Role of tactile stimulation during the preweaning period on the development of the peripheral sensory sural (SU) nerve in adult artificially reared female rat.

Maternal deprivation, as a result of the artificial rearing (AR) paradigm, disturbs electrophysiological and histological characteristics of the peripheral sensory sural (SU) nerve of infant and adult male rats. Such changes are prevented by providing tactile or social stimulation during isolation. AR also affects the female rat's brain and behavior; however, it is unknown whether this early adverse experience also alters their SU nerve development or if tactile stimulation might prevent these possible developmental effects. To assess these possibilities, the electrophysiological and histological characteristics of the SU nerve from adult diestrus AR female rats that: (i) received no tactile stimulation (AR group), (ii) received tactile stimulation in the anogenital and body area (AR-Tactile group), or (iii) were mother reared (MR group) were determined. We found that the amplitude, but not the area, of the evoked compound action potential response in SU nerves of AR rats was lower than those of SU nerves of MR female rats. Tactile stimulation prevented these effects. Additionally, we found a reduction in the outer diameter and myelin thickness of axons, as well as a large proportion of axons with low myelin thickness in nerves of AR rats compared to the nerves of the MR and AR-Tactile groups of rats; however, tactile stimulation only partially prevented these effects. Our data indicate that maternal deprivation disturbs the development of sensory SU nerves in female rats, whereas tactile stimulation partially prevents the changes generated by AR. Considering that our previous studies have shown more severe effects of AR on male SU nerve development, we suggest that sex-associated factors may be involved in these processes.

Cortical cellular encoding of thermotactile integration.

Recent evidence suggests that primary sensory cortical regions play a role in the integration of information from multiple sensory modalities. How primary cortical neurons integrate different sources of sensory information is unclear, partly because non-primary sensory input to a cortical sensory region is often weak or modulatory. To address this question, we take advantage of the robust representation of thermal (cooling) and tactile stimuli in mouse forelimb primary somatosensory cortex (fS1). Using a thermotactile detection task, we show that the perception of threshold-level cool or tactile information is enhanced when they are presented simultaneously, compared with presentation alone. To investigate the cortical cellular correlates of thermotactile integration, we performed in vivo extracellular recordings from fS1 in awake resting and anesthetized mice during unimodal and bimodal stimulation of the forepaw. Unimodal stimulation evoked thermal- or tactile- specific excitatory and inhibitory responses of fS1 neurons. The most prominent features of combined thermotactile stimulation are the recruitment of unimodally silent fS1 neurons, non-linear integration features, and response dynamics that favor longer response durations with additional spikes. Together, we identify quantitative and qualitative changes in cortical encoding that may underlie the improvement in perception of thermotactile surfaces during haptic exploration.

Encoding contact size using static and dynamic electrotactile finger stimulation: natural decoding vs. trained cues.

Electrotactile stimulation through matrix electrodes is a promising technology to restore high-resolution tactile feedback in extended reality applications. One of the fundamental tactile effects that should be simulated is the change in the size of the contact between the finger and a virtual object. The present study investigated how participants perceive the increase of stimulation area when stimulating the index finger using static or dynamic (moving) stimuli produced by activating 1 to 6 electrode pads. To assess the ability to interpret the stimulation from the natural cues (natural decoding), without any prior training, the participants were instructed to draw the size of the stimulated area and identify the size difference when comparing two consecutive stimulations. To investigate if other "non-natural" cues can improve the size estimation, the participants were asked to enumerate the number of active pads following a training protocol. The results demonstrated that participants could perceive the change in size without prior training (e.g., the estimated area correlated with the stimulated area, p < 0.001; ≥ two-pad difference recognized with > 80% success rate). However, natural decoding was also challenging, as the response area changed gradually and sometimes in complex patterns when increasing the number of active pads (e.g., four extra pads needed for the statistically significant difference). Nevertheless, by training the participants to utilize additional cues the limitations of natural perception could be compensated. After the training, the mismatch in the activated and estimated number of pads was less than one pad regardless of the stimulus size. Finally, introducing the movement of the stimulus substantially improved discrimination (e.g., 100% median success rate to recognize ≥ one-pad difference). The present study, therefore, provides insights into stimulation size perception, and practical guidelines on how to modulate pad activation to change the perceived size in static and dynamic scenarios.

Pupil dilation reveals the intensity of touch.

