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Slow frequency repetitive transcranial magnetic stimulation affects reaction times, but not priming effects, in a masked prime task.

OBJECTIVE: Slow frequency repetitive transcranial magnetic stimulation (rTMS) reduces motor cortex excitability, but it is unclear whether this has behavioural consequences in healthy subjects. METHODS: We examined the effects of 1 Hz rTMS (train of 20 min; stimulus intensity 80% of active motor threshold) over left motor or left premotor cortex on performance in a visually cued choice reaction time task, using a 'masked prime' paradigm to assess whether rTMS might affect more automatic motor processes. Twelve healthy volunteers participated. RESULTS: Motor cortex rTMS and, to a lesser extent, premotor cortex rTMS resulted in a slowing of right (stimulated) hand responses, but not of left (unstimulated) hand responses. In a control experiment, rTMS of the left somatosensory cortex did not lead to slower right hand responses. DISCUSSION: We conclude that long trains of low intensity 1 Hz rTMS over the motor or premotor cortex can have subtle behavioural consequences outlasting the stimulation. rTMS did not affect the modulation of reaction times by subliminal primes, suggesting that priming effects triggered by subliminal primes are not generated at the level of motor or pre-motor cortex.

Adult↗

The effect of burst patterning of preganglionic input on the efficacy of transmission at the cat stellate ganglion.

1. The effect of burst patterned preganglionic stimulation on the efficacy of transmission at the cat stellate ganglion in vivo was studied to determine whether the increase in acetylcholine (ACh) release that occurs at preganglionic terminals with similar stimulation is synaptically active.2. Stimulation of the whole or a portion of the thoracic sympathetic trunk between rami T4 and T5 with recording of evoked compound action potentials in the inferior cardiac nerve yielded a preparation with a subliminal fringe with a mean value 2.5 times the size of the discharge zone.3. Preganglionic stimulation with 0.5 s bursts at 10, 20 and 40 Hz with 10 s interburst intervals caused an increase with time in the area of the compound action potential evoked by a single interburst test stimulus. The increase reached 70-75% of the final value after the first burst, 75-90% after 5 bursts and was virtually complete after 5 min. It was then maintained without attenuation as stimulation was continued.4. On cessation of burst patterned stimulation test compound action potentials returned to control levels with a half-time of 5 min.5. The increase in area of test compound action potentials with 40 Hz intraburst frequency was always as great as the increase following tetanization of the pathway. The increases with 20 and 10 Hz bursts were less.6. There was no increase in area of compound action potentials when equally spaced pulses at 2 Hz or less were applied preganglionically, nor was there any increase when 40 Hz burst patterns were delivered directly to the inferior cardiac nerve.7. It is concluded that burst patterned preganglionic activity at frequencies similar to those observed in vivo can recruit rapidly into the discharge zone all of the ganglionic neurones that were originally in the subliminal fringe. It is proposed that this effect is related directly to the increase in ACh release at ganglionic synapses that such activity has been shown to induce.

Action Potentials↗

Afferent conditioning of motor evoked potentials following transcranial magnetic stimulation of motor cortex in normal subjects.

The present study determined the effects of percutaneous electrical stimulation of the plantar surface on motor evoked potentials (MEPs) in tibialis anterior (TA) and soleus (SOL) of normal subjects following transcranial magnetic stimulation of motor cortex. The conditioning stimulation consisted of a 20 msec train of electrical pulses (500 Hz; 0.1 msec rectangular) delivered to the medial border of the sole of the foot at an intensity just subthreshold for evoking a flexion reflex. The conditioning (C) stimulation preceded the test (T) cortical stimulation by intervals of 20-130 msec. Magnetic stimulation of motor cortex (Cadwell MES-10) was delivered through a 9.5 cm focal point coil positioned tangential to the scalp and located with the rim over vertex. Five healthy adults served as subjects and each was investigated on at least 2 occasions. At C-T intervals 20-50 msec there was a mild inhibition of MEPs in both TA and SOL. This was followed by marked facilitation (greater than 300%) of MEPs at C-T intervals 50-85 msec in both TA and SOL in all subjects. At longer C-T intervals greater than 110 msec, there was an inhibition of MEPs in TA but not in SOL. Based on the time course of these 3 phases of MEP amplitude modulation, and different stimulation thresholds for each phase, it appears that separate neurophysiological processes underlie each phase of MEP modulation. These observations also suggest that percutaneous electrical stimulation may be useful as a means of enhancing low amplitude or subliminal MEPs in normal subjects or patients with myelopathy.

