Cortical modulation of thalamo-cortical neurons relaying exteroceptive information: a microstimulation study in the guinea pig

Summary The nature and organization of cortical influences on somatosensory thalamic neurons were investigated in the guinea pig in order to ascertain if mechanisms subserving sensory-motor integration in the thalamus are as precise as has previously been demonstrated in the agranular frontal cortex (AGr) and granular parietal cortex (Gr). The study was carried out on 14 chronically-implanted awake animals. In each experiment one or two motor foci within AGr and Gr were identified according to the region of the movement evoked by intracortical microstimulation at the lowest threshold stimulation (usually 5–15 µA). Spontaneous activity of 182 thalamo-cortical single neurons was recorded in the nucleus ventralis thalami (VT). The neurons were also identified by their response to activation of cutaneous receptive fields (RFs) located in regions of vibrissae or limbs, and then tested for cortical stimulation with a pulse intensity equal to the threshold for evoking motor effects. During the cortico-thalamic tests, the duration of stimulating trains was reduced in order to avoid the appearance of limb or vibrissa movements which could activate somatosensory ascending pathways forwarding peripheral messages to VT. The cortical control on VT neurons appears to be organized in a very precise manner. It was seen that: 1) The influences on these neurons relaying exteroceptive signals specifically emanated from AGr and Gr areas which in turn received exteroceptive input. 2) The vibrissa units responded to stimulation of foci in either AGr or Gr but the reactivity was greater upon stimulation of Gr than AGr. The incidence of responses was very high when the vibrissa RF was overlapping or adjacent to the region of the cortically-evoked vibrissa movement. The response pattern was mostly excitatory. Responses were rarely observed when vibrissa RF lay distant from the vibrissa moved by cortical stimulation. 3) Neurons with limb RFs responded constantly to stimulation of Gr foci only when the RF was overlapping or adjacent to the region of the cortical motor target; in these two conditions the response pattern was excitatory and inhibitory, respectively. Inhibitions only concerned neurons with forelimb RFs. Responses to stimulation of AGr were rarely obtained. From a functional point of view, the excitatory nature of the cortical control on thalamo-cortical VT neurons suggests that a cortical signal inducing movement of a given body part is able to enhance the afferent transmission of somatosensory messages arising in the same body part. Concerning the control on forelimb neurons, this enhancement would be further amplified by a sort of descending surround inhibition which impairs transmission of messages coming by adjacent body parts.     

Angiotensin II as a factor inhibiting the fear response

Angiotensin II, if injected into the lateral ventricles of rabbits in doses of 0.015–0.15 g, has an inhibitory action on the fear response evoked by electrical stimulation of the ventromedial hypothalamic nucleus, but in doses of 1–10 ng it blocks the inborn behavioral fear responses in rats. On microionophoretic application of angiotensin II to single neurons in the cerebral cortex and parafascicular complex of the thalamus, predominantly activation responses were observed. Predominance of inhibitory neuronal responses were noted in structures of the hypothalamus and mesencephalic reticular formation to angiotensin II. Responses of cortical and subcortical neurons to angiotensin II are potentiated after stimulation of the fear center in the ventromedial hypothalamus. The hypothesis was put forward that depression of the fear response after administration of angiotensin II is connected with changes in cortico-subcortical relations, during which ascending activating influences of the mesencephalic reticular formation on the cerebral cortex are abolished due to descending influences of cortical and thalamic neurons.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 72, No. 6, pp. 713–722, June, 1986.     

Facts and reflections on thalamocortical reverberation of impulses

Experiments on cats, either unanesthetized or anesthetized with various doses of pentobarbital, showed that the cortical rhythmic after-discharge (slow after-activity), which has been regarded as a manifestation of reverberation of impulses in thalamocortical circuits [17], consists of a burst of spontaneous spindles evoked by stimulation. This conclusion is supported by the following facts: Spontaneous spindles and the rhythmic after-discharge respond absolutely identically (disappear) to activation of the EEG and deepening of pentobarbital anesthesia. The absence of thalamocortical reverberation is also indicated by the preservation of a rhythmic after-discharge (to clicks), synchronous with the cortex, in the thalamic relay nucleus (the medial geniculate body) after cooling or after removal of its projection zone.Translated from Neirofiziologiya, Vol. 7, No. 4, pp. 339–345, July–August, 1975.     

