Conditioning transcutaneous electrical nerve stimulation induces delayed gating effects on cortical response: a magnetoencephalographic study

The present study was undertaken to investigate after-effects of 7 Hz non-painful prolonged stimulation of the median nerve on somatosensory-evoked fields (SEFs). The working hypothesis that conditioning peripheral stimulations might produce delayed interfering ("gating") effects on the response of somatosensory cortex to test stimuli was evaluated. In the control condition, electrical thumb stimulation induced SEFs in ten subjects. In the experimental protocol, a conditioning median nerve stimulation at wrist preceded 6 electrical thumb stimulations. Equivalent current dipoles fitting SEFs modeled responses of contralateral primary area (SI) and bilateral secondary somatosensory areas (SII) following control and experimental conditions. Compared to the control condition, conditioning stimulation induced no amplitude modulation of SI response at the initial stimulus-related peak (20 ms). In contrast, later response from SI (35 ms) and response from SII were significantly weakened in amplitude. Gradual but fast recovery towards control amplitude levels was observed for the response from SI-P35, while a slightly slower cycle was featured from SII. These findings point to a delayed "gating" effect on the synchronization of somatosensory cortex after peripheral conditioning stimulations. This effect was found to be more lasting in SII area, as a possible reflection of its integrative role in sensory processing.     

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimulation of median and tibial nerve: an fMRI study

Functional magnetic resonance imaging (fMRI) was used to study the cortical activity of the bilateral secondary somatosensory cortex (SII) during nonpainful (motor threshold) and painful electrical stimulation of median and tibial nerves. fMRI recordings were performed in eight normal young adults. The aim was at evaluating the working hypothesis of a spatial segregation of nonpainful and painful populations not only in the "hand" representation of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study. NeuroImage 20, 1625-1638.] but also in its "foot" representation. Results showed that, in both "hand" and "foot" representations of bilateral SII, the activity elicited by the painful stimulation was localized more posteriorly with respect to that elicited by the nonpainful stimulation. A fine spatial analysis of the SII responses revealed a clear somatotopic organization in the bilateral SII subregion especially reactive to the nonpainful stimuli (i.e., segregation of the hand and foot representations). In contrast, it was not possible to disentangle the "hand" and "foot" representations of SII for painful stimuli. These results extended to the SII "foot" representation previous evidence of a spatial segregation in the SII "hand" representation of subregions for the painful and nonpainful stimuli. Furthermore, they suggest that noxious information is not somatotopically represented in human bilateral SII, at least as inferred from fMRI data at 1.5 T.     

Human secondary somatosensory cortex is involved in the processing of somatosensory rare stimuli: an fMRI study

In the human somatosensory system, the contralateral primary somatosensory cortex (SI) is presumed to process and encode type and intensity of the sensory inputs, whereas the bilateral secondary somatosensory cortex (SII) is believed to perform higher order functions including sensorimotor integration, integration of information from the two body halves, attention, learning and memory. In this fMRI study we investigated the effect of attention on the activation of SI and SII, as induced by nonpainful and painful rare deviant electric stimuli during somatosensory oddball tasks. The working hypothesis is of stronger effects of attention on SII with respect to SI. Four runs were acquired according to an oddball scheme. Frequent nonpainful electrical stimuli were delivered to the ulnar nerve at motor threshold, whereas rare/deviant stimuli were delivered to median nerve in four conditions (one condition per run): nonpainful, painful, counting nonpainful, and counting painful. Results showed a statistically significant fMRI activation in bilateral SII but not in contralateral SI when the rare/deviant median nerve stimuli were delivered at nonpainful and painful levels as well as at the two levels of attention considered (i.e., associated with counting and non-counting tasks). Furthermore, fMRI activation in SII did not differ across the different levels of stimulus intensity (nonpainful, painful) and attention (non-counting, counting). These results corroborate the notion that SII is the target of independent pathways for the processing and integration of nonpainful and painful somatosensory stimuli salient for further high-order elaborations.     