Touch is important for many aspects of our daily activities. One of the most important tactile characteristics is its perceived intensity. However, quantifying the intensity of perceived tactile stimulation is not always possible using overt responses. Here, we show that pupil responses can objectively index the intensity of tactile stimulation in the absence of overt participant responses. In Experiment 1 (n = 32), we stimulated three reportedly differentially sensitive body locations (finger, forearm, and calf) with a single tap of a tactor while tracking pupil responses. Tactile stimulation resulted in greater pupil dilation than a baseline without stimulation. Furthermore, pupils dilated more for the more sensitive location (finger) than for the less sensitive location (forearm and calf). In Experiment 2 (n = 20) we extended these findings by manipulating the intensity of the stimulation with three different intensities, here a short vibration, always at the little finger. Again, pupils dilated more when being stimulated at higher intensities as compared to lower intensities. In summary, pupils dilated more for more sensitive parts of the body at constant stimulation intensity and for more intense stimulation at constant location. Taken together, the results show that the intensity of perceived tactile stimulation can be objectively measured with pupil responses - and that such responses are a versatile marker for touch research. Our findings may pave the way for previously impossible objective tests of tactile sensitivity, for example in minimally conscious state patients.

Comparing the Perceived Intensity of Vibrotacitle Cues Scaled Based on Inherent Dynamic Range.

Wearable devices increasingly incorporate vibrotactile feedback notifications to users, which are limited by the frequency-dependent response characteristics of the low-cost actuators that they employ. To increase the range and type of information that can be conveyed to users via vibration feedback, it is crucial to understand user perception of vibration cue intensity across the narrow range of frequencies that these actuators operate. In this paper, we quantify user perception of vibration cues conveyed via a linear resonant actuator embedded in a bracelet interface using two psychophysical experiments. We also experimentally determine the frequency response characteristics of the wearable device. We then compare user perceived intensity of vibration cues delivered by the bracelet when the cues undergo frequency-specific amplitude modulation based on user perception compared to modulation based on the experimental or manufacturer-reported characterization of the actuator dynamic response. For applications in which designers rely on user perception of cue amplitudes across frequencies to be equivalent, it is recommended that a perceptual calibration experiment be conducted to determine appropriate modulation factors. For applications in which only relative perceived amplitudes are important, basing amplitude modulation factors on manufacturer data or experimentally determined dynamic response characteristics of the wearable device should be sufficient.

An improved conflict avoidance assay reveals modality-specific differences in pain hypersensitivity across sexes.

ABSTRACT: Abnormal encoding of somatosensory modalities (ie, mechanical, cold, and heat) are a critical part of pathological pain states. Detailed phenotyping of patients' responses to these modalities have raised hopes that analgesic treatments could one day be tailored to a patient's phenotype. Such precise treatment would require a profound understanding of the underlying mechanisms of specific pain phenotypes at molecular, cellular, and circuitry levels. Although preclinical pain models have helped in that regard, the lack of a unified assay quantifying detailed mechanical, cold, and heat pain responses on the same scale precludes comparing how analgesic compounds act on different sensory phenotypes. The conflict avoidance assay is promising in that regard, but testing conditions require validation for its use with multiple modalities. In this study, we improve upon the conflict avoidance assay to provide a validated and detailed assessment of all 3 modalities within the same animal, in mice. We first optimized testing conditions to minimize the necessary amount of training and to reduce sex differences in performances. We then tested what range of stimuli produce dynamic stimulus-response relationships for different outcome measures in naive mice. We finally used this assay to show that nerve injury produces modality-specific sex differences in pain behavior. Our improved assay opens new avenues to study the basis of modality-specific abnormalities in pain behavior.

Human Foot Outperforms the Hand in Mechanical Pain Discrimination.

Tactile discrimination has been extensively studied, but mechanical pain discrimination remains poorly characterized. Here, we measured the capacity for mechanical pain discrimination using a two-alternative forced choice paradigm, with force-calibrated indentation stimuli (Semmes-Weinstein monofilaments) applied to the hand and foot dorsa of healthy human volunteers. In order to characterize the relationship between peripheral nociceptor activity and pain perception, we recorded single-unit activity from myelinated (A) and unmyelinated (C) mechanosensitive nociceptors in the skin using microneurography. At the perceptual level, we found that the foot was better at discriminating noxious forces than the hand, which stands in contrast to that for innocuous force discrimination, where the hand performed better than the foot. This observation of superior mechanical pain discrimination on the foot compared to the hand could not be explained by the responsiveness of individual nociceptors. We found no significant difference in the discrimination performance of either the myelinated or unmyelinated class of nociceptors between skin regions. This suggests the possibility that other factors such as skin biophysics, receptor density or central mechanisms may underlie these regional differences.

Physical Stimulation Methods Developed for In Vitro Neuronal Differentiation Studies of PC12 Cells: A Comprehensive Review.

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-ß cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells.

Spatial factors influencing the pain-ameliorating effect of CT-optimal touch: a comparative study for modulating temporal summation of second pain.

