Evoked motor response thresholds during transcranial magnetic stimulation in patients with symptomatic partial epilepsy

Transcranial magnetic stimulation (TMS) occupies a leading position among noninvasive neurophysiological methods used for evaluating the balance of processes of cortical inhibition and excitation. The aim of the present work was to assess motor cortical excitability in symptomatic partial epilepsy using TMS in relation to the effects of antiepileptic treatment. A total of 31 patients were studied. A decrease in the motor response threshold was seen in a group consisting of untreated patients, with changes in cortical excitability during seizures. Treated patients showed no difference as compared with healthy subjects. The shorter the interval between a seizure and TMS, the smaller the evoked motor response threshold. The low threshold seen in patients with symptomatic partial epilepsy showed a significant correlation with clinical signs of neuromuscular excitability. The data obtained here provide evidence of changes in the functional state of the cortex and, thus, the motor response threshold, in patients with epilepsy. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Supplement, Epilepsiya, No. 1, pp. 75–78, 2006.     

Motor cortex stimulation in rats with chronic constriction injury

Motor cortex stimulation (MCS) has gained a significant role in treatment of neuropathic pain. In order to evaluate effect of MCS in experimental animals we applied MCS to rats with neuropathic pain, which was evoked by chronic constriction injury (CCI) to the left sciatic nerve. Pain thresholds of both hind limbs were measured before, immediately after MCS, 1 h after MCS and 1 day after MCS. Effect of the stimulation was studied with respect to laterality (contralateral and ipsilateral MCS) and duration (short-term 10-min and long-term 1-h stimulation). It was found out that in control rats MCS did not affect thermal nociceptive thresholds. However, in CCI animals following results were obtained: difference score (difference in paw withdrawal latency between ligated and non-ligated hind limb) significantly decreased after both short- and long-term contralateral MCS; the difference score after the long-term ipsilateral MCS (related to the ligated hind limb) was not significantly different from that of intact animals; the effects of the contralateral short-term and the ipsilateral long-term stimulation faded within 1 h after the end of MCS, while the effect of the contralateral long-term MCS remained 1 h after the end of the MCS and faded within 24 h. It is concluded that MCS in experimental animals exerts similar effects as in human suffering from neuropathic pain and that the effect might be evoked from both cerebral cortices.     

Motor cortex excitability following repetitive electrical stimulation of the common peroneal nerve depends on the voluntary drive

Previously, long-term changes in the motor cortex have been reported after repetitive electrical nerve stimulation (rES) as well as after motor exercise. The purpose of this study was to investigate whether the effects of voluntary motor cortical drive and of rES on the motor cortical output in healthy subjects interact with each other. A 30-min exercise session was performed during the following conditions: rES of the right common peroneal nerve (CPN) during rES at rest (A); voluntary exercise of the right ankle dorsiflexors alone (B); rES combined with voluntary dorsiflexion exercise (C); voluntary exercise of ankle plantar flexors alone (D); and plantar flexion exercise combined with rES (E). Motor evoked potentials (MEPs) were obtained before and after the exercise with a stimulation intensity of 125% of the threshold of the relaxed right tibialis anterior (TA). rES was ON for 1 s and OFF for 2 s in a cycle, and consisted of trains of five pulses, duration 1 ms and frequency 30 Hz, as applied in functional electrical stimulation (FES). MEPs of the TA muscle elicited after the training were increased in A by 38%, in B by 35%, and in C by 66%. In D and E, the MEPs of TA were decreased by 29% and 35%, respectively. The effect was maintained for at least 30 min after the nerve stimulation was completed. Consistent with previous studies (Khaslavskaia et al. (2002) Exp Brain Res 145:309–315), MEPs after the CPN rES are shown to be partly due to increased TA cortical excitability. These results suggest that the effect of FES on motor cortical excitability depends on the concurrent motor cortical drive present at the time of FES, and the combination of these factors modulates neural excitability and probably reorganization. The decrease in motor cortical excitability after plantar flexor exercise probably means that voluntary effort antagonistic to the electrical exercise is stronger and cancels out the effects of rES. Improving FES effects through an agonist voluntary drive implies an enhancement of sensorimotor reorganization through the addition of a voluntary component to a trained movement. Possible mechanisms and implications of these results on the rehabilitation of patients with paralysis and spasticity are discussed.     

周围神经趋化性再生研究新进展

周围神经损伤后修复及功能重建一直是临床治疗的难题.现从周围神经趋化性再生的概念,感觉与运动神经元自身差异、远侧端神经、施万细胞、成纤维细胞以及轴突导向因子等方面阐述了目前周围神经趋化性再生的研究进展,为将来开发更好的工程化神经组织,促进神经功能良好的恢复提供基础知识.     

Afferent electrical nerve stimulation: Human tracking performance relevant to prosthesis sensory feedback

Afferent electrical nerve stimulation has been suggested for use in prosthesis sensory feedback by several authors. This paper deals with some basic properties of afferent-nerve stimulation when applied continuously for 2 min with dynamic changes in the stimulation parameters. The stimulation was well tolerated but the adaptation was pronounced and had to be compensated. The accuracy, transinformation and delay of the response to afferent-nerve stimulation was studied in tracking experiments with different patterns and stimulation modes. It was found that accuracy was promoted by the use of current-amplitude modulation as opposed to current-pulse-frequency modulation. In addition, slowly changing stimulation patterns yielded higher accuracy than rapidly changing ones. Stimulation patterns consisting of a large number of distinct stimulation levels gave higher transinformation than patterns consisting of a small number of levels. Rapidly changing stimulation patterns yielded a shorter delay than slow patterns. In general, tracking with afferent electrical nerve stimulation yielded an accuracy and a transinformation of about 75% of that of visual tracking. The delay time was found to be three times that of visual tracking. In conclusion, afferent electrical nerve stimulation has properties that make it suitable for conveying sensory feedback from motorised prostheses.     

Characterization and control of muscle response to electrical stimulation

The maintenance of upright posture in neurologically intact human subjects is mediated by two major nervous pathways. The first, leading from the cerebral cortex through the spinal cord to motor neurons, activates muscles which produce postural movements. The second, leading from various sensory organs to higher centers, provides sensory feedback regarding the postural state. The path through the spinal cord is no longer intact in victims of spinal cord injury and loss of normal control of muscle activity results. Functional neuromuscular stimulation (FNS) has been shown as a feasible method for obtaining muscle contraction in paraplegic and has been proposed as a means for control of antero-posterior sway to make upright posture possible for these individuals. Before muscle can be controlled through the use of FNS, the response of muscle to electrical stimulation must be understood. In past studies, linear control theory has been applied to the analysis of this response and to the testing of various controllers. The aim of this study was to demonstrate some control issues in FNS using linear control theory, as it applies to electrical stimulation of muscle for stabilization of posture. The linearity of the muscle response was improved through closed-loop control using pole compensation techniques. The excess phase shift of the system due to the time delay in the muscle response, however, limits the ability to increase the open-loop gain in order to obtain improved performance. A suggestion for further study is the application of this methodology for uses in posture control.     

Olfactory experience mediates response to pain in preterm newborns

We assessed the effects of a familiar odor during routine blood draws in healthy preterm newborns. Infants were observed as they were undergoing either a capillary puncture on the heel (heelstick) or a venous puncture on the hand. During the procedure, one third of the infants were presented with an odor they had been familiarized with prior to the procedure, one third of the infants were presented with an odor, they had not been previously exposed to, and one third were presented with no odor. Heelsticks elicited more behavioral distress than venipunctures. Infants who were presented with a familiar odor during venipuncture showed no significant increase in crying and grimacing during the procedure compared to baseline levels. By comparison, infants presented with an unfamiliar odor or with no odor either during the heelstick or the venipuncture had a significant increase in crying and grimacing. When the pain was milder, i.e., during a venipuncture, and a familiar odor was presented, infants showed little to no crying. These results are consistent with a body of evidence on early memory and olfactory competence in fetuses and newborns.     

Energy metabolism in type I and type II human muscle fibres during short term electrical stimulation at different frequencies

The degradation of adenosine triphosphate, phosphocreatine and glycogen was determined in type I and type II fibres of the human quadriceps femoris muscle during intermittent electrical stimulation at 20 and 50 Hz, (1.6 seconds stimulation, 1.6 seconds rest). Seven healthy volunteers took part in the study. Muscle biopsy samples were obtained at rest and after 10 and 20 seconds of stimulation (six and 12 contractions, respectively). The resting contents of adenosine triphosphate, phosphocreatine and glycogen were all higher (P < 0.05) in type II fibres compared to type I fibres. By the end of stimulation, whole muscle force production had declined to 84 and 77% of the initial force at 20 and 50 Hz, respectively. The phosphocreatine degradation rate after 10 and 20 seconds of stimulation was greater in type II fibres (P < 0.05) compared to type I fibres at both 20 and 50 Hz. The rates of glycogenolysis after 20 seconds stimulation in type II fibres were 3.18±1.1 and 6.31±1.39mmol glycosyl units kg^-1 s^-1. The corresponding rates in type I fibres were 0.46 ± 0.73 and 0.60 ± 0.39 mmol glycosyl units kg^-1 s^-1 which were not significantly different from zero. It is hypothesized that the decline in whole muscle force observed during electrical stimulation may be a consequence of the rapid loss of PCr stores in type II fibres.     

Submaximal-exercise-induced impairment of human muscle to develop and maintain force at low frequencies of electrical stimulation

The aim of this study was to test the hypothesis that low intensity exercise-induced low frequency fatigue is caused by failure of excitation-contraction coupling. Changes in knee extension torque at 5, 10, 15, 20 and 50 Hz electrical stimulation of quadriceps muscle in ten healthy, young, male subjects were recorded during 20-min voluntary exercise followed by 60-min recovery. In seven of the ten subjects, changes in torque during 3 min of 10-Hz stimulation were recorded 2 min and 20 min after 20 min voluntary exercise. Exercise was performed at 30% of maximal voluntary contraction with a contraction plus relaxation period of 6 plus 4 s. Torque at 5, 10, 15, 20 and 50-Hz stimulation at the end of exercise was reduced to mean 91.0 (SEM 5.4)%, 68.7 (SEM 5.4)%, 67.2 (SEM 3.9)%, 66.5 (SEM 4.5)% and 74.7 (SEM 4.3)% of control values, respectively. During the first 30 s of the 3 min 10-Hz stimulation, torque was reduced in exercised muscle and increased in nonfatigued muscle. The reduction in torque was more marked 20 min after exercise than after 2 min. In conclusion, the pattern of depression and recovery of muscle force observed was in agreement with the hypothesis that the main cause of low intensity exercise-induced low frequency fatigue is an impairment of excitation-contraction coupling.     

Motor unit recruitment in human genioglossus muscle in response to hypercapnia

Study Objectives:

Single motor unit recordings of the genioglossus (GG) muscle indicate that GG motor units have a variety of discharge patterns, including units that have higher discharge rates during inspiration (inspiratory phasic and inspiratory tonic), or expiration (expiratory phasic and expiratory tonic), or do not modify their rate with respiration (tonic). Previous studies have shown that an increase in GG muscle activity is a consequence of increased activity in inspiratory units. However, there are differences between studies as to whether this increase is primarily due to recruitment of new motor units (motor unit recruitment) or to increased discharge rate of already active units (rate coding). Sleep-wake state studies in humans have suggested the former, while hypercapnia experiments in rats have suggested the latter. In this study, we investigated the effect of hypercapnia on GG motor unit activity in humans during wakefulness.

Setting:

Sleep research laboratory.

Participants:

Sixteen healthy men.

Measurements and Results:

Each participant was administered at least 6 trials with P_etCO₂ being elevated 8.4 (SD = 1.96) mm Hg over 2 min following a 30-s baseline. Subjects were instrumented for GG EMG and respiratory measurements with 4 fine wire electrodes inserted subcutaneously into the muscle. One hundred forty-one motor units were identified during the baseline: 47% were inspiratory modulated, 29% expiratory modulated, and 24% showed no respiratory related modulation. Sixty-two new units were recruited during hypercapnia. The distribution of recruited units was significantly different from the baseline distribution, with 84% being inspiratory modulated (P < 0.001). Neither units active during baseline, nor new units recruited during hypercapnia, increased their discharge rate as P_etCO₂ increased (P > 0.05 for all comparisons).

Conclusions:

Increased GG muscle activity in humans occurs because of recruitment of previously inactive inspiratory modulated units.

Citation:

Nicholas CL; Bei B; Worsnop C; Malhotra A; Jordan AS; Saboisky JP; Chan JKM; Duckworth E; White DP; Trinder J. Motor unit recruitment in human genioglossus muscle in response to hypercapnia. SLEEP 2010;33(11):1529-1538.     

