Ultralate Laser Evoked Potentials Research Articles

Assessment of C Fibers Evoked Potentials in Healthy Subjects by Nd : YAP Laser.

Although laser stimuli activate both Ad- and C-fibres, the corresponding laser evoked potentials (LEPs) remain restricted to the Ad-fibers input, while the C-fibers related potential is hardly detectable. To evaluate multichannel ultralate LEPs (U-LEPs) by using Nd : Yap laser pulses in healthy volunteers to stimulation of face and lower and upper limbs, in order to estimate the reliability of C-LEPs elicited from both trigeminal and somatic sites. Twenty healthy volunteers participated in two stimulation sessions to record Aδ-LEPs and C-LEPs. We used a Nd : YAP Laser and 62 EEG recording electrodes. Stimuli parameters were set to activate either small myelinated (Aδ), eliciting purely warmth sensations, or unmyelinated (C) afferents, and eliciting pinprick sensations. At the trigeminal level, we obtained a negative-positive complex in a time interval compatible with the C fibers activation. In the somatic districts, the averaged responses consisted of an earlier negative-positive complex, followed by a later one. Single trials analysis of U-LEPs showed a maximal positive peak in a time interval in the range of C fibers. Topographical analysis of U-LEPs resembled that of LEPs. All subjects exhibited readable U-LEPs in at least 2 stimulated sites. Discussion. A purely warmth sensation seems to correspond to Aδ and C-fibers coactivation, at least in the somatic districts. While the related cortical waves seem hardly readable, their total absence could be a sign of systemic involvement of warm related C-fibers in specific clinical conditions.

Could autonomic system assessment be helpful in disorders of consciousness diagnosis? A neurophysiological study

Although patients with chronic disorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), show a limited repertoire of awareness signs, owing to a large-scale cortico-thalamo-cortical functional disconnectivity, an activation of some cortical areas in response to relevant stimuli has been described by means of electrophysiological and functional neuroimaging approaches. In addition, cognitive processes associated with autonomic nervous system (ANS) responses elicited by nociceptive stimuli have been identified in some DOC patients. In an attempt to identify ANS functionality markers that could be useful in differentiating UWS and MCS individuals, we measured the amplitude, latency and γ-band power (γPOW) of ultra-late laser-evoked potentials (CLEPs) and skin reflex (SR), which both express some aspects of cognitive processes related to ANS functionality, besides other ANS parameters either during a 24(hh)-polygraphy or following a solid-state laser repetitive nociceptive stimulation. MCS showed physiological modification of vital signs (O2 saturation, hearth rate, hearth rate variability) throughout the night and a preservation of SR-γPOW, whereas UWS did not show significant variations. Following repetitive nociceptive stimulation, MCS patients had a significant increase in CLEP-γPOW, O2 saturation, hearth rate, and hearth rate variability, whereas UWS individuals did not show any significant change (but two patients, who reached high Coma Recovery Scale-Revised scores). Hence, our work suggests that a wide-spectrum electrophysiological evaluation of ANS functionality may support DOC differential diagnosis. Interestingly, the two above-mentioned UWS patients showed MCS-like vital sign modifications and electrophysiological pain responsiveness. It is therefore hypothesizable that our approach could be helpful in identifying residual aware autonomic system-related cognitive processes even in some UWS patients. Such issue draws the attention to either DOC clinical diagnosis or adequate pain treatment in DOC patients.