Adaptation, Physiological↗

A TMS study of the ventral projections from V1 with implications for the finding of neural correlates of consciousness.

The study of subliminal perception in normal and brain lesioned subjects has long been of interest to scholars studying the neural mechanisms behind conscious vision. Using brief durations and a developed methodology of introspective reporting, we present an experiment with visual stimuli that gives rise to little or no subliminal perception under normal viewing conditions. Coupled with transcranial magnetic stimulation, however, we find a dissociation between correctness and conscious awareness. Furthermore, we find support for the hypothesis that the ventral projection streams from V1 are necessary for visual consciousness.

Adult↗

Frequency-dependent excitability of "membrane" slow responses of Rabbit left atrial trabeculae in the presence of Ba2+ and high K+.

Small trabeculae of rabbit left atrium immersed in TKBa solution (Tyrode with 10 mM K+ and 1 mM Ba2+) were used to study frequency dependence of "membrane" slow response excitability at long cycle lengths (greater than 1 s). In TKBa, stimuli generate graded, low-amplitude (2-15 mV) subliminal responses of variable long duration (up to 450 ms). A full all-or-none slow response is generated when a subliminal response depolarizes the membrane to about--35 mV. Subliminal response amplitude and rate of rise augment with stimulus intensity-duration product. For a fixed stimulus, the subliminal response is larger and faster at higher frequencies. Sudden changes in stimulus frequency or time course induce changes in subliminal response tha take four to eight cycles to attain steady state. For a fixed stimulus, slow response latency shortens progressively during the first few cycles after a sudden increase in frequency or when a rested preparation is excited (latency adaptation phenomenon, LAP). Slow response threshold stimulus requirements decrease during LAP (excitability hysteresis). The degree of excitability hysteresis is dependent on stimulation frequency and is more pronounced at higher frequencies. Frequency sensitivity of subliminal response (which causes frequency sensitivity of slow response excitability) is explained in terms of a transient state of enhancement set up by each stimulus. The enhanced state decays between stimuli with a half-time of approximately 4 s, thus allowing cumulative effects to become evident at rates above 0.1 Hz.

Action Potentials↗

Synergistic activation of human T cells by interleukin 1 and interleukin 6.

Purified human interleukin 6 (IL 6) was found to stimulate the proliferation of human tonsillar and peripheral rosetting T cells subliminally activated with phytohemagglutinin (PHA). This response seemed independent of IL 2 but highly dependent on the presence of accessory cells. Indeed, when accessory cell-depleted tonsillar T cells were activated with PHA and exposed to IL 6, only minimal proliferations were observed. A similar result was obtained with IL 1. However, a combination of these two cytokines induced strong proliferations, indicating that IL 1 and IL 6 plays a synergistic role in the interactions between accessory cells and T lymphocytes.

Antigen-Presenting Cells↗

Condition-dependent immunoregulatory control of contact sensitivity by levamisole.

The immunostimulatory activity of levamisole [1-(-),2,3,5,6-tetrahydro-6-phenylimidazo(2,1-beta)-thiazole] was investigated using oxazolone-induced contact sensitivity in C57Bl mice. Oxazolone sensitivity was induced by applying 0.1 ml of 3 or 5% oxazolone in ethanol to the shaved abdomen (day 0). Challenge with oxazolone followed on day 2 (45 h) or day 3, and was accomplished by painting a 1--5% solution of oxazolone in ethanol to the left hind paw. The response at 24 h was determined plethysmographically. Levamisole (50 mg/kg, p.o., days 0--3 or day 0 only) failed to stimulate consistently the oxazolone response in a 3-day (minimal) sensitization period regimen. Use of a subliminal (45 h) sensitization, by contrast, revealed a consistent immunostimulatory effect of levamisole (12.5--100 mg/kg, p.o., day 0 only). It is speculated that the observed difference in levamisole effectiveness is attributable to (1) the ability of levamisole to stimulate both effector and suppressor mechanisms, and (2) the apparent absence of significant suppressor influence at 2-day postsensitization, leaving only the effector mechanism to be stimulated by levamisole.

