedure offers an integrated, internally consistent method for processing TMS response maps to estimate the spatial distribution of motor cortex activations and inhibitions.

Repetitive magnetic stimulation of cerebral cortex in normal subjects.

Changes of excitability in the neuraxis were studied in 11 healthy subjects with repetitive transcranial magnetic stimuli of the motor cortex at frequencies of 1-10 Hz. Following trains of four stimuli, compound muscle action potentials (CMAPs) were obtained from the flexor carpi radialis muscle. At an interstimulation interval (ISI) of 100-180 ms. the amplitudes of the CMAPs evoked by stimuli II and IV were inhibited as compared with the amplitude of the CMAPs evoked by the first stimulus. In contrast, the amplitude of the CMAPs evoked by stimulus III was almost unchanged. Changes in excitability depended on the stimulation intensity. Thus, it was demonstrated that the amplitude of the CMAPs evoked by stimulus III was reduced at low stimulation intensities (100 and 110% of threshold intensity) but normalized at higher stimulation intensities (120 and 130% of threshold intensity). Results of H-reflex studies indicated that excitability changes at the segmental level are not necessarily involved in the inhibition of the CMAPs evoked by stimuli II and IV at an ISI of 100 ms. It is proposed that long acting neurotransmitter modulation can explain part of the inhibition during repetitive magnetic stimulation, and that recruitment of different neurons, due to electric field differences, explains the dependence of excitability on stimulation intensity.

Diagnostic nerve-muscle stimulation, including electromagnetic stimulation of cerebral cortex

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Focal elevations in neocortical interstitial K + produced by stimulation of the fastigial nucleus in rat

We studied whether K +, a potent cerebrovasodilator released by active neurons, participates in the increase in cortical cerebral blood flow (CBF) elicited by stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized by continuous administration of halothane (1–3%), paralyzed and artificially ventilated. FN was stimulated electricaly (8 s trains, 50 Hz, 5–10 V) through microelectrodes positioned stereotaxically. K + o (mM) was measured in sensory cortex by K +-sensitive micropipettes. In some experiments neocortical CBF was monitored continuously by laser-doppler flowmetry. Stimulation of the FN produced significant increases in K + o that averaged 0.91 ± 0.16 mM (range 0.5–2.9 mM; n = 19) and were confined to sites corresponding to the intermediate cortical laminae ( P < 0.05, ANOVA). To determine whether such K + o elevations were able to produce increases in CBF comparable to those elicited by FN stimulation, cortical K + o was increased by superfusing the sensory cortex with 20–30 mM K + in Ringer. K + o elevations of 2.8 ± 0.6 mM increased CBF by 17 ± 2% ( n = 5), an increase considerably smaller than that elicited by FN stimulation in cerebral cortex. We conclude that K + is unlikely to mediate the cortical cerebrovasodilation. Furthermore, the restricted spatial distribution of the K + o increase indicates that the cortical neural activity evoked by FN stimulation is highly focal. Thus the findings support the hypothesis that, in cortex, the vasodilation is mediated by activation of a restricted group of neural elements, perhaps neurons in laminae III-IV.

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 oriented MC stimulation. Conduction time from motor cortex to motoneuron was estimated by subtracting peripheral conduction time and monosynaptc 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 oriented 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.

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats: Part II: Stimulation of cerebral cortex and hypothalamus

This experimental work was carried out to examine whether activation of autonomic cortical and hypothalamic areas by electrical stimulation is related to changes in the intracranial pressure (ICP) in cats anaesthetized lightly with sodium pentobarbital. Electrical stimulation was performed using a concentric electrode with a train of electrical pulses (pulse duration, 0.4 ms; frequency, 40 Hz; intensity, 50-400 microA). Stimulation of sites in the anterior cingulate gyrus produced a rise in ICP associated with a fall in systemic arterial blood pressure (BP) or with no change in BP. Stimulation of sites in the anterior hypothalamus produced a fall in BP with an increase in ICP. Stimulation of sites in the area extending from the anterior hypothalamus to the posterior hypothalamus produced rises in BP and ICP. These observations suggest that activation of autonomic cortical and hypothalamic areas is involved in changes in ICP.

