Mechanisms of intracerebral pain and itch perception in humans

Electrophysiological studies involving techniques such as magnetoencephalography (MEG) and hemodynamic studies involving techniques such as functional magnetic resonance imaging (fMRI) have recently been intensively used to elucidate the mechanisms underlying pain and itch perception in humans. The MEG results obtained after A-delta fiber (first pain) and C fiber (second pain) stimulation were similar, except for longer latency in the case of C fibers. Initially, the primary somatosensory cortex (SI) contralateral to the stimulation is activated, and the secondary somatosensory cortex (SII), insula, amygdala, and anterior cingulate cortex (ACC) in both hemispheres are then activated sequentially. The fMRI findings obtained after the stimulation of C fibers and those obtained after the stimulation of A-delta fibers both showed activation of the bilateral thalamus, bilateral SII, right (ipsilateral) middle insula, and bilateral Brodmann's area (BA) 24/32, with most of the activity being detected in the posterior region of the ACC. However, the magnitude of activity in the anterior insula on both sides and in BA 32/8/6, including the ACC and pre-supplementary motor area (pre-SMA), after the stimulation of C nociceptors was significantly stronger than that after the stimulation of A-delta nociceptors. We have recently developed a new stimulation electrode that causes an itching sensation via electrical stimulation applied to skin. The conduction velocity (CV) of the signals caused by this stimulation is approximately 1 m/sec in a range of CV of C fibers. The findings obtained after itch stimulation were similar to those obtained after pain stimulation, but the precuneus may be an itch-selective brain region. This unique finding was confirmed by both MEG and fMRI studies.     

Experimental brush-evoked allodynia activates posterior parietal cortex.

OBJECTIVE: To study the brain activation pattern of coexisting experimental ongoing pain and brush-evoked allodynia (pain evoked by innocuous brush) with the use of PET. BACKGROUND: Neuropathic pain usually has two essential phenomena: ongoing pain and brush-evoked allodynia, which coexist and may influence each other. Capsaicin induces both ongoing pain and brush-evoked allodynia. METHODS: Eight healthy right-handed volunteers participated in eight H2(15)O PET scans with two blocks of four randomized conditions: 1) rest, 2) brush, 3) capsaicin pain, and 4) capsaicin pain + brush (brush-evoked allodynia). Capsaicin was injected intradermally on the nondominant forearm and the subjects rated pain intensity and unpleasantness on 100-mm visual analogue scales. RESULTS: Pain intensity and unpleasantness were significantly higher during brush-evoked allodynia (74 +/- 4 and 67 +/- 4 mm) compared with capsaicin pain alone (60 +/- 4 and 51 +/- 5 mm). Brush-evoked allodynia, but not capsaicin pain alone, increased blood flow significantly in the contralateral right sensory association cortex Brodmann area (BA) 5/7, and in bilateral prefrontal cortex BA 9/10/47 and insula. No significant activity was seen in thalamus or primary somatosensory cortex (SI). Direct comparison between capsaicin pain and brush-evoked allodynia revealed significant increase in contralateral BA 5/7 only. CONCLUSIONS: The specific activation of contralateral BA 5/7 indicates that this brain region is important to the processing of brush-evoked allodynia. The involvement of BA 5/7 in brush-evoked allodynia is claimed to reflect multisensory input to this region, its role in conscious pain perception, and its neuroplastic properties.     

Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study

Two- or 100-Hz electrical acupoint stimulation (EAS) can induce analgesia via distinct central mechanisms. It has long been known that the extent of EAS analgesia showed tremendous difference among subjects. Functional MRI (fMRI) studies were performed to allocate the possible mechanisms underlying the frequency specificity as well as individual variability of EAS analgesia. In either frequencies, the averaged fMRI activation levels of bilateral secondary somatosensory area and insula, contralateral anterior cingulate cortex and thalamus were positively correlated with the EAS-induced analgesic effect across the subjects. In 2-Hz EAS group, positive correlations were observed in contralateral primary motor area, supplementary motor area, and ipsilateral superior temporal gyrus, while negative correlations were found in bilateral hippocampus. In 100-Hz EAS group, positive correlations were observed in contralateral inferior parietal lobule, ipsilateral anterior cingulate cortex, nucleus accumbens, and pons, while negative correlation was detected in contralateral amygdala. These results suggest that functional activities of certain brain areas might be correlated with the effect of EAS-induced analgesia, in a frequency-dependent dynamic. EAS-induced analgesia with low and high frequencies seems to be mediated by different, though overlapped, brain networks. The differential activations/de-activations in brain networks across subjects may provide a neurobiological explanation for the mechanisms of the induction and the individual variability of analgesic effect induced by EAS, or that of manual acupuncture as well.     

Altered somatosensory processing in trigeminal neuralgia

Trigeminal neuralgia (TN) is a pain state characterized by intermittent unilateral pain attacks in one or several facial areas innervated by the trigeminal nerve. The somatosensory cortex is heavily involved in the perception of sensory features of pain, but it is also the primary target for thalamic input of nonpainful somatosensory information. Thus, pain and somatosensory processing are accomplished in overlapping cortical structures raising the question whether pain states are associated with alteration of somatosensory function itself. To test this hypothesis, we used functional magnetic resonance imaging to assess activation of primary (SI) and secondary (SII) somatosensory cortices upon nonpainful tactile stimulation of lips and fingers in 18 patients with TN and 10 patients with TN relieved from pain after successful neurosurgical intervention in comparison with 13 healthy subjects. We found that SI and SII activations in patients did neither depend on the affected side of TN nor differ between operated and nonoperated patients. However, SI and SII activations, but not thalamic activations, were significantly reduced in patients as compared to controls. These differences were most prominent for finger stimulation, an area not associated with TN. For lip stimulation SI and SII activations were reduced in patients with TN on the contra‐ but not on the ipsilateral side to the stimulus. These findings suggest a general reduction of SI and SII processing in patients with TN, indicating a long‐term modulation of somatosensory function and pointing to an attempt of cortical adaptation to potentially painful stimuli. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

体感刺激激活人脑听觉皮层

目的 初步探讨体感刺激是否可以激活听觉皮层,为听觉皮层作为多重感觉皮层提供证据.方法 5例颞叶占位的患者术中暴露颞上回后,分别接受声音(100 dB)和体感刺激,通过光学成像在红光下(610±10)nm观察初级、次级听觉皮层(BA41、42)反射内源光信号变化特征.结果 红光(610±lO)nm下我们观察到听觉刺激后听觉皮层(BA41、42)明显激活(n=5),体感刺激后可观察到和听觉刺激时相似区域的激活,且响应的方式与听觉刺激无明显差异(n=4).结论 体感刺激可激活听觉皮层,这可能是听觉皮层作为多重感觉皮层的一个证据.

Abstract：

Objective This paper is to explore whether somatosensory stimulation could activate human anditory cortex(AI)and provide a new evidence for the multisensory center.Methods Intrinsic optical signals from the superior temporal gyrus were measured intraoperatively in five anesthetized patients with temporal lobe tumors.We detected the activation of the auditory cortex(BA41、42)during auditory and somatosensory stimuli respectively under red illuminating light(610±10)nm.Results Under the illumination of red light wavelength we clearly detected hemodynamic responses in the primary and secondary auditory cortex(BA 41,42)by the stimulus of the 100 dB clicks(n=5)and similar response area during the somatosensory paradigm(n=4).Conclusion Somatosensory stimulation can activate the auditory cortex which may be a new evidence of the multisensory center.     