Animals↗

The use of technology-supported mental imagery in neurological rehabilitation: a research protocol.

The human brain can simulate motor actions without physically executing them, and there is a neuro-psychological relationship between imaging and performing a movement. These are shared opinions. In fact there is scientific evidence showing that the mental simulation of an action is correlated to a subliminal activation of the motor system. There is also evidence that virtual stimulation can enhance the acquisition of simple motor sequences. In some situations, virtual training was found to be as beneficial as real training and more beneficial than workbook and no training in teaching complex motor skills to people with learning disabilities. Moreover, studies of brain-injured hemiplegics patients suggest that these patients retain the ability to generate accurate motor images even of actions that they cannot perform. Combined with evidence indicating that motor imagery and motor planning share common neural mechanisms, these observations suggest that supporting mental imagery through non-immersive, low-cost virtual reality (VR) applications may be a potentially effective intervention in the rehabilitation of brain-injured patients. Starting from this background, our goal is to design and develop a new technique for the acquisition of new motor abilities- "imagery enhanced learning" (or I-learning)-to be used in neuro-psychological rehabilitation. A key feature of I-learning is the use of potentially low-cost, Virtual Reality enhanced technology to facilitate motor imagery creating a compelling sense of presence. This paper will discuss the rationale and a preliminary rehabilitation protocol for investigating mental imagery as a means of promoting motor recovery in patients with a neurological disorder. The treatment strategy aims at evoking powerful imaginative responses using an innovative technique which makes no attempt to simulate the real-world motor behavior, but draws the patient's attention to its underlying dynamic structure. This is done by displaying highly stylized sketches of the motor behavior on a computer screen and gradually increasing the perceptual realism of the visualization. This strategy assumes that optimal learning will be achieved when the patient is allowed to elaborate his own schema and sequences of movements, thereby constructing his own personal image of the motor behavior to be trained.

Activities of Daily Living↗

The origin of tic douloureux: a unified view.

An hypothesis on the mechanism of pain attacks in trigeminal neuralgia is presented. It is based on the analysis of clinical characteristics and pathology of a series of 278 cases submitted to different methods of treatment, and on physiological data of the literature. The hypothesis is that trigeminal neuralgia is a sort of sensory reflex epilepsy. The posterior root, damaged and distorted by a vessel or compressed by other lesions shows demyelination, micro-neuromas, and so on. At the site of this chronic damage ectopic impulses and afterdischarges are generated; the gasserian ganglion cells too give rise to spontaneous impulse generation. Owing to this chronic anomalous afferent barrage, an epileptic subliminal focus is "kindled" in the trigeminal nucleus. The pain paroxysms develop when this subliminal activity is driven in prolonged seizure discharges by peripheral (trigger zone stimulation) or other (not perceived) afferences. Clinical characteristics of the attacks (triggering by innocuous stimulations; persistence of pain after stimulus stops; diffusion of pain outside the stimulated division; refractory period after each paroxysm; increase in frequency of the attacks up to an epileptic-like status; sensibility to carbamazepine and phenytoin) and recurrence following diverse procedures are discussed on the basis of experimental research in reflex epilepsy and "kindling". If this hypothesis is true, the treatment of choice of trigeminal neuralgia should be a direct approach to the posterior fossa in order to relieve neurovascular compression which, in more than 75% of the cases, is the causative factor of the disease.

Adolescent↗

Interocular suppression in the visual cortex of strabismic cats.

