Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation.

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.

Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.

BACKGROUND: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. OBJECTIVE: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. DESIGN: This is an explorative study. SETTINGS: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. PATIENTS: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. MAIN OUTCOME MEASURES: Cortical evoked potentials were measured. RESULTS: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in ß (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and ß and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. LIMITATIONS: This is an explorative study of limited size. CONCLUSIONS: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Activation of C-fiber nociceptors by low-power diode laser.

OBJECTIVE: The evaluation of selective activation of C-fibers to record evoked potentials using the association of low-power diode laser (810 nm), tiny-area stimulation and skin-blackening. METHOD: Laser-evoked potentials (LEPs) were obtained from 20 healthy young subjects. An aluminum plate with one thin hole was attached to the laser probe to provide tiny-area stimulation of the hand dorsum and the stimulated area was covered with black ink. RESULTS: The mean intensity used for eliciting the ultra-late laser-evoked potential (ULEP) was 70 ± 32 mW. All subjects showed a clear biphasic potential that comprised a negative peak (806 ± 61 ms) and a positive deflection (1033 ± 60 ms), corresponding to the ULEP related to C-fiber activation. CONCLUSION: C-fiber-evoked responses can be obtained using a very low-power diode laser when stimulation is applied to tiny areas of darkened skin. This strategy offers a non-invasive and easy methodology that minimizes damage to the tissue.

Activation of C-fiber nociceptors by low-power diode laser / Ativação por laser de diodo de baixa potência de nociceptores relacionados a fibras C

ABSTRACT Objective The evaluation of selective activation of C-fibers to record evoked potentials using the association of low-power diode laser (810 nm), tiny-area stimulation and skin-blackening. Method Laser-evoked potentials (LEPs) were obtained from 20 healthy young subjects. An aluminum plate with one thin hole was attached to the laser probe to provide tiny-area stimulation of the hand dorsum and the stimulated area was covered with black ink. Results The mean intensity used for eliciting the ultra-late laser-evoked potential (ULEP) was 70 ± 32 mW. All subjects showed a clear biphasic potential that comprised a negative peak (806 ± 61 ms) and a positive deflection (1033 ± 60 ms), corresponding to the ULEP related to C-fiber activation. Conclusion C-fiber-evoked responses can be obtained using a very low-power diode laser when stimulation is applied to tiny areas of darkened skin. This strategy offers a non-invasive and easy methodology that minimizes damage to the tissue.

RESUMO Objetivo Avaliação da ativação de fibras C para o registro de potenciais evocados utilizando-se laser de baixa potência, áreas pequenas de estimulação e escurecimento da pele. Método Potenciais evocados foram obtidos de 20 sujeitos. Uma placa de alumínio com uma pequena abertura foi acoplada à ponteira do laser para estimular área escurecida do dorso da mão. Resultados A intensidade média utilizada para estimulação foi de 70 ± 32 mW. Todos os sujeitos apresentaram respostas claras compreendendo dois picos um negativo (806 ± 61 ms) seguido por outro positivo (1033 ± 60 ms), correspondendo ao potencial evocado tardio por estimulação de fibras C. Conclusão Respostas de fibras C podem ser obtidas utilizando-se laser de baixa potência quando a estimulação é aplicada a pequenas áreas de pele escurecida. Esta estratégia oferece uma metodologia não invasiva que minimiza danos teciduais.

Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening.

Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn't affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications.

Thermal detection thresholds of Aδ- and C-fibre afferents activated by brief CO2 laser pulses applied onto the human hairy skin.

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO(2) laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.

TRPV4 channels mediate the infrared laser-evoked response in sensory neurons.

Infrared laser irradiation has been established as an appropriate stimulus for primary sensory neurons under conditions where sensory receptor cells are impaired or lost. Yet, development of clinical applications has been impeded by lack of information about the molecular mechanisms underlying the laser-induced neural response. Here, we directly address this question through pharmacological characterization of the biological response evoked by midinfrared irradiation of isolated retinal and vestibular ganglion cells from rodents. Whole cell patch-clamp recordings reveal that both voltage-gated calcium and sodium channels contribute to the laser-evoked neuronal voltage variations (LEVV). In addition, selective blockade of the LEVV by micromolar concentrations of ruthenium red and RN 1734 identifies thermosensitive transient receptor potential vanilloid channels as the primary effectors of the chain reaction triggered by midinfrared laser irradiation. These results have the potential to facilitate greatly the design of future prosthetic devices aimed at restoring neurosensory capacities in disabled patients.

Effects of changing illuminance on somatosensory function.

Artificial sources of illumination can be easily used, regardless of the time and place, to improve visibility at night and in dark places. Illuminance and color temperature are particularly important factors since they are known to elicit physiological effects. However, the relationship between changes in illuminance and somatosensory function has not been sufficiently clarified. Thus, the purpose of this study was to construct a laboratorial model to examine the effects of lowering or raising illuminance on somatosensory function. Three illuminance levels (200 lx, 50 lx, and 0 lx), which were changed using all combinations, and an artificial sensory stimulus maintained at a constant intensity were presented to the subjects of this study. Objective sensory function in response to the sensory stimulus was investigated by somatosensory evoked potential (SEP), and subjective sensory evaluation in response to the stimulus was investigated using a visual analogue scale (VAS) and by interview. In many cases, the SEP amplitude and VAS value tended to decrease when illuminance was lowered and tended to increase when illuminance was raised. However, in a few cases, SEP amplitude and VAS value tended to increase in spite of the low illuminance. The occurrence of attention responses and unpleasant emotional responses caused by lowering the illuminance seems to be related to this study finding.

Inhibitory effects of visible 650-nm and infrared 808-nm laser irradiation on somatosensory and compound muscle action potentials in rat sciatic nerve: implications for laser-induced analgesia.

Low-level laser therapy (LLLT) has been shown in clinical trials to relieve chronic pain and the World Health Organization has added LLLT to their guidelines for treatment of chronic neck pain. The mechanisms for the pain-relieving effects of LLLT are however poorly understood. We therefore assessed the effects of laser irradiation (LI) on somatosensory-evoked potentials (SSEPs) and compound muscle action potentials (CMAPs) in a series of experiments using visible (λ = 650 nm) or infrared (λ = 808 nm) LI applied transcutaneously to points on the hind limbs of rats overlying the course of the sciatic nerve. This approximates the clinical application of LLLT. The 650-nm LI decreased SSEP amplitudes and increased latency after 20 min. CMAP proximal amplitudes and hip/ankle (H/A) ratios decreased at 10 and 20 min with increases in proximal latencies approaching significance. The 808-nm LI decreased SSEP amplitudes and increased latencies at 10 and 20 min. CMAP proximal amplitudes and H/A ratios decreased at 10 and 20 min. Latencies were not significantly increased. All LI changes for both wavelengths returned to baseline by 48 h. These results strengthen the hypothesis that a neural mechanism underlies the clinical effectiveness of LLLT for painful conditions.

Differential processing of laser stimuli by Aδ and C fibres in major depression.

Clinical studies have revealed that up to 92% of major depressed patients report pain complaints such as back or abdominal pain. Furthermore, patients suffering from depression exhibit increased superficial pain thresholds and decreased ischemic (deep) pain thresholds during experimental pain testing in comparison to healthy controls. Here, we aimed to investigate a putative role of Aδ- and C-fibre activation in altered pain perception in the disease. Laser-evoked potentials (LEPs) of 27 unmedicated depressed patients and 27 matched controls were recorded. Aδ and C fibres were activated separately. Amplitudes and latencies of N2 and P2 peaks of Aδ- (Aδ-LEP) and C-fibre- (C-LEP) related LEPs were evaluated. Depressed patients showed significantly decreased Aδ-LEP amplitudes (N2 peak: P=0.019; P2 peak: P=0.024) and delayed C-LEP latencies (P2 peak: P=0.0495; N2 peak: P=0.0556). In contrast, C-LEP amplitudes and Aδ-LEP latencies were unaffected. Our results might be suggestive of the differential impact of physiological changes on pain processing in depression. Thus, Aδ-LEP might reflect the physiological correlate of the augmented superficial pain thresholds during depression. On the contrary, the C-fibre component mediates the facets of pain processing, outlasting the stimulation period, and has been shown to be exaggerated in chronic pain states. Therefore, the functional over-representation of the C-fibre component found in our study might be a possible link between depression and associated pain complaints.

Comparison of LEP and QST and their contribution to standard sensory diagnostic assessment of spinal lesions: a pilot study.

This study evaluates the additional use of laser-evoked potentials (LEP) and quantitative sensory testing (QST) in the sensory assessment of spinal lesions. Four consecutive patients with spinal lesions verified by MRI and clinical evidence for mild spinothalamic tract involvement were included. The electrophysiological workup [somatosensory evoked potentials (SEP) and LEP] was compared to QST. Electrophysiology and QST were reassessed after about 6 months. LEP detected impaired spinothalamic tract function in 7/8 examinations. QST pointed to spinothalamic tract lesions by loss of thermal function (3/8); most frequent positive sensory signs (3/8) were paradoxical heat sensations. LEP and QST results were concordant in 6/8 examinations. SEPs were abnormal in 2/8 examinations. Congruent results between SEP and both LEP and QST were obtained in 3/8 examinations. LEP detected more deficits than any single QST parameter or their combination but additional QST allows the detection of positive sensory signs. The diagnostic gain of SEP was limited.

Laser evoked potential recording from intracerebral deep electrodes.

OBJECTIVE: To investigate whether recording from deep intracerebral (IC) electrodes can disclose laser evoked potential (LEP) components generated under the cerebral cortex. METHODS: LEPs were recorded to hand and/or perioral region stimulation from 7 patients suffering from Parkinson's disease, who underwent implant of IC electrodes in the globus pallidum pars interna (GPi), in the subthalamic nucleus (STN) and in the pedunculopontine nucleus (PPN). LEPs were obtained from the IC electrode contacts and from the Cz vertex, referred to the nose. RESULTS: The scalp traces showed a triphasic response (P1-N2-P2). The IC electrodes recorded two main components (ICP2 and ICN2), showing the same latencies as the scalp N2 and P2 potentials, respectively. The ICP2-ICN2 complex was sometimes preceded by a ICP1 wave at the same latency of the scalp P1 response. CONCLUSIONS: The LEP components recorded from the IC electrodes mirrored the ones picked up from the Cz lead, thus suggesting that they are probably generated by the opposite pole of the same cortical sources producing the scalp responses. SIGNIFICANCE: In the IC traces, there was no evidence of earlier potentials possibly generated within the thalamus or of subcortical far-field responses. This means that the nociceptive signal amplification occurring within the cerebral cortex is necessary to produce identifiable LEP components.

Neurophysiological and histopathological evaluation of low-dose radiation on the cauda equina and postlaminotomy fibrosis: an experimental study in the rat.

STUDY DESIGN: We evaluated the electrophysiological changes to the cauda equina after low-dose external irradiation in a postlaminotomy fibrosis model in rats. OBJECTIVE: To clarify the immediate and long-term electrophysiological responses of antifibrotic radiation therapy in a fibrosis model. SUMMARY OF BACKGROUND DATA: Low-dose perioperative radiation therapy inhibits scar formation. However, its efficacy for preventing fibrosis-induced compressive neuropathy and its potential adverse effect on underlying neural structures have not been studied. METHODS: Twenty-four rats were placed in 3 groups of 8: group I, sham operation (laminar exposure alone) with a single fraction of 700 cGy external irradiation given using a 9-MeV electron beam 24 hours postsurgery; group II, left L5 hemilaminectomy (laminotomy) alone; and group III, left L5 hemilaminectomy with the same radiation protocol as group 1. We recorded mixed-nerve-elicited somatosensory-evoked potentials (M-SSEP)- and dermal (D)-SSEP at the thoracolumbar junction, and L1-L2 interspinous ligament after percutaneously stimulating the posterior tibial nerve at the bilateral medial ankle and L5 dermatomal fields. We compared the potentials recorded immediately before, 30 minutes, 2 weeks, and 1, 2, and 3 months after surgery on the operated and nonoperated sides. We used gross dissection and histologic sections to evaluate the degree of perineural fibrosis and walking-track analysis for neurologic evaluation. RESULTS: Pre- and postoperative (30 minutes and 2 weeks) M- and D-SSEP were not statistically different. In group II, the relative amplitude of D-SSEP (elicited from 5 dermatomes) 1, 2, and 3 months postsurgery was lower; however, the M-SSEP in all groups and D-SSEP of groups I and III remained constant. Histologic evaluation of radiation efficacy showed that the frequency and extent of peridural fibrosis was consistently lower in group II than in group III. CONCLUSION: Low-dose irradiation reduced peridural fibrosis and prevented fibrosis-induced radiculopathy. The radiation caused no adverse neuropathic complications.

Cerebral columnar organization of the first nociceptive component induced by CO2 laser on the tail of the rat.

The somatotopic map of the first nociceptive component in the primary somatosensory cortex (S1) is still unclear. In this study, a CO(2) laser was applied to the tail of the rat to induce nociception without the interference from large myelinated (A(beta)) fibers. Thus, only noxious fibers could be activated. Two-dimensional current-source-density analysis was used to analyze the evoked field potentials. Using this method, the nociceptive responses of A(delta)-fibers in S1 were verified, and the somatotopic map of the first nociceptive component in S1 was identified. We found that whether light touch or laser-induced nociception was applied to the tail of the rat, the responsive topography in S1 was consistent. Discrimination of these two modalities was achieved vertically in the same column; the deeper layer represented the nociceptive response while the superficial layer encoded the response to light touch. This is quite different from that of a primate brain.

Determinants of laser-evoked EEG responses: pain perception or stimulus saliency?

Although laser-evoked electroencephalographic (EEG) responses are increasingly used to investigate nociceptive pathways, their functional significance remains unclear. The reproducible observation of a robust correlation between the intensity of pain perception and the magnitude of the laser-evoked N1, N2, and P2 responses has led some investigators to consider these responses a direct correlate of the neural activity responsible for pain intensity coding in the human cortex. Here, we provide compelling evidence to the contrary. By delivering trains of three identical laser pulses at four different energies, we explored the modulation exerted by the temporal expectancy of the stimulus on the relationship between intensity of pain perception and magnitude of the following laser-evoked brain responses: the phase-locked N1, N2, and P2 waves, and the non-phase-locked laser-induced synchronization (ERS) and desynchronization (ERD). We showed that increasing the temporal expectancy of the stimulus through stimulus repetition at a constant interstimulus interval 1) significantly reduces the magnitudes of the laser-evoked N1, N2, P2, and ERS; and 2) disrupts the relationship between the intensity of pain perception and the magnitude of these responses. Taken together, our results indicate that laser-evoked EEG responses are not determined by the perception of pain per se, but are mainly determined by the saliency of the eliciting nociceptive stimulus (i.e., its ability to capture attention). Therefore laser-evoked EEG responses represent an indirect readout of the function of the nociceptive system.

The effects of low-frequency environmental-strength electromagnetic fields on brain electrical activity: a critical review of the literature.

Reports dealing with the stimulus-response relationship between low-level, low-frequency electromagnetic fields (EMFs) and changes in brain electrical activity permit assessment of the hypothesis that EMFs are detected by the body via the process of sensory transduction. These reports, as well as those involving effects on brain activity observed after a fixed time of exposure, are critically reviewed here. A consistent stimulus-response relationship between EMFs and changes in brain activity has been demonstrated in animal and human subjects. The effects, which consisted of onset and offset evoked potentials, were observed under conditions permitting the inference that the fields were transduced like ordinary stimuli such as light and sound. However, unlike the changes in brain activity induced by these stimuli, the changes induced by EMFs were governed by nonlinear laws. The studies involving attempts to determine whether a period of EMF exposure caused a metabolic effect reflected in pre-exposure/post-exposure differences in brain activity were generally inconclusive.

Electrical low-frequency stimulation induces homotopic long-term depression of nociception and pain from hand in man.

OBJECTIVE: Electrical low-frequency stimulation (LFS) of cutaneous afferents evokes long-term depression (LTD) of nociception. In vitro studies suggest a sole homosynaptic effect on the conditioned pathway. The present study addresses homotopy of LTD in human nociception and pain. METHODS: In 30 healthy volunteers, nociceptive Adelta fibers were electrically stimulated by a concentric electrode. Test stimulation (0.125 Hz) was alternately applied unilateral to radial and ulnar side of right hand dorsum (ExpUni) or bilateral to radial side of right and left hand dorsum (ExpBi). Conditioning LFS (1 Hz, 1,200 pulses) was applied to radial side of right hand dorsum. Somatosensory evoked cortical vertex potentials (SEP) were recorded, and volunteers rated stimulus intensity. RESULTS: After homotopic LFS, SEP amplitude (ExpUni: -34.6%; ExpBi: -33.6%) and pain rating (ExpUni: -44.1%; ExpBi: -29.1%) significantly decreased. Amplitude reduction after heterotopic LFS did not differ from habituation effects in Control experiment without LFS. Heterotopic pain perception was not affected. CONCLUSIONS: The electrophysiological and psychophysical study on synaptic plasticity in healthy man demonstrates homotopic organization of LTD. SIGNIFICANCE: Homotopy is probably due to a homosynaptic effect at first nociceptive synapse, but descending inhibitory systems may also be involved. These experiments may help to judge the potency of LTD for future therapy in chronic pain.

Dissociated effects of quiet stance on standard and high-frequency (600 Hz) lower limb somatosensory evoked potentials.

OBJECTIVE: To verify whether standing can modulate somatosensory input from lower limb to the cortex. Somatosensory afferents have been evaluated not only by means of somatosensory evoked potentials recorded by means of classical wide-bandpass filtering (standard SEPs), but also by high-frequency somatosensory evoked potentials (HF-SEPs), which probably play a role in the processing of rapid adaptive changes. METHODS: Eight healthy subjects underwent right posterior tibial nerve (PTN) stimulation in two different conditions (standing and lying supine). Standard SEPs reflecting the activity of both subcortical and cortical generators further underwent digital filtering (300-800 Hz), in order to enhance HF-SEP components. RESULTS: Stance significantly reduces the P40 cortical component of standard SEPs. By contrast, HF-SEPs did not show any significant change between the two conditions. CONCLUSIONS: The lack of any gating effect on HF-SEPs lends further substance to the hypothesis that HF-SEPs play a pivotal role in the processing of somatosensory inputs related to rapid adaptive changes. SIGNIFICANCE: Our data confirm that standard and HF-SEPs reflect two distinct mechanisms with strongly different functional significance. Further studies are needed to definitively establish whether this dissociation is merely caused by the activation of anatomically different neuronal pools, or by the involvement of distinct functional mechanisms.

Pre-stimulus alpha power affects vertex N2-P2 potentials evoked by noxious stimuli.

It is well known that scalp potentials evoked by nonpainful visual and auditory stimuli are enhanced in amplitude when preceded by pre-stimulus low-amplitude alpha rhythms. This study tested the hypothesis that the same holds for the amplitude of vertex N2-P2 potentials evoked by brief noxious laser stimuli, an issue of interest for clinical perspective. EEG data were recorded in 10 subjects from 30 electrodes during laser noxious stimulation. The artifact-free vertex N2-P2 complex was spatially enhanced by surface Laplacian transformation. Pre-stimulus alpha power was computed at three alpha sub-bands according to subject's individual alpha frequency peak (i.e. about 6-8Hz for alpha 1, 8-10Hz for alpha 2 and 10-12Hz for alpha 3 sub-band). Individual EEG single trials were divided in two sub-groups. The strong-alpha sub-group (high band power) included halfway of all EEG single trials, namely those having the highest pre-stimulus alpha power. Weak-alpha sub-group (low band power) included the remaining trials. Averaging procedure provided laser evoked potentials for both trial sub-groups. No significant effect was found for alpha 1 and alpha 2 sub-bands. Conversely, compared to strong-alpha 3 sub-group, weak-alpha 3 sub-group showed vertex N2-P2 potentials having significantly higher amplitude (p<0.05). These results extend to the later phases of pain processing systems the notion that generation mechanisms of pre-stimulus alpha rhythms and (laser) evoked potentials are intrinsically related and subjected to fluctuating "noise". That "noise" could explain the trial-by-trial variability of laser evoked potentials and perception.