Attention to aversive emotion and specific activation of the right insula and right somatosensory cortex

The evaluation of emotional stimuli is based on different levels of information processing, ranging from rather automatic processes to focused attention to the emotional relevance of stimuli. The role of specific brain areas for these processes is a matter of debate. In this event-related fMRI study, we varied the information processing mode of participants exposed to aversive and neutral pictures. Based on four different tasks, participants' attentional focus onto the emotional quality of the stimuli and the own emotional involvement was increased systematically across tasks. Regardless of task, stronger activation to threatening vs. neutral pictures was found in several regions such as the amygdala, anterior insula, anterior cingulate cortex, primary somatosensory cortex and medial prefrontal cortex. However, there was a parametric increase of activation with increasing attention to one's own emotion specifically in the right posterior insula and right primary and secondary somatosensory cortex, i.e. in areas implicated in self-awareness of a person's own body. These findings are in accordance with theories suggesting a crucial role of the perception of bodily states for emotional experiences.     

Neural correlates of unconditioned response diminution during Pavlovian conditioning

Pavlovian conditioning research has shown that unconditioned responses (UCR) to aversive unconditioned stimuli (UCS) are reduced when a UCS is predictable. This effect is known as UCR diminution. In the present study, we examined UCR diminution in the functional magnetic resonance imaging (fMRI) signal by varying the rate at which a neutral conditioned stimulus (CS) was paired with an aversive UCS. UCR diminution was observed within several brain regions associated with fear learning, including the amygdala, anterior cingulate, auditory cortex, and dorsolateral prefrontal cortex when a CS continuously relative to intermittently predicted the UCS. In addition, an inverse relationship between UCS expectancy and UCR magnitude was observed within the amygdala, anterior cingulate, and dorsolateral prefrontal cortex, such that as UCS expectancy increased the UCR decreased. These findings demonstrate UCR diminution within the fMRI signal, and suggest that UCS expectancies modulate UCR magnitude.     

Distributed digit somatotopy in primary somatosensory cortex

We obtained high-resolution somatotopic maps of the human digits using 4.0 T functional magnetic resonance imaging (fMRI). In separate experiments, the volar surface of either the right thumb, index, or ring finger was stimulated in a sliding-window fashion in both distal-to-proximal and proximal-to-distal directions using a custom-built pneumatic apparatus. Analysis of the functional images was restricted to Brodmann's areas 3b and 1 and control areas 4 and 3a, as well as a randomized simulation of the functional data in each of these areas. Using in-house algorithms, we detected discrete regions of cortical activation showing phase reversal coinciding with alternation in stimulation direction. Most stimulation-related phase maps of the digits were obtained in areas 3b and 1, rather than areas 3a or 4, despite the somatic input to the latter two areas. The area 3b and 1 representations thus appear to be relatively discrete and somatotopic compared to other somatic processing regions. Our results within areas 3b and 1 confirm the nonlinear mapping of the body surface suggested by recordings in nonhuman primates in terms of phase band topography, scaling, and frequency relative to the actual digit surfaces. The scaling and frequency nonlinearities were more evident within area 3b than area 1, suggesting a functional differentiation of these regions as has previously been observed only in more invasive recordings. Specifically, the area 1 representations were larger overall than those observed in area 3b, and the frequencies of area 3b phase bands and voxels were related disproportionately to thumb and index finger stimulation and to particular areas on the digit surface, suggesting a weighting based in part on receptor distribution.     

