Constant Stimulus Intensity Research Articles

Covariation of the amplitude and latency of motor evoked potentials elicited by transcranial magnetic stimulation in a resting hand muscle

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to study human neurophysiology. A single TMS pulse delivered to the primary motor cortex can elicit a motor evoked potential (MEP) in a target muscle. MEP amplitude is a measure of corticospinal excitability and MEP latency is a measure of the time taken for intracortical processing, corticofugal conduction, spinal processing, and neuromuscular transmission. Although MEP amplitude is known to vary across trials with constant stimulus intensity, little is known about MEP latency variation. To investigate MEP amplitude and latency variation at the individual level, we scored single-pulse MEP amplitude and latency in a resting hand muscle from two datasets. MEP latency varied from trial to trial in individual participants with a median range of 3.9 ms. Shorter MEP latencies were associated with larger MEP amplitudes for most individuals (median r = − 0.47), showing that latency and amplitude are jointly determined by the excitability of the corticospinal system when TMS is delivered. TMS delivered during heightened excitability could discharge a greater number of cortico-cortical and corticospinal cells, increasing the amplitude and, by recurrent activation of corticospinal cells, the number of descending indirect waves. An increase in the amplitude and number of indirect waves would progressively recruit larger spinal motor neurons with large-diameter fast-conducting fibers, which would shorten MEP onset latency and increase MEP amplitude. In addition to MEP amplitude variability, understanding MEP latency variability is important given that these parameters are used to help characterize pathophysiology of movement disorders.

Offset Analgesia and The Impact of Treatment with Oxycodone and Venlafaxine: A Placebo-Controlled, Randomized Trial in Healthy Volunteers.

Offset analgesia (OA) is a pain-modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a discrete decrease in stimulus temperature. The role of the opioidergic, serotonergic and noradrenergic systems on OA remains unclear. The aim of this study was to evaluate whether OA is modulated by an opioid (oxycodone) and a serotonin and noradrenaline reuptake inhibitor (venlafaxine) in terms of psychophysical assessments. In this randomized, double-blinded, placebo-controlled cross-over study, 20 healthy male participants (mean age: 24.6 ± 2.5 years) received 10 mg oxycodone, 37.5 mg venlafaxine or placebo twice daily for 5 days in three periods. OA was induced by noxious thermal stimulation on the forearm at baseline and last day of treatment. A control session of constant stimulus intensity was included for comparison. OA magnitude was unaffected by oxycodone and venlafaxine (p = 0.20 and p = 0.90, respectively). Oxycodone affected the control paradigm where a decreased rating of pain intensity was observed compared to placebo (p = 0.001). OA could not be modulated by oxycodone or venlafaxine and may be a robust phenomenon in healthy volunteers and not suitable for exploring pharmacological mechanisms of analgesia in human beings.

A task-independent neural representation of subjective certainty in visual perception.

Am I really sure? This is a question not only scientists ask themselves but practically everybody every day. A recent study provides behavioral evidence supporting the view that one’s subjective confidence in a decision (i.e., feeling sure that a decision is correct) is represented in a task-independent format. Previous neuroimaging studies identified neural correlates of decision confidence but whether or not these are task-dependent remains unclear. Here, combining two perceptual decision tasks with functional magnetic resonance imaging (fMRI), we provide neural evidence for a task-independent representation of degrees of subjective certainty (i.e., a neural representation of subjective certainty that remains constant across two visual tasks). Importantly, due to the constant stimulus-intensity used this result is independent of task-difficulty and stimulus properties. Our data provide strong evidence for a generic mechanism underlying the computation of subjective perceptual certainty in vision.