Strength of prefrontal activation predicts intensity of suggestion‐induced pain

Suggestion, a powerful factor in everyday social interaction, is most effective during hypnosis. Subjective evaluations and brain‐imaging findings converge to propose that hypnotic suggestion strongly modulates sensory processing. To reveal the brain regions that mediate such a modulation, we analyzed data from a functional‐magnetic‐resonance‐imaging study on hypnotic‐suggestion‐induced pain on 14 suggestible subjects. Activation strengths in the right dorsolateral prefrontal cortex (DLPFC) during initiation of suggestion for pain correlated positively with the subjective intensity of the subsequent suggestion‐induced pain, as well as with the strengths of the maximum pain‐related activation in the in the secondary somatosensory (SII) cortex. Furthermore, activation of the insula and the anterior cingulate cortex predicted the pain‐related SII activation. The right DLPFC, as an area important for executive functions, likely contributes to functional modulation in the modality‐specific target areas of given suggestions. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects

Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.     

Attentional modulation of visceral and somatic pain

A better understanding of the cortical processes underlying attentional modulation of visceral and somatic pain in health are essential for interpretation of future imaging studies of hypervigilance towards bodily sensations which is considered to be an aetiologically important factor in the heightened pain reported by patients with irritable bowel syndrome and fibromyalgia. Twelve healthy subjects were recruited for this study. Simultaneous trains of electrical pulses (delivered to either the rectum or lower abdomen) and auditory tones lasting 6 s were delivered to the subjects during a whole-brain functional scan acquisition. Subjects were instructed to attend to the auditory tones (distracter task) or electrical pulses (pain task). Pain intensity ratings were significantly lower during the distraction task compared with the pain task (P < 0.01) in both sensory modalities. The left primary somatosensory cortex increased in activity with increasing pain report, during attention to visceral pain. Bilateral anterior insula (aIns) cortex activity increased with increasing somatic pain report independent of the direction of attention. Conversely, the primary and secondary auditory cortices significantly increased in activation with decreased pain report. These results suggest that pain intensity perception during attentional modulation is reflected in the primary somatosensory cortex (visceral pain) and aIns cortex activity (somatic pain).     

Decreased bilateral cortical representation patterns in writer’s cramp: a functional magnetic resonance imaging study at 3.0 T

Functional magnetic resonance imaging was used to characterize patterns of cortical activation in response to sensory and motor tasks in patients with writer’s cramp. 17 patients and 17 healthy subjects were examined during finger-tapping, index finger flexion, and electrical median nerve stimulation of both hands during electromyographic monitoring. SPM2 was used to evaluate Brodmann area (BA) 4, 1, 2, 3, 6, 40. Patients showed decreased activation in the left BA 4 with motor tasks of both hands and the left BA 1–3 with right finger-tapping. With left finger-tapping there was bilateral underactivation of single areas of the somatosensory cortex. Patients exhibited decreased activation in the bilateral BA 6 with left motor tasks and in the right BA 6 with right finger-tapping. Patients had decreased activation in bilateral BA 40 with finger-tapping of both hands. The findings suggest decreased baseline activity or an impaired activation in response to motor tasks in BA 1–4, 6, 40 in patients with writer’s cramp for the dystonic and the clinically unaffected hand.     

Cortical representation of tympanic membrane movements due to pressure variation: an fMRI study

Middle ear sensory information has never been localized in the homunculus of the somatosensory cortex (S1). We investigated the somatosensory representation of the middle ear in 15 normal hearing subjects. We applied small air pressure variations to the tympanic membrane while performing a 3T-fMRI study. Unilateral stimulations of the right ear triggered bilateral activations in the caudal part of the postcentral gyrus in Brodmann area 43 (BA 43) and in the auditory associative areas 42 (BA 42) and 22 (BA 22). BA 43 has been found to be involved in activities accompanying oral intake and could be more largely involved in pressure activities in the oropharynx area. The tympanic membrane is indirectly related to the pharynx area through the action of tensor tympani, which is a Eustachian tube muscle. The Eustachian tube muscles have a role in pressure equalization in the middle ear and also have a role in the pharyngeal phase of swallowing. Activation of BA 42 and BA 22 could reflect activations associated with the bilateral acoustic reflex triggered prior to self-vocalization to adjust air pressure in the oropharynx during speech. We propose that BA 43, 42, and 22 are the cortical areas associated with middle ear function. We did not find representation of tympanic membrane movements due to pressure in S1, but its representation in the postcentral gyrus in BA 43 seems to suggest that at least part of this area conveys pure somatosensory information.     