Recent studies show that CT-optimal touch, gentle slow stroking of the skin, can reduce pain. However, much is unknown regarding the factors influencing its pain-ameliorating effect, such as tactile attention and touch application site. The current study investigates in 36 healthy individuals, whether CT-optimal touch can reduce temporal summation of second pain (TSSP) compared to CT non-optimal touch and tapping the skin. TSSP refers to activation of the C-nociceptors; by stimulating these fibers a burning and/or tingling sensation can be elicited. All participants underwent three conditions on both the contralateral and ipsilateral side of pain induction. The results show that tapping the skin did not reduce TSSP, meaning that pain reduction through touch cannot be explained by tactile attention effects. CT non-optimal touch only reduced TSSP when applied on the ipsilateral side. Importantly, CT-optimal touch effectively reduced TSSP when applied on the contralateral or ipsilateral side. Furthermore, CT-optimal touch was more effective in reducing TSSP compared to CT non-optimal touch and Tapping. This study shows that that CT-optimal touch can reduce TSSP and this effect appears to be independent of touch application site, which is highly relevant for implementing CT-optimal touch as a treatment.

Hello from the other side: Robust contralateral interference in tactile detection.

Touch is unique among the sensory modalities in that our tactile receptors are spread across the body surface and continuously receive different inputs at the same time. These inputs vary in type, properties, relevance according to current goals, and, of course, location on the body. Sometimes, they must be integrated, and other times set apart and distinguished. Here, we investigate how simultaneous stimulation to different body sites affects tactile cognition. Specifically, we characterized the impact of irrelevant tactile sensations on tactile change detection. To this end, we embedded detection targets amidst ongoing performance, akin to the conditions encountered in everyday life, where we are constantly confronted with new events within ongoing stimuli. In the set of experiments presented here, participants detected a brief intensity change (.04 s) within an ongoing vibrotactile stimulus (1.6 s) that was always presented in a constantly attended location. The intensity change (i.e., the detection target) varied parametrically, from hardly detectable to easily detectable. In half of the trials, irrelevant ongoing stimulation was simultaneously presented to a site across the body midline, but participants were instructed to ignore it. In line with previous bimanual studies employing brief onset targets, we document robust interference on performance due to the irrelevant stimulation at each of the measured body sites (homologous and nonhomologous fingers, and the contralateral ankle). After describing this basic phenomenon, we further examine the conditions under which such interference occurs in three additional tasks. In each task, we honed in on a different aspect of the stimulation protocol (e.g., hand distance, the strength of the irrelevant stimulation, the detection target itself) in order to better understand the principles governing the observed interference effects. Our findings suggest a minimal role for exogenous attentional capture in producing the observed interference effects (Exp. 2), and a principled distribution of attentional resources or sensory integration between body sides (Exps. 3, 4). In our last study (Exp. 4), we presented bilateral tactile targets of varying intensities to both the relevant and irrelevant stimulation sites. We then characterized the degree to which the irrelevant stimulation is also processed. Our results-that participants' perception of target intensity is always proportional to the combined bilateral signal-suggest that both body sites are equally weighed and processed despite clear instructions to attend only the target site. In light of this observation and participants' inability to use selection processes to guide their perception, we propose that bilateral tactile inputs are automatically combined, quite possibly early in the hierarchy of somatosensory processing.

Identification of areas of the brain activated by active stimulation in hairless skin.

In the past few decades, neuroscientists have studied the physiological basis of pleasant touch. Unmyelinated low-threshold mechanoreceptors are central to the study of the physiological basis of pleasant touch. Research on pleasant stimuli has mostly focused on passive stimuli, and the brain activation sites for active pleasant stimuli are not clear. Therefore, the purpose of this study was to identify brain activation sites during active pleasant stimulation of hairless skin using functional magnetic resonance imaging. Forty-two healthy subjects aged 19 years or older were asked to actively grasp in five stimulus tasks. The comfort and sensations that occurred during the tasks were investigated using a questionnaire. Significant activation was found in the middle frontal gyrus when the hair ball and slime ball were grasped, while there was significant activation in the amygdala when grasping a squeeze ball compared to the tennis ball. In a questionnaire survey of the subjects, there was a significant difference in the comfort score between the tennis ball and the squeeze ball, but no significant correlation was found between the comfort scores and the brain sites of activation. Therefore, although active stimulation with the squeeze ball significantly activated the amygdala, it was not clear that the amygdala was significantly activated by active pleasant stimulation. In the future, it will be necessary to investigate the texture of the squeeze ball in more detail, and to increase the number of subjects for further study.

Cortical circuitry mediating interareal touch signal amplification.

Sensory cortical areas are organized into topographic maps representing the sensory epithelium. