Transient and permanent deficits in motion perception after lesions of cortical areas MT and MST in the macaque monkey.
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We examined the nature and the selectivity of the motion deficits produced by lesions of extrastriate areas MT and MST. Lesions were made by injecting ibotenic acid into the representation of the left visual field in two macaque monkeys. The monkeys discriminated two stimuli that differed either in stimulus direction or orientation. Direction and orientation discrimination were assessed by measuring thresholds with gratings and random-dots placed in the intact or lesioned visual fields. At the start of behavioral testing, we found pronounced, motion-specific deficits in thresholds for all types of moving stimuli, including pronounced elevations in contrast thresholds and in signal-to-noise thresholds measured with moving gratings, as well as deficits in direction range thresholds and motion coherence measured with random-dot stimuli. In addition, the accuracy of direction discrimination was reduced at smaller spatial displacements (i.e. step sizes), suggesting an increase in spatial scale of the residual directional mechanism. Subsequent improvements in thresholds were seen with all motion stimuli, as behavioral training progressed, and these improvements occurred only with extensive behavioral testing in the lesioned visual field. These improvements were particularly pronounced for stimuli not masked by noise. On the other hand, deficits in the ability to extract motion from noisy stimuli and in the accuracy of direction discrimination persisted despite extensive behavioral training. These results demonstrate the importance of areas MT and MST for the perception of motion direction, particularly in the presence of noise. In addition, they provide evidence for the importance of behavioral training for functional recovery after cortical lesions. The data also strongly support the idea of functional specialization of areas MT and MST for motion processing. (+info)
Spinal cord-evoked potentials and muscle responses evoked by transcranial magnetic stimulation in 10 awake human subjects.
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Transcranial magnetic stimulation (TCMS) causes leg muscle contractions, but the neural structures in the brain that are activated by TCMS and their relationship to these leg muscle responses are not clearly understood. To elucidate this, we concomitantly recorded leg muscle responses and thoracic spinal cord-evoked potentials (SCEPs) after TCMS for the first time in 10 awake, neurologically intact human subjects. In this report we provide evidence of direct and indirect activation of corticospinal neurons after TCMS. In three subjects, SCEP threshold (T) stimulus intensities recruited both the D wave (direct activation of corticospinal neurons) and the first I wave (I1, indirect activation of corticospinal neurons). In one subject, the D, I1, and I2 waves were recruited simultaneously, and in another subject, the I1 and I2 waves were recruited simultaneously. In the remaining five subjects, only the I1 wave was recruited first. More waves were recruited as the stimulus intensity increased. The presence of D and I waves in all subjects at low stimulus intensities verified that TCMS directly and indirectly activated corticospinal neurons supplying the lower extremities. Leg muscle responses were usually contingent on the SCEP containing at least four waves (D, I1, I2, and I3). (+info)
Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers.
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A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 microM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-delta units [conduction velocity (c.v.) 5-18 m/s] but only 50% (5/10) of slow A-delta units (1.5 +info)
Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey.
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We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain. (+info)
Quantitative structure-activity relationships for nasal pungency thresholds of volatile organic compounds.
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A model was developed for describing the triggering of nasal pungency in humans, based on the partition of volatile organic compounds (VOCs) between the air phase and the biophase. Two partition parameters are used in the model: the water-air partition coefficient and the octanol-water partition coefficient. The model was validated using data from the literature, principally on alcohols, acetates and ketones. The model suggests that all test compounds, regardless of their chemical functional groups, bind to a common receptor site within the hydrophobic interior of the bilayer membrane of the trigeminal nerve endings. There is probably only a slight, non-specific interaction between the VOC molecule and the receptor molecule, whereas this type of non-specific interaction for the detection of odor is much stronger. In practical terms, the suggestion that all VOCs share a common irritation receptor site implies that nasal-pungency thresholds of individual VOCs may be additive. Quantitative structure-activity relationships (QSARs) for nasal-pungency thresholds were also developed from the model, which can be used to predict nasal-pungency thresholds of common VOCs. Although the present model does not offer additional precision over that of M.H. Abraham et al., 1996, Fundam. Appl. Toxicol. 31, 71-76, it requires fewer descriptors and offers a physiological basis to the QSAR. Another advantage of the present model is that it also provides a basis for comparison between the olfactory process and nasal pungency. (+info)
Paradoxical heat sensation in healthy subjects: peripherally conducted by A delta or C fibres?