Vibrotactile thresholds in non-Pacinian mechanoreceptive afferents: the importance of temporal parameters

Vibrotactile thresholds of non-Pacinian mechanoreceptive afferents (RA, SAI, SAII) were determined as a function of stimulus duration (100–800 ms) at three frequencies (20–240 Hz). Altogether 64 units innervating the hairy skin of the cat were tested. At all frequencies SAII units had the lowest thresholds whereas SAI units had the highest thresholds. At all frequencies and in all unit populations the absolute thresholds (1 impulse/stimulus train) were independent of stimulus duration, whereas the tuning thresholds (1 impulse/cycle) were elevated as a function of increasing stimulus duration. The present results suggest that the detection threshold decreases as a function of increasing stimulus duration are not based on peripheral properties of non-Pacinian mechanoreceptors.     

Facilitation of motor evoked potentials in the anterior tibial muscle by repetitive subthreshold electrical stimulation

Subthreshold electrical stimulation with an intensity less than the threshold for evoking M-waves is applied repetitively to the common peroneal nerve via surface electrodes. The stimulation intensity is varied by adjusting the pulse width from 0 to 240 μs, while the pulse interval (40 ms) and current amplitude are kept constant. Single magnetic stimuli are applied to the motor cortex using a circular coil. Motor evoked potentials are recorded from the anterior tibial muscle in six normal subjects for various subthreshold stimulation intensities. Signal processing (filtering in the time and frequency domains) removes the artifact caused by the subthreshold electrical stimulation from the motor evoked potential. Statistically significant motor evoked potential facilitation (p<0.05) is observed for pulse widths ranging from 72 to 240 μs in all the tested subjects. A pulse width corresponding to 90% of the electrical threshold facilitated the motor evoked potential in five of the six subjects.     

Influence of electrophysiological heterogeneity on electrical stimulation in healthy and failing human hearts

The application of strong electrical stimuli is a common method used for terminating irregular cardiac behaviour. The study presents the influence of electrophysiological heterogeneity on the response of human hearts to electrical stimulation. The human electrophysiology was simulated using the ten Tusscher-Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in three-dimensional virtual myocardial preparations was calculated using bidomain equations. The research was carried out on different types of virtual cardiac wedge. The selection of the modelling parameters emphasises the influence of cellular electrophysiology on the response of the human myocardium to electrical stimulation. The simulations were initially performed on a virtual cardiac control model characterised by electrophysiological homogeneity. The second preparation incorporated the transmural electrophysiological heterogeneity characteristic of the healthy human heart. In the third model type, the normal electrophysiological heterogeneity was modified by the conditions of heart failure. The main currents responsible for repolarisation (I_to, I_Ks and I_Kl) were reduced by 25%. Successively, [Na⁺]_i was increased by the regulation of the Na⁺−Ca²⁺ exchange function, and fibrosis was represented by decreasing electrical conductivity. Various electrical stimulation configurations were used to investigate the differences in the responses of the three different models. Monophasic and biphasic electrical stimuli were applied through rectangular paddles and needle electrodes. A whole systolic period was simulated. The distribution of the transmembrane voltage indicated that the modification of electrophysiological heterogeneity induced drastic changes during the repolarisation phase. The results illustrated that each of the heart failure conditions amplifies the modification of the response of the myocardium to electrical stimulation. Therefore a theoretical model of the failing human heart must incorporate all the characteristic features.     

ATP content in single fibres from human skeletal muscle after electrical stimulation and during recovery

The ATP content was measured in type I and type II fibres from human vastus lateralis muscle at rest, after electrical stimulation and during recovery. At rest the mean values were 25.2 ± 4.02 and 25.9 ± 3.62 mmol kg^-1 dry muscle (mean ± SD) for type I and type II fibres respectively. Normal distribution curves were found for both types I and II fibres. After intermittent electrical stimulation for 83 s (1.6 s Stimulation, 1.6 s pause) with occluded blood flow, the force generation decreased to 22± of the initial value and the muscle tissue showed a mean decrease in ATP to 14.8 and in phosphocreatine to 5.44 mmol kg^-1 dry muscle; lactate increased to 128.9 mmol kg^-1 dry muscle. The ATP content in isolated fibres was equally decreased in both fibre types to 16 mmol kg^-1 dry muscle. In 11± of the fibres the ATP content was lower than 10 mmol kg^-1 dry muscle. After 15 min rest with intact blood circulation ATP was completely resynthesized in type I fibres and to 91± in type II fibres.     

Effects of different types of contingent tactile stimulation on crying,smiling, and sleep in newborns: An observational study

Sleep, the brain and the ability to interact with the environment change a great deal over the first year of life; however, there are no studies on the possible influence of different environmental stimulations on the organization of subsequent sleep–wake cycles in infants. The hypothesis of this study was that greater continuity of contingent tactile stimulation decreases crying behavior, subsequent active sleep (AS) and its fragmentation, and increases smiling behavior and subsequent quiet sleep in newborns. Forty out of the 82 newborns (15‐ to 30‐hr old) of the initial sample satisfied the inclusion criteria and completed the first cycle of sleep during the period between two feedings. The 40 newborns were randomly assigned to four groups after 2′ of baseline observation: continuous stimulation (CS, n = 10); discontinuous nonperiodic stimulation (DnPS, n = 10); discontinuous periodic stimulation (DPS, n = 10); absent stimulation (AbS, n = 10). During baseline measurements, there were no significant differences in crying and smiling behaviors between the four groups, while during the subsequent stimulated wake, the CS group compared to the DnPS group showed more smiling (p < .05) and less crying (p < .05), longer poststimulation wake before sleep (p < .01) as well as AS with a lower percentage of grouped‐rapid eye movements [grouped REM (GREM); p < .001]. The number of GREM during AS was negatively correlated to the number of smiles (p < .05) and positively to the number of cries (p < .05) of the previous stimulated wake. These findings suggest that, after birth, different continuity levels of contingent tactile stimulations may affect crying and smiling behaviors and the organization of behavioral states. AS could have an important role in processing affective states. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 508–517, 2013     

Spread of electrical activity at cortical level after repetitive magnetic stimulation in normal subjects

In normal subjects, focal repetitive transcranial magnetic stimulation (rTMS) of the hand motor area evokes muscle potentials (MEPs) from muscles in the hand (target muscles) and the arm (non-target muscles). In this study we investigated the mechanisms underlying the spread of MEPs induced by focal rTMS in non-target muscles. rTMS was delivered with a Magstim stimulator and a figure-of-eight coil placed over the first dorsal interosseus (FDI) motor area of the left hemisphere. Trains of 10 stimuli were given at a suprathreshold intensity (120% of motor threshold) and at frequencies of 5, 10 and 20 Hz at rest. Electromyographic (EMG) activity was recorded simultaneously from the FDI (target muscle) and the contralateral biceps muscle and from the FDI muscle ipsilateral to the side of stimulation (non-target muscle). rTMS delivered in trains to the FDI motor area of the left hemisphere elicited MEPs in the contralateral FDI (target muscle) that gradually increased in amplitude over the course of the train. Focal rTMS trains also induced MEPs in the contralateral biceps (non-target muscle) but did so only after the second or third stimulus; like target-muscle MEPs, in non-target muscle MEPs progressively increased in amplitude during the train. At no frequency did rTMS elicit MEPs in the FDI muscle ipsilateral to the site of stimulation. rTMS left the latency of EMG responses in the FDI and biceps muscles unchanged during the trains of stimuli. The latency of biceps MEPs was longer after rTMS than after a single TMS pulse. In conditioning-test experiments designed to investigate the cortical origin of the spread, a single TMS pulse delivered over the left hemisphere at an interstimulus interval (ISI) of 50, 100 and 150 ms reduced the amplitude of the test MEP evoked by a single TMS pulse delivered over the right hemisphere; and a conditioning rTMS train delivered over the left hemisphere increased the amplitude of the test MEP evoked by a single TMS pulse over the right hemisphere. A conditioning rTMS train delivered over the left hemisphere and paired magnetic shocks (test stimulus) at 3 and 13 ms ISIs over the right hemisphere reduced MEP inhibition at the 3-ms ISI but left the MEP facilitation at 13 ms unchanged. Using a control MEP size matched with that observed after a conditioning contralateral rTMS, we found that paired-pulse inhibition remained unchanged. Yet a single TMS conditioning pulse sufficiently strong to evoke a MEP in the contralateral FDI and biceps muscles simultaneously (as rTMS did) left paired-pulse inhibition unchanged. We conclude that the spread of EMG activity to non-target muscles depends on cortical mechanisms, mainly including changes in the excitability of the interneurones mediating intracortical inhibition. Electronic Publication     

