Stimulus intensity determines experience‐dependent modifications in neocortical neuron firing rates

Although subthreshold inputs of neocortical sensory neurons are broadly tuned, the spiking output is more restricted. These subthreshold inputs provide a substrate for stimulus intensity‐dependent changes their spiking output, as well as for experience‐dependent plasticity to alter firing properties. Here we investigated how different stimulus intensities modified the firing output of individual neurons in layer 2/3 of the mouse barrel cortex. Decreasing stimulus intensity over a 30‐fold range lowered the firing rates evoked by principal whisker stimulation and reduced the overall size of the responding ensemble in whisker‐undeprived animals. We then examined how these responses were changed after single‐whisker experience (SWE). After 7 days of SWE, the mean magnitude of response to spared whisker stimulation at the highest stimulus intensity was not altered. However, lower‐intensity whisker stimulation revealed a more than 10‐fold increase in mean firing output compared with control animals. Also, under control conditions, only ~15% of neurons showed any firing at low stimulus intensity, compared with more than 70% of neurons after SWE. However, response changes measured in the immediately surrounding representations were detected only for the highest stimulus intensity. Overall, these data showed that the measurement of experience‐dependent changes in the spike output of neocortical neurons was highly dependent upon stimulus intensity.     

Crossed and direct effects of digital nerves stimulation on motor evoked potential: a study with magnetic brain stimulation

We studied the influence of contralateral and ipsilateral cutaneous digital nerve stimulation on motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation (TMS). We tested the effect of different magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE) muscles of the right hand while an electrical conditioning stimulus was delivered to the second finger of the same hand with an intensity four times above the sensory threshold. Amplitude decrement of conditioned MEPs as a function of magnetic stimulus intensity was observed. The lowest TMS stimulus intensity produced the largest decrease in conditioned MEPs. Moreover, we investigated the effects of ipsilateral and contralateral electrical digital stimulation on MEPs elicited in the right TE and biceps muscle using an intensity 10% above the threshold. Marked MEP inhibition in TE muscles following both ipsilateral and contralateral digital stimulation is the main finding of this study. The decrease in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of unconditioned MEP amplitude with the circular coil and 30% with the focal coil. The amplitude of conditioned MEPs to contralateral digital stimulation showed a decrease of 60% with the circular coil and more than 50% with the focal coil. The onset of the inhibitory effect of contralateral stimulation using the focal coil occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP inhibition was observed when recording from proximal muscles. Ipsilateral and contralateral digital stimulation had no effect on F wave at appropriate interstimulus intervals, where the main MEP suppression was noted. We stress the importance of selecting an appropriate test stimulus intensity to evaluate MEP inhibition by digital nerves stimulation. Spinal and cortical sites of sensorimotor integration are adduced to explain the direct and crossed MEP inhibition following digital nerves stimulation.     

The effect of repetitive transcranial magnetic stimulation on long-term potentiation in rat hippocampus depends on stimulus intensity

We investigated the effect of repetitive transcranial magnetic stimulation (rTMS) on long-term potentiation (LTP) in the rat hippocampus. Rats were magnetically stimulated at a rate of 1000 pulses/day for 7 days by a round coil, in which the peak magnetic fields at the center of the coil were 0.75 and 1.00 T. LTP enhancement was observed only in the 0.75-T rTMS group, while no change was observed in the 1.00-T rTMS group. These results suggest that the effect of rTMS on LTP depends on the stimulus intensity.     

Transcranial magnetic double stimulation: influence of the intensity of the conditioning stimulus

The influence of stimulus parameters on compound muscle potentials evoked by transcranial magnetic double stimulation was systematically investigated. Two magnetic stimulators were discharged via a figure-of-eight-shaped magnetic coil (outer diameter of each circular coil, 7 cm) over the left hemisphere, 6 cm lateral to Cz, using a Bistim interface. Recordings were made from the right first dorsal interosseus muscle. In experiment I, in 12 healthy volunteers the intensity of the conditioning subthreshold stimulus was varied from 0 to 100% of the relaxed motor threshold at an interstimulus interval of 1 ms. In experiment II, interstimulus intervals of 1, 3 and 5 ms were used to investigate the effect of conditioning stimuli of 3 fixed intensities. Maximal reduction of the amplitude of motor evoked potentials was found at a conditioning stimulus intensity of 65% of the relaxed motor threshold (and at an interstimulus interval of 1 ms). Because intensities of the conditioning stimulus higher than 65% reduced amplitudes of motor evoked potentials less effectively than at this intensity, refractoriness of pyramidal neurons can be ruled out as the main mechanism contributing to the observed inhibition. Activation of inhibitory interneurons by intensities lower than is necessary to activate pyramidal neurons is discussed as a possible mechanism for the inhibitory effects evoked by transcranial magnetic stimulation.     

Afferent excitation of human motor cortex as revealed by enhancement of direct cortico-spinal actions on motoneurones

Changes in motor cortex excitability induced by somatosensory afferences were evaluated in 5 subjects by testing how the short-latency cortico-spinal effects evoked by transcranial magnetic stimulation in flexor carpi radialis (FCR) motoneurones were influenced by volleys in median nerve afferent fibres. Transcranial magnetic stimulation induced two facilitatory peaks on FCR H reflex, the first at a conditioning-test interval of about −3 msec and the second at 0 msec, separated by a phase of inhibition. If an electric shock to the median nerve at the wrist, 0.8-1 × motor threshold (MT) for thenar muscles, preceded the cortical stimulus by 18–25 msec, an increase in size of both facilitatory peaks was observed. The increase was partly due to a direct action of the median nerve volley on motoneurones. When this contribution was subtracted, two peaks of additional facilitation resulted as the effect of combined conditioning. Additional facilitation was present even during the short-lasting phase ascribed to monosynaptic cortico-spinal excitation of motoneurones, i.e., the first millisecond of the earliest facilitatory peak. This result indicates that cortical responsiveness to magnetic stimulation had been enhanced by the peripheral stimulus. The time course of the excitability changes in motor cortex was compared with the cortical somatosensory evoked potentials (SEPs) induced by the same peripheral stimulus. Additional facilitation was present immediately after the N20 peak of SEPs and lasted 8–10 msec. Additional facilitation had the same threshold as N20 (0.6 × MT) and grew in parallel with it when grading the afferent stimulus up to 1 MT.     

Acute effects of alcohol on hemodynamic changes during visual stimulation assessed using 24-channel near-infrared spectroscopy

The purpose of this study was to evaluate the effects of alcohol on hemodynamic changes induced by visual stimulation. Ten healthy human subjects were examined using Optical Topography((R)) (Hitachi Medical Corporation: ETG-100). Each subject gradually drank 0.4 ml/kg alcohol over 10 min. Changes in oxy-hemoglobin (Hb), deoxy-Hb and total-Hb concentration were measured five times: 20 min before alcohol intake, immediately after alcohol intake, and at 20, 40 and 60 min after alcohol intake. A questionnaire was used to assess subjective feelings of alcohol. Blood-alcohol concentration (BAC) was estimated from ethanol concentration in expired air four times: immediately after alcohol intake and at 20, 40 and 60 min after alcohol intake. The visual stimulation tool was a checkerboard. It showed alternations of black and red patterns at a frequency of 8 Hz. The stimulus was displayed for 10 s after a rest of 30 s. The stimulus was repeated 10 times. Oxy-Hb concentration increased and deoxy-Hb concentration decreased during visual stimulation before and after alcohol intake, despite changes in the score of subjective feelings of alcohol and BAC. Alcohol intake does not significantly affect hemodynamic changes caused by visual stimulation in the visual cortex.     

Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation

We performed transcranial magnetic stimulation (TMS) to elucidate the D- and I-wave components comprising the motor evoked potentials (MEPs) elicited from the leg motor area, especially at near-threshold intensity. Recordings were made from the tibialis anterior muscle using needle electrodes. A figure-of-eight coil was placed so as to induce current in the brain in eight different directions, starting from the posterior-to-anterior direction and rotating it in 45 degrees steps. The latencies were compared with those evoked by transcranial electrical stimulation (TES) and TMS using a double cone coil. Although the latencies of MEPs ranged from D to I3 waves, the most prominent component evoked by TMS at near-threshold intensity represented the I1 wave. With the double cone coil, the elicited peaks always represented I1 waves, and D waves were evoked only at very high stimulus intensities, suggesting a high effectiveness of this coil in inducing I1 waves. Using the figure-of-eight coil, current flowing anteriorly or toward the hemisphere contralateral to the recorded muscle was more effective in eliciting large responses than current flowing posteriorly or toward the ipsilateral hemisphere. The effective directions induced I1 waves with the lowest threshold, whereas the less effective directions elicited I1 and I2 waves with a similar frequency. Higher stimulus intensities resulted in concomitant activation of D through I3 waves with increasing amount of D waves, but still the predominance of I1 waves was apparent. The amount of I waves, especially of I1 waves, was greater than predicted by the hypothesis that TMS over the leg motor area activates the output cells directly, but rather suggests predominant transsynaptic activation. The results accord with those of recent human epidural recordings.     

Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.     

Sympathetic skin responses: the influence of electrical stimulus intensity and habituation on the waveform

Abstract Repeated stimulation of the sympathetic skin response (SSR) causes habituation. The aim of this study was to determine the effects of electrical stimulus intensity on SSR in 40 healthy controls (mean age±SD, 28.0±6.7 years). Electrical stimuli at three intensities (5, 15 and 30 mA) were applied to the median nerve at the wrist in four consecutive sessions, after which a magnetic stimulus was applied to the neck. SSR were classified according to the proportion of positive (P) and negative (N) waveform components.Twentyfour subjects had both P and N waveforms. In the first session, 75% of these subjects had a P waveform, indicative of a greater SSR, in response to the 30 mA shock. In the progressive sessions, the SSR waveform was predominately negative (N waveform, session 2, 65%; session 3, 83%; session 4, 75% in response to 30 mA shock), indicating that the SSR was weaker as a result of habituation. There was no clear relationship between stimulus intensity and waveform type, indicating that SSR waveforms are more strongly influenced by habituation than stimulus intensity. However, there was a directly proportional relationship between stimulus intensity and amplitude of the SSR wave (F=70.9, P<0.0001, two-way repeated measure ANOVA), be it positive or negative. The relationship between stimulus intensity and amplitude persisted, even after habituation. Suddenly switching to a magnetic stimulus reverted the SSR wave back to positive (80%), indicating that habituation was rapidly reversible if stimulation of the SSR is altered.     

Comparison of descending volleys evoked by transcranial magnetic and electric stimulation in conscious humans

Objectives: The present experiments were designed to compare the understanding of the transcranial electric and magnetic stimulation of the human motorcortex.Methods: The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of two conscious human subjects. These volleys were termed D- and I waves, according to their latency. Magnetic stimulation was performed with a figure-of-eight coil held over the right motor cortex at the optimum scalp position, in order to elicit motor responses in the contralateral FDI using two different orientations over the motor strip. The induced current flowed either in a postero-anterior or in a latero-medial direction.Results: At active motor threshold intensity, the electric anodal stimulation evoked pure D activity. At this intensity, magnetic stimulation with the induced current flowing in a posterior-anterior direction evoked pure I₁ activity. When a latero-medial induced current was used, magnetic stimulation evoked both D and I₁ activity. Using electric anodal stimulation, at a stimulus intensity of 9% of the stimulator output above the active motor threshold (corresponding approximately to 1.5 active motor threshold), a small I₁ wave appeared only in subject 1. Using magnetic stimulation with a posterior-anterior induced current, at a stimulus intensity of 21% of maximum stimulator output above the active motor threshold (corresponding approximately to 1.8 times threshold in subject 1 and to two times threshold in subject 2), a small D wave appeared in subject 1 but not in subject 2.Conclusions: Present results demonstrate that, in conscious humans at threshold intensities, electric stimulation evokes D waves and magnetic stimulation (with a posterior-anterior induced current) evokes I waves, while magnetic stimulation (with a latero-medial induced current) evokes both activities.     

H-coil: Induced electric field properties and input/output curves on healthy volunteers,comparison with a standard figure-of-eight coil

ObjectiveTo acquire information about the physical properties and physiological effects of the H-coil.MethodsWe used a robotized system to measure the electric field (E-field) generated by a H-coil prototype and compared it with a standard figure-of-eight coil. To explore the physiological properties of the coils, input/output curves were recorded for the right abductor digiti minimi muscle (ADM) as target muscle. To explore focality of stimulation, simultaneous recordings were performed for the left ADM, right abductor pollicis brevis (APB), extensor digitorum communis (EDC) and biceps brachii (BB) muscles.ResultsPhysical measurements of the H-coil showed four potentially stimulating foci, generating different electric field intensities along two different spatial orientations. RMT was significantly lower for H-coil- as compared to figure-of-eight coil stimulation. When stimulation intensity for the input–output curve was determined by percent of maximum stimulator output, the H-coil produced larger MEPs in the right ADM, as compared to the figure-of-eight coil, due to the larger relative enhancement of stimulation intensity of the H-coil. When stimulation intensity was adjusted to RMT, MEPs elicited at the right ADM were larger for figure-of-eight coil than for H-coil stimulation, while this relation was reversed for distant non-target muscles, with low stimulation intensities. With high stimulation intensities, the H-coil elicited larger MEPs for all tested muscles. Onset latency of the MEPs was never shorter for H-coil than for figure-of-eight coil stimulation of the target muscles.ConclusionsThese results are in favor for a non-focal, but not deeper effect of the H-coil, as compared to a figure-of-eight coil.SignificanceThis is the first neurophysiological study exploring the focality and depth of stimulation delivered by the H-coil systematically in humans. We found no advantage of this coil with regard to depth of stimulation in comparison to the figure-of-eight coil. Future studies have to show if the non-focality of this coil differs relevantly from that of other non-focal coils, e.g. the round coil.     

The effects of pulse configuration on magnetic stimulation.

A study is presented in which the authors have examined the effects of pulse configuration, stimulation intensity, and coil current direction during magnetic stimulation. Using figure-8 and circular coils, the median nerve was stimulated at the cubital fossa and at the wrist of 10 healthy volunteers, and the response amplitude and site of stimulation were determined. The key findings of this study are in agreement with other researchers' findings and confirm that biphasic stimulating pulses produce significantly higher M-wave amplitudes than monophasic stimulating pulses for the same stimulus intensity. Mean response amplitudes for biphasic stimuli applied by both coils at the elbow and wrist are consistently higher for the normal current direction. Mean response amplitudes for monophasic pulses are almost always higher for reversed currents. The site for effective stimulation (the position of the virtual cathode) cannot be defined within a fixed distance from the center of the coil (3 to 4 cm), as has been suggested by other researchers, but was found to vary depending on the coil current amplitude and direction as well as the degree of inhomogeneity of the tissues surrounding the nerve. There is a statistically significant relationship between virtual cathode shift and stimulus intensity for biphasic and monophasic pulses. Reversing the coil current direction has no statistically significant effect on the virtual cathode position. Virtual cathode shifts can be measured for biphasic and monophasic stimulations using a figure-8 coil at the wrist and the elbow. However, such a shift is difficult to determine with a circular coil.     

Reliability of a new measure of H-reflex excitability.

OBJECTIVE: This study examined the intraclass reliability of different measures extracted from Hoffmann reflex (H-reflex) stimulus-response curve that are used to assess neuromuscular excitability. The following measures were compared: (1) the peak-to-peak amplitude of the H-reflex at a stimulus intensity associated with 5% of the maximum M-wave; (2) the slope of the regression line of the H-reflex stimulus-response curve; and (3) the peak of the first derivative of the H-reflex stimulus-response curve, a new measure introduced in this paper. METHODS: The H-reflex was elicited in the soleus for 24 subjects (12 males and 12 females) on 5 separate days. Vibration was applied to the Achilles tendon prior to stimulation to test the sensitivity of the measures on test day 4. The stimulus intensity was gradually increased from below the threshold for an H-reflex response to above the maximum M-wave (Mmax) response. The means of 5 evoked potentials at each intensity level were used to create both the H-reflex and M-wave stimulus-response curves for each subject across test days. Determination of reliability involves the consideration of both the stability and consistency of the measures. A repeated measures analysis of variance evaluated the stability of the group means across test sessions. The consistency of scores within individuals was determined by calculating the intraclass correlation coefficient (ICC). Calculation of the 95% confidence interval of estimation was used to assess significant differences between ICCs. RESULTS: The H-reflex measures were both stable and consistent across the first 3 test days. Achilles tendon vibration resulted in a profound reduction (59-70%) on test day 4, and then there was a return to baseline levels on test day 5. The ICC for H-reflex at a stimulus intensity associated with 5% of the maximum M-wave was 0.85. The ICC for the slope of the regression line of the H-reflex stimulus-response curve was 0.79, while it was 0.89 for the peak of the first derivative of the H-reflex stimulus-response curve. However, there was no statistical significance (P>0.05) between the 3 EMG measures of the H-reflex arc. Maximum M-wave amplitude had an ICC of 0.96 attesting to careful methodological controls. CONCLUSIONS: The peak of the first derivative of the H-reflex stimulus-response curve was shown to have comparable sensitivity and reliability as other more established measures. SIGNIFICANCE: The first derivative of the H-reflex stimulus-response curve provides the rate of change, rather than amplitude, making it a robust measure of reflex arc excitability. The higher ICC for the first derivative offers greater statistical power, which is of practical significance.     

Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity.

We studied the effects of coil orientation, stimulus intensity, and shape of the induced current pulse on the amplitudes of motor evoked potentials in the left abductor pollicis brevis of 10 normal adults who had transcranial magnetic stimulation. The optimal direction of currents induced in the brain is approximately perpendicular to the central sulcus, flowing diagonally from back to front. The most effective coil orientation depends on the shape of the induced current pulse and, when the first and second phases of the pulse are of similar size, also on the intensity of stimulation. Optimal mapping of the human motor cortex with magnetic stimulation requires knowledge of the influences of all these factors.     

Non-linear input-output properties of the cortical networks mediating TMS-induced short-interval intracortical inhibition in humans

The effects of transcranial magnetic stimulation (TMS) on post-discharge histograms of single motor units in the first dorsal interosseous have been tested to estimate the input-output properties of cortical network-mediating short-interval intracortical inhibition (SICI) to pyramidal cells of the human primary motor cortex. SICI was studied using the paired pulse paradigm (2-ms interval): test TMS intensity was varied to evoke peaks of different size in post-discharge histograms, reflecting the corticospinal excitatory post-synaptic potential in the relevant spinal motoneuron, and conditioning TMS intensity was constant (0.6 × the resting motor threshold). Navigated brain stimulation was used to monitor the coil position. A linear relationship was observed between test peak size and test TMS intensity, reflecting linear summation of excitatory inputs induced by TMS. SICI was estimated using the difference between conditioned (produced by the paired pulses) and test peaks (produced by the isolated test pulse). Although the conditioning intensity (activating cortical inhibitory interneurons mediating SICI) was kept constant throughout the experiments, the level of SICI changed with the test peak size, in a non-linear fashion, suggesting that low-threshold cortical neurons (excitatory interneurons/pyramidal cells) are less sensitive to SICI than those of higher threshold. These findings provide the first experimental evidence, under physiological conditions, for non-linear input/output properties of a complex cortical network. Consequently, changes in the recruitment gain of cortical inhibitory interneurons can greatly modify the excitability of pyramidal cells and their response to afferent inputs.     

The timing of galvanic vestibular stimulation affects responses to platform translation

We compared the effects of galvanic vestibular stimulation applied at 0, 0.5, 1.5 and 2.5 s prior to a backward platform translation on postural responses. The effect of the galvanic stimulation was largest on the final equilibrium position of the center of pressure (CoP). The largest effects occurred for the 0.5 and 0-s pre-period, when the dynamic CoP pressure changes in response to both the galvanic stimulus and the platform translation coincided. The shift in the final equilibrium position was also larger than the sum of the shifts for the galvanic stimulus and the platform translation alone for the 0.5 and 0-s pre-periods. The initial rate of change of the CoP response to the platform translation was not significantly affected in any condition. Changes in the peak CoP position could be accounted for by local interaction of CoP velocity changes induced by the galvanic and translation responses alone, but the changes in final equilibrium position could only be accounted for by a change in global body orientation. These findings suggest that the contribution of vestibulospinal information is greatest during the dynamic phase of the postural response, and that the vestibular system contributes most to the later components of the postural response, particularly to the final equilibrium position. These findings suggest that a nonlinear interaction between the vestibular signal induced by the galvanic current and the sensory stimuli produced by the platform translation occurs when the two stimuli are presented within 1 s, during the dynamic phase of the postural response to the galvanic stimulus. When presented at greater separations in time, the stimuli appear to be treated as independent events, such that no interaction occurs.     

Normal variability of the brain-stem auditory evoked response in young and old adult subjects.

The brain-stem auditory evoked response was studied under three combinations of intensity and rate of click stimulation in 25 young and 25 old adult subjects. The responses show a great intra and inter subject variability. Waves 1, 3 and 5 are constant and reproducible markers of the response while waves 2, 4, 6, and 7 are variable and frequently asymmetrical or absent. Wave peak latencies increase with an increase in stimulation rate, a decrease in stimulus intensity and an increase in age. Interpeak conduction times, except those involving wave 2, are unaffected by a change in stimulus intensity. Wave 1-3 time increases with an increase in stimulus rate and an increase in age while wave 3-5 time is not affected by any change in stimulus parameters or age. Wave amplitude alone is not a reliable measure of normality. Normal values for peak latencies, interpeak conduction times and interear symmetry are presented. One tailed 95 and 99% confidence intervals for normal interpeak conduction times are presented with appropriate corrections for stimulus rate used and patient age. No corrections need to be made for changes in stimulus intensity. This suggests that no correction is necessary when studying patients with conductive type hearing deficits. Laboratories using the same stimulation technique appear to produce equivalent normative conduction time values.     

Corticospinal volleys evoked by transcranial stimulation of the brain in conscious humans

Abstract

The direct recording in conscious humans of corticospinal volleys evoked by different magnetic and electric techniques of transcranial stimulation demonstrates that it is possible to activate neurones of the motor cortex in several different ways. Lateral electrical stimulation of the motor cortex preferentially activates the axons of corticospinal neurones in the subcortical white matter, and evokes a D-wave in pyramidal tract. The way of activation of corticospinal neurones using magnetic stimulation depends on the direction of the electrical current induced in the brain and on the shape of the coil. Monophasic magnetic stimulation with a focal figure-of-eight coil inducing posterior–anterior current in the brain activates corticospinal neurones trans-synaptically recruiting an I1-wave, with later I-waves appearing in sequence at higher intensities and a D-wave at very high intensities. If the induced current is rotated to the anterior–posterior direction late I-waves are preferentially recruited and when a D-wave is recruited, it has a later onset than the electrical D-wave, suggesting an activation nearer the cell body of the pyramidal neurones. A latero–medial induced current activates both corticospinal axons at the same point as electrical stimulation evoking a D wave and cortico–cortical axons evoking I-waves. A nonfocal large circular coil centered at the vertex is capable of activating pyramidal neurones both at the initial segment and transsynaptically evoking a D wave with a longer latency than the electrical D-wave and I-waves. Using a biphasic magnetic stimulation, both phases of the biphasic pulse are capable of activating descending motor output and the pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.     

Corticospinal volleys evoked by transcranial stimulation of the brain in conscious humans

The direct recording in conscious humans of corticospinal volleys evoked by different magnetic and electric techniques of transcranial stimulation demonstrates that it is possible to activate neurones of the motor cortex in several different ways. Lateral electrical stimulation of the motor cortex preferentially activates the axons of corticospinal neurones in the subcortical white matter, and evokes a D-wave in pyramidal tract. The way of activation of corticospinal neurones using magnetic stimulation depends on the direction of the electrical current induced in the brain and on the shape of the coil. Monophasic magnetic stimulation with a focal figure-of-eight coil inducing posterior-anterior current in the brain activates corticospinal neurones trans-synaptically recruiting an 11-wave, with later I-waves appearing in sequence at higher intensities and a D-wave at very high intensities. If the induced current is rotated to the anterior-posterior direction late I-waves are preferentially recruited and when a D-wave is recruited, it has a later onset than the electrical D-wave, suggesting an activation nearer the cell body of the pyramidal neurones. A latero-medial induced current activates both corticospinal axons at the same point as electrical stimulation evoking a D wave and cortico-cortical axons evoking I-waves. A nonfocal large circular coil centered at the vertex is capable of activating pyramidal neurones both at the initial segment and trans-synaptically evoking a D wave with a longer latency than the electrical D-wave and I-waves. Using a biphasic magnetic stimulation, both phases of the biphasic pulse are capable of activating descending motor output and the pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.     

Potentiation and depression following stimulus interruption in young rat hippocampi.

We examined the effect of stimulus interruption on dual component field EPSPs in the hippocampal CA1 region. Resuming test stimulation at 0.1 Hz after 10-60 min silent periods led to an increase of the response followed by a decline, involving AMPA and NMDA components to a similar extent. Similar changes were seen when stimulation was initially applied to a naive pathway or the stimulus strength was increased during an experiment. The potentiation of the AMPA response was largely blocked by prior application of the NMDA antagonist AP5 while application of this drug immediately after the initial potentiation prevented the following decline. The results demonstrate that NMDA-dependent potentiation and depression, possibly equivalent to LTP and LTD, can both be induced by the same, very low, test stimulus frequency. Furthermore, the depression appeared to have a longer time window for its induction than the potentiation.