Dipole theory of interactions of nerve signals.
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Electric Stimulation↗
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The ability of the mesocortical dopamine system to operate in distinct temporal modes.
BACKGROUND: This review discusses evidence that cells in the mesocortical dopamine (DA) system influence information processing in target areas across three distinct temporal domains. DISCUSSIONS: Phasic bursting of midbrain DA neurons may provide temporally precise information about the mismatch between expected and actual rewards (prediction errors) that has been hypothesized to serve as a learning signal in efferent regions. However, because DA acts as a relatively slow modulator of cortical neurotransmission, it is unclear whether DA can indeed act to precisely transmit prediction errors to prefrontal cortex (PFC). In light of recent physiological and anatomical evidence, we propose that corelease of glutamate from DA and/or non-DA neurons in the VTA could serve to transmit this temporally precise signal. In contrast, DA acts in a protracted manner to provide spatially and temporally diffuse modulation of PFC pyramidal neurons and interneurons. This modulation occurs first via a relatively rapid depolarization of fast-spiking interneurons that acts on the order of seconds. This is followed by a more protracted modulation of a variety of other ionic currents on timescales of minutes to hours, which may bias the manner in which cortical networks process information. However, the prolonged actions of DA may be curtailed by counteracting influences, which likely include opposing actions at D1 and D2-like receptors that have been shown to be time- and concentration-dependent. In this way, the mesocortical DA system optimizes the characteristics of glutamate, GABA, and DA neurotransmission both within the midbrain and cortex to communicate temporally precise information and to modulate network activity patterns on prolonged timescales.
Animals↗
Modulation of heteronymous reflexes from ankle dorsiflexors to hamstring muscles during human walking.
In 16 human subjects, stimulation of the common peroneal nerve (CPN) was applied during walking and standing. The effect of the stimulation was evaluated from the rectified and averaged biceps femoris (BF) electromyographic (EMG) activity. In the swing phase of walking, the CPN stimulation evoked a suppression in the BF EMG in 12 of the subjects. In the early stance phase, the suppression was replaced by facilitation at a similar latency in 9 of the subjects. Of the other 3 subjects, in whom a suppression was observed during swing, a decrease in the suppression was observed in the stance phase in two of them. During a voluntary co-contraction of BF and tibialis anterior while standing, a suppression similar to that observed in the swing phase was observed. The thresholds of the suppression and facilitation were identical, suggesting that afferents of similar diameter were responsible. Cutaneous stimuli, which mimicked the sensation evoked by the CPN stimulation, but without activation of muscle afferents, did not produce similar effects in the BF EMG activity. It is suggested that the observed response and reflex reversal may reflect opening of an excitatory group I pathway in the early stance phase of walking with a concomitant shut-down of heteronymous group I inhibition.
Adolescent↗
Non-nociceptive upper limb afferents modulate masseter muscle EMG activity in man.
Recent electrophysiological data obtained in anaesthetized rats evidenced jaw muscle excitatory responses to the electrical stimulation of type II limb somatosensory afferents. In the present work, we describe an inhibitory reflex evoked in human masseter muscles by stimulation of non-nociceptive fibres travelling in the median and radial nerves (MED and RAD, respectively). Eighteen healthy volunteers participated in the study. Subjects were seated on a comfortable chair, with the complex head-mandible-neck-trunk and the limbs securely fixed to the chair. Attempts were made to minimize possible interferences due to the activation of afferents other than the stimulated ones. The subjects were instructed to contract masseter muscles at a submaximal level and to maintain a stable level of muscle contraction during all trials. EMG voluntary activity was recorded from both masseter muscles by means of coaxial needle electrodes before and after the electrical stimulation of MED and/or RAD at intensities below pain threshold. In all subjects, MED stimulation induced bilaterally a marked depression of masseter EMG activity, which occurred at a latency of 23.6 +/- 2.1 ms and lasted 27.8 +/- 6.6 ms. RAD stimulation also induced a marked reduction in masseter EMG activity, but this effect was clearly observed in 9 out of 18 subjects, and it showed latency (30.2 +/- 7.5 ms) and duration (44.9 +/- 5.4 ms) significantly longer in comparison with the MED-induced effect. All subjects exhibited the inhibitory period in masseter EMG following the simultaneous stimulation of both nerves; this one appeared at a latency not significantly different (25.3 +/- 5.9 ms) and lasted much more (37.4 +/ - 8.2 ms) than EMG depression evoked by MED stimulation. The duration of masseter muscle inhibition, induced by MED and/or RAD stimulation, was inversely related to the level of EMG activity, while latency was not related to it. Significant increases in the inhibitory period duration were also observed by increasing stimulus intensity, within a subthreshold range for the activation of nociceptive fibres. In all cases, the inhibitory period was followed by a later excitatory rebound activity, whose latency and duration depended on the duration of the preceding EMG inhibition and on the background level of masseter activation. In conclusion, results evidenced that the activation of arm somatosensory fibres modulates masseter muscle activity in normal man. This might lead to a coordination between limb and masticatory muscle activity, which is required in several complex motor acts.
Action Potentials↗
Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability.
Weak transcranial direct current stimulation (tDCS) can induce long lasting changes in cortical excitability. In the present study we asked whether tDCS applied to the left primary motor cortex (M1) also produces aftereffects distant from the site of the stimulating electrodes. We therefore tested corticospinal excitability in the left and the right M1 and transcallosal excitability between the two cortices using transcranial magnetic stimulation (TMS) before and after applying tDCS. Eight healthy subjects received 10 min of anodal or cathodal tDCS (1 mA) to the left M1. We examined the amplitude of contralateral motor evoked potentials (MEPs) and the onset latency and duration of transcallosal inhibition with single pulse TMS. MEPs evoked from the tDCS stimulated (left) M1 were increased by 32% after anodal and decreased by 27% after cathodal tDCS, while transcallosal inhibition evoked from the left M1 remained unchanged. The effect on MEPs evoked from the left M1 lasted longer for cathodal than for anodal tDCS. MEPs evoked from the right M1 were unchanged whilst the duration of transcallosal inhibition evoked from the right M1 was shortened after cathodal tDCS and prolonged after anodal tDCS. The duration of transcallosal inhibition returned to control values before the effect on the MEPs from the left M1 had recovered. These findings are compatible with the idea that tDCS-induced aftereffects in the cortical motor system are limited to the stimulated hemisphere, and that tDCS not only affects corticospinal circuits involved in producing MEPs but also inhibitory interneurons mediating transcallosal inhibition from the contralateral hemisphere.
Adult↗
Propagation velocity and triggering threshold of retinal spreading depression are not correlated.
Spreading depression (SD) is a pronounced but transient disturbance of cellular homeostasis in the neuropil of the central nervous system which spreads in a wave-like manner across the tissue. At the wavefront the cells depolarize and a distinct ion redistribution between intra- and extracellular space is observed. In the aftermath of SD the recovering tissue is refractory: during an early absolute refractory period no further SD can be triggered, during the subsequent relative refractory period SD waves spread at lower velocity than usual. In this paper we shall examine the influence of temperature on SD triggering and on SD propagation in the chicken retina (retinal spreading depression, rSD) and we shall examine rSD triggering and rSD propagation in the refractory period. It will be shown that cooling decreases the threshold of rSD triggering, i.e. it becomes easier to trigger rSD when the temperature is reduced. At the same time cooling slows rSD propagation. In contrast, during the relative refractory period triggering rSD is more difficult than usual while rSD propagation is also slowed. These results demonstrate that the propagation velocity of rSD is not correlated with the triggering threshold. In particular, the propagation velocity of rSD must not be used to predict the influence of experimental conditions on the triggering threshold.
Animals↗
Changes in the centrifugal gating effect on somatosensory evoked potentials depending on the level of contractile force.
In this study, we investigated the somatosensory evoked potentials (SEPs) during the preparatory period of self-initiated plantar flexion at different force levels of muscle contraction and elucidated the mechanism behind the centrifugal gating effect on somatosensory information processing. We recorded SEPs following stimulation of the tibial nerve at the popliteal fossa during the preparatory period of a 20% maximal voluntary contraction (MVC) and 50% MVC. The preparatory period was divided into two sub-periods based on the components of movement-related cortical potentials, the negative slope (NS sub-period) and the Bereitschaftspotential (BP sub-period). The subjects were instructed to concentrate on the movement and not to pay attention to the continuous electrical stimulation. Pre-movement SEPs were averaged separately during the two sub-periods under each MVC condition. The mean amplitudes of BP and NS were larger during the 50% MVC than the 20% MVC. As for the components of SEPs, during the NS sub-period the amplitude of P30 under the 50% MVC and N40 under both conditions were significantly smaller than that in the stationary sequence, and N40 amplitude was significantly smaller during the 50% MVC than the 20% MVC. During the BP sub-period, the amplitude of P30 and N40 during the 50% MVC was significantly smaller than during the stationary sequence, while it was not significantly different between the 20% and 50% MVCs. In conclusion, the extent of the centrifugal gating effect on SEPs was dependent on the activities of motor-related areas, which generated the NS and BP.
Adult↗
Effects of paired pulse TMS of primary somatosensory cortex on perception of a peripheral electrical stimulus.
Paired pulse transcranial magnetic stimulation (paired TMS) was introduced to study local inhibitory or facilitatory intracortical circuits of the primary motor cortex. However, similar interactions can be shown in other areas of cortex. The current study tests the effects of paired pulse TMS of the right primary somatosensory cortex (S1) on the sensory perception of electrical stimuli applied on the contralateral thumb finger. In the main experiment a subthreshold conditioning stimulus (CS) preceded a suprathreshold test stimulus (TS) at different inter-stimulus intervals. We found that perception of a peripheral electrical stimulus was markedly attenuated by paired TMS in comparison to single pulse TMS when the ISIs was 10 or 15 ms, while there was no effect at shorter ISIs. There was no additional effect of the CS pulse if the intensity of the TS was subthreshold. In control experiments we observed that the effect vanished when the delay between the peripheral stimulus and the TS was 10 or 30 ms rather than 20 ms or if the pairs of pulses were applied over the vertex rather than the hand area. Furthermore, there was no change at longer ISIs when paired TMS was applied over the posterior parietal cortex of the same hemisphere. These results demonstrate that paired pulse TMS is able to probe intracortical circuits in S1 and that the intrinsic properties of these circuits differ even between closely adjacent areas of the cortex.
Adult↗
Modulation of presynaptic inhibition of la afferents during voluntary wrist flexion and extension in man.
Changes in presynaptic inhibition of Ia terminals directed to flexor carpi radialis (FCR) motoneurones (MNs) were investigated in normal human subjects at rest and during voluntary wrist flexion and extension. To that end, two independent methods were used: (1) the radial-induced D1 inhibition of the FCR H reflex, which assesses the excitability of PAD (primary afferent depolarisation) interneurones controlling presynaptic inhibition of Ia terminals mediating the afferent volley of the FCR H reflex; and (2) the heteronymous monosynaptic Ia facilitation induced in the FCR H reflex by intrinsic muscle Ia afferent stimulation, which assesses the ongoing presynaptic inhibition of Ia terminals. With respect to results at rest, it was found that at the onset of (and during tonic) voluntary wrist flexion, D1 inhibition was reduced and heteronymous monosynaptic Ia facilitation was increased. This suggests that, as in the lower limb, presynaptic inhibition is decreased on Ia terminals projecting to MNs involved in the voluntary contraction. In contrast with results observed in the lower limb, presynaptic inhibition of Ia terminals to FCR MNs was also found to be reduced at the onset of a voluntary contraction involving the antagonistic wrist extensors, suggesting that presynaptic inhibition of Ia terminals projecting to wrist flexors and extensors might be mediated through the same subsets of PAD interneurones. This is in keeping with other features showing that the organisation of reflex pathways between wrist flexors and extensors differs from that observed at other (elbow, ankle) joints.
Electric Stimulation↗
Symmetric facilitation between motor cortices during contraction of ipsilateral hand muscles.
Using transcranial magnetic stimulation (TMS) over the contralateral motor cortex, motor evoked potentials (MEPs) were recorded from resting abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles of eight subjects while they either rested or produced one of six levels of force with the APB ipsilateral to the TMS. F-waves were recorded from each APB at rest in response to median nerve stimulation while subjects either rested or produced one of two levels of force with their contralateral APB. Contraction of the APB ipsilateral to TMS produced facilitation of the MEPs recorded from resting APB and FDI muscles contralateral to TMS but did not modulate F-wave amplitude. Negligible asymmetries in MEP facilitation were observed between dominant and subdominant hands. These results suggest that facilitation arising from isometric contraction of ipsilateral hand muscles occurs primarily at supraspinal levels, and this occurs symmetrically between dominant and subdominant hemispheres.
Adult↗
Motor cortex excitability following short trains of repetitive magnetic stimuli.
Trains of repetitive transcranial magnetic stimuli (rTMS) appear to have effects on corticospinal excitability that outlast the duration of the train. In order to investigate the mechanism of this effect in more detail we applied short periods of rTMS consisting of up to 20 stimuli at 5 Hz, 10 Hz or 20 Hz (rTMS) to the motor cortex at an intensity equal to resting threshold in 11 healthy, relaxed subjects. Spinal excitability, as judged by effects on the H-reflex or on transcranial anodal facilitation of the H-reflex, was not affected by the rTMS. However, cortical excitability, as judged by the effect on the size of EMG responses evoked by a suprathreshold TMS pulse, was decreased for up to 1 s after the end of rTMS. Post-train suppression was more powerful following longer trains or higher frequencies of rTMS. The predominant suppression contrasts with previous reports of facilitation, particularly after high-frequency rTMS. A second set of experiments, however, showed that this could be converted into facilitation if the intensity of rTMS was increased. We conclude that the after-effects of rTMS depend on its frequency, intensity and duration. The results are consistent with a model in which inhibition and facilitation build up gradually during the course of a conditioning train. Inhibition reaches its maximum effect after only a small number of stimuli, whereas facilitation takes longer. The threshold for evoking inhibition is lower than that for facilitation. Thus if moderate intensities of conditioning train are applied, inhibition is predominant after short trains, whereas facilitation dominates after long trains.
Adult↗
Cutaneomotor integration in human hand motor areas: somatotopic effect and interaction of afferents.
The aim of this study was to elucidate sensorimotor integration in human hand motor areas, its time course, somatotopy and the interaction of sensory fields arising from two different fingers. We studied the influence of different intensities of electrical digital stimulation of two different fingers on motor-evoked potentials elicited in hand muscles by transcranial magnetic stimulation (TMS). Single conditioning electrical stimuli were applied to the right second (D2) and fifth fingers (D5) individually and also to both fingers (D2+D5) simultaneously in six normal volunteers. Magnetic tests, adjusted to produce a response in the abductor digiti minimi muscle of the right hand, were delivered using a circular and a focal coil. The digital stimuli were delivered to the finger at the sensory threshold (ST), at 3 and 5 times the ST, and over the pain threshold at interstimulus intervals (ISIs) ranging from 10 to 100 ms. In order to define the anatomical level of the sensorimotor interactions, the effect of the digital stimulation on TMS was compared to the effect on transcranial electrical stimulation. When the peripheral stimulation was delivered at the ST a small inhibitory effect was found only when stimulating both fingers. At 3 times the ST we detected a topographic distribution of motor-evoked potential inhibition, which partially disappeared at higher intensity (5 times the ST); two types of convergence effects took place at different ISIs. When conditioning stimuli were painful, somatotopy and convergence were lost. Sensorimotor integration shows somatotopy and interaction of afferents at different sites. The intensity of the conditioning stimulus plays an important role in topography and sensory convergence. The importance of these mechanisms in physiology and physiopathology is discussed.
Afferent Pathways↗
Changes in motor planning of feedforward postural responses of the trunk muscles in low back pain.
Changes in trunk muscle recruitment have been identified in people with low-back pain (LBP). These differences may be due to changes in the planning of the motor response or due to delayed transmission of the descending motor command in the nervous system. These two possibilities were investigated by comparison of the effect of task complexity on the feedforward postural response of the trunk muscles associated with rapid arm movement in people with and without LBP. Task complexity was increased by variation of the expectation for a command to either abduct or flex the upper limb. The onsets of electromyographic activity (EMG) of the abdominal and deltoid muscles were measured. In control subjects, while the reaction time of deltoid and the superficial abdominal muscles increased with task complexity, the reaction time of transversus abdominis (TrA) was constant. However, in subjects with LBP, the reaction time of TrA increased along with the other muscles as task complexity was increased. While inhibition of the descending motor command cannot be excluded, it is more likely that the change in recruitment of TrA represents a more complex change in organisation of the postural response.
Adaptation, Physiological↗
Motor cortex excitability in transient global amnesia.
OBJECTIVE: To investigate the physiology of motor cortical areas in patients with transient global amnesia (TGA). MATERIALS AND METHODS: We performed transcranial magnetic stimulation (TMS) and single photon emission computed tomography (SPECT) in 13 patients during and after the acute phase of a typical episode of TGA. Measures of cortical excitability included motor threshold (MT) to magnetic stimulation, cortical silent period (SP) duration and intracortical inhibition (ICI) using a paired-pulse TMS technique. RESULTS: We found thalamic hypoperfusion and an ipsilateral significantly decreased ICI during the acute phase of TGA. CONCLUSIONS: Reduced activity in inhibitory circuits may explain why PET studies of patients with TGA showed neocortical hypometabolism. Our findings are consistent with the hypothesis that frontal cortex dysfunction probably due to damage affecting the thalamocortical circuits may play an important role in the pathogenesis of the syndrome.
Adult↗
Global and local synchrony of coupled neurons in small-world networks.
Synchronous firing of neurons is thought to play important functional roles such as feature binding and switching of cognitive states. Although synchronization has mainly been investigated so far using model neurons with simple connection topology, real neural networks have more complex structures. Here we examine the behavior of pulse-coupled leaky integrate-and-fire neurons with various network structures. We first show that the dispersion of the number of connections for neurons influences dynamical behavior even if other major topological statistics are kept fixed. The rewiring probability parameter representing the randomness of networks bridges two spatially opposite frameworks: precise local synchrony and rough global synchrony. Finally, cooperation of the global connections and the local clustering property, which is prominent in small-world networks, forces synchrony of distant neuronal groups receiving coherent inputs.
Action Potentials↗
Inhibition modifies the effects of slow calcium-activated potassium channels on epileptiform activity in a neuronal network model.
Generation of epileptiform activity typically results from a change in the balance between network excitation and inhibition. Experimental evidence indicates that alterations of either synaptic activity or intrinsic membrane properties can produce increased network excitation. The slow Ca(2+)-activated K(+) currents (sI(AHP)) are important modulators of neuronal firing rate and excitability and have important established and potential roles in epileptogenesis. While the effects of changes in sI(AHP) on individual neuronal excitability are readily studied and well established, the effects of such changes on network behavior are less well known. The experiments here utilize a defined small network model of multicompartment pyramidal cells and an inhibitory interneuron to study the effects of changes in sI(AHP) on network behavior. The benefits of this model system include the ability to observe activity in all cells in a network and the effects of interactions of multiple simultaneous influences. In the model with no inhibitory interneuron, increasing sI(AHP) results in progressively decreasing burst activity. Adding an inhibitory interneuron changes the observed effects; at modest inhibitory strengths, increasing sI(AHP) in all network neurons actually results in increased network bursting (except at very high values). The duration of the burst activity is influenced by the length of delay in a feedback loop, with longer loops resulting in more prolonged bursting. These observations illustrate that the study of potential antiepileptogenic membrane effects must be extended to realistic networks. Network inhibition can dramatically alter the observations seen in pure excitatory networks.
Action Potentials↗
Nissen fundoplication has a vagolytic effect on the lower esophageal sphincter.
BACKGROUND: Laparoscopic Nissen fundoplication is an increasingly utilized option for the treatment of gastroesophageal reflux disease (GERD). However, many questions remain as to the mechanism by which this operation prevents GERD in those without hiatal hernias or incompetent lower esophageal sphincters (LES). It is known that these patients experience reflux due to excess transient lower esophageal sphincter relaxations (TLESR), inappropriate and short-lived relaxation of the LES and crural diaphragm. The purpose of this study was to determine if Nissen fundoplication affects the neural pathways involved in the TLESR reflex. METHODS: Five dogs were anesthetized and intubated. Both vagal nerves and the right phrenic nerve were isolated. A continuous water perfusion manometric catheter was situated at the LES. The nerves were then electrically stimulated and the resultant pressure at the LES measured at baseline, and during and after an open Nissen fundoplication. RESULTS: The mean LES pressures before dissection, after esophago-gastric mobilization, and after fundoplication were 47 +/- 13 mmHg, 21 +/- 9 mmHg, and 14 +/- 4 mmHg, respectively. All differences were significant. There was no change noted in LES pressure with stimulation of either or both of the phrenic nerves without concomitant vagal stimulation. CONCLUSION: Nissen fundoplication may prevent GERD in those without a hiatal hernia or incompetent LES by disrupting the efferent vagal fibers to the LES. Such fibers mediate TLESR which are responsible for GERD in these patients.
Animals↗
A novel Cx32 mutation causes X-linked Charcot-Marie-Tooth disease with brainstem involvement and brain magnetic resonance spectroscopy abnormalities.
The objective of this study was to study genetic and phenotypic features of a family with X-linked Charcot-Marie-Tooth consisting of a healthy father, affected mother, two affected sons and one healthy one. A detailed electrophysiological and neuroimaging study, along with sequencing of the Cx32 gene, was performed in all family members. A novel Cx32 123 G>C mutation, determining an aminoacid variation (Glu41Asp), was found in the mother and the affected sons. An alteration in brainstem evoked potentials was found in the mother and one affected son. The affected son, who underwent magnetic resonance imaging, showed symmetrical hyperintensities in paratrigonal white matter, not found in his heterozygous mother, while both subjects exhibited alterations in brain metabolite ratios derived from localised proton-magnetic resonance spectroscopy. These data extend previous findings about central nervous system involvement in Cx32 mutated subjects and further support a functional role of the protein expression in oligodendrocytes.
Adolescent↗