Action of serotonin microinjected into hypothalamic sites at which electrical stimulation produced aversive responses in the rat

A bipolar chemitrode was implanted unilaterally in the hypothalamus of the rat so that the tip rested in the medial forebrain bundle. Upon aversive electrical stimulation with pulses delivered at a rate of 2/sec, each rat learned to avoid this stimulation by depressing a lever in the test chamber. Microinjections in a volume of 0.4–0.7 μl of an artificial CSF solution or of doses of 1.0 or 5.0 μg of acetylcholine, dopamine or norepinephrine into the neuron mass directly at the tip of the electrode failed to alter the rate of avoidance responding to the electrical stimulation. However, serotonin (5-HT) microinjected similarly in a dose of 5.0 μg at the tip of the electrode caused a fourfold increase in the acceptance of this aversive electrical stimulation. It is concluded that serotonergic neurons function to attenuate punishing stimuli within the negatively reinforcing pathways located in the diencephalon.     

Vasomotor response to cold stimulation in human capsaicin-induced hyperalgesic area

Cooling the skin induces sympathetically driven vasoconstriction, with some vasoparalytic dilatation at the lowest temperatures. Neurogenic inflammation, on the other hand, entails vasodilatation. In this study we investigated the balance between vasoconstriction and vasodilatation in an area of experimentally induced secondary hyperalgesia (2° HA), in response to low-temperature stimulations. Fourteen healthy volunteers were exposed to three 30-s long cold stimuli (20, 10, and 0°C) applied, at three adjacent sites, before (baseline) and 8 min after intradermal injection of 50 g capsaicin to the volar forearm. The cold stimuli were applied distally to the injection site within the 2° HA. Blood flux (BF) and skin temperatures were measured at four different regions (proximally, and distally to the capsaicin injection and at the 0, 10, and 20°C thermode sites) all within the 2° HA. The vascular measurements were conducted five times. Results showed a marked increase in BF after baseline cold stimulation (P<0.001) at the 0°C compared with the three other sites. In addition, vasodilatory effect (elevated BF) was found following the capsaicin injection compared with baseline for all regions (P<0.001): the non-cooled area was dilated by 450±5.1%; The vasoconstrictive effect for the 10 and 20°C did not overcome the capsaicin vasodilatation, but did reduce it, with dilatation of 364±7.0% and 329±7.3%, respectively. For 0°C, a dilatation of 407±6.5% was seen. It is concluded that in this experimental model, and potentially in the equivalent clinical syndromes, vasodilatation induced by the inflammation is only slightly reduced by cold stimulation such that it is still dominant, despite some cold-induced vasoconstriction.     

A hypothalamic alpha-adrenergic mechanism mediating the thermogenic response to electrical stimulation of the lower brainstem in the guinea pig

Summary Electrical stimulation of the lower brain stem (ESLB) at sites presumed to be parts of the ascending noradrenergic system was carried out in unanaesthetized young guinea pigs. At neutral ambient temperature ESLB elicited a thermogenic response resembling that evoked by microinjection of noradrenaline into the hypothalamus. The response consisted of a rise in oxygen uptake (to more than 50% of the resting value) and of body temperatures, especially of the interscapular adipose tissue. In some cases shivering was also evoked. The thermogenic response to ESLB was completely blocked by additional microinjection of an adrenergic alpha-receptor blocker, phentolamine, into the hypothalamic area where the noradrenergic fibres were presumed to terminate. Subsequent intrahypothalamic injection of noradrenaline, which had formerly been shown to restore the decreased responses to repeated ESLB, failed to restore the effectiveness of ESLB after phentolamine. It is concluded that the thermogenic responses to ESLB are mediated by a noradrenergic pathway ascending to the hypothalamus and not by direct stimulation of efferent pathways controlling the peripheral target system. The hypothalamic transmission can be prevented by an alpha-adrenergic blockade.Supported by the Deutsche Forschungsgemeinschaft SFB 122, Projeckt B 1