Representation of the ear in human primary somatosensory cortex

We studied 13 healthy subjects with a multichannel magnetoencephalography (MEG) system to investigate the somatotopic representation of the ear in the primary somatosensory cortex (SI). We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. The somatosensory-evoked magnetic fields (SEFs) were successfully measured in 7 of 13 subjects. Short-latency responses were analyzed using both single dipole and multidipole models (brain electric source analysis, BESA). From the single dipole model, the equivalent current dipole (ECD) following the helix stimulation was estimated to be near the neck area of SI in all the subjects. In the lobulus stimulation, the ECDs were estimated around the neck area of SI in four subjects, in the face area in one subject, and in the deep white matter in two subjects. In the tragus stimulation, the ECDs were estimated around the neck area of SI in three subjects, in the hand area of SI in two subjects, and in the deep white matter in two subjects. When the ECDs were estimated to be located in unlikely sites (hand area and deep white matter), a two-dipole model, (1) the neck area of SI and (2) face area of SI, was found to be the most appropriate. Although this might be a preliminary study due to a relatively small number of subjects, it revealed that receptive fields of some part of the ear, such as the lobulus and tragus, might be present in both the neck and face areas of SI. These findings suggested that the "ear area" of SI has variability between subjects, unlike the other areas of SI, possibly because the ear is located on the border between the neck and face.     

Asymmetry in the human primary somatosensory cortex and handedness

Brain asymmetry is a phenomenon well known for handedness and language specialization and has also been studied in motor cortex. Less is known about hemispheric asymmetries in the somatosensory cortex. In the present study, we systematically investigated the representation of somatosensory function analyzing early subcortical and cortical somatosensory-evoked potentials (SEP) after electrical stimulation of the right and left median nerve. In 16 subjects, we compared thresholds, the peripheral neurogram at Erb point, and, using MRI-based EEG source analysis, the P14 brainstem component as well as N20 and P22, the earliest cortical responses from the primary sensorimotor cortex. Handedness was documented using the Edinburgh Inventory and a dichotic listening test was performed as a measure for language dominance. Whereas thresholds, Erb potential, and P14 were symmetrical, amplitudes of the cortical N20 showed significant hemispheric asymmetry. In the left hemisphere, the N20 amplitude was higher, its generator was located further medial, and it had a stronger dipole moment. There was no difference in dipole orientation. As a possible morphological correlate, the size of the left postcentral gyrus exceeded that of the right. The cortical P22 component showed a lower amplitude and a trend toward weaker dipole strength in the left hemisphere. Across subjects, there were no significant correlations between laterality indices of N20, the size of the postcentral gyrus, handedness, or ear advantage. These data show that asymmetry of median nerve SEP occurs at the cortical level, only. However, both functional and morphological cortical asymmetry of somatosensory representation appears to vary independently of motor and language functions.     

The primary somatosensory cortex largely contributes to the early part of the cortical response elicited by nociceptive stimuli

Research on the cortical sources of nociceptive laser-evoked brain potentials (LEPs) began almost two decades ago (Tarkka and Treede, 1993). Whereas there is a large consensus on the sources of the late part of the LEP waveform (N2 and P2 waves), the relative contribution of the primary somatosensory cortex (S1) to the early part of the LEP waveform (N1 wave) is still debated.To address this issue we recorded LEPs elicited by the stimulation of four limbs in a large population (n = 35). Early LEP generators were estimated both at single-subject and group level, using three different approaches: distributed source analysis, dipolar source modeling, and probabilistic independent component analysis (ICA).We show that the scalp distribution of the earliest LEP response to hand stimulation was maximal over the central-parietal electrodes contralateral to the stimulated side, while that of the earliest LEP response to foot stimulation was maximal over the central-parietal midline electrodes. Crucially, all three approaches indicated hand and foot S1 areas as generators of the earliest LEP response.Altogether, these findings indicate that the earliest part of the scalp response elicited by a selective nociceptive stimulus is largely explained by activity in the contralateral S1, with negligible contribution from the secondary somatosensory cortex (S2).     