46. Late and ultralate laser-evoked potentials using a laser YAG stimulator

Laser-evoked potentials (LEPs) currently represent the most reliable and widely used method of investigating the Ad-fibre pathways in the diagnosis of neuropathic pain. The aim of our study was to investigate the usefulness of a new laser evoked simulator and its application in clinical neurophysiology. Using the Tm:YAG laser simulator ( λ 1.9 μm) we recorded LEPs after face, hand, and foot bilateral stimulation in 30 normal subjects. We performed late and ultralate LEPs recordings using two different setting of stimuli for C – fibers and for A delta – fibers. We measured the perceptive threshold, latency and amplitude of the main vertex components, and their side-to-side differences. We also studied the correlations between LEP data and age and body height, as well as gender differences. In all normal subjects we obtained a N2P2 complex at the vertex after both A delta and C stimuli. Laser perceptive threshold increased and LEP amplitude decreased from face to foot ( P < 0.005). The amplitude correlated with age ( P < 0.001. LEP data did not significantly differ between genders ( P < O0.3). This study provides the usefulness of a new laser simulator able to obtain also at the foot reliable ultralate C Leps. We collect normative values for the main LEP data and their absolute and side-to-side limits, confirming the physiological differences assessed in Literature for others Laser stimulators. Our preliminary data may help to improve the clinical application of late and ultralate LEPs as a diagnostic tool in clinical practice.

Tobacco Smoking Can Potentiate C-fiber Evoked Potentials in Human Brain

The effects of smoking and nicotine on ultralate laser evoked potentials (LEPs), the EEG responses to C-fiber stimulation by a laser beam, were investigated in humans. Ultralate LEPs were repeatedly measured in two sessions, one after smoking, and the other in abstinence from smoking. The dominant frequency of the background EEG alpha activity, heart rate and venous plasma nicotine concentration were also measured. The peak-to-peak amplitude of the two major components (N2 and P2) of ultralate LEPs was significantly correlated both with the plasma nicotine concentration and with the background alpha frequency. The results suggest an arousal effect of nicotine on C-fiber mediated pain. The effect of nicotine on C-fiber LEPs was in the opposite direction of that on Afiber LEPs. The difference between C and Afibers might indicate a difference in effects of nicotine on first and second pain responses.

Conduction Velocities of Aδ-fibers and C-fibers in Human Peripheral Nerves and Spinal Cord After CO2 Laser Stimulation

Conduction velocities (CVs) in two nociceptive afferents were estimated to clarify the mechanism of pain transmission. Late and ultra-late laser evoked potentials (LEPs) were recorded by stimulating Adelta- and C-nociceptive nerve endings at different skin sites (the hand, foot, and skin overlying the 7th cervical and 12th thoracic vertebrae), by which data CVs of the arm (CVA), leg (CVL), and spinothalamic tract (CVSTT) were estimated. In late LEPs, Adelta-CVA and Adelta-CVL respectively were between 6.7 and 23.7 (mean +/- SD, 12.8 +/- 5.2) m/s, and 9.0 and 26.7 (17.2 +/- 5.6) m/s. Adelta-CVSTT was between 4.1 and 22.1 m/s (10.6 +/- 5.8). In ultra-late LEPs, C-CVA and C-CVL respectively varied between 1.0 and 2.1 (mean +/- SD, 1.5 +/- 0.3) m/s, and 1.0 and 1.9 (1.4 +/- 0.2) m/s. C-CVSTT was between 1.0 and 3.9 (1.8 +/- 0.8) m/s. No significant difference was found among CVA, CVL, and CVSTT values calculated from late or ultra-late LEP latencies. Nociceptive signals of the primary Adelta- and C-afferents therefore may be conveyed separately by myelinated (Adelta-) and unmyelinated (C) axons through peripheral nerves and spinal cord.