O3-D-10. Epidermal electrical stimulation-induced brain potential and sympathetic activity are diminished during expiration

To investigate the effects of respiration on pain sensations and brain or autonomic responses, we recorded EEG, sympathetic skin response (SSR), digital plethysmogram (DPG), subjective pain rating scale and exhaled CO 2 in 10 healthy volunteers. Electrical stimulation to the epidermis of the dorsum of the left hand was applied once or twice a minute when an exhaled CO 2 level exceeded 20 mmHg (early expiratory phase, EP) or when it fell below 20 mmHg (early inspiratory phase, IP). The stimulus intensity was set at the threshold of pain or 4 times the threshold in each subject. Despite constant stimulus intensity, subjective pain rating scales fluctuated between EP and IP. In either stimulus intensity, EP stimulation produced weaker pain feeling compared to IP stimulation. The mean amplitudes of N1/P1 in the pain-related potentials and SSR were smaller at EP stimulation than IP stimulation. The DPG wave in synchronization with a heartbeat gradually decreased after EP or IP stimulation and showed a trough on the 6th or 7th beat post-stimulus; but a decrease in DPG wave was less evident at EP stimulation. Our findings suggest that pain information processing fluctuates during respiration and that pain may be gated in the expiratory phase.

Electrically induced quantitative sudomotor axon reflex test in human volunteers

Chemically-induced quantitative sudomotor axon reflex test (QSART) and quantitative sensory testing (QST) are established clinical tools to assess thin fiber function in humans. We investigated stimulus-response functions to transcutaneous electrical stimuli of different current intensity (3.75 to 10 mA) and pulse frequency (5 to 100 Hz) comparing sweat output (ml/h/m 2) and pain intensity (numeric rating scale [NRS], 0–10). Efferent sudomotor and afferent nociceptive responses were recorded after a 30 s electrical stimulation period of distal (hand and foot) and proximal (forearm and thorax) body sites with 3 repetitive measures per body site. Sweat responses increased intensity dependently and peaked (~ 100 ml/h/m 2) at highest currents (10 mA) that had been administered. Similarly, pain ratings increased with an escalating current intensity. At a constant stimulus intensity of 7.5 mA, sudomotor activity was highest (~ 75 ml/h/m 2) at a stimulus frequency of 20 Hz without further increase at 50 or 100 Hz. In contrast, pain ratings increased frequency dependently and reached NRS 7 at 100 Hz. Sudomotor activity, but not pain ratings, was significantly different between the body sites (p < 0.05, ANOVA) with maximum sweat responses obtained at the ventral forearm. Varying response patterns for higher stimulation frequencies between sweating (peak maximum at 20 Hz) and pain (maximum at 100 Hz) might indicate differential axonal properties of sympathetic efferent and nociceptive afferent fibers. Electrically induced QSART could be a useful explorative and clinical method to indirectly study characteristics of frequency-dependent axonal excitability changes of sudomotor fibers.

Vestibular evoked myogenic potentials in response to lateral skull taps are dependent on two different mechanisms

To explore the mechanisms for skull tap induced vestibular evoked myogenic potentials (VEMP). The muscular responses were recorded over both sternocleidomastoid (SCM) muscles using skin electrodes. A skull tapper which provided a constant stimulus intensity was used to test cervical vestibular evoked myogenic potentials (VEMP) in response to lateral skull taps in healthy subjects (n=10) and in patients with severe unilateral loss of vestibular function (n=10). Skull taps applied approximately 2 cm above the outer ear canal caused highly reproducible VEMP. There were differences in VEMP in both normals and patients depending on side of tapping. In normals, there was a positive-negative ("normal") VEMP on the side contra-lateral to the skull tapping, but no significant VEMP ipsi-laterally. In patients, skull taps above the lesioned ear caused a contra-lateral positive-negative VEMP (as it did in the normals), in addition there was an ipsi-lateral negative-positive ("inverted") VEMP. When skull taps were presented above the healthy ear there was only a small contra-lateral positive-negative VEMP but, similar to the normals, no VEMP ipsi-laterally. The present data, in conjunction with earlier findings, support a theory that skull-tap VEMP responses are mediated by two different mechanisms. It is suggested that skull tapping causes both a purely ipsi-lateral stimulus side independent SCM response and a bilateral and of opposite polarity SCM response that is stimulus side dependent. Possibly, the skull tap induced VEMP responses are the sum of a stimulation of two species of vestibular receptors, one excited by vibration (which is rather stimulus site independent) and one excited by translation (which is more stimulus site dependent). Skull-tap VEMP probably have two different mechanisms. Separation of the two components might reveal the status of different labyrinthine functions.

Skull tap induced vestibular evoked myogenic potentials: An ipsilateral vibration response and a bilateral head acceleration response?

Objective To explore the mechanisms for skull tap induced vestibular evoked myogenic potentials (VEMP). Methods An electro-mechanical “skull tapper” (that provided a constant stimulus intensity) was used to test the effects of different midline stimulus sites/directions in healthy subjects ( n = 10) and in patients with severe unilateral loss of vestibular function ( n = 8). Results The standardized midline skull taps caused highly reproducible VEMP. There were highly significant differences in amplitude and latency in both normals and patients depending on site/direction of tapping (suggesting a stimulus direction dependency). Occiput skull taps caused, in comparisons to forehead and vertex taps, larger amplitude VEMP with more pronounced differences between the lesioned and the healthy side in the patients. Conclusions The present data, in conjunction with earlier findings, support a theory that skull tap VEMP are mediated by two different mechanisms. It is suggested that skull tapping causes both skull vibration and head acceleration. Further, the VEMP would be the sum of the direction-independent vibration-induced response (from the sound-sensitive part of the saccule) and the direction-dependent head acceleration response (from other parts of the labyrinth). Significance Skull tap VEMP, as a diagnostic test, is not equivalent to sound-induced VEMP.

Neurosteroid‐induced enhancement of short‐term facilitation involves a component downstream from presynaptic calcium in hippocampal slices

We used Magnesium Green AM to measure Ca(2+) transients in Schaffer collateral presynaptic terminals simultaneously with postsynaptic field potentials (fEPSPs) to investigate the mechanism of neurosteroid enhancement of short-term synaptic facilitation. Measurement of [Ca(2+)](i), isolated to presynaptic events, using the fluorescence ratio (DeltaF/F(0)) demonstrated that at a constant stimulus intensity there was no change in the excitability of presynaptic fibres between paired stimuli or between ACSF and 1 mum pregnenolone sulphate (PREGS). Paired-pulse facilitation (PPF) was correlated with residual Ca(2+) ([Ca(2+)](res)), and there was an additional increase in the integralDeltaF/F(0) for the [Ca(2+)](res)-subtracted response to the second of paired stimuli, resulting primarily from a slowing of the decay time constant. In addition to the role of presynaptic [Ca(2+)](res) in PPF, we observed a decrease in EC(50) and a greater maximum for Hill function fits to fEPSP versus DeltaF/F(0) during the second of paired responses. The enhancement of fEPSP PPF by PREGS did not result from an increase of DeltaF/F(0). The data presented here support a PREGS-induced increase in presynaptic glutamate release from the second, but not the first, of a pair of stimuli for a given presynaptic [Ca(2+)] because: (a) there is actually a decrease in the integralDeltaF/F(0) of the [Ca(2+)](res)-subtracted second response over that seen in ACSF; (b) PREGS causes no change in presynaptic Ca(2+) buffering; and (c) there is a decrease in EC(50) and an increase of y(max) in the Hill function fits to DeltaF/F(0) versus fEPSP data. We hypothesize that PREGS enhances short-term facilitation by acting on the Ca(2+)-dependent vesicle release machinery and that this mechanism plays a role in the cognitive effects of this sulphated neurosteroid.

Variability of motor potentials evoked by transcranial magnetic stimulation depends on muscle activation

The purpose of this research was to determine whether motor cortex excitability assessed using transcranial magnetic stimulation (TMS) is less variable when subjects maintain a visually controlled low-level contraction of the muscle of interest. We also examined the dependence of single motor evoked potential (MEP) amplitude on stimulation intensity and pre-stimulus muscle activation level using linear and non-linear multiple regression analysis. Eight healthy adult subjects received single pulse TMS over the left motor cortex at a point where minimal stimulation intensity was required to produce MEPs in extensor digitorum communis (EDC). Voluntary activation of the muscle was controlled by visual display of a target force (indicated by a stable line on an oscilloscope) and the isometric force produced as the subject attempted to extend the fingers (indicated by a line on the oscilloscope representing the finger extension force) while subjects were instructed to: exert zero extension force (0%) and produce forces equal to 5 and 10% of maximum voluntary finger extension under separate conditions. Relative variability (coefficient of variation) of single MEPs at a constant stimulus intensity and of pre-stimulus muscle EMG was lower during maintained 5 and 10% contractions than at 0% contraction levels. Therefore, maintaining a stable low intensity contraction helps stabilize cortical and spinal excitability. Multiple regression analyses showed that a linear dependence of single MEPs on stimulation intensity and pre-stimulus muscle activation level produced similar fits to those for a non-linear dependence on stimulus intensity and a linear dependence on pre-stimulus EMG. Thus, a simple linear method can be used to assess dependence of single MEP amplitudes on both stimulus intensity (to characterize slope of the recruitment curve) and low intensity background muscle activation level.

Hemodynamic Signals Correlate Tightly with Synchronized Gamma Oscillations

Functional imaging methods monitor neural activity by measuring hemodynamic signals. These are more closely related to local field potentials (LFPs) than to action potentials. We simultaneously recorded electrical and hemodynamic responses in the cat visual cortex. Increasing stimulus strength enhanced spiking activity, high-frequency LFP oscillations, and hemodynamic responses. With constant stimulus intensity, the hemodynamic response fluctuated; these fluctuations were only loosely related to action potential frequency but tightly correlated to the power of LFP oscillations in the gamma range. These oscillations increase with the synchrony of synaptic events, which suggests a close correlation between hemodynamic responses and neuronal synchronization.

Modeling metacontrast masking with varying target and mask durations

In metacontrast, a target is rendered invisible by a surrounding mask that appears after the target's offset, providing a tool for investigating temporal aspects of visual coding. Previous manipulations of target and mask duration have used constant stimulus intensity, so that longer-lasting stimuli appear brighter. When brightness is controlled by compensating longer duration with lower intensity, increasing target duration has little effect on U-shaped metacontrast, but increasing mask duration monotonically decreases target visibility when the mask follows a 10 msec target immediately. These results were simulated with four models: efficient masking (Francis), decaying-trace (Anbar & Anbar), two-channel (Weisstein, 1968), and lateral inhibition (Bridgeman). Using parameters in each model that had successfully simulated metacontrast in the past, the efficient masking model yielded a monotonically increasing function of visibility in as target duration increased, while the other models gave U-shaped functions. Testing the remaining models in the increasing mask duration experiment, the decaying-trace model gave an increasing function where the psychophysics showed a decreasing function, the two-channel model showed a plateau of high visibility at low mask duration while the psychophysical function began declining immediately, and the lateral inhibition model accurately simulated the results. We also tested a recurrent processing model (DiLollo, Enns & Rensink), which did well here but does not have the parameters to test the target-duration condition. The lateral inhibition model performed best overall, perhaps because it relies on distributed coding rather than discrete detectors to simulate target visibility. In a single layer of simulated neurons, each cell inhibits six near neighbors; secondary interactions spread stimulus-specific activity across the network.