A Possible Mechanism for the Dopamine-Evoked Synergistic Disinhibition of Thalamic Neurons Via the “Direct” and “Indirect” Pathways in the Basal Ganglia

The mechanism of synaptic plasticity which we have previously proposed for striatal spiny neurons, along with published data on the predominance of dopamine-sensitive D1/D2 receptors on strionigral/striopallidal neurons, was used as the basis to propose the hypothesis that the induction of long-term potentiation/depression of the efficiency of the cortical inputs to these cells may result from the excitatory/inhibitory actions of dopamine on the activity of the neurons originating the direct and indirect pathways through the basal ganglia. Thus, the action of dopamine increases disinhibition of thalamic neurons via the direct pathway and decreases their inhibition via the indirect pathway. Both effects lead to increases in the activity of thalamic cells and in the activity of the efferent neocortical neurons which they excite. The actions of dopamine on striosomal neurons, which mainly have D1 receptors, may also be to induce long-term potentiation of cortical inputs. This effect should lead to increased inhibition of dopaminergic cells and decreases in their dopamine release, which may promote the maintenance of a stable dopamine concentration in the cortex-basal ganglia-thalamus-cortex neural network.     

The specificity of the response of preoptic-septal area neurons to estrogen: 17α-estradiol versus 17β-estradiol and the response of extrahypothalamic neurons

Summary The purpose of this study was to determine the specificity of the response of medial preoptic-septal neurons (mPOA-S) to microelectrophoresed 17-estradiol hemisuccinate (17E₂S). In vitro studies were conducted initially to determine the release of the labeled 17E₂S from multibarrel glass micropipettes. Subsequently, an isomer of 17E₂S, 17-estradiol hemisuccinate (17E₂S), was synthesized and purified. Thirty-six mPOA-S neurons from normal cycling female rats were tested with both 17E₂S and 17E₂S. Twelve of these units responded with inhibition to 17E₂S, while none responded to 17E₂S. Furthermore, fifty extrahypothalamic (cortical, hippocampal, thalamic) neurons were tested with 17E₂S. The majority (N = 45) showed no response, three showed excitation and two inhibition to the microelectrophoresed steroid ester. These findings suggest that a specific receptor mechanism is responsible for the changes in mPOA-S unit activity, and that these effects may be important in the regulation of reproductive events.Supported by NIH Grant NS10434-END, awarded to R.L. MossPresently an NIH Postdoctoral Fellow at Max-Planck Institute for Biophysical Chemistry, Göttingen, West GermanyRecipient of an USPHS Career Development Award No. HD00146     

Neural correlates of isometric force in the “motor” thalamus

Summary The relationship between single cell activity in the motor thalamus and the generation of isometric force between the fingers has been investigated in 2 monkeys. Neurons related to the task were found in the thalamic motor regions VLo, VPLo, and VA where microstimulation occasionally elicited motor reactions in hand and fingers. 58% of these 55 neurons, designated typical, showed modulation of their discharge patterns with force similar to neurons in precentral cortex and could be assigned to one of 5 discharge patterns described for the motor cortex. Only a small percentage of the thalamic neurons were found to have phasic activity. The other atypical neurons (42%) had discharge patterns with complex sequences of phasic and tonic activation with respect to force. For 18 typical and atypical neurons with tonic and phasic-tonic modulation of their firing rate with force significant regression coefficients between firing rate and static force were observed. The mean index of force sensitivity (rateforce slope) was 54.5 Hz/N for the neurons increasing their discharge rate with force, i.e. approximately that of precentral cells. Neurons tested for their sensory properties had receptive fields located on hand and/or fingers and were activated mainly by stimulation of muscle and joint receptors.The characteristics of these thalamic neurons are compared to those of precentral cells recorded under identical experimental conditions and are discussed in relation to the known input-output relationships of the motor thalamic nuclei. The data strongly support the hypothesis that parameters of movement, in particular force, are represented by the activity of neurons in the motor thalamus.     

