Bilateral activation of the trigeminothalamic tract by acute orofacial cutaneous and muscle pain in humans

The conscious perception of somatosensory stimuli is thought to be located in the contralateral cerebral cortex. However, recent human brain imaging investigations in the spinal system report bilateral primary somatosensory cortex (SI) activations during unilateral noxious stimuli and that this ipsilateral spinal representation may be independent of transcallosal connections. In the trigeminal system, there is primate evidence for an ipsilateral somatosensory pathway through the thalamus to the face SI. However, the organization of the trigeminal nociceptive pathway in the human is not clear. The aim of this study was to determine whether noxious stimuli applied to the face are transmitted to the cerebral cortex by bilateral pathways. We used functional magnetic resonance imaging (fMRI) to compare ipsilateral and contralateral activation of the thalamus, SI and secondary somatosensory cortex (SII) during muscle and cutaneous orofacial pain and innocuous facial stimulation in healthy human subjects. We found that both muscle and cutaneous noxious stimuli, from injections of hypertonic saline into the right masseter or overlying skin, evoked bilateral increases in signal intensity in the region encompassing the ventral posterior thalamus as well as the face region of SI and SII. In contrast, innocuous unilateral brushing of the lower lip evoked a strict contralateral ventroposterior thalamic activation, but bilateral activation of SI and SII. These data indicate that, in contrast to innocuous inputs from the face, noxious information ascends bilaterally to the face SI through the ventroposterior thalamus in humans.     

Representation of different trigeminal divisions within the primary and secondary human somatosensory cortex

Clinical, neurophysiological, and neuroimaging studies have yielded controversial results about the representation of the face in the somatosensory cortex. To clarify this issue we mechanically stimulated the left forehead (ophthalmic trigeminal division, V1) and left lower lip (mandibular trigeminal division, V3) in 14 healthy volunteers during acquisition of whole-brain fMRI images. During V1 and V3 stimulation the fMRI signal in the primary (SI) and secondary (SII) somatosensory cortices in the contralateral hemisphere increased. Within both SI and SII, the foci activated by stimulation of the two trigeminal divisions largely overlapped. In contrast, the ipsilateral representation differed. Whereas V3 stimulation activated the contralateral somatosensory cortex alone, V1 stimulation activated SI and SII bilaterally. These results to some extent contrast with electrophysiological data in monkeys and disclose distinct cortical representations within facial territories in humans.     

Behavioral correlates of negative BOLD signal changes in the primary somatosensory cortex

Functional magnetic resonance imaging (fMRI) hypothesis testing based on the blood oxygenation level dependent (BOLD) contrast mechanism typically involves a search for a positive effect during a specific task relative to a control state. However, aside from positive BOLD signal changes there is converging evidence that neuronal responses within various cortical areas also induce negative BOLD signals. Although it is commonly believed that these negative BOLD signal changes reflect suppression of neuronal activity direct evidence for this assumption is sparse. Since the somatosensory system offers the opportunity to quantitatively test sensory function during concomitant activation and has been well-characterized with fMRI in the past, the aim of this study was to determine the functional significance of ipsilateral negative BOLD signal changes during unilateral sensory stimulation. For this, we measured BOLD responses in the somatosensory system during unilateral electric stimulation of the right median nerve and additionally determined the current perception threshold of the left index finger during right-sided electrical median nerve stimulation as a quantitative measure of sensory function. As expected, positive BOLD signal changes were observed in the contralateral primary and bilateral secondary somatosensory areas, whereas a decreased BOLD signal was observed in the ipsilateral primary somatosensory cortex (SI). The negative BOLD signal changes were much more spatially extensive than the representation of the hand area within the ipsilateral SI. The negative BOLD signal changes in the area of the index finger highly correlated with an increase in current perception thresholds of the contralateral, unstimulated finger, thus supporting the notion that the ipsilateral negative BOLD response reflects a functionally effective inhibition in the somatosensory system.     

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.     