Age effect on subcortical structures in healthy adults

Schizophrenia is characterized by significant problems in control of behavior; however, the disturbances in neural systems that control movement remain poorly characterized. We used functional magnetic resonance imaging (fMRI) to evaluate the origin of motor overflow in schizophrenia. Twenty-seven clinically stable medicated outpatients with Diagnostic and Statistical Manual, 4th edition, text revision (DSM-IV-TR)-defined schizophrenia (SZ), and 18 healthy control (HC) subjects, all right-handed, performed a dominant-handed, single-choice visual sensorimotor reaction time paradigm during fMRI. Voxel-wise analyses were conducted within sensorimotor cortical and striatal regions on general linear model (GLM)-derived measures of blood oxygen level-dependent (BOLD) signal change. The SZ group was not different from the HC group in reaction time, activation in somatosensory or motor cortices ipsilateral to the active (intended) descending corticospinal tract, nor visual cortex. However, in the right hemisphere (contralateral to the active M1), the SZ group showed significantly higher activation in primary motor cortex and adjacent premotor and somatosensory cortices (right Brodmann areas (BA) 1 through 4, and 6), and significantly lower activation in bilateral basal ganglia. Right BA 4 activation was strongly related to disorganization and poverty symptoms (and unrelated to medications) in the patient group. This study provides evidence in SZ of excessive neural activity in motor cortex contralateral to the intended primary motor cortex, which may form the basis for altered motor laterality and motor overflow previously observed, and disorganized behavior. This pathological motor overflow may be partly due to altered modulation of intended movement within the basal ganglia and premotor cortex.     

The sense of touch: embodied simulation in a visuotactile mirroring mechanism for observed animate or inanimate touch

Previous studies have shown a shared neural circuitry in the somatosensory cortices for the experience of one's own body being touched and the sight of intentional touch. Using functional magnetic resonance imaging (fMRI), the present study aimed to elucidate whether the activation of a visuotactile mirroring mechanism during touch observation applies to the sight of any touch, that is, whether it is independent of the intentionality of observed touching agent. During fMRI scanning, healthy participants viewed video clips depicting a touch that was intentional or accidental, and occurring between animate or inanimate objects. Analyses showed equal overlapping activation for all the touch observation conditions and the experience of one's own body being touched in the bilateral secondary somatosensory cortex (SII), left inferior parietal lobule (IPL)/supramarginal gyrus, bilateral temporal-occipital junction, and left precentral gyrus. A significant difference between the sight of an intentional touch, compared to an accidental touch, was found in the left primary somatosensory cortex (SI/Brodmann's area [BA] 2). Interestingly, activation in SI/BA 2 significantly correlated with the degree of intentionality of the observed touch stimuli as rated by participants. Our findings show that activation of a visuotactile mirroring mechanism for touch observation might underpin an abstract notion of touch, whereas activation in SI might reflect a human tendency to "resonate" more with a present or assumed intentional touching agent.     