Comparative Analysis of the Frequency of Neuron Spike Activity in the Sensorimotor Cortex of the Right and Left Hemispheres in Conditions of Immobilization Catatonia in Rabbits

Multineuron activity was recorded from the sensorimotor cortex of the right and left hemispheres during immobilization catatonia in rabbits. The first session of immobilization of the animals was followed by changes in spike frequency in 47% of neurons in the sensorimotor cortex of the right hemisphere. Of these, 30% showed decreases in spike frequency and 17% showed increases. Spike frequency in the sensorimotor cortex of the left hemisphere changed in only 18% of cells, of which 13% showed decreases in spike frequency and 5% showed increases. The spike frequency of neighboring (recorded with the same electrode) neurons could change reciprocally. Differences in neuron activity in the two hemispheres were virtually absent after the second session of immobilization (several days after the first) – spike activity changed in 21% of neurons in the right hemisphere and 24% in the left hemisphere. The ratios of the numbers of neurons with increases and decreases in spike activity in hypnosis also became identical in the cortex of the right and left hemispheres. A hypothesis is proposed for the involvement of cortical neurons in the organization of hypnosis-like states.     

Dual mode of projections from the parietal to the motor cortex in the cat

Summary 1. The cortico-cortical projection from area 5 to area 4 was studied in anesthetized cats. 2. Intracortical microstimulation of area 5 produced EPSPs in pyramidal tract (PT) cells in area 4 . Such EPSPs were analysed in a total of 54 fast PT cells. The rising phase of these EPSPs was often composed of fast and slow components. 3. Fast-rising EPSPs (fast component) were produced predominantly by stimulation within layer III of area 5 while slow-rising EPSPs (slow component) were evoked predominantly by stimulation within layer V of area 5. 4. The amplitudes of the fast and slow components of EPSPs produced during repetitive stimulation within layers III and V of area 5 decreased and increased, respectively, with an increase in the stimulus frequency without any appreciable changes in their latency and time-to-peak. The slow component was much less influenced by membrane hyperpolarization than the fast component. 5. Retrogradely labeled neurons were found not only in layer III but also in layer V of area 5 following HRP injection centered on superficial layers (I–III) of area 4. 6. It is suggested that there are two groups of cortico-cortical neurons in layers III and V of area 5, which may make monosynaptic contact with the proximal and distal sites of fast PT cells in area 4, respectively.     

In vivo intracellular recordings of medial septal and diagonal band of Broca neurons: relationships with theta rhythm

Transmembrane potentials from medial septal and diagonal band of Broca (MS-DBB) neurons and hippocampal field activity were recorded in curarized and urethanized rats. MS-DBB cells were studied during large amplitude irregular activity and during hippocampal rhythm, elicited by either sensory (i.e. stroking the fur on the animal's back) or electrical stimulation of the reticularis pontis oralis nucleus (RPO). Three types of cells were described according to their firing pattern and the characteristics of their intracellular rhythm. Type A neurons displayed continuous rhythmic oscillations in the membrane potential (Vm) of approximately 17 mV. These oscillations generated rhythmic high-frequency spike trains which were phase-locked with hippocampal rhythm. Type A cells revealed intracellular rhythm even in the absence of hippocampal rhythm, suggesting that the activity of this type of cell was the most important in hippocampal genesis. Type B cells were characterized by marked postspike afterhyperpolarization and intracellular oscillations of smaller amplitude than in type A cells. Type C cells revealed a post-spike afterdepolarization and a lower amplitude, intracellular rhythm only in the presence of hippocampal rhythm. Type C neurons could fire slow spikes at depolarizing (46% of cells) or hyperpolarizing (15% of cells) Vms. Type B and C cells were intracellularly stained with Lucifer yellow. Although type B and C neurons revealed dissimilar electrophysiological properties, they had comparable morphological shapes. RPO electrical stimulation generated hippocampal rhythm and intracellular rhythm in types A and B cells but not in type C cells, and increased the spike rate in type C neurons. Electrical stimulation of the fornix only evoked synaptic responses in type B and C neurons, with antidromic responses being elicited in 12% of type C cells. These results indicate that probably most of the type A rhythmic cells did not receive direct hippocampal feedback and that at least some type C cells were projecting neurons. The present findings demonstrate that rhythm oscillations in the Vm of MS-DBB neurons elicit different rhythmic discharge patterns.     