Role of primary somatosensory cortex in the coding of pain

The intensity and submodality of pain are widely attributed to stimulus encoding by peripheral and subcortical spinal/trigeminal portions of the somatosensory nervous system. Consistent with this interpretation are studies of surgically anesthetized animals, demonstrating that relationships between nociceptive stimulation and activation of neurons are similar at subcortical levels of somatosensory projection and within the primary somatosensory cortex (in cytoarchitectural areas 3b and 1 of somatosensory cortex, SI). Such findings have led to characterizations of SI as a network that preserves, rather than transforms, the excitatory drive it receives from subcortical levels. Inconsistent with this perspective are images and neurophysiological recordings of SI neurons in lightly anesthetized primates. These studies demonstrate that an extreme anterior position within SI (area 3a) receives input originating predominantly from unmyelinated nociceptors, distinguishing it from posterior SI (areas 3b and 1), long recognized as receiving input predominantly from myelinated afferents, including nociceptors. Of particular importance, interactions between these subregions during maintained nociceptive stimulation are accompanied by an altered SI response to myelinated and unmyelinated nociceptors. A revised view of pain coding within SI cortex is discussed, and potentially significant clinical implications are emphasized.     

Sustained spatial attention to vibration is mediated in primary somatosensory cortex

Focusing attention to a specific body location has been shown to improve processing of events presented at this body location. One important debate concerns the stage in the somatosensory pathway at which the neural response is modulated when one attends to a tactile stimulus. Previous studies focused on components of the somatosensory evoked potential to transient stimuli, and demonstrated an early cortical attentional modulation. The neural basis of sustained spatial stimulus processing with continuous stimulation remains, however, largely unexplored. A way to approach this topic is to present vibrating stimuli with different frequencies for several seconds simultaneously to different body locations while subjects have to attend to the one or the other location. The amplitude of the somatosensory steady-state evoked potential (SSSEP) elicited by these vibrating stimuli increases with attention. On the basis of 128 electrode recordings, we investigated the topographical distribution and the underlying cortical sources by means of a VARETA approach of this attentional amplitude modulation of the SSSEP. Sustained spatial attention was found to be mediated in primary somatosensory cortex with no differences in SSSEP amplitude topographies between attended and unattended body locations. These result patterns were seen as evidence for a low-level sensory gain control mechanism in tactile spatial attention.     

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.     

A regression analysis study of the primary somatosensory cortex during pain

Several functional imaging studies of pain, using a number of different experimental paradigms and a variety of reference states, have failed to detect activations in the somatosensory cortices, while other imaging studies of pain have reported significant activations in these regions. The role of the somatosensory areas in pain processing has therefore been debated. In the present study the left hand was immersed in painfully cold water (standard cold pressor test) and in nonpainfully cold water during 2 min, and PET-scans were obtained either during the first or the second minute of stimulation. We observed no significant increase of activity in the somatosensory regions when the painful conditions were directly compared with the control conditions. In order to better understand the role of the primary somatosensory cortex (S1) in pain processing we used a regression analysis to study the relation between a ROI (region of interest) in the somatotopic S1-area for the stimulated hand and other regions known to be involved in pain processing. We hypothesized that although no increased activity was observed in the S1 during pain, this region would change its covariation pattern during noxious input as compared to the control stimulation if it is involved in or affected by the processing of pain. In the nonpainful cold conditions widespread regions of the ipsilateral and contralateral somatosensory cortex showed a positive covariation with the activity in the S1-ROI. However, during the first and second minute of pain this regression was significantly attenuated. During the second minute of painful stimulation there was a significant positive covariation between the activity in the S1-ROI and the other regions that are known to be involved in pain processing. Importantly, this relation was significantly stronger for the insula and the orbitofrontal cortex bilaterally when compared to the nonpainful state. The results indicate that the S1-cortex may be engaged in or affected by the processing of pain although no differential activity is observed when pain is compared with the reference condition.     