Innocuous skin cooling modulates perception and neurophysiological correlates of brief CO 2 laser stimuli in humans

The present study examined the influence of innocuous skin cooling on the perception and neurophysiological correlates of brief noxious CO 2 laser stimuli. In nine normal subjects, brief CO 2 laser pulses of four different intensities (duration 50 ms; diameter 5 mm; intensity range 5.8–10.6 mJ/mm 2) were delivered at random every 5–10 s on the dorsum of the hand. Innocuous skin cooling was performed by a thermode (20 °C; 3 × 3 cm) with a central hole for the laser test stimuli. Quality and intensity (VAS) of perceptions, reaction times and laser evoked potentials (LEPs) were examined. Signal detection theory analysis was performed to evaluate discrimination performance and decision criterion. During innocuous skin cooling, detection threshold increased from 4.8 ± 1.81 to 8.2 ± 1.05 mJ/mm 2 and pain threshold from 8.7 ± 1.53 to 13.5 ± 1.57 mJ/mm 2. proportion of detected stimuli decreased from 87% to 48% and pain reports from 42% to 10%. The well localized ‘pricking’ sensation mediated by Aδ-nociceptors almost vanished. The intensity of sensations (VAS scores) was considerably reduced. Sensory discriminative performance was significantly depressed but decision criterion remained unchanged. Reaction times were delayed. The late-LEPs, correlates of Aδ-nociceptor activations, were also significantly depressed while the ultra-late LEPs, correlates of C-nociceptors, were not affected. Taken together, these results strongly suggest that innocuous skin cooling interfered with the sensory processing of laser heat stimuli and more prominently with those related to Aδ-nociceptive input.

Trigeminal responses to laser stimuli

The majority of the studies on laser evoked potentials (LEPs) have been focused on hand and foot stimulations and only lately on the trigeminal system. Because of a high receptor density in the facial skin and the very short conduction distance, LEP recordings after trigeminal stimulation are easier and quicker than those after stimulation of the limb extremities. Laser pulses with a stimulus intensity close to perception threshold can evoke well-defined LEPs. Few trials are sufficient to yield stable and reproducible averages. Even ultralate LEPs related to the C-fibre input are comparatively easily obtained from the trigeminal territory. The brain generators of the main LEP waves are probably very close for the trigeminal and limb stimulations. Trigeminal LEPs have been found absent or delayed in patients with trigeminal neuralgia, trigeminal neuropathies, posterior fossa tumors, and brainstem infarctions or demyelinating plaques. Conversely, trigeminal LEPs appear to be enhanced in patients with migraine. High-intensity pulses directed to any trigeminal division also elicit reflex responses: a blink-like reflex in the orbicularis oculi and a single silent period in the contracting masseter muscle. The availability of a neurophysiological method of assessing function of the trigeminal nociceptive pathways reaching both the cerebral cortex and the brainstem reflex circuits, has provided new opportunities for investigating the pathophysiology of orofacial pain syndromes.

Exogenous and endogenous components of ultralate (C-fibre) evoked potentials following CO 2 laser stimuli to tiny skin surface areas in healthy subjects

CO 2 laser stimulation of tiny skin surface areas on the hand dorsum generate ultralate laser evoked potentials (LEPs) with a major positivity maximal at the vertex at a latency of about 1 s. These potentials follow selective and direct activation of C-fibres in the superficial layers of the skin. To identify the endogenous P3 component in ultralate LEPs, we used a 2-stimulus oddball paradigm (20% probability of targets). Ultralate LEPs were recorded in eight healthy subjects with 19 channels EEG and EOG. Laser stimuli ( n = 200/subject, < 0.5 mm diameter, 5 ms duration, 9.4 mJ/mm 2 energy density) were applied in a pseudo-random order to the proximal phalanx of either middle finger (target) or index (non-target) of the left hand. Vigilance was maintained during recording sessions. Subject’s task was to press a button to any kind of sensation perceived at the target zone. We observed a negative-positive (N965-P1139) complex maximal at Cz for all stimulus conditions. This complex was of significantly larger amplitude for rare events. For the target responses, a second distinct positive peak was observed with a mean latency of 1343 ± 103.5 ms with maximum amplitude at Pz. This latest peak may represent an endogenous P3-like component as it is linked to the subject’s detection of the target stimulus (rare events).