Somatosensory evoked magnetic fields from the primary and secondary somatosensory cortices in healthy newborns

Although brain development has been actively investigated in animals, maturation of the cerebral cortex in human newborns is still poorly understood. This study aimed at characterizing the cortical areas participating in tactile processing in human neonates. Somatosensory-evoked magnetic fields were recorded from 21 healthy full-term newborns during natural sleep. Altogether, four cortical areas were activated by tactile stimulation: the contra- and ipsilateral primary (SI) and secondary (SII) somatosensory cortices. The contralateral SI was activated first in all the newborns. This early activity was not affected by the interstimulus interval or the sleep stage. The contralateral SII activation at around 200 ms was prominent in quiet sleep (QS) but attenuated in active sleep (AS). Activity in this area was strongly depressed by a faster rate of stimulation. Ipsilateral activity was seen in most subjects: more often in QS than AS. The ipsilateral activity originated from SII in most babies, but in some the ipsilateral SI was also activated. We conclude that both the contra- and ipsilateral SI and SII can participate in the processing of somatosensory information in human neonates.     

A time-varying source connectivity approach to reveal human somatosensory information processing

Exploration of neural sources and their effective connectivity based on transient changes in electrophysiological activities to external stimuli is important for understanding brain mechanisms of sensory information processing. However, such cortical mechanisms have not yet been well characterized in electrophysiological studies since (1) it is difficult to estimate the stimulus-activated neural sources and their activities and (2) it is difficult to identify transient effective connectivity between neural sources in the order of milliseconds. To address these issues, we developed a time-varying source connectivity approach to effectively capture fast-changing information flows between neural sources from high-density Electroencephalography (EEG) recordings. This time-varying source connectivity approach was applied to somatosensory evoked potentials (SEPs), which were elicited by electrical stimulation of right hand and recorded using 64 channels from 16 subjects, to reveal human somatosensory information processing. First, SEP sources and their activities were estimated, both at single-subject and group level, using equivalent current dipolar source modeling. Then, the functional integration among SEP sources was explored using a Kalman smoother based time-varying effective connectivity inference method. The results showed that SEPs were mainly generated from the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), and cingulate cortex (CC). Importantly, we observed a serial processing of somatosensory information in human somatosensory cortices (from SI to SII) at earlier latencies (<150 ms) and a reciprocal processing between SII and CC at later latencies (>200 ms).     

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.     

Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome

In the complex regional pain syndrome (CRPS), several theories proposed the existence of pathophysiological mechanisms of central origin. Recent studies highlighted a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) during non-painful stimulation of the affected side. We addressed the question whether reorganizational changes can also be found in the secondary somatosensory cortex (SII). Moreover, we investigated whether cortical changes might be accompanied by perceptual changes within associated skin territories. Seventeen patients with CRPS of one upper limb without the presence of peripheral nerve injuries (type I) were subjected to functional magnetic resonance imaging (fMRI) during electrical stimulation of both index fingers (IFs) in order to assess hemodynamic signals of the IF representation in SI and SII. As a marker of tactile perception, we tested 2-point discrimination thresholds on the tip of both IFs. Cortical signals within SI and SII were significantly reduced contralateral to the CRPS-affected IF as compared to the ipsilateral side and to the representation of age- and sex-matched healthy controls. In parallel, discrimination thresholds of the CRPS-affected IF were significantly higher, giving rise to an impairment of tactile perception within the corresponding skin territory. Mean sustained, but not current pain levels were correlated with the amount of sensory impairment and the reduction in signal strength. We conclude that patterns of cortical reorganization in SI and SII seem to parallel impaired tactile discrimination. Furthermore, the amount of reorganization and tactile impairment appeared to be linked to characteristics of CRPS pain.     

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.     

Temporo-spatial analysis of cortical activation by phasic innocuous and noxious cold stimuli--a magnetoencephalographic study

Clinical findings and recent non-invasive functional imaging studies pinpoint the insular cortex as the crucial brain area involved in cold sensation. By contrast, the role of primary (SI) and secondary (SII) somatosensory cortices in central processing of cold is controversial. So far, temporal activation patterns of cortical areas involved in cold processing have not been examined. Using magnetoencephalography, we studied, in seven healthy subjects, the temporo-spatial dynamics of brain processes evoked by innocuous and noxious cold stimulation as compared to tactile stimuli. For this purpose, a newly designed and magnetically silent cold-stimulator was employed. In separate runs, cold and painful cold stimuli were delivered to the dorsum of the right hand. Tactile afferents were stimulated by pneumatic tactile stimulation.