Neurovascular coupling during nociceptive processing in the primary somatosensory cortex of the rat

Neuroimaging methods such as functional magnetic resonance imaging (fMRI) have been used extensively to investigate pain-related cerebral mechanisms. However, these methods rely on a tight coupling of neuronal activity to hemodynamic changes. Because pain may be associated with hemodynamic changes unrelated to local neuronal activity (eg, increased mean arterial pressure [MAP]), it is essential to determine whether the neurovascular coupling is maintained during nociceptive processing. In this study, local field potentials (LFP) and cortical blood flow (CBF) changes evoked by electrical stimulation of the left hind paw were recorded concomitantly in the right primary somatosensory cortex (SI) in 15 rats. LFP, CBF, and MAP changes were examined in response to stimulus intensities ranging from 3 to 30 mA. In addition, LFP, CBF, and MAP changes evoked by a 10-mA stimulation were examined during immersion of the tail in non-nociceptive or nociceptive hot water (counter-stimulation). SI neurovascular coupling was altered for stimuli of nociceptive intensities (P < 0.001). This alteration was intensity-dependent and was strongly associated with MAP changes (r = 0.98, P < 0.001). However, when the stimulus intensity was kept constant, SI neurovascular coupling was not significantly affected by nociceptive counter-stimulation (P = 0.4), which similarly affected the amplitude of shock-evoked LFP and CBF changes. It remains to be determined whether such neurovascular uncoupling occurs in humans, and whether it also affects other regions usually activated by painful stimuli. These results should be taken into account for accurate interpretation of fMRI studies that involve nociceptive stimuli associated with MAP changes.     

Functional organization of primary somatosensory cortex depends on the focus of attention

We used magnetic source imaging in human subjects to reveal within-subject variations of the homuncular hand representation within the primary somatosensory cortex modulated by attention. In one condition subjects were trained to detect sequential leftward or rightward stimulus motion across the fingers of the left hand ("hand" condition) and in a different condition to detect stimulus motion at a specific finger on this hand ("finger" condition). Afferent input was controlled by applying exactly the same stimulus pattern to the digits in the two tasks. Segregation of the somatotopic hand representation (an increase in the distance between the representations of digits 2 and 5) was observed, commencing with the onset of practice, in the finger relative to the hand condition. Subsequent training in the hand and finger conditions with feedback for correctness did not modify segregation, indicating that segregation was a task effect and not a training effect. These findings indicate that the hand representation within the primary somatosensory cortex is not statically fixed but is dynamically modulated by top-down mechanisms to support task requirements. A greater capacity for modulation of the functional cortical organization was positively correlated with superior learning and task performance.     

Altered nociceptive C fibre input to primary somatosensory cortex in an animal model of hyperalgesia

Evaluating potentially analgesic effects of drugs and various treatments is critically dependent on valid animal models of pain. Since primary somatosensory (SI) cortex is likely to play an important role in processing sensory aspects of pain, we here assess whether monitoring SI cortex nociceptive C fibre evoked potentials can provide useful information about central changes related to hyperalgesia in rats. Recordings of tactile and CO₂‐laser C fibre evoked potentials (LCEPs) in forelimb and hind limb SI cortex were made 20–24 h after UV‐B irradiation of the heel at a dose that produced behavioural signs of hyperalgesia. LCEPs from irradiated skin increased significantly in duration but showed no significant change in magnitude, measured as area under curve (AUC). By contrast, LCEPs in hind limb SI cortex from skin sites nearby the irradiated skin showed no increase in duration or onset latency but increased significantly in magnitude after UV‐B irradiation. The LCEPs in forelimb or hind limb SI cortex elicited from forelimb skin did not change in magnitude, but were significantly delayed in hind limb SI cortex. Tramadol, a centrally acting analgesic known to reduce hyperalgesia, induced changes that counteracted the changes produced by UV‐B irradiation on transmission to SI cortex from the hind paw, but had no significant effect on time course of LCEPs from forelimb skin. Tactile evoked potentials were not affected by UV‐B irradiation or tramadol. We conclude that altered sensory processing related to hyperalgesia is reflected in altered LCEPs in SI cortex.     