The effects of A-fiber pressure block on perception and neurophysiological correlates of brief non-painful and painful CO 2 laser stimuli in humans

This study examined the relative capacity of Aδ- and C-fibers to encode non-painful and painful brief CO 2 laser stimuli by comparing the effects of Aδ/C-fiber activation versus C-fiber activation alone. In nine normal subjects, brief CO 2 laser pulses of four different intensities (range 5.8– 10.6 mJ/ mm 2 ) were delivered at random on the first intermetacarpal zone of the dorsum of the hand. A-fiber pressure block of the superficial radial nerve was performed to fully isolate the activity of C-fibers. Quality and intensity (VAS) of percepts, reaction time (RT) and laser-evoked potentials (LEPs) were examined in baseline and A-fiber block conditions. During A-fiber block, absolute detection threshold increased dramatically from 4.8±1.8 to 10.9±4.8 mJ/ mm 2 , proportion of detected stimuli decreased from 87% to 47% and proportion of pain reports from 39% to 10%. The quality of sensations became mainly ‘light touch’ and the ‘pricking’ sensation almost vanished. The stimulus-VAS curve shifted to the right and the slope was reduced. Signal Detection Theory analysis revealed that discrimination performance (P(A)) was significantly depressed and that response bias (B) evolved from a neutral towards a stoical attitude. Median RT increased from 492 to 1355 ms. The late LEPs, attributed to the activation of Aδ-fibers, disappeared and ultra-late LEPs were recorded at Cz with a positivity peaking around 800 ms. Collectively, these observations lead to the conclusion that Aδ-fibers are the main peripheral mediators for the perception of brief CO 2 laser stimuli and that they provide more sensory information than C-fibers.

Effects of attention, distraction and sleep on CO(2) laser evoked potentials related to C-fibers in humans.

The objective of this study is to evaluate the effects of attention, distraction and sleep on CO(2) laser-evoked potentials (LEP) relating to C-fibers (ultra-late LEP). Non-painful CO(2) laser pulses were delivered to a tiny skin area of the dorsum of the right hand. Ultra-late LEP were recorded from 10 normal subjects in 5 different conditions: control (wakefulness), attention, distraction, drowsiness and sleep (stage 2). The amplitude of ultra-late LEP was slightly increased during attention and significantly decreased during distraction, relative to the control. The ultra-late LEP decreased much in amplitude or almost disappeared during sleep. However, significant differences in latency among the conditions were not found. We confirmed that the brain responses relating to signals ascending through C-fibers were much affected by the level of consciousness, being consistent with the findings of late LEP relating to Adelta-fibers. This is the first study to indicate the important characteristics of ultra-late LEP relating to consciousness, suggesting that they include cognitive function and also that one has to be careful of the change in alertness when recording.

Attention-related modifications of ultra-late CO 2 laser evoked potentials to human trigeminal nerve stimulation

Our study aimed at investigating the scalp topography of ultra-late CO 2 laser evoked potentials (LEPs), which are related to C fiber activation, and at exploring the effect of attention deviation on ultra-late LEPs. Brain responses to non-painful CO 2 laser stimuli were recorded in ten healthy subjects in three different conditions: (i) neutral condition in which subjects did not have any task; (ii) distraction condition in which subjects were asked to perform a mathematical task; and (iii) attention condition in which subjects had to count the number of stimuli. In all subjects, also Að fiber-related late LEPs were recorded after painful CO 2 laser stimulation. The ultra-late LEPs in attention condition included an earlier negative potential (ultra-late N1) in the contralateral temporal region and a simultaneous frontal positive response (ultra-late P1). Later, a vertex biphasic component (ultra-late N2a and ultra-late P2) was identifiable. The vertex ultra-late LEP amplitude was significantly decreased in both neutral and distraction condition. Ultra-late LEPs showed a longer latency than late LEPs, but the scalp distributions of both ultra-late and late LEPs were very similar, thus suggesting that the same cerebral areas may be involved in their generation. Since attention deviations have a strong effect on ultra-late LEP amplitude, the subject's attention should be addressed to CO 2 laser stimuli when ultra-late LEPs are used for clinical purposes.

Scalp topography of ultralate (C-fibres) evoked potentials following thulium YAG laser stimuli to tiny skin surface areas in humans

Aim: To investigate (1) the scalp topography of ultralate laser evoked potentials (LEPs) related to C-fibre activation, which can directly be obtained by thulium YAG (Tm YAG) laser stimulation of tiny skin surface areas (about 0.23 mm 2) and (2) the influence of the performance of a motor task on ultralate LEPs. Methods: Laser stimuli were applied to the dorsum of the left hand. LEPs were recorded with 58 scalp electrodes from 9 healthy subjects in two different conditions, with and without a reaction time (RT) task (press a button upon detection). Results: On high resolution electroenchephalogram recordings, ultralate LEPs were characterized by a broad positive component (peak latency: 1133±91 ms) with maximum amplitude about the vertex. Moreover, the performance of a RT task had no influence on latency, amplitude and topographical patterns of two maps chosen at the positive peak latency in ultralate LEPs. Nevertheless, a negative inflexion (latency 1300 ms) appeared after the positive component in the task condition possibly reflecting movement-related potentials. Conclusion: Tm YAG laser stimulation of tiny skin surface areas allows recording the dynamic scalp topography of ultralate (C-fibres) LEPs, with or without the performance of a RT task.

Dipole analysis of ultralate (C-fibres) evoked potentials after laser stimulation of tiny cutaneous surface areas in humans

Ultralate (C-fibres) laser evoked potentials (LEP) can be obtained by stimulation of a tiny skin surface area (0.23 mm 2). Since their generators are unknown up to now, we performed brain source analyses of ultralate LEPs using high resolution electroencephalography (64 channels) and a realistic head model that was based on individual magnetic resonance images. Ultralate LEPs were characterized by a negative–positive complex with a large positive component maximal at the vertex. Source analysis revealed that ultralate LEPs could be explained by two dipole sources in the upper bank of the contralateral and ipsilateral Sylvian fissure (SII) and one dipole in the median region corresponding to the anterior cingulate gyrus.

C- and Aδ-fiber components of heat-evoked cerebral potentials in healthy human subjects

Feedback-controlled laser heat was used to stimulate the hairy skin of the hand dorsum and forearm, and heat-evoked cerebral potentials were recorded at midline (Fz, Cz, Pz) and temporal (T3, T4) scalp positions. Based on data from primary afferent electrophysiology a stimulus level (40°C) was chosen, which is above C-fiber heat threshold, but clearly below Aδ-nociceptor heat threshold in order to excite selectively C-fibers without concomitant excitation of Aδ-fibers. Feedback-controlled stepped heat stimuli to 40°C elicited ultralate laser evoked potentials (LEPs) at the vertex in a high proportion of experiments (90%). Estimates of conduction velocity calculated from latency shifts between the hand and forearm sites of ultralate LEPs (2.4 m/s) and of reaction times (2.8 m/s) confirmed mediation of ultralate potentials by unmyelinated nerve fibers (nociceptors and/or warm fibers). The ultralate LEP could be differentiated from resolution of contingent negative variation (CNV), an endogenous potential related to expectation and response preparation, by its scalp topography. Strong heat stimuli of 48°C, which is suprathreshold for most Aδ- and C-fiber nociceptors, elicited the well-known late LEPs mediated by nociceptive Aδ-fibers confirming previous studies. The LEP waveform to strong heat stimuli also contained an ultralate component reminiscent of an ultralate LEP following the late LEP. Ultralate and late LEP had identical scalp topography. In conclusion, the method of temperature-controlled laser heat stimuli allows the selective and reliable examination of Aδ- and C-fiber-mediated afferent pathways and the related cortical processing without the complication of dissociating A-fiber nerve blocks.