5-Hydroxytryptamine2C receptors on pudendal motoneurons innervating the external anal sphincter

The aim of this study was to determine the localization of 5-hydroxytryptamine2C (5-HT2C) receptors on the motoneurons innervating the external anal sphincter (EAS) of male rats. Motoneurons were retrogradely labeled after percutaneous intramuscular injection of Fluorogold (FG) into the EAS. Using fluorescent immunohistochemistry, FG-positive EAS motoneurons that were immunoreactive for the 5-HT2C receptor (5-HT2C-IR) were targeted for specific examination with widefield microscopy or confocal laser scanning microscopy with spectral separation. Widefield microscopy revealed distributions of FG-positive EAS motoneurons in the L5-S1 gray matter corresponding to the dorsomedial cell group. 5-HT2C-IR positive cells were distributed in the intermediolateral cell column and the ventral horn. Ventral horn 5-HT2C-IR labeling included the dorsomedial cell group as well as the dorsolateral, ventromedial and ventrolateral areas. Confocal analysis of FG-positive EAS motoneurons and 5-HT2C-IR positive motoneuron profiles adjacent to EAS motoneurons that were not labeled with FG but presumably innervate the bulbospongiosus muscle confirmed that EAS motoneurons were immunopositive for the 5-HT2C receptor. These data suggest that previously identified descending serotonergic immunopositive fibers observed terminating on EAS motoneurons might mediate their input through the activation of 5-HT2C receptors.     

fMRI shows multiple somatotopic digit representations in human primary somatosensory cortex

Using electrical finger nerve stimulation in normal human subjects, fMRI detected separate representations for all 5 fingers in the primary somatosensory cortex. Responses were located in the posterior wall of the deep central sulcus (most likely corresponding to Brodmann Area (BA) 3b), and the anterior (BA 1) or posterior crown of the postcentral gyrus (BA 2) with rare activations in BA 3a and 4. In BA 3b we found a regular somatotopic mediolateral digit arrangement for fingers 5 to 1 with a mean Euclidean distance of 16 mm between fingers 1 and 5. In contrast BA 1/2 showed a greater number of adjacent activation foci with significantly more overlap and partly even reversed ordering of neighbouring fingers.     

Distinct contributions of Brodmann areas 1 and 2 to body ownership

Although body ownership—i.e. the feeling that our bodies belong to us—modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person’s finger by asking participants to hold their palm against another person’s palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person’s finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousness.     

Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury

Stimulation of the somatosensory system is more likely to evoke pain in patients with chronic pain after nervous system injury than in patients without somatosensory abnormalities. We now describe results of stimulation through a microelectrode at microampere thresholds (threshold microstimulation; TMIS) in the region of the human thalamic principal sensory nucleus (ventral caudal; Vc) during operations for treatment of movement disorders or of chronic pain. Patients were trained preoperatively to use a standard questionnaire to describe the location (projected field) and quality of sensations evoked by TMIS intraoperatively. The region of Vc was divided on the basis of projected fields into areas representing the part of the body where the patients experienced chronic pain (pain affected) or did not experience chronic pain (pain unaffected) and into a control area located in the thalamus of patients with movement disorders and no experience of chronic pain. The region of the Vc was also divided into a core region and a posterior-inferior region. The core was defined as the region above a standard radiologic horizontal line (anterior commissure-posterior commisure line; ACPC line) where the majority of cells responded to innocuous somatosensory stimulation. The posterior-inferior area was a cellular area posterior and inferior to the core. In both the core and the posterior-inferior regions, the proportion of sites where TMIS evoked pain was larger in pain-affected and unaffected areas than in control areas. The number of sites where thermal (warm or cold) sensations were evoked was correspondingly smaller, so that the total of pain-plus-thermal (sensation of warmth or cold) sites was the same in all areas. Therefore, sites pain where stimulation evoked pain in patients with neuropathic pain (i.e., pain following an injury to the nervous system) may correspond to sites where thermal sensations were evoked by stimulation in patients without somatosensory abnormality. J. Comp. Neurol. 399:125–138, 1998. © 1998 Wiley-Liss, Inc.     

Empathy examined through the neural mechanisms involved in imagining how I feel versus how you feel pain

Perspective-taking is a stepping stone to human empathy. When empathizing with another individual, one can imagine how the other perceives the situation and feels as a result. To what extent does imagining the other differs from imagining oneself in similar painful situations? In this functional magnetic resonance imaging experiment, participants were shown pictures of people with their hands or feet in painful or non-painful situations and instructed to imagine and rate the level of pain perceived from different perspectives. Both the Self's and the Other's perspectives were associated with activation in the neural network involved in pain processing, including the parietal operculum, anterior cingulate cortex (ACC; BA32) and anterior insula. However, the Self-perspective yielded higher pain ratings and involved the pain matrix more extensively in the secondary somatosensory cortex, the ACC (BA 24a'/24b'), and the insula proper. Adopting the perspective of the Other was associated with specific increase in the posterior cingulate/precuneus and the right temporo-parietal junction. These results show the similarities between Self- and Other-pain representation, but most interestingly they also highlight some distinctiveness between these two representations, which is a crucial aspect of human empathy. It may be what allows us to distinguish empathic responses to others versus our own personal distress. These findings are consistent with the view that empathy does not involve a complete Self-Other merging.     

Brain imaging of analgesic and antihyperalgesic effects of cyclooxygenase inhibition in an experimental human pain model: a functional MRI study

One of the most distressing symptoms of many neuropathic pain syndromes is the enhanced pain sensation to tactile or thermal stimulation (hyperalgesia). In the present study we used functional magnetic resonance imaging (fMRI) and explored brain activation patterns during acute impact pain and mechanical hyperalgesia in the human ultraviolet (UV)-B model. To investigate pharmacological modulation, we examined potential differential fMRI correlates of analgesic and antihyperalgesic effects of two intravenous cyclooxygenase inhibitors, i.e. parecoxib and acetylsalicylic acid (ASA). Fourteen healthy volunteers participated in this double-blinded, randomized and placebo-controlled crossover study. Tactile stimuli and mechanical impact hyperalgesia were tested at the site of a UV-B irradiation and acute mechanical pain was tested at a site distant from the irradiated skin. These measurements were conducted before and 30 min after a 5-min intravenous infusion of either saline (placebo), parecoxib 40 mg or ASA 1000 mg. Acute mechanical pain and mechanical hyperalgesia led to widespread activations of brain areas known to comprise the human pain matrix. Analgesic effects were found in primary (S1) and secondary (S2) somatosensory cortices, parietal association cortex (PA), insula, anterior parts of the cingulate cortex and prefrontal cortices. These brain areas were also modulated under antihyperalgesic conditions. However, we observed a greater drug-induced modulation of mainly PA and inferior frontal cortex during mechanical hyperalgesia; during acute mechanical pain there was a greater modulation of mainly bilateral S2. Therefore, the results of the present study suggest that there is a difference in the brain areas modulated by analgesia and antihyperalgesia.     

Habituation within the somatosensory processing hierarchy

Habituation is a basic process of learning evident in a decrement in neuronal/behavioral responses to repeated sensory stimulation. It is generally accepted that habituation affects all sensory systems in the human brain, including the somatosensory network. However, it is not clear where habituation originates within this hierarchically organized network. In this study, we examined whether habituation effects increase relatively uniformly along the processing hierarchy or rather distinctly at a particular processing stage. We addressed these questions by performing functional magnetic resonance imaging (fMRI) on 43 healthy subjects during unilateral electrical median nerve stimulation using a block design. We found a time-dependent decrease in the positive BOLD response (indicative of habituation) in all areas of the somatosensory network with the exception of Brodmann area (BA) 3b. The increase in habituation within the presumed processing stream was most pronounced between subareas of the primary somatosensory cortex (BA3b, BA1, BA2), and no further increase in habituation effects was observed in the subsequent processing stages within either the secondary somatosensory cortex or the insula. Moreover, we found a relatively strong habituation effect within the thalamus. These findings indicate that the increase in habituation along the processing hierarchy is measurable primarily between subareas of the primary somatosensory cortex, and we hypothesize that this increase originates in thalamocortical interactions early in the processing stream.