Following innocuous cold stimulation (ΔT=5±0.3°C in 50±2 ms), magnetic source imaging revealed an exclusive activation of the contra- and ipsilateral posterior insular cortex. The mean peak latencies were 194.3±38.1 and 241.0±31.7 ms for the response in the ipsi- and contralateral insular cortex, respectively. Based on the measurement of onset latencies, the estimated conduction velocity of peripheral nerve fibres mediating cold fell in the range of Aδ-fibres (7.4±0.8 m/s).

Noxious cold stimulation (ΔT=35±5°C in 70±12 ms) initially activated the contra- and ipsilateral insular cortices in the same latency ranges as innocuous cold stimuli. Additionally, we found an activation of the contra- and ipsilateral SII areas (peak latencies 304±22.7 and 310.1±19.4 ms, respectively) and a variable activation of the cingulate cortex. Notably, neither cold- nor painful cold stimulation produced an activation of SI. By contrast, the evoked cortical responses following tactile stimulation could be located to the contralateral SI cortex and bilateral SII.

In conclusion, this study strongly corroborates the posterior insular cortex as the primary somatosensory area for cortical processing of cold sensation. Furthermore, it supports the role of SII and the cingulate cortex in mediating freeze-pain. Therefore, these results suggest different processing of cold, freeze-pain and touch in the human brain.     

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.     

Parallel input makes the brain run faster

In serial sensory processing, information flows from the thalamus via primary sensory cortices to higher-order association areas. However, association cortices also receive, albeit weak, direct thalamocortical sensory inputs of unknown function. For example, while information proceeds from primary (SI) to secondary (SII) somatosensory cortex in a serial fashion, both areas are known to receive direct thalamocortical sensory input. The present study examines the potential roles of such parallel input arrangements. The subjects were presented with median nerve somatosensory stimuli with the instruction to respond with the contralateral hand. The locations and time courses of the activated brain areas were first identified with magnetoencephalography (MEG). In a subsequent session, these brain areas were modulated with single-pulse transcranial magnetic stimulation (TMS) at 15-210 ms after the somatosensory stimulus while electroencephalography (EEG) was recorded. TMS pulses at 15-40 ms post-stimulus significantly speeded up reaction times and somatosensory-evoked responses, with largest facilitatory effects when the TMS pulse was given to contralateral SII at about 20 ms. To explain the results, we propose that the early somatosensory-evoked physiological SII activation exerts an SII-->SI influence that facilitates the reciprocal SI-->SII pathway - with TMS to SII we apparently amplified this mechanism. The results suggest that the human brain may utilize parallel inputs to facilitate long-distance cortico-cortical connections, resulting in accelerated processing and speeded reaction times. This arrangement could also allow very early top-down modulation of the bottom-up stream of sensory information.     

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.     

Temporomandibular Disorder Modifies Cortical Response to Tactile Stimulation

Individuals with temporomandibular disorder (TMD) suffer from persistent facial pain and exhibit abnormal sensitivity to tactile stimulation. To better understand the pathophysiological mechanisms underlying TMD, we investigated cortical correlates of this abnormal sensitivity to touch. Using functional magnetic resonance imaging (fMRI), we recorded cortical responses evoked by low-frequency vibration of the index finger in subjects with TMD and in healthy controls (HC). Distinct subregions of contralateral primary somatosensory cortex (SI), secondary somatosensory cortex (SII), and insular cortex responded maximally for each group. Although the stimulus was inaudible, primary auditory cortex was activated in TMDs. TMDs also showed greater activation bilaterally in anterior cingulate cortex and contralaterally in the amygdala. Differences between TMDs and HCs in responses evoked by innocuous vibrotactile stimulation within SI, SII, and the insula paralleled previously reported differences in responses evoked by noxious and innocuous stimulation, respectively, in healthy individuals. This unexpected result may reflect a disruption of the normal balance between central resources dedicated to processing innocuous and noxious input, manifesting itself as increased readiness of the pain matrix for activation by even innocuous input. Activation of the amygdala in our TMD group could reflect the establishment of aversive associations with tactile stimulation due to the persistence of pain.     

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.     

Inhibitory impact of subliminal electrical finger stimulation on SI representation and perceptual sensitivity of an adjacent finger

Simultaneous stimulation of two adjacent fingers above sensory perception threshold (supraliminal stimulation) leads to an inhibitory interaction effect on responses in primary somatosensory cortex (SI). Moreover, during electrical finger stimulation closely below threshold for conscious perception (subliminal stimulation) inhibitory interneurons in cortical layer 4 are assumed to be activated preferentially as compared to excitatory interneurons. Using fMRI in humans, here we show that interspersed subliminal electrical stimulation of an adjacent finger reduces the response to target finger stimulation in contralateral SI. This effect was shown in a complementary study to be associated behaviorally with a diminished detectability of test pulses on the target finger. We propose the mechanism underlying this lateral inhibitory effect to be related to a representational overlap of inhibitory interneurons in SI based on the divergence of thalamocortical feedforward projections, or to intracortical lateral inhibitory projections targeting juxtaposed receptive fields, or both.     

Functional MRI detection of bilateral cortical reorganization in the rodent brain following peripheral nerve deafferentation

Evidence is emerging for significant inter-hemispheric cortical plasticity in humans, opening important questions about the significance and mechanism for this long range plasticity. In this work, peripheral nerve deafferentation was performed on both the rat forepaw and hindpaw and cortical reorganization was assessed using functional MRI (fMRI). Sensory stimulation of the forepaw or the hindpaw in rats that experienced only partial denervation resulted in activation in only the appropriate, contralateral, primary somatosensory cortex (SI). However, 2-3 weeks following complete denervation of the rats' forepaw or hindpaw, stimulation of the intact paw resulted in fMRI activation of ipsilateral as well as contralateral SI. To address whether inter-cortical communication is required for this cortical reorganization, the healthy hindpaw SI representation was stereotaxically lesioned in rats which had the other hindpaw denervated. No fMRI activation was detected in the ipsilateral SI cortex after lesioning of the contralateral cortex. These results indicate that extensive inter-hemispheric cortical-cortical reorganization can occur in the rodent brain after peripheral nerve deafferentation and that cortical-cortical connections play a role in mediating this inter-hemispheric cortical reorganization.     

Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7 Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI was accompanied by commensurate decreases in relative regional cerebral blood flow (rCBF). Conjunction analysis of the fMRI and PET data revealed a region in the ipsilateral postcentral gyrus showing overlap of negative BOLD signals and relative rCBF decreases. The current perception threshold (CPT) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition.     

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.     

Reliable detection of bilateral activation in human primary somatosensory cortex by unilateral median nerve stimulation

In non-human primates, a bilateral representation of unilaterally presented somatosensory information can be found at the lowest level of cortical processing as indicated by the presence of neurons with bilateral receptive fields in the hand region of primary somatosensory (SI) cortex. In humans, such bilateral activation of SI is considered controversial due to highly variable detection rates for the much weaker ipsilateral response across different studies (ranging from 3% to 100%). Second-order blind identification (SOBI) is a blind source separation algorithm that has been successfully used to isolate neuronal signals from functionally distinct brain regions, including the left- and right-SI. SOBI-aided extraction of left- and right-SI responses to median nerve stimulation from high-density EEG has been previously validated against the fMRI and MEG literature. Here, we applied SOBI to EEG data and examined whether relatively weaker ipsilateral activations could be reliably detected across subjects. In single subject analysis, statistically significant somatosensory evoked potentials (SEPs) in response to unilateral stimulation were detected from both SI contralateral to and SI ipsilateral to the side of stimulation. Furthermore, these ipsilateral responses were observed in both the left and right hemispheres of all 10 subjects studied. Together these results demonstrate that unilateral stimulation of the median nerve, whether applied to the left or right wrist, can activate both the left- and right-SI, raising the possibility that in humans, unilateral sensory input may be bilaterally represented at the lowest level of cortical processing.