Influence of cerebral cortex stimulation upon cough-like spasmodic expiratory response (SER) and cough in the cat

In 27 pentobarbitalized cats, the influence of electrical stimulation of the cerebral cortex upon the spasmodic expiratory response (SER) was studied and compared with cortical influences on coughing induced by stimulation of the superior laryngeal nerve (sup. laryngeal N.). This cortical influence was evoked by electrical stimulation of the cortical nucleus of amygdala (Aco), and was very similar to coughing accompanying changes in emotional behavior and was depressed more effectively by psychotropics than by centrally acting antitussives like codeine. When anterior cingulate gyrus (ant. cingulate G.) or orbital gyrus (orbital G.) were stimulated simultaneously with Aco or sup. laryngeal N., weak stimulation was sufficient to inhibit SER, while stronger stimuli were needed for the suppression of cough. If the same cortical regions were stimulated after initiation of SER or cough, SER was markedly suppressed but cough little affected. Production of SER was facilitated by simultaneous stimulation of the piriform lobe (piriform L.) or olfactory tract (olfactory T.), whereas cough production was facilitated by simultaneous stimulation of the suprasylvian gyrus. These results suggest that SER and coughing are differently controlled by the cerebral cortex, and that SER is modulated by the limbic cortex, in particular, by ant. cingulate G., orbital G. and piriform L. The mechanism of modulation for SER is discussed.

Specificity of the newly-formed corticorubral synapses in the kitten red nucleus

We have examined the formation of new synapses that occurs in the kitten red nucleus (RN) following lesions of the cerebral cortex or cerebellum. In normal 2–3 month old kittens, stimulation of the cerebral cortex or cerebral peduncle (CP) produces slow-rising monosynaptic EPSPs in ipsilateral RN cells; while fast-rising EPSPs are produced by stimulating the contralateral nucleus interpositus (IP) of the cerebellum. In these normal animals stimulation of the contralateral cerebral cortex, or CP, or the ipsilateral IP never produces detectable postsynaptic potentials. In contrast, in kittens with chronic lesions of the ipsilateral sensorimotor cortex performed less than 2 months after birth, it was found that (1) stimulation of the contralateral sensorimotor cortex or CP produced slow-rising EPSPs. (2) Upon stimulation of the contralateral IP a slow-rising component appeared superimposed on the fast-rising IP-EPSPs. (3) In some cells, stimulation of the ipsilateral IP produced slow-rising EPSPs. These results indicate that new synapses were formed on the dendrites of RN cells by neurons from the contralateral CP, contralateral IP and ipsilateral IP. The majority of denervated RN neurons were found to receive new synapses from only one of these three inputs, those from the contralateral cerebral cortex being most prominent. The conduction velocities of corticorubral fibers responsible for the EPSPs recorded in these lesioned animals are similar to those of slow conducting pyramidal tract fibers. Sometimes IPSPs were also produced by a train of CP stimuli. The IPSPs are probably mediated by fast conducting pyramidal tract fibers because their threshold is lower than that of the EPSPs. These findings suggest that newly formed crossed corticorubral projections have organizational specificity with respect to excitatory vs. inhibitory connections which is similar to that of normal ipsilateral corticorubral projections. Somatotopical organization was found in the newly-formed corticorubral excitatory projections. The forelimb cortical area was found to project to contralateral RN neurons innervating the forelimb spinal segments, while the hindlimb cortical area was found to project to RN neurons innervating the lumbar segments. However, after chronic ablation of the forelimb area of the contralateral sensorimotor cortex, in addition to the ipsilateral cerebral cortex, a new connection was formed from the hindlimb area of the contralateral cerebral cortex to the RN neurons innervating the spinal forelimb segments. This indicates that the specificity of the topographical organization is subject to reorganization. In chronically hemicerebellectomized kittens, ipsilateral IP stimulation produced fast-rising monosynaptic EPSPs in some cases. Thus, it was concluded that new synapses were formed on the somatic or proximal dendritic portion of RN cells from the ipsilateral IP after ablation of the contralateral IP.