Coding in tuberous and ampullary organs of a gymnotid electric fish

The coding mechanisms of the tuberous and ampullary organs of Gymnotus carapo were studied. The tuberous fibers had no or irregular spontaneous discharges and showed phasic on and/or off responses to 50 msec electric pulses, while the ampullary fibers had regular spontaneous discharges and showed tonic responses to the pulses. The threshold measured with the electric pulses was 1.5 mV/cm on the average for the tuberous fibers and 0.26 mV/cm for the ampullary fibers. For the tuberous fibers, a 0.5–1.0 msec electric pulse was sufficiently long to evoke the maximum response when the intensity of the pulse was 3–10 times higher than the threshold of a given fiber. However, responses of the ampullary fibers were more dependent on duration. To repetitive stimuli of 0.5 msec electric pulses, the tuberous fibers discharged several impulses per stimulus; while the ampullary fibers responded by changingpontaneous discharges from an unlocked to a locked state only in a certain range of intensity and repetition rate of stimulus pulses. The number of impulses per stimulus in the locked state was not modified by change in stimulus intensity. More than half the tuberous fibers and all amullary fibers were mechanically excitable. However, these organs are not considered to act as mechanoreceptors in natural conditions, but to act as electroreceptors.     

Preferential activation of muscle fibers with peripheral magnetic stimulation of the limb

Magnetic and electric activation of limb nerve and muscle were compared in normal subjects of different age, gender, and habitus. Direct stimulation of nerve and muscle showed that activation of intramuscular nerve fibers in the arm and leg occurs at a lower threshold for magnetic stimulation than for electric stimulation. Sensory nerve fibers had a lower threshold with electric stimulation. Muscle activation and stimulus artifact with magnetic stimulation precluded reliable recording of distal sensory nerve action potential in all subjects.     

Suppression of cutaneous perception by magnetic pulse stimulation of the human brain.

We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex.     

Inhibitory phenomena in individual motor units induced by transcranial magnetic stimulation

It is well known that a silent period (SP) can be observed in voluntary tonic EMG activity starting directly after the initial early response when magnetic stimuli are delivered through the skull over the contralateral primary motor cortex. It is, however, unknown as to how an individual motoneurone (MN) contributes to the SP observed in the surface EMG. The present investigation was conducted to investigate inhibitory phenomena at the level of individual motor units. It demonstrates that the duration of the SP in single motor units is inhomogeneously distributed within the pool of active MNs. At various stimulation strengths, SP durations in single motor units can be similar or longer when compared to that observable in surface EMG records. In some motor units, which show low thresholds for early excitation and appearance of the SP, durations of SP can exceed 1000 msec. The length of suppression of spontaneous MN firing is maximal at stimulus intensities a little higher than those required for an early excitatory response. Although in general thresholds for early excitation and appearance of SPs are similar, at threshold stimulation in a number of trials inhibitory effects on the firing of voluntarily activated motoneurones were present, even in the absence of early excitations. This proves the independent nature of inhibitory as opposed to excitatory effects induced by transcranial magnetic stimulation. An SP in the absence of early excitation underlines its cortical origin. Inhibition and excitation of single MNs were maximal over the same small scalp area. We suggest that cortical inhibitory control plays an important role in the organization of natural movements.     

A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex.

The effects of different orientations of a Cadwell round magnetic coil (MC) were compared with each other and with surface electrical stimulation of motor cortex in monkeys anesthetized with pentobarbital or urethane. Recordings were made from within the lateral corticospinal tract, either from axonal populations or with a microelectrode from individual axons. A lateral-sagittally orientated MC directly excited corticospinal neurons at lower stimulus intensity than was required for indirect, i.e., transsynaptic excitation via inputs to corticospinal neurons. By contrast, in 2 out of 3 macaques tested, a vertex-tangential orientation could excite corticospinal neurons indirectly at lower intensities than were required for direct excitation; at higher intensities, direct excitation also occurred. The site of direct corticospinal excitation by a lateral-sagittally orientated MC was inferred by comparing the response variability and latency to MC and surface electrical stimuli. Cathodal stimuli elicited more variable corticospinal population responses and later individual axonal responses than were obtained with anodal stimuli. The variability in response is attributed to interaction between nearby, on-going synaptic bombardment and the stimulus, implying that surface cathodal stimuli directly activate corticospinal neurons at the spike trigger zone (presumably the initial segment). By contrast, the consistency and reduced latency of the corticospinal responses to surface anodal stimuli are attributed to the direct excitation of corticospinal fibers within the white matter. When the stimulus intensity is clearly above threshold, surface anodal and cathodal stimuli can activate corticospinal neurons both directly and indirectly. Direct corticospinal excitation by the MC can resemble the effects of either surface anodal or surface cathodal stimuli. We conclude that the MC can activate corticospinal neurons at the spike trigger zone or their fibers deeper in white matter. The findings in the monkey are used to interpret the effects of different MC orientations in the human.     

A comparison of magnetic and electrical stimulation of peripheral nerves

We compared magnetic stimulation using different coil designs (2 rounded coils and a butterfly-prototype coil) with electrical stimulation of the median and ulnar nerves in 5 normal subjects. Using magnetic stimulation we were able to record technically satisfactory maximal sensory and motor responses only with the butterfly coil. Submaximal electrical stimuli preferentially activated sensory rather than motor axons, but submaximal magnetic stimuli did not. The onset latency, amplitude, area and duration of responses elicited electrically or magnetically with the butterfly coil during routine sensory and motor nerve conduction studies were similar, and motor and sensory conduction velocities were comparable when studied over long segments of nerve. However, the motor conduction velocities with magnetic and electrical stimulation differed by as much as 18 m/sec in the across-elbow segment of ulnar nerve. Thus, recent developments in magnetic stimulator design have improved the focality of the stimulus, but the present butterfly coil design cannot replace electrical stimulation for the detection of focal changes in nerve conduction velocity at common entrapment sites, such as in the across-elbow segment of the ulnar nerve.     

H reflex behavior in Parkinson's disease patients. Effect of stimulus duration

Electrical stimulus, with duration starting at 0.1 ms and gradually increasing to 1.0 ms, was used for eliciting the H reflex in 21 normal subjects and 48 patients with Parkinson's disease (PD). In 19 normal subjects (90.5%), the threshold for sensory fibers was lower than for motor fibers, and the H reflex was obtained before the M response for all duration stimuli. In 19 PD patients (39.6%), with mild or moderate rigidity (according to the motor part of UPDRS), the threshold for the H reflex and M response was the same or the M response threshold was lower in at least one of the legs for short stimulus duration (0.1–0.2 ms). In 15 PD (31.2%) patients (most of them with severe rigidity), the threshold for M response was lower for all stimulus duration, and it was obtained before the H reflex. In 14 PD (29.2%) patients, the H reflex behavior was the same as in most normal subjects in one or both legs.

These very significant differences in the behavior of the H reflex in PD patients (Fisher exact test, P<0.0001) could possibly be explained by changes in agonist–antagonist inhibition, and could be used as another parameter in the clinical assessment of extrapyramidal rigidity in PD patients.     

Differential sensitivity of motor and sensory fibres in human ulnar nerve

The human ulnar nerve has been stimulated with square-wave pulses of various fixed durations. Measurements were made of the growth of hand myograms compared with elbow neurograms and of hand myograms compared with finger neurograms, for fixed durations of pulses and increasing strength. The effect of blocking sensory action potentials with stimuli of various durations has been investigated, as well as the blocking of action potentials in motor nerve fibres by voluntary activity. It is concluded that pulses of long duration (1 msec or more) selectively stimulate sensory fibres at threshold, whereas short duration pulses (less than 200 μsec) selectively stimulate motor fibres.     

Modulation of motor activity by cutaneous input: inhibition of the magnetic motor evoked potential by digital electrical stimulation

We examined the inhibitory effect of a brief train of digital (D2) electrical stimuli at 4 times perception threshold on transcranial magnetic motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles ipsilateral to the side of D2 stimulation. We compared this to the inhibitory effect of ipsilateral D2 stimulation on averaged rectified EMG recorded at 10% maximum voluntary contraction and on F-responses and H-reflexes recorded from these same muscles. We also compared MEPs recorded following D2 stimulation just above perception threshold to MEPs following higher intensity D2 stimulation. As well, we assessed the effect of preceding D2 stimulation on MEPs recorded from a relaxed versus tonically contracted hand muscle. D2 stimulation elicited a triphasic response of modest MEP facilitation followed by inhibition and further facilitation. The duration and onset of MEP inhibition correlated with those of the initial period of rectified EMG inhibition, however, the magnitude of MEP inhibition was generally less than the magnitude of EMG inhibition, consistent with a greater inhibitory effect of digital afferents on smaller motor neurons. MEN were not facilitated during the rebound of EMG activity (the E2 period) that usually followed the initial period of EMG inhibition (I1 period). The behavior of H-reflexes and F-responses following ipsilateral D2 stimulation suggested that inhibition of both EMG and MEPs is not mediated via presynaptic inhibition of la afferents, and that inhibition is augmented by descending rather than segmental input to spinal motor neurons. Tonic contraction of the target muscle during D2 stimulation decreased the inhibitory effect of the preceding digital stimulus possibly due to recruitment of larger spinal motor neurons less likely to be inhibited by cutaneous input.     

Intracortical inhibition and facilitation of the response of the diaphragm to transcranial magnetic stimulation.

Respiratory muscles respond to a subcortical automatic command and to a neocortical voluntary command. In diseases such as stroke or motor neurone disease, an abnormal diaphragmatic response to single transcranial magnetic stimuli can identify a central source for respiratory disorders, but this is not likely to be the case in disorders affecting intracortical inhibitory and facilitatory mechanisms. This study describes the response of the diaphragm to paired transcranial magnetic stimulation. Thirteen normal subjects were studied (age range, 22 to 43 years; 7 men; phrenic conduction, <6.8 msec; latency of diaphragmatic motor evoked potential, <20.5 msec). Motor evoked potentials in response to paired stimulation were obtained in eight subjects only, with the motor threshold in the remaining five subjects too high to absorb the loss of power inherent in the double-stimulation montage. Interstimulus intervals less than 5 msec resulted in a statistically significant inhibition (p < 0.01 for interstimulus intervals of 1 and 3 ms), whereas intervals longer than 6 msec were facilitatory (maximal, 15 msec). The diaphragmatic pattern matched that of the biceps brachii. The authors conclude that it is possible to study intracortical inhibition and facilitation of diaphragmatic control, although not in all subjects. Technical improvement should alleviate current limitations and make paired transcranial magnetic stimulation a tool to study respiratory muscle abnormalities in settings in which intracortical interactions are important, such as movement disorders.     

Changes in excitability of motor cortical circuitry in patients with parkinson's disease

Using the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age-matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1–5 msec) interstimulus intervals in patients relative to their controls, which improved after L -dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.     

Electric vs magnetic trans-cranial stimulation of the brain in healthy humans: a comparative study of central motor tracts 'conductivity' and 'excitability'

Motor evoked potentials (MEPs) were elicited in the thenar muscles of 11 healthy volunteers via individual electric unifocal and magnetic trans-cranial stimuli (TCS). The effects of TCS strength, of the muscular state (relaxed, contracted) as well as of the amplitude-latency characteristics and the duration of the motor tracts central conduction times (CCTs) to hand muscles, were evaluated and compared between the two types of brain excitation. MEPs with the shortest latency (18.91 +/- 1.31 ms) were recorded in the voluntarily contracted muscle during electric TCS, whilst those with maximal latency (23.3 +/- 1.63 ms) were found after magnetic TCS with an intensity at threshold for eliciting an MEP of about 0.1 mV in the relaxed muscle. Mean CCTs for electric and magnetic TCS calculated in the contracted target muscles, were respectively 5.07 +/- 0.51 and 6.34 +/- 0.46 ms. MEPs with larger amplitudes and durations were observed during magnetic TCS, being maximal when suprathreshold stimuli were delivered. A restricted range of liminar values of magnetic TCS was obtained by defining the threshold for raising motor responses in complete muscle relaxation, indicating that magnetic pulses might represent a useful probe for testing the 'excitability' of the motor tracts.     

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.     

Asymmetry of cortical excitability revealed by transcranial stimulation in a patient with focal motor epilepsy and cortical myoclonus

Motor cortex excitability was analyzed with transcranial stimulation in a patient with motor focal epilepsy and cortical myoclonus originating from the right motor cortex. The motor threshold to single transcranial magnetic shocks, but not to electric stimuli, was higher in the epileptic motor cortex than the normal left motor cortex. Single magnetic shocks elicited a short cortical silent period (50 ms) in the epileptic motor cortex. Paired magnetic stimuli also showed reduced cortico-cortical inhibition. These findings reveal an asymmetry in cortical excitability presumably due to impaired inhibition in the epileptic motor cortex.     

Renshaw cell activity in man

The H-reflex elicited in triceps surae by percutaneous stimulation of the posterior tibial nerve was conditioned by stimuli applied through the same electrode. The differential sensitivity of motor and sensory fibres to duration of the stimulus pulse made it possible to condition the H-reflex with either a motor or a sensory stimulus. With both types of conditioning, the H-reflex was inhibited at conditioning-test intervals of 2-3 msec and was then facilitated, the peak of facilitation occurring at 5-8 msec with motor conditioning and 6-10 msec with sensory conditioning. The phase of facilitation was followed by further inhibition. We have concluded (1) that the effects of motor conditioning on the H-reflex result from the discharge of Renshaw cells activated by the antidromic volley in the motor axons, and (2) that the effects of sensory conditioning (at the times used in these experiments) are largely due to the activation of Renshaw cells secondary to the discharge of alpha motoneurones by the conditioning volley.     

Standardization of facilitation of compound muscle action potentials evoked by magnetic stimulation of the cortex. Results in healthy volunteers and in patients with multiple sclerosis.

To establish the importance of standardization of the facilitation of central motor conduction measured by magnetic stimulation we studied the effect of increasing voluntary muscle contraction on the central motor conduction time (CMCT) and motor evoked potential (MEP) amplitudes for 3 upper and 2 lower limb muscles. MEPs were elicited by magnetic stimulation of the cortex and the spinal roots. Muscle force was indirectly assessed from the integrated electrical muscle activity and expressed as the root mean square (RMS) and was varied from 0 to 40% of maximal activity. The central motor conduction time (CMCT) decreased during increasing muscle contraction, reaching constant values at approximately 10-20% RMSmax. Similarly, the increases of MEP amplitude tapered off at about the same RMS level. For each muscle an optimal RMS level was defined. The shortening of the CMCTs at the optimal RMS levels were: the brachial biceps, 3.4 msec; the radial carpal flexor of the wrist, 2.7 msec; the first dorsal interosseus muscle of the hand, 2.9 msec; the anterior tibial, 4.2 msec; and the abductor hallucis, 2.4 msec. The standardizing procedure was applied to 10 patients with multiple sclerosis. The stimulus thresholds were higher in these patients compared with those of the normals. Only the CMCT reduction of the BB was significantly larger (8.1 msec) than in the controls. Using standardized facilitation the diagnostic value of the amplitudes seems to be only a little less than that of the CMCTs.     

Lateral geniculate spikes, muscle atonia and startle response elicited by auditory stimuli as a function of stimulus parameters and arousal state

We have investigated the motor and ponto-geniculo-occipital (PGO) wave response to startle eliciting stimuli in the unanesthetized cat. We found that the amplitude of the PGO spike recorded in the lateral geniculate nucleus (LGN) increases monotonically with increasing intensities of auditory stimuli. In contrast, the motor response to low intensity (less than 75 dB) stimuli is characterized by electromyographic (EMG) suppression, while at higher intensities an EMG excitation is superimposed on this suppression. Thus PGO elicitation is accompanied by EMG suppression at low intensities and by a net EMG excitation at high intensities. While the amplitude of the auditory elicited PGO response is a graded function of stimulus intensity, somatic stimuli tend to elicit the PGO response in all-or-none fashion. Both the motor and PGO responses to sensory stimulation change with behavioral state. The EMG suppression by auditory stimulation increases in duration during the transition to rapid eye movement (REM) sleep. Elicited PGO amplitude is highest in transitional sleep, lower in quiet waking and REM sleep and lowest in active waking. Prepulse inhibition of PGO spikes is greatly attenuated during transitional and REM sleep. We hypothesize the existence of 3 phasic response systems, a motor suppression system, a motor excitation (startle) system and a PGO elicitation system. While these systems are triggered concurrently by intense phasic stimuli in waking, they are modulated independently by stimulus intensity and behavioral state, and have different rates of habituation. These systems act in concert to produce behavioral responses to sudden onset stimuli.     

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease

Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1–7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired‐pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment. © 2011 Movement Disorder Society     

Determining the site of stimulation during magnetic stimulation of a peripheral nerve.

Magnetic stimulation has not been routinely used for studies of peripheral nerve conduction primarily because of uncertainty about the location of the stimulation site. We performed several experiments to locate the site of nerve stimulation. Uniform latency shifts, similar to those that can be obtained during electrical stimulation, were observed when a magnetic coil was moved along the median nerve in the region of the elbow, thereby ensuring that the properties of the nerve and surrounding volume conductor were uniform. By evoking muscle responses both electrically and magnetically and matching their latencies, amplitudes and shapes, the site of stimulation was determined to be 3.0 +/- 0.5 cm from the center of an 8-shaped coil toward the coil handle. When the polarity of the current was reversed by rotating the coil, the latency of the evoked response shifted by 0.65 +/- 0.05 msec, which implies that the site of stimulation was displaced 4.1 +/- 0.5 cm. Additional evidence of cathode- and anode-like behavior during magnetic stimulation comes from observations of preferential activation of motor responses over H-reflexes with stimulation of a distal site, and of preferential activation of H-reflexes over motor responses with stimulation of a proximal site. Analogous behavior is observed with electrical stimulation. These experiments were motivated by, and are qualitatively consistent with, a mathematical model of magnetic stimulation of an axon.     

Inhibition of hand muscle motoneurones by peripheral nerve stimulation in the relaxed human subject. Antidromic versus orthodromic input

In active muscle, a supramaximal conditioning stimulus to peripheral nerve produces a classic silent period in the EMG. The present experiments examined the effect of this type of conditioning stimulus on motoneurone excitability in relaxed muscle.EMG responses evoked by transcranial magnetic stimulation of the brain were recorded from the first dorsal interosseus muscle (FDI) in 10 healthy subjects and 5 patients with sensory neuropathy. These responses (motor evoked potentials) were conditioned by supramaximal peripheral nerve stimuli given 0–150 msec beforehand. In the normal subjects, the classic silent period in the FDI lasted about 100 msec. The same conditioning stimulus only abolished motor evoked potentials when the conditioning-test interval was so short that the antidromic peripheral nerve volley collided with the orthodromic volley set up by magnetic brain stimulation. At longer conditioning-test intervals, although remarkably inhibited (65% mean suppression between 10 and 40 msec), the test motor potential was never completely abolished and gradually recovered by 100 msec.Inhibition of cortically evoked motor potentials did not depend upon activity set up by the conditioning stimulus in peripheral nerve sensory fibres. The patients with complete peripheral sensory neuropathy had the same extent and time-course of inhibition as the normal subjects. We conclude that in relaxed subjects the inhibitory effect of peripheral conditioning results almost exclusively from the motoneuronal inhibitory mechanisms consequent to antidromic invasion.