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Paradoxical heat sensation upon cooling of the skin has been reported in central as well as in peripheral neurological conditions. In our study, we examined this phenomenon in 35 naive healthy test subjects, of whom 23 experienced paradoxical heat sensation under test conditions. We measured the peripheral conduction velocities of cold sensation, warm sensation and of paradoxical heat sensation by using a quantitative sensory testing model of indirect peripheral conduction velocity measurement. This was based on comparison of measurements at a proximal and a distal site using two measurement methods, one inclusive and the other exclusive of reaction time. We found that the conduction velocity of paradoxical heat sensation (0.70 m/s) was similar to that of warm sensation (0.68 m/s), and that the conduction velocity of cold sensation (7.74-8.01 m/s) was considerably faster. Thus, we conclude that paradoxical heat sensation in healthy subjects is conducted peripherally via slow unmyelinated C fibres and not via the faster A delta fibres. Consequently, we propose that paradoxical heat sensation is encoded via the heat sensing pathway, in accordance with the labelled-line code theory. The mechanisms proposed suggest a malfunctioning cold-sensing pathway disinhibiting the heat-sensing pathway, at peripheral, central or both levels, thus facilitating a paradoxical heat sensation. (+info)
Impairment in preattentive visual processing in patients with Parkinson's disease.
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We explored the possibility of whether preattentive visual processing is impaired in Parkinson's disease. With this aim, visual discrimination thresholds for orientation texture stimuli were determined in two separate measurement sessions in 16 patients with idiopathic Parkinson's disease. The results were compared with those of 16 control subjects age-matched and 16 young healthy volunteers. Discrimination thresholds were measured in a four-alternative spatial forced-choice paradigm, in which subjects judged the location of a target embedded in a background of distractors. Four different stimulus configurations were employed: (i) a group of vertical targets among horizontal distractors ('vertical line targets'); (ii) targets with varying levels of orientation difference on a background of spatially filtered vertically oriented noise ('Gaussian filtered noise'); (iii) one 'L' among 43 '+' signs ('texton'), all of which assess preattentive visual processing; and (iv) control condition, of one 'L' among 43 'T' distractors ('non-texton' search target), which reflects attentive visual processing. In two of the preattentive tasks (filtered noise and texton), patients with Parkinson's disease required significantly greater orientation differences and longer stimulus durations, respectively. In contrast, their performance in the vertical line target and non-texton search target was comparable to that of the matched control subjects. These differences were more pronounced in the first compared with the second session. Duration of illness and age within the patient group correlated significantly with test performance. In all conditions tested, the young control subjects performed significantly better than the more elderly control group, further indicating an effect of age on this form of visual processing. The results suggest that, in addition to the well documented impairment in retinal processing, idiopathic Parkinson's disease is associated with a deficit in preattentive cortical visual processing. (+info)
NOS inhibitor antagonism of PGE2-induced mechanical sensitization of cutaneous C-fiber nociceptors in the rat.
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Prostaglandins, metabolites of arachidonic acid, released during tissue injury and inflammation sensitize primary afferent nociceptors. While it has been suggested that this effect on nociceptors is mediated mainly via the cAMP second messenger system, recent evidence suggests that nitric oxide (NO) is also involved in peripheral pain mechanisms. To test the hypothesis that NO contributes to the sensitization of nociceptors to mechanical stimuli induced by hyperalgesic prostaglandins, we compared von Frey hair mechanical threshold as well as the response evoked by 10-s sustained threshold mechanical stimulation before and after injection of prostaglandin E2 (PGE2) alone, and NOS inhibitor NG-methyl-L-arginine (L-NMA) or its inactive stereoisomer NG-methyl-D-arginine (D-NMA) plus PGE2, adjacent to the receptive field of C-fiber nociceptors. The reduction of mechanical threshold and increase in number of action potentials to sustained mechanical stimulation induced by intradermal application of PGE2 was blocked by L-NMA, but not D-NMA. It is suggested that NO contributes to nociceptor sensitization induced by hyperalgesic prostaglandins. (+info)