Depressant effect on a C-fibre reflex in the rat, of RB101, a dual inhibitor of enkephalin-degrading enzymes

The effect of N-[( R, S)-2-benzyl-3[( S)-(2-amino-4-methylthio)butyldithiol]-1-oxopropyl]- l-phenylalanine benzyl ester (RB101), a dual inhibitor of the enkephalin-degrading enzymes, neutral endopeptidase and aminopeptidase N, was assessed in anaesthetised rats on the C-fibre reflex elicited by electrical stimulation within the sural nerve territory and recorded from the ipsilateral biceps femoris muscle. The temporal evolution of the pharmacological response was monitored by the repeated application of a constant stimulus intensity, namely three times threshold (3 T). In addition, recruitment curves were built by varying the stimulus intensity from 0 to 7 T. RB101 (7.5, 15 and 30 mg kg −1, i.v.) induced a dose-dependent, naloxone-reversible depression of the reflex, which lasted around 60 min with the highest dose. The ED 50 was calculated as 16.9 mg kg −1. Analyses of the recruitment curves revealed: (1) a significant increase of threshold; (2) a significant depression of the reflex in the ascending part of the curve; and (3) a lack of major depressive effects on the responses elicited by the strongest stimuli (corresponding to the plateau of the curve). The increase in the nociceptive threshold by enkephalin-degrading enzyme inhibitors, confirms previous data obtained from behavioural tests. In addition, the present study revealed an efficacy of these compounds over a wide range of stimulus intensities, albeit excluding the highest.

Effects of activity on axonal excitability: implications for motor control studies.

In many motor control studies, such as those involving H reflexes in human subjects, stimuli are delivered to nerves in which axons are or have recently been active. It is assumed that a constant stimulus intensity ensures that the same population of axons has been activated, particularly when there is little change in the M wave. However, the neurophysiological literature is replete with evidence that activity depresses axonal excitability. Indeed, some motor control studies have exploited this phenomenon to stimulate specific afferent populations selectively. This chapter will review studies performed in human subjects demonstrating that a voluntary contraction can have profound effects on the excitability of the active axons and on their ability to transmit impulses. These data need to be considered when interpreting human reflex studies.

Development of auditory function in the tammar wallaby Macropus eugenii

Auditory brainstem responses (ABRs) were evoked in developing wallabies by click and tone burst stimuli delivered by bone conduction and air conduction, at progressive stages of post-natal (pouch) life. ABRs were recorded through the onset of auditory responses (95–110 days), the opening of the external ear canal (125–130 days) and the maturation of ABR thresholds and latencies to values corresponding to those in adults (>180 days). ABRs were evoked in response to bone-conducted clicks some days prior to the age at which an acoustically evoked response was first observed (around 95 days of pouch life). ABRs could be evoked by bone-conducted and intense air-conducted stimuli prior to opening of the ear canal. A trend of decreasing threshold and latency with age was observed for both modes of stimulation. The morphology of the ABR became more complex, according to both increased age and increased stimulus intensity. The ABR waveforms indicated relatively greater mechanosensitivity to bone-conducted stimuli than to air-conducted stimuli, prior to opening of the ear canal. Following opening of the ear canal, thresholds to air-conducted clicks and tones were substantially reduced and decreased further over the next 10–20 days, while thresholds to bone-conducted clicks continued slowly to decrease. Thresholds to tone bursts in the centre frequency range (4–12 kHz) remained less than those for low (0.5–1.5 kHz) and higher (16 kHz) frequencies. Latencies of an identified peak in ABR waveforms characteristically decreased with age (at constant stimulus intensity) and with stimulus intensity (for a given age). ABR waveforms obtained at progressive ages, but judged to be at corresponding sensation levels, underwent maturational changes, independent of conductive aspects of the wallabies' hearing, for 2–3 weeks after opening of the ear canal.

Electrically induced blink reflex in horses.

The electrically induced blink reflex was studied electromyographically in 21 healthy adult, detomidine-sedated horses. Using surface electrodes, the supraorbital nerve was electrically stimulated at the supraorbital foramen. The responses were recorded from the ipsilateral and contralateral orbicularis oculi muscles with concentric needle electrodes inserted in the lateral aspect of the ventral eyelids. Ipsilateral and contralateral recordings were made on successive stimulations of the same side of the face, maintaining a constant stimulus intensity. The electromyographically recorded responses consisted of an early R1 response in the orbicularis oculi muscle ipsilateral to the side of stimulation, a bilateral late response (ipsilateral R2 and contralateral Rc) and a third, R3 response, in the ipsilateral orbicularis oculi muscle. All the responses were polyphasic muscle potentials of variable duration and peak to peak amplitudes. The reflex latency of the R1 response was, as in man, fairly stable. The R2 response showed greater variability both within and between individual horses. The Rc response was recorded in only 13 of the 21 horses and showed a slightly longer latency than the corresponding R2. The R3 response, which is significantly related to pain sensation in man, appeared in 19 horses and showed the greatest variability in latency.

Effects of clonidine on a C-fibre reflex in the rat

A C-fibre reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anaesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 × threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 × threshold. The intravenous administration of 0.02–0.2 mg/kg clonidine resulted in a dose-dependent depression of the C-fibre reflex. The α 2-adrenoceptor antagonist idazoxan completely prevented this depressive effect of clonidine. The effects of clonidine on the C-fibre reflex elicited by a wide range of stimulus intensities were investigated using recruitment curves: following 0.16 mg/kg clonidine, a dramatic shift of the recruitment curve to the right was seen with both an increase in the threshold and a decrease in the slope. Clonidine also produced a dose-dependent increase in blood pressure, but this was not correlated with the depression of the nociceptive reflex.

Regulation of synaptic facilitation by postsynaptic Ca2+/CaM pathways in hippocampal CA1 neurons.

1. Current- and voltage-clamp recordings with simultaneous field potential recordings were used to study the cellular and molecular mechanisms that contribute to synaptic facilitation at CA1 synapses in rat hippocampal slices. Microelectrodes used for intracellular recordings were also used to inject modulators of intracellular signal pathways into postsynaptic CA1 neurons. 2. Paired-pulse stimulation at constant stimulus intensity was used to analyze the relationship between the first evoked response (R1) and the absolute value of paired-pulse synaptic facilitation (R2-R1). The magnitudes of these two measures were inversely correlated. Compared with synapses that control motor functions, the synapses of CA1 pyramidal neurons did not exhibit accumulative synaptic facilitation during repetitive stimulation, which is often believed to be mediated by presynaptic residual Ca2+. 3. During studies on the cellular location of mechanisms contributing to synaptic facilitation, we observed that postsynaptic injections of 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid or [Ala286]CaMKII281-302 [a Ca2+/calmodulin-dependent protein kinase II (CaM-KII) inhibitor peptide] prevented the decreases in paired-pulse facilitation (PPF) and synaptic potentiation induced by elevating extracellular Ca2+. These results show that raising extracellular Ca2+ enhances synaptic transmission in part by activating postsynaptic Ca2+ signal pathways. 4. The injection of Ca2+/calmodulin (CaM) into postsynaptic neurons significantly decreased PPF in 50 of 57 experiments while inducing synaptic potentiation; the Ca2+/CaM-induced synaptic potentiation and PPF attenuation occluded subsequent high Ca(2+)-induced enhancements of synaptic transmission. The changes in PPF induced by postsynaptic injections of Ca2+/CaM were inversely correlated with R1 potentiation. 5. The decreases in PPF induced by postsynaptic Ca2+/CaM injections were prevented by coinjecting pseudosubstrate inhibitors or substrate peptides of CaM-KII and protein kinase C (PKC), and were reversed by subsequent application of cyclothiazide (a blocker of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor desensitization). 6. Our results reveal that postsynaptic Ca2+/CaM signal pathways can modulate synaptic facilitation in the CNS, and the activities of CaM-KII and PKC are involved in this modulation. The physiological significance of such modulation is that synaptic strength could be potentiated by activation of Ca2+/CaM pathways during integration of important sensory input (e.g., learning and memory), whereas decreases in synaptic facilitation may protect synaptic transmission during extreme stimulation so that neuronal signal mechanisms can more accurately code neural information.

Trial-to-trial variability of corticospinal volleys in human subjects.