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study

The regional activity of the contralateral primary (SI) and the bilateral secondary (SII) somatosensory areas during median nerve stimulations at five intensity levels (ranging from nonpainful motor threshold to moderate pain) was studied by means of functional magnetic resonance imaging (fMRI). The aim was to characterize the functional topography of SII compared to SI as a function of the stimulus intensity. Results showed that the galvanic stimulation of the median nerve activated the contralateral SI at all stimulus intensities. When considered as a single region, SII was more strongly activated in the contralateral than in the ipsilateral hemisphere. When a finer spatial analysis of the SII responses was performed, the activity for the painful stimulation was localized more posteriorly compared to that for the nonpainful stimulation. This is the first report on such a SII segregation for transient galvanic stimulations. The activity (relative signal intensity) of this posterior area increased with the increase of the stimulus intensity. These results suggest a spatial segregation of the neural populations that process signals conveyed by dorsal column-medial lemniscus (nonpainful signals) and neospinothalamic (painful signals) pathways. Further fMRI experiments should evaluate the functional properties of these two SII subregions during tasks involving sensorimotor integration, learning, and memory demands.     

Altered central sensorimotor processing in patients with complex regional pain syndrome

Alterations in tactile sensitivity are common in patients with chronic pain. Recent brain imaging studies have indicated that brain areas activated by acute experimental pain partly overlap with areas processing innocuous tactile stimuli. However, the possible effect of chronic pain on central tactile processing has remained unclear. We have examined, both clinically and with whole-head magnetoencephalography, six patients suffering from complex regional pain syndrome (CRPS) of the upper limb. The cortical somatosensory responses were elicited by tactile stimuli applied to the fingertips and the reactivity of spontaneous brain oscillations was monitored as well. Tactile stimulation of the index finger elicited an initial activation at 65 ms in the contralateral SI cortex, followed by activation of the ipsi- and contralateral SII cortices at about 130 ms. The SI responses were 25-55% stronger to stimulation of the painful than the healthy side. The distance between SI representations of thumb and little finger was significantly shorter in the hemisphere contralateral than ipsilateral to the painful upper limb. In addition, reactivity of the 20-Hz motor cortex rhythm to tactile stimuli was altered in the CRPS patients, suggesting modified inhibition of the motor cortex. These results imply that chronic pain may alter central tactile and motor processing.     

fMRI reflects functional connectivity of human somatosensory cortex

Unilateral sensory stimulation reliably elicits contralateral somatotopic activation of primary (SI) and secondary (SII) somatosensory cortex. There is an ongoing debate about the occurrence and nature of concomitant ipsilateral SI and SII activation. Here we used functional magnetic resonance imaging (fMRI) in healthy human subjects with unilateral tactile stimulation of fingers and lips, to compare somatosensory activation patterns from distal and proximal body parts. We hypothesized that fMRI in humans should reflect the functional connectivity of somatosensory cortex as predicted by animal studies. We show that both unilateral finger and lip stimulations activate contra- and ipsilateral SI and SII cortices with high detection frequency. Correlations of BOLD-signals to the applied hemodynamic reference function were significantly higher in contralateral as compared to ipsilateral SI and SII cortices for both finger and lip stimulation, reflecting strong contribution of contralateral thalamocortical input. Furthermore, BOLD-signal correlations were higher in SI than in SII activations on the contralateral but not on the ipsilateral side. While these asymmetries within and across hemispheres were consistent for finger and lip stimulations, indicating analogous underlying organizing principles, they were less prominent for lip stimulation. Somatotopic organization was detected in SI but not in SII representations of fingers and lips. These results qualitatively and quantitatively support the prevalent concepts of anatomical and functional connectivity in the somatosensory system and therefore may allow interpretation of sensory evoked fMRI signals in terms of normal human brain function. Thus, the assessment of human somatosensory function with fMRI may permit in the future investigations of pathological conditions.     

Nociceptive and non-nociceptive sub-regions in the human secondary somatosensory cortex: an MEG study using fMRI constraints

Previous evidence from functional magnetic resonance imaging (fMRI) has shown that a painful galvanic stimulation mainly activates a posterior sub-region in the secondary somatosensory cortex (SII), whereas a non-painful sensory stimulation mainly activates an anterior sub-region of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625-1638.]. The present study, combining fMRI with magnetoencephalographic (MEG) findings, assessed the working hypothesis that the activity of such a posterior SII sub-region is characterized by an amplitude and temporal evolution in line with the bilateral functional organization of nociceptive systems. Somatosensory evoked magnetic fields (SEFs) recordings after alvanic median nerve stimulation were obtained from the same sample of subjects previously examined with fMRI [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625-1638.]. Constraints for dipole source localizations obtained from MEG recordings were applied according to fMRI activations, namely, at the posterior and the anterior SII sub-regions. It was shown that, after painful stimulation, the two posterior SII sub-regions of the contralateral and ipsilateral hemispheres were characterized by dipole sources with similar amplitudes and latencies. In contrast, the activity of anterior SII sub-regions showed statistically significant differences in amplitude and latency during both non-painful and painful stimulation conditions. In the contralateral hemisphere, the source activity was greater in amplitude and shorter in latency with respect to the ipsilateral. Finally, painful stimuli evoked a response from the posterior sub-regions peaking significantly earlier than from the anterior sub-regions. These results suggested that both ipsi and contra posterior SII sub-regions process painful stimuli in parallel, while the anterior SII sub-regions might play an integrative role in the processing of somatosensory stimuli.     

Magnetoencephalographic correlates of audiotactile interaction

To seek for correlates of an interaction between auditory and somatosensory processing, the brain's magnetic field in response to simultaneously presented auditory (A) and tactile (T) stimuli was compared with the sum of the respective unimodal responses (A+T). The stimuli were binaural 1047-Hz tone bursts of 60 dB sensation level and tactile pressure pulses to the right thumb. The mean interval between two stimuli of the same modality was 1.95 s. The magnetic field was recorded using a 306-channel whole-scalp neuromagnetometer. A clear audiotactile interaction was revealed in the hemisphere contralateral to the side of tactile stimulation in six of eight subjects, whereas in the ipsilateral hemisphere an interaction was noticed in only three subjects. The time courses of these audiotactile interaction fields typically showed major deflections of opposite polarities around 140 and 220 ms. The first deflection appeared to arise in the region of the secondary somatosensory cortex (SII). The polarity of this interaction was consistent with the view that the auditory stimulus resulted in a partial inhibition in SII. In two subjects, strong indications of auditory contributions to the interaction were available, although in different hemispheres. The relatively high interindividual variability of the observed interaction, which represents potential neural substrates for multisensory integration, could indicate that the way subjects perceive the simultaneous presentation of auditory and tactile stimuli differs.     

Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study

The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. To investigate the somatotopic organization of the nociceptive system, we applied Thulium-YAG-laser evoked pain stimuli, which have no concomitant tactile component, to the dorsum of the left hand and foot in randomized order. We used single-trial functional magnetic resonance imaging (fMRI) to assess differential hemodynamic responses to hand and foot stimulation for the group and in a single subject approach. The primary somatosensory cortex (SI) shows a clear somatotopic organization ipsi- and contralaterally to painful stimulation. Furthermore, a differential representation of hand and foot stimulation appeared within the contralateral opercular--insular region of the secondary somatosensory cortex (SII). This result provides evidence that both SI and SII encode spatial information of nociceptive stimuli without additional information from the tactile system and highlights the concept of a redundant representation of basic discriminative stimulus features in human somatosensory cortices, which seems adequate in view of the evolutionary importance of pain perception.     

Left-hemisphere-dominant SII activation after bilateral median nerve stimulation

We used bilateral median nerve stimuli to find out possible hemispheric dominance in the activation of the second somatosensory cortex, SII. Somatosensory evoked fields (SEFs) were recorded from 14 healthy adults (7 right-handed, 7 left-handed) with a 306-channel neuromagnetometer. Electrical stimuli were applied once every 3 s simultaneously either to the left and right median nerves at the wrists or to the palmar skin of both thumbs. Sources of SEFs were modeled with four current dipoles, located in the SI and SII cortices of both hemispheres. The SI activation strengths did not differ between the hemispheres, whereas the SII responses were significantly stronger in the left than in the right hemisphere. In right-handers, the left/right SII ratios were 1.9 and 1.8 for wrist and thumb stimuli, respectively. The corresponding values were 1.5 and 1.7 in left-handers. The results indicate handedness-independent functional specialization of the human SII cortices.     

Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.     

Interaction of tactile input in the human primary and secondary somatosensory cortex--a magnetoencephalographic study

Interaction of simultaneous tactile input at two finger sites in primary (SI) and secondary somatosensory cortex (SII) was studied by whole-head magnetoencephalography. Short pressure pulses were delivered to fingers of the right and left hand at an interstimulus interval of 1.6 s. The first phalanx of the left digit 1 and four other sites were stimulated either separately or simultaneously. We compared four sites with increasing distance: the second phalanx of left digit 1, left digit 5, and digits 1 and 5 of the right hand. The temporal evolution of source activity in the contralateral SI and bilateral SII was calculated using spatiotemporal source analysis. Interaction was assessed by comparing the source activity during simultaneous stimulation with the sum of the source activities elicited by separate stimulation. Significant suppressive interaction was observed in contralateral SI only for stimuli at the same hand, decreasing with distance. In SII, all digits of the same and the opposite hand interacted significantly with left digit 1. When stimulating bilaterally, SII source waveforms closely resembled the time course of the response to separate stimulation of the opposite hand. Thus, in bilateral simultaneous stimulation, the contralateral input arriving first in SII appeared to inhibit the later ipsilateral input. Similarly, the separate response to input at two unilateral finger sites which arrived slightly earlier in SII dominated the simultaneous response. Our results confirm previous findings of considerable overlap in the cortical hand representation in SII and illustrate hemispheric specialization to contralateral input when simultaneous stimuli occur bilaterally.     

Oral structure representation in human somatosensory cortex

To clarify the topography of the areas representing whole intraoral structures and elucidate bilateral neuronal projection to those areas in the primary somatosensory (S1) cortex, we recorded somatosensory-evoked magnetic fields (SEFs), which reflect the earliest cortical responses to pure tactile stimulation, using magnetoencephalography and a piezo-driven tactile stimulation device. Subjects consisted of 10 healthy male adults. Following tactile stimulation of 6 sites on the oral mucosa (inferior/superior buccal mucosa, posterior/anterior tongue mucosa, and upper/lower lip mucosa), SEFs with a peak latency of 15 ms (1M) were identified bilaterally. In contrast, SEFs with a peak latency of 30 ms following right index finger tactile stimulation were identified only in the contralateral hemisphere. Equivalent current dipoles (ECDs) generating 15 ms components were found along the posterior wall of the central sulcus, bilaterally. The ECD locations for oral mucosa-representing areas were located inferiorly to those for the index finger, with the following pattern of organization from top to bottom along the central sulcus: index finger, upper or lower lip, anterior or posterior tongue and superior or inferior buccal mucosa, with a wide distribution, covering 30% of the S1 cortex. Source strength for 1M in the ipsilateral hemisphere was weaker than that in the contralateral hemisphere. These results clearly indicate that sensory afferents innervating the intraoral region project to both the contralateral and ipsilateral 3b areas via the trigeminothalamic tract, where contralateral projection is predominant. The results clarify the intraoral structure-representing areas in the S1 cortex, adding those areas to the classical "sensory homunculus".     

Hand posture modulates cortical finger representation in SII

Somatosensory magnetic fields evoked by electrical stimuli of the thumb or the index finger were recorded using a whole head magnetoencephalography (MEG) system in 10 subjects performing different finger postures, open hand posture and close hand posture for picking up a small object. The mean Euclidean distances between the ECD (equivalent current dipole) locations for the thumb and index finger in the secondary somatosensory cortex (SII) across the subjects were 8.5 +/- 2.1 mm in the close hand posture and 11.2 +/- 2.6 mm in the open hand posture. The distance was significantly shorter in the close hand posture (paired t test, P = 0.002, n = 8). However, the distances of the P38m and P60m components in the primary somatosensory cortex (SI) were not significantly different between the two hand postures (P38m: 13.4 +/- 5.6 mm in the open and 13.5 +/- 3.9 mm in the close; P60m: 12.4 +/- 2.6 mm in the open and 16.2 +/- 5.3 mm in the close). This shortening of the spatial distance between the cortical finger representations suggests a similarity in humans of the rapid changes in the dynamics of cortical circuits reported in animal studies. In addition, the overlap of the cortical finger representations, which might be suggested by the shortening of the distance between the ECDs in SII, is likely to play a role in information integration between sensory inputs from the thumb and index finger.     

Area-specific representation of mechanical nociceptive stimuli within SI cortex of squirrel monkeys

While functional imaging studies in humans have consistently reported activation of primary somatosensory cortex (SI) with painful stimuli, the specific roles of subdivisions of areas 3a, 3b, and 1 within SI during pain perception are largely unknown, particularly in the representation of mechanical evoked pain. In this study, we investigated how modality, location, and intensity of nociceptive stimuli are represented within SI by using high-spatial resolution optical imaging of intrinsic signals in Pentothal-anesthetized squirrel monkeys. Perceptually comparable mechanical nociceptive and innocuous tactile stimuli were delivered by indenting the glabrous skin of the distal finger pads with 0.2 and 2 mm diameter probes, respectively. Within each of areas 3a, 3b, and 1, activations to mechanical nociceptive stimulation of individual distal finger pads were spatially distinct and somatotopically organized. We observed differential cortical activation patterns. Areas 3a, 3b, and 1 were all activated during mechanical nociceptive stimulation and were modulated by nociceptive stimulus intensity. However, with innocuous tactile stimulation, mainly areas 3b and 1 exhibited response modulation with different levels of stimulation. In summary, mechanical nociceptive inputs are area-specific and topographically represented within SI. We propose that all areas of SI are implicated in encoding the features of mechanical nociception, where areas 3a and 3b are distinctively involved in coding nociceptive and pressure sensation components of stimulation.     

Modulation of alpha oscillations in insular cortex reflects the threat of painful stimuli

Pain is a sensory and emotional experience that involves numerous brain areas. Among these areas the insular cortex has been shown to be involved in the expectation and processing of pain. Alpha power modulation has been associated with the experience of pain. The aim of this study was to test the hypothesis that the threat of a painful stimulus affects alpha rhythm oscillation in the insular cortex and to find the time intervals during which the insular cortex is most active. We used a beamforming method in the frequency domain to estimate alpha power associated with source activity during psychologically different conditions, namely a sequence of nonpainful somatosensory stimuli (non-threatening condition) and a sequence of nonpainful stimuli randomly intermixed with painful stimuli (threatening condition). The results revealed that the anterior insula alone was involved during the threat of painful stimuli. Conversely, the posterior insula – as well as other brain areas such as SII – was involved in the processing of somatosensory stimuli regardless their painfulness. Additionally, the involvement of the anterior insula should not be accounted for by fear, arousal, habituation effect or by the occurrence of randomly interleaved different stimuli, but it is likely to be related mainly to expectancy mechanisms enhancing activity of specific neuronal populations.     

MEG localization of rolandic spikes with respect to SI and SII cortices in benign rolandic epilepsy

The purpose of this study was to study the relationship between interictal spike sources and somatosensory cortices in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We recorded spontaneous magnetoencephalography (MEG) and EEG signals and cortical somatosensory-evoked magnetic fields (SEFs) to electric stimulation of the median nerve in 9 children with BREC. Interictal rolandic discharges (RDs) and SEFs were analyzed by equivalent current dipole (ECD) modeling. Based on the orientation and locations of corresponding ECDs, we compared generators of RDs with primary (SI) and second somatosensory cortices (SII). Our results showed that RDs and SII responses had similar ECD orientation on the magnetic field maps. The ECDs of RDs were localized 15.3 +/- 1.9 and 12.2 +/- 2.8 mm anterior to SI and SII, respectively. The spatial distance on average from the location of RDs to SII (21.9 +/- 1.6 mm) cortex was significantly shorter than to SI cortex (29.7 +/- 1.7 mm) (P<0.01, Wilcoxon signed-rank test). In conclusion, the cortical generators for RDs in patients with BREC are localized in the precentral motor cortex, closer to hand SII than to SI cortex.     

Spatiotemporal brain dynamics in response to muscle stimulation

The objective of the present study was to assess the spatiotemporal scenario of brain activity associated with sensory stimulation of the abductor pollicis brevis muscle. Spatiotemporal dipole models, using realistic individual boundary element head models, were built from somatosensory evoked potentials (SEPs; 64 Ch. EEG) to nonpainful and painful intramuscular electrostimulation (IMES) as well as to cutaneous electrostimulation delivered to the distal phalanx of the thumb. Nonpainful and painful muscle stimuli resulted in activation of the same brain regions. In temporal order, these were: the contralateral primary sensorimotor cortex, contralateral dorso-lateral premotor area (PM), bilateral operculo-insular cortices, caudal cingulate motor area (CMA), and posterior cingulate cortex/precuneus. Brain processing induced by muscle sensory input showed a characteristic pattern in contrast to cutaneous sensory input, namely: (1) no early SEP components to IMES; (2) an initial IMES component likely generated by proprioceptive input is not present for digit stimulation; (3) one source was located in the PM only for IMES. This source was unmasked by the lower stimulus intensity; (4) a source for IMES was located in the contralateral caudal CMA rather than being located in the cingulate gyrus. Cerebral sensory processing of input from the muscle involved several sensory and motor areas and likely occurs in two parallel streams subserving higher order somatosensory processing as well as sensory-motor integration. The two streams might on one hand involve sensory discrimination via SI and SII and on the other hand integration of sensory feedback for further motor processing via MI, lateral PM area, and caudal CMA.     

Differential effects of stimulus intensity on peripheral and neuromagnetic cortical responses to median nerve stimulation

To study the differential effects of tactile stimulus intensity on cortical and peripheral responses, we measured neuromagnetic cortical responses, compound muscle action potentials (CMAP), sensory nerve action potentials (SNAP), and the subjective estimation of tactile magnitude to electric median nerve stimulation at the wrist in 13 male healthy adults. The sensory perception threshold (ST) for electric pulses at wrist skin was determined and then various levels of stimulus intensity (1 approximately 6 ST) were given to each subject. At 1 ST, only the P50m components of the primary somatosensory (SI) cortical responses were recorded. The second somatosensory (SII) cortical responses were saturated at 2 ST, while the SI responses reached maximum at 3 ST equivalent to the subjective threshold intensity for "strong" tactility. The CMAP and SNAP were maximum at 4-5 ST. At 2 ST, >70% of maximum SI responses were produced, whereas only <40% of maximum CMAP or SNAP responses were obtained. We concluded that the stimulus intensities for activating or saturating somatosensory cortical responses were lower than those for CMAP and SNAP. The differential intensity effects on cortical and peripheral responses suggest a polysynaptic organization underlying the central amplification for somatosensory cortical activation. The optimal intensity levels for producing maximum SI and SII responses were 3 and 2 ST, respectively. Compared with the SII, the SI plays a crucial role in the coding of the tactile stimulus intensity.     

The analgesic effect of crossing the arms

The ability to determine precisely the location of sensory stimuli is fundamental to how we interact with the world; indeed, to our survival. Crossing the hands over the body midline impairs this ability to localize tactile stimuli. We hypothesized that crossing the arms would modulate the intensity of pain evoked by noxious stimulation of the hand. In two separate experiments, we show (1) that the intensity of both laser-evoked painful sensations and electrically-evoked nonpainful sensations were decreased when the arms were crossed over the midline, and (2) that these effects were associated with changes in the multimodal cortical processing of somatosensory information. Critically, there was no change in the somatosensory-specific cortical processing of somatosensory information. Besides studies showing relief of phantom limb pain using mirrors, this is the first evidence that impeding the processes by which the brain localises a noxious stimulus can reduce pain, and that this effect reflects modulation of multimodal neural activities. By showing that the neural mechanisms by which pain emerges from nociception represent a possible target for analgesia, we raise the possibility of novel approaches to the treatment of painful clinical conditions.