Neuromagnetic evidence that gingiva area is adjacent to tongue area in human primary somatosensory cortex

The somatotopic organization of the human primary somatosensory (SI) area in the cerebral cortex has been intensively studied for the hand, lip, and tongue, but little is known about the gingiva. Penfield concluded that the gingival SI area was above the tongue area, as shown in his famous homunculus map. However, our recent study suggested that the lingual gingiva area was not so different to the tongue area. To delineate the fine SI somatotopy of the gingiva area, evoked magnetic fields were measured in 6 healthy subjects for the stimulus of the anterior or posterior and upper or lower parts of the lip, buccal and lingual gingiva, and tongue. Source position was estimated by a current dipole model at the first peak of the posterior-oriented current in a total of 12 cerebral hemispheres contralateral to the stimulation side. No significant difference was found between the positions of anterior and posterior or upper and lower parts of each structure. Both buccal and lingual gingiva areas were localized adjacent to the tongue area, but significantly lower than the lip area. We believe that the fine SI somatotopy of the human oral structures should be reconsidered.     

An integrative MEG-fMRI study of the primary somatosensory cortex using cross-modal correspondence analysis

We develop a novel approach of cross-modal correspondence analysis (CMCA) to address whether brain activities observed in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) represent a common neuronal subpopulation, and if so, which frequency band obtained by MEG best fits the common brain areas. Fourteen adults were investigated by whole-head MEG using a single equivalent current dipole (ECD) and synthetic aperture magnetometry (SAM) approaches and by fMRI at 1.5 T using linear time-invariant modeling to generate statistical maps. The same somatosensory stimulus sequences consisting of tactile impulses to the right sided: digit 1, digit 4 and lower lip were used in both neuroimaging modalities. To evaluate the reproducibility of MEG and fMRI results, one subject was measured repeatedly. Despite different MEG dipole locations and locations of maximum activation in SAM and fMRI, CMCA revealed a common subpopulation of the primary somatosensory cortex, which displays a clear homuncular organization. MEG activity in the frequency range between 30 and 60 Hz, followed by the ranges of 20-30 and 60-100 Hz, explained best the defined subrepresentation given by both MEG and fMRI. These findings have important implications for improving and understanding of the biophysics underlying both neuroimaging techniques, and for determining the best strategy to combine MEG and fMRI data to study the spatiotemporal nature of brain activity.     

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.     

Spinal NMDA-receptor dependent amplification of nociceptive transmission to rat primary somatosensory cortex (SI)

The role of NMDA mechanisms in spinal pathways mediating acute nociceptive input to the somatosensory cortex is not clear. In this study, the effect of NMDA-antagonists on nociceptive C fibre transmission to the primary somatosensory cortex (SI) was investigated. Cortical field potentials evoked by CO(2)-laser stimulation of the skin were recorded in the halothane/nitrous oxide anaesthetized rat. The SI nociceptive evoked potential (EP) amplitudes were dependent on the frequency of noxious heat stimulation. The amplitudes of SI potentials evoked by CO(2)-laser pulses (duration 15-20 ms, stimulation energy 21-28 mJ/mm(2)) delivered at a frequency of 0.1 Hz were approximately 40% of the amplitudes of potentials evoked by 1.0 Hz stimulation. After intrathecal lumbar application of either of the NMDA-antagonists CPP or MK-801, the amplitudes of nociceptive SI potentials, evoked by 1.0 Hz stimulation of the contralateral hindpaw, were reduced to approximately 40% of controls. By contrast, field potentials evoked by 0.1 Hz stimulation of the hindpaw were unaffected by MK-801. SI potentials evoked by 1.0 Hz stimulation of the contralateral forepaw did not change after lumbar application of CPP or MK-801, indicating that the depression of hindpaw EPs was due to a segmental effect in the spinal cord. It is concluded that spinal NMDA-receptor mechanisms amplify the acute transmission of nociceptive C fiber input to SI in a frequency-dependent way.