The trial-to-trial variability of the different components of corticospinal volleys evoked by transcranial electrical stimulation of the motor cortex using a constant stimulus intensity was measured from epidural recordings during surgery to correct scoliosis. The recordings were made when there was no operative interference, and blood pressure, temperature, ventilation and anaesthetic regimen were stable. A simple D wave with a single negative peak of 10-30 microV amplitude was recorded in 4 patients. It varied little in amplitude (S.D.s < 8% for 100 consecutive single responses). In 4 patients the stimulus was adjusted to produce a complex D wave with 3 components, the earliest 2 of which arise from subcortical/brain-stem sites. The variability of amplitude of these components was high (S.D.s of 13-50%), but the variability of latency was low (S.D.s of 2-3%). Eighteen I waves were recorded in 6 of the subjects. Their variability from trial to trial was similar to that of the components of the complex D wave. It is argued that there would be greater trial-to-trial variability of the corticospinal volley in the awake state, particularly when the stimulus was magnetic rather than electrical. Explanations for changes in the compound muscle action potential produced by transcranial stimulation, electrical or magnetic, must take into account that a constant stimulus does not evoke an identical descending volley.

Trial-to-trial variability of corticospinal volleys in human subjects

The trial-to-trial variability of the different components of corticospinal volleys evoked by transcranial electrical stimulation of the motor cortex using a constant stimulus intensity was measured from epidural recordings during surgery to correct scoliosis. The recordings were made when there was no operative interference, and blood pressure, tempearature, ventilation and anaesthetic regimen were stable. A simple D wave with a single negative peak of 10–30 μV amplitude was recorded in 4 patients. It varied little in amplitude (S.D.s <8% for 100 consecutive single responses). In 4 patients the stimulus was adjusted to produce a complex D wave with 3 components, the earliest 2 of which arise from subcortical/brain-stem sites. The variability of amplitude of these components was high (S.D.s of 13-50%), but the variability of latency was low (S.D.s of 2–3%). Eighteen I waves were recorded in 6 of the subjects. Their variability from trial to trial was similiar to that of the components of the complex D wave. It is argued that there would be greater trial-to-trial variability of the corticospinal volley in the awake state, particularly when the stimulus was magnetic rather than electrical. Explanations for changes in the compound muscle action potential produced by transcranial stimulation, electrical or magnetic, must take into account that a constant stimulus does not evoke an identical descending volley.

Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. I. Stimulus intensity

Paired pulse stimulation of the perforant path provides a measure of inhibition of dentate granule cell field potentials that is reflected in the depression of the second (test) population spike (PS) relative to the first (conditioning) PS. The assumption that the strength of paired pulse depression is dependent upon the amplitude of the conditioning PS was investigated by increasing the stimulus intensity of both pulses (5–100% of maximum, Experiment 1), or by increasing the stimulus intensity of the conditioning pulse (5–100%) while maintaining a constant stimulus intensity of the test pulse (50%, Experiment 2). In both experiments, the threshold for early paired pulse depression (20 ms interpulse interval, IPI) was reached with moderate stimulation (30–40% of maximum). Above threshold, the test PS was depressed to a relatively constant amplitude in Experiment 1, in contrast to a nearly linear decrease observed in Experiment 2 with increasing stimulus intensity. This difference most likely reflects the lower stimulus intensity of the test pulse, relative to the conditioning pulse, in the second study, thereby allowing the increasing strength of early paired pulse depression to be detected more easily. The threshold for late paired pulse depression was reached near (20%, Experiment 1) or below (5%, Experiment 2) the PS threshold of dentate granule cells, and a paradoxical decrease in late paired pulse depression was detected with maximal stimulation in both studies. Together, these results suggest that early paired pulse depression exhibits a strong dependence upon the amplitude of the conditioning PS, whereas late paired pulse depression is marginally affected by the conditioning PS amplitude and is influenced by additional processes at both extremes of the stimulus intensity continuum.