The Involvement of Dopamine in Strengthening Cortical Signals Activating NMDA Receptors in the Striatum (a hypothetical mechanism)

A possible mechanism is proposed for the enhancement/weakening of those cortical signals in the cortex-basal ganglia-thalamus-cortex neural network which induce/do not induce opening of NMDA channels in the spiny neurons of the striatum and which can be regarded as strong/weak in terms of this measure. The mechanism is based on the modulatory influences of dopamine on changes in the efficiency of corticostriatal inputs. In the absence of dopamine, relative increases in the intensity of strong (weak) cortical signals can lead to the induction of long-term potentiation (depression) of corticostriatal synapses. In this case, because of the differently directed influences on thalamic cells of signals passing via strionigral and striopallidal cells, strong signals at the output of the thalamus are weakened, while weak signals are strengthened. Activation of dopamine D₁ (D₂) receptors on strionigral (striopallidal) neurons may facilitate increases in the extent of long-term potentiation/depression (decreases in the extent of long-term potentiation/depression or induction of long-term potentiation/depression). The consequence of this is that strong signals at the output of the thalamus can be strengthened synergistically, while weak signals cab be weakened synergistically. Background cortical signals evoking tonic release of dopamine in the striatum can decrease strengthening because of weakening of the modulatory influence of dopamine on the modification of corticostriatal synapses.     

Intracellular recordings from rat thalamic VL neurons: a study combined with intracellular staining

Summary Intracellular recordings from thalamic neurons receiving cerebellar inputs were performed under urethane anesthesia in the rat. A total of 64 neurons were recorded intracellularly with micropipettes filled with 4% biocytin solution (dissolved in 0.5 M K-acetate), and cerebellar-induced EPSPs (CN-EPSPs), the membrane resistance and firing properties were analyzed with intracellular current injections. The mean latency of CN-EPSPs was 1.9 ± 0.8 ms and the mean input resistance measured in 10 neurons was 17.6 ± 5.0 M. Thirty-two out of 35 stained neurons were analysed morphologically; 28 of these neurons were located in the VL, and 26 received CN-EPSPs. Their somata were round or polygonal in shape and the mean size was 22.5 × 15.2 m. They had radially extending spinous dendrites, and the mean radii of the dendritic fields were 214.7 m in the frontal and 171.4 m in the sagittal planes. These morphological features were similar to those observed in the sensory relay nucleus of the thalamus.     

Individual variations in the development of motor activity of rabbits in the early postnatal period

Summary Data presented in this work confirm P. S. Kupalov's observations on the presence of so-called explosiveness in the activity of pathologically unaffected cortical cells. At the same time it is pointed out that phenomena of explosiveness of the nervous processes with reduction of the positive conditioned reflexes may serve as a symptom of preneurotic state.(Presented by Active Member AMN SSSR P. S. Kupalov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 9, pp. 8–10, September, 1962     

Partitioning of Cortical and Deep Cytoskeleton Responses from Transient Magnetic Bead Twisting

We attempted to estimate in living adherent epithelial alveolar cells, the degree of structural and mechanical heterogeneity by considering two individualized cytoskeleton components, i.e., a submembranous cortical cytoskeleton and a deep cytoskeleton (CSK). F-actin structure characterizing each CSK component was visualized from spatial reconstructions at low and high density, respectively, especially in a 10-m-cubic neighborhood including the bead. Specific mechanical properties (Young elastic and viscous modulus E and ) were revealed after partitioning the magnetic twisting cytometry response using a double viscoelastic solid model with asymmetric plastic relaxation. Results show that the cortical CSK response is a faster ( ₁ 0.7s), softer (E₁: 63-109 Pa), moderately viscous (₁: 7-18 Pa s), slightly tensed, and easily damaged structure compared to the deep CSK structure which appears slower (₂ min), stiffer (E₂: 95-204 Pa), highly viscous (₂: 760-1967 Pa s), more tensed, and fully elastic, while exhibiting a larger stress hardening behavior. Adding drug depolymerizing actin filaments decreased predominantly the deep CSK stiffness. By contrast, an agent altering cell–matrix interactions affected essentially the cortical CSK stiffness. We concluded that partitioning the CSK within cortical and deep structures is largely consistent with their respective functional activities. © 2003 Biomedical Engineering Society. PAC2003: 8716Ka, 8716Ac, 8380Lz     

Thermoafferent signal processing in rats: an electrophysiological analysis of midbrain influences on thermoresponsive neurons in the ventrobasal thalamus

The influence of electrical midbrain stimulation on thalamic cells which respond to scrotal skin warming with steep increases in firing rate was studied in anaesthetized rats. Square-wave stimuli of 200 s duration and 30–250 A intensity at 15 Hz were applied in trains lasting about 1 min.At low scrotal temperatures stimulation of the nucleus raphe dorsalis, the adjacent central grey or the median raphe nucleus was nearly always followed by a rise in thalamic activity. Inhibition occurred only in 4 of 75 experiments. Often midbrain stimulation caused neuronal responses similar to those following scrotal warming. Single stimulation experiments and the combination of electrical stimulation and electrolytic lesions indicated local interactions between excitatory and inhibitory neuronal networks in midbrain. Poststimulus latencies revealed polysynaptic midbrain/thalamic connections. Direct projections with no more than a few synaptic interruptions were seen in about 10% of the experiments.It is concluded that medial midbrain neurons influence the transmission of peripheral thermal information to the specific thalamus and contribute to the typical switching form of thalamic responses to scrotal warming.This work was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich No. 114 BIONACH     

Changes in reactivity of neurons of the visual cortex under influence of the posterolateral hypothalamus and the nuclei of the midbrain raphe

An analysis of the influence of the posterolateral hypothalamus, which elicits positive reactions in behavioral testing, and of the midbrain raphe nuclei, on the plastic properties of the neurons of the visual cortex, was carried out in acute experimental conditions on diplacin-immobilized rabbits, based on a model of cortical trace processes. The different types of change in the reactivity of cortical cells under the influence of rhythmic sensory stimulation are described. The results of statistical analysis point to a dependence of hypothalamic and serotoninergic influences on the initial reaction of neurons to sensory stimulation. It is demonstrated that the plastic changes in the activity of cortical neurons reveal similar features under the influence both of the positive emotiogenic zone of the hypothalamus and of the midbrain raphe nuclei. Similar regularities are observed also in an analysis of the interaction of cortical neurons which were recorded in one microvolume identified by the method of cross-interval histograms.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 74, No. 5, pp. 617–624, May, 1988.     

Neurochemical Relationships in the Action of Opioid Analgesics on Cerebral Cortex

The experiments with unrestrained cats showed that opioid analgesics in near-analgesic doses decreased the amplitude of the primary test response recorded in the second sensorimotor zone of the cerebral cortex in 20-150-msec interval between the stimuli applied to thalamocortical fibers radiating from thalamic n. VPL. Application of test substances affecting certain neurotransmitter processes and microionophoretic application of drugs and neurotransmitters to cortical neurons showed that the inhibitory effect of opioid analgesics on cerebral cortex is probably realized through GABA-, serotonin-, -adreno-, and cholinergic structures. The excitatory amino acids are also involved into this process.     

Influence du réveil d'origine réticulaire sur l'étendue des champs visuels des neurones de la région genouillée chez le Chat avec cerveau intact ou avec cerveau isolé

Summary In alert cat, geniculate cells respond more strongly to visual stimulus when preceeded by somatic stimulation. Moreover, the somatic stimulation can enlarge the visual receptive field of these neurons which then even discharge when the light stimulus is applied outside and near to the border of the field as previously determined without any somatic stimulation.These modifications are partly explained by direct action following upon somatic stimulation of the reticular structures responsible for the arousal; indeed, in cerveau isolé cat, the size of the visual receptive fields increases during EEG activation caused by the reticular formation stimulation. On the other hand, no strong effet of somatic stimulation is observed in a cat the mesencephalic reticular formation of which was extensively destroyed. During arousal, the selective directionally cells also respond more vigorously to the moving spot.The visual threshold of suprageniculate cells appears to be increased in intact animal. But in cerveau isolé cat or in animal with destroyed mesencephalic reticular formation, the suprageniculate cells exhibit large receptive fields extending all over a half visual field, and they often respond to moving spot. During arousal, the firing rate upon visual stimulation is increased in the cerveau isolé cat; in the cat the reticular formation of which was destroyed, no strong effect of the somatic stimulation is observed.

     

Responses of cat ventroposterolateral thalamic neurons to vibrotactile stimulation of forelimb footpads

Summary Responses of neurons in the ventroposterolateral nucleus of the thalamus to vibration applied to the forelimb footpads were analyzed in anesthetized cats in order to describe the signalling properties of thalamic neurons that received input from the different classes of tactile afferents innervating the glabrous skin of the distal forelimb. Seventy-six thalamic neurons, the majority of which (60 of 76) were positively identified as thalamocortical projection neurons, were classified into two broad groups according to their responses to 1-s step indentations of the skin. A minority (24%) comprised neurons that had slowly adapting (SA) responses, whereas the remainder (76%), the dynamically sensitive neurons, had transient responses to the onset and offset phase of the step and were further classified according to their sensitivity to cutaneous vibrotactile stimuli into those activated by low-frequency vibration (rapidly adapting, RA, neurons) and those activated by high frequencies (Pacinian afferent, PC, neurons). Thalamic RA neurons displayed phaselocked responses to vibration at frequencies up to 100 Hz, while PC neurons displayed phaselocked responses to vibration up to 400–500 Hz. Thalamic SA neurons varied in their responses to vibrotactile stimuli; half were most sensitive to vibration frquencies of 50 Hz or less, while the others responded over a broader range of frequencies. Although three major classes of footpad-related thalamic neurons were identified, there was evidence of convergent input to a small proportion of them. The study demonstrates that thalamic neurons have the capacity for responding to cutaneous vibration with phaselocked, patterned impulse trains, which would enable them to encode information about vibrotactile frequencies up to 300 Hz.     

Neurochemical mechanisms of the involvement of cortical sensorimotor neurons in alimentary and orientational behavior

The object of these experiments was the study of the features of the neurochemical mechanisms of the involvement of individual neurons of the sensorimotor cortex of the rabbit brain the orienting reaction and the goal-oriented alimentary behavior elicited by stimulation of the hunger center of the lateral hypothalamus using electrical current of varying intensity. It is demonstrated that the neurotransmitters acetylcholine and norepinephrine, in approximately equal percentages, reorganize the reaction of neurons at the subthreshold as much as at the threshold level of stimulation. The microiontophoretic application to cortical sensorimotor neurons of the protein synthesis blocker, cycloheximide, also elicits alterations in their reactions to threshold and subthreshold stimulation of the lateral hypothalamus which are apparently linked to the suppression of synthesis of neuropeptides specific to both behaviors. It is proposed that the orienting, and especially the alimentary, motivational reactions are achieved by the activation of the synthesis of specific peptide molecules in the cortical sensorimotor neurons, which in fact may induce a change in their sensitivity to neurotransmitters.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 70, No. 9, pp. 1311–1315, September, 1984.     

Präzisierung der Reizwirkung mittelfrequenter Wechselströme

Zusammenfassung Bei der Mittelfrequenz-Impuls-Reizung ist streng darauf zu achten, daß keine polaritären Reizkomponenten auftreten. Die diesbezügliche Kontrolle wird am besten mit Hilfe des Konvertibilitätstestes vorgenommen, d. h., es darf beim Vertauschen der Zuführungen zu den Reizelektroden weder die Reizschwelle bzw. die Größe des kollektiven Reizerfolges noch dessen Latenzzeit eine signifikante Änderung erfahren. Auf diese Weise wird die Phasenunabhängigkeit des echten Mittelfrequenz-Reizeffektes nachgewiesen.Diesen Anforderungen entsprechen Mittelfrequenz-Impulse, deren Trägerfrequenz über einige wenige Perioden sich aufschaukelt und ebenso wieder abklingt. Demgegenüber sind Mittelfrequenz-Stromstöße mit phasenstarrem Einsatz und Ende nicht unbedingt frei von polaritären Ein- bzw. Ausschalt-effekten, indem sowohl die erste als auch die letzte Trägerperiode einen polaritären Wechselimpuls-Reizeffekt ergeben kann, je nach Phasenlage bezogen auf die wirksame Reizelektrode und Art der Ansprechbarkeit des Reizobjektes (Nerv) auf entsprechend kurze gleitspiegelsymmetrische Wechselimpulse. Für eine echte Mittelfrequenz-Stromstoß-Reizung ist demnach ebenfalls ein Aufschaukeln und Abklingen der Trägerfrequenz über einige wenige Perioden erforderlich.Es besteht ein prinzipieller Unterschied zwischen der echten Mittelfrequenz-Reizung, die phasen -bzw. periodenunabhängig ist und schon früher als apolaritär bezeichnet wurde, und der konventionellen polaritären Reizung, die als polaritäre Komplikation der Mittelfrequenz-Reizung auftreten kann.Diese Präzisierung der Reizwirkung mittelfrequenter Wechselströme wurde angeregt durch zwei im Text erwähnte Publikationen, in denen in keineswegs überzeugender Weise versucht wird, die Mittelfrequenz-Reizung letzten Endes auf das polare Gesetz der Erregung zurückzuführen.

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Summary The particular excitatory action exerted by middle-frequency alternating current can only be revealed if care is taken to eliminate the occurrence of so-called polarity effects. Such effects are produced by the short alternating impulses represented by the first and the last period of a middle-frequency current pulse and are based on the polar law of excitation.In order to prevent such polarity intrusions, it is necessary to increase and decrease the amplitude of the middle-frequency current pulses over a few carrierperiods, or, to use amplitude-modulated middle-frequency impulses of variable shape and duration of envelope.A true middle-frequency excitatory effect is easily demonstrated by resorting to the convertibility test. It will then become evident that stimulation threshold, magnitude as well as latency of response do not change during reversal of the stimulating poles. This means, that no significant phase change of the response with regard to the carrier-frequency occurs when the leads to the stimulating electrodes are commuted, and that, as a result, true middle-frequency effects do not depend upon one particular catelectrotonic variation among the carrier-periods of a middle-frequency current pulse.It can thus be concluded that a fundamental difference exists between true middle-frequency stimulation, which is based on a non-polarity or apolarity principle, and the conventional stimulation of the polar or polarity type.This paper has been written in the hope of dispelling some errors of interpretation (discussed in the text) tending to ascribe the excitatory effects of middle-frequency impulse stimulation to the classical polar law of excitation.