Strabismic humans usually experience powerful suppression of vision in the nonfixating eye. In an attempt to demonstrate physiological correlates of such suppression, we recorded from the primary visual cortex of cats with surgically induced squint and studied the responses of neurons to drifting gratings of different orientation, spatial frequency, and contrast in the two eyes. Only 1 of 50 apparently monocular cells showed any evidence of remaining, subliminal excitatory input from the "silent" eye when the two eyes were stimulated with gratings of similar orientation, and even among the small proportion of cells that remained binocularly driven, very few exhibited facilitation when stimulated binocularly. The majority of cells from both exotropes and esotropes, even those that could be independently driven through either eye, displayed nonspecific interocular suppression: stimulation of the nondominant eye with a drifting grating of any orientation depressed the response to an optimal grating being presented to the dominant eye. This phenomenon exhibited a gross nonlinearity in that it was dependent on the temporal sequence of stimulus presentation: stimulation of the nondominant eye caused significant suppression only if the neuron was already responding to an appropriate stimulus in the dominant eye, but not when onset of stimulation in the two eyes was simultaneous. Interocular suppression was always independent of the relative spatial phase of the two grating stimuli, and usually broadly tuned for the spatial frequency of the suppressive stimulus. Suppression may depend on inhibitory interaction between neighboring ocular dominance columns, combined with the loss of conventional disparity-selective binocular interactions for matched stimuli in the two eyes. The similarity of interocular suppression in strabismic cats and that caused by orthogonal gratings in the two eyes in normal cats (Sengpiel and Blakemore, 1994; Sengpiel et al., 1994) suggests that strabismic suppression and binocular rivalry depend on similar neural mechanisms.

Animals↗

Monitoring the excitability of neocortical efferent neurons to direct activation by extracellular current pulses.

1. Extracellular action potentials were recorded from antidromically activated efferent neurons in visual, somatosensory, and motor cortex of the awake rabbit using low-impedance metal microelectrodes. Efferent neurons were also activated by current pulses delivered near the soma [juxtasomal current pulses (JSCPs)] through the recording microelectrode. Action potentials generated by JSCPs were not directly observed (because of the stimulus artifact), but were inferred with the use of a collision paradigm. Efferent populations studied include callosal neurons [CC (n = 80)], ipsilateral corticocortical neurons [C-IC (n = 21)], corticothalamic neurons of layer 6 [CF-6 (n = 57)], and descending corticofugal neurons of layer 5 [CF-5, corticotectal neurons of the visual cortex (n = 48)]. 2. Most CC neurons (45/46) and all C-IC (8/8) and CF-6 neurons (39/39) were directly activated by JSCPs at near-threshold intensities. Some CF-5 neurons (9/38), however, showed evidence of indirect activation. All efferent classes had similar current thresholds (means 1.85-2.10 microA) to direct activation by JSCPs, and thresholds were inversely related to extracellular spike amplitude. For each neuron, the range of JSCP intensities that generated response probabilities of between 0.2 and 0.8 was measured, and this "range of uncertainty" was significantly greater in CF-5 neurons (mean 32.7% of threshold) than in CC (mean 19.0%) or CF-6 (mean 20.4%) neurons. 3. Several factors indicate that the threshold of efferent neurons to JSCPs is very sensitive to excitatory and inhibitory synaptic inputs. Iontophoretic applications of gamma-aminobutyric acid (GABA) increased the threshold to JSCPs, and glutamate reduced the threshold. Electrical stimulation of afferent pathways at intensities just below threshold for eliciting action potentials resulted in a dramatic decrease in JSCP threshold. This initial short-latency threshold decrease was specific to stimulation of particular afferent pathways and is thought to reflect excitability changes associated with EPSPs. Examination of such subliminal responses revealed subthreshold synaptic inputs that were not revealed by examination of all-or-none action potentials. In contrast to the specificity of the short-latency threshold decrease, a long-lasting increase in JSCP threshold was seen in virtually all neurons after stimulation of each of the afferent pathways tested. This increase in threshold usually began 20-40 ms after stimulation, lasted for 100-200 ms, and is thought to reflect excitability changes associated with a long-lasting inhibitory postsynaptic potential (IPSP) seen in many cortical neurons. 4. Many neurons in primary somatosensory cortex of rat, cat, and rabbit have no demonstrable receptive fields.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

On the potential role of the corticospinal tract in the control and progressive adaptation of the soleus h-reflex during backward walking.

When untrained subjects walk backward on a treadmill, an unexpectedly large amplitude soleus H-reflex occurs in the midswing phase of backward walking. We hypothesized that activity in the corticospinal tract (CST) during midswing depolarizes the soleus alpha-motoneurons subliminally and thus brings them closer to threshold. To test this hypothesis, transcranial magnetic stimulation (TMS) was applied to the leg area of the motor cortex (MCx) during backward walking. Motor-evoked potentials (MEPs) were recorded from the soleus and tibialis anterior (TA) muscles in untrained subjects at different phases of the backward walking cycle. We reasoned that if soleus MEPs could be elicited in midswing, while the soleus is inactive, this would be strong evidence for increased postsynaptic excitability of the alpha-motoneurons. In the event, we found that in untrained subjects, despite the presence of an unexpectedly large H-reflex in midswing, no soleus MEPs were observed at that time. The soleus MEPs were in phase with the soleus electromyographic (EMG) activity during backward walking. Soleus MEPs increased more rapidly as a function of the EMG activity during voluntary activity than during backward walking. Furthermore, a conditioning stimulus to the motor cortex facilitated the soleus H-reflex at rest and during voluntary plantarflexion but not in the midswing phase of backward walking. With daily training at walking backward, the time at which the H-reflex began to increase was progressively delayed until it coincided with the onset of soleus EMG activity, and its amplitude was considerably reduced compared with its value on the first experimental day. By contrast, no changes were observed in the timing or amplitude of soleus MEPs with training. Taken together, these observations make it unlikely that the motor cortex via the CST is involved in control of the H-reflex during the backward step cycle of untrained subjects nor in its progressive adaptation with training. Our observations raise the possibility that the large amplitude of H-reflex in untrained subjects and its adaptation with training are mainly due to control of presynaptic inhibition of Ia-afferents by other descending tracts.

Adaptation, Physiological↗

Effects of emorfazone on the nociceptive response induced by bradykinin in rats and dogs.

Effects of emorfazone on the nociceptive responses induced by the liminal dose of bradykinin (BK alone-induced response), the combined use of the subliminal dose of BK and prostaglandin E (PGE-potentiated response) and the electrical stimulation of the sensory nerve were investigated. BK and PGE were injected into the femoral artery of dogs and the right common carotid artery of rats. In lightly anesthetized dogs, emorfazone (5-20 mg/kg, i.v.), aminopyrine (30 mg/kg, i.v.) and aspirin (50 mg/kg, i.v.) inhibited the vocalization response induced by BK alone but did not by the electrical stimulation of the saphenous nerve. Unlike morphine hydrochloride, these drugs showed a blocking action on the saphenous nerve activity evoked by BK. However, these three drugs differed from each other with respect to the action on the PGE-potentiated response; emorfazone inhibited the PGE-potentiated response to the same extent as in the case of the BK alone-induced response, while aminopyrine was more less active in inhibiting the PGE-potentiated response than BK alone-induced response and aspirin showed no action on the PGE-potentiated response. Such mode of action of emorfazone on BK-induced nociception was confirmed with a similar experiment using conscious rats. These results suggest that the main site of anti-nociceptive action of emorfazone may be in the periphery, and that its action may be not due to inhibition of PGs-synthesis or release.

Analgesics↗

Somatosensory evoked potentials associated with tactile stimulation at detection threshold in man.

Somatosensory evoked potentials elicited by sub- and supraliminal tactile pulses were studied during continuous threshold measurement. Two threshold methods were used: a modified tracking method and a detection method. With both methods threshold estimates of the same order of magnitude were obtained. Stimuli just above the threshold elicited a distinct somatosensory evoked potential with components P50, P100, N190 and P400. No such SEP was associated with the subliminal stimuli. However, in some cases some potential oscillations were obtained, time-locked to the subliminal stimuli; these are suggested to be due to errors in responding. In control experiments detected stimuli elicited a distinct SEP, but no SEP was associated with undetected stimuli of identical amplitude. The results indicate that in the psychophysical threshold determination the neural processing reflected in the SEP is associated only with supraliminal tactile stimulation. The lack of evoked brain activity associated with subliminal tactile stimuli supports the hypothesis derived from human microneurographic studies, stating that the tactile detection threshold may be based on an extremely small peripheral input, perhaps only on a single impulse in a single peripheral fiber.

Adult↗

Transcranial magnetic stimulation of the human frontal eye field facilitates visual awareness.

What are the brain mechanisms allowing a stimulus to enter our awareness? Some theories suggest that this process engages resources overlapping with those required for action control, but experimental support for these ideas is still required. Here, we investigated whether the human frontal eye field (FEF), an area known to control eye movements, is involved in visual awareness. Volunteers participated in a backward masking task in which they were able to detect a target in a small proportion of trials. We observed that a single pulse of transcranial magnetic stimulation applied over the FEF shortly before the target's onset facilitated visual sensitivity; subjects were able to detect an otherwise subliminal object. These results show that modulating the neuronal activity of the FEF can enhance visual detection, thereby yielding new insights into the neural basis of visual awareness.

Adult↗

Innervation of pelvic viscera in the rat. Evoked potentials in nerves to bladder and penis (clitoris).

In 29 rats, responses evoked by pelvic and hypogastric nerve stimulation were recorded from postganglionic nerves to bladder and penis (clitoris). Responses to pelvic nerve stimulation had nonsynapsing and synapsing components. The nonsynapsing component was relatively large in main nerve to penis and small in lateral nerve to penis and nerves to bladder. Pelvic nerve fiber synapsing on pelvic ganglion neurons to bladder had a large subliminal fringe, while fibers synapsing on neurons supplying penis (clitoris) had a small subliminal fringe. Recruitment was greater in nerves to bladder and lateral nerve to penis (clitoris) compared to main nerve to penis (clitoris), indicating more synapsing fibers in the former nerves. Almost all hypogastric fibers to bladder were direct. A small subliminal fringe was demonstrated for hypogastric fibers synapsing on neurons supplying penis. No subliminal fringe was evident for the bladder. Pelvic and hypogastric nerve interaction on pelvic ganglion neurons could not be demonstrated with either single shock or tetanic trains of conditioning stimuli. With antidromic stimulation, conduction velocities of afferent fibers in pelvic nerve ranged from 0.15 m per sec to 2.9 m per sec. In hypogastric nerve they ranged from 0.35 m per sec to 2.8 m per sec.

Animals↗

Role of solitarial GABAergic mechanisms in control of swallowing.

The role of solitarial gamma-aminobutyric acid (GABA)-ergic mechanisms in deglutition was investigated in urethane-anesthetized rats. When applied to the dorsal extraventricular surface of the nucleus tractus solitarii (NTS), muscimol reversibly inhibited 1) buccopharyngeal swallows evoked by either electrical or chemical stimulation of the NTS and 2) esophageal peristalsis evoked by muscarinic agonists. Bicuculline (5-1,000 pmol) applied to the NTS surface evoked rhythmic swallowing, which was reversibly blocked by DL-2-amino-7-phosphonoheptanoic acid (5-500 pmol). Methscopolamine (5-100 pmol) applied at the same site abolished the esophageal component of the response. Intrasolitarial application of bicuculline at s-glutamate-responsive loci in the intermediate and central subnuclei gave rise to buccopharyngeal and esophageal responses, respectively, and to a concomitant facilitation of glutamate-evoked responses. In subliminal doses ejected at esophageal loci, bicuculline induced deglutitive esophageal peristalsis during elicitation of buccopharyngeal swallowing by chemical (kainate or norepinephrine) or electrical stimulation of the NTS. We conclude that solitarial GABA neurons exert a tonic inhibition of the medullary deglutitive pattern generator and control buccopharyngeal-esophageal coupling.

Animals↗

Evidence for transliminality from a subliminal card-guessing task.

In this experiment we sought to provide evidence for transliminality from a test of subliminal perception that was disguised as a computerised ESP card-guessing task. It was predicted that highly transliminal individuals would outperform those with low levels of transliminality when given subliminal primes or 'clues' to the correct choice of card, but not when no primes were given. In line with the prediction, higher levels of transliminality were found to be associated with a greater number of correct selections of the target card on the primed trials, but not on the unprimed trials. In addition, a positive correlation was obtained between transliminality and detection accuracy, suggesting that higher levels of transliminality are associated with a greater sensitivity to visual stimulation. The results are discussed with reference to the possibility that transliminality might offer an alternative explanation for some ostensibly psychic perceptual experiences if subliminally acquired material is wrongly attributed to psychic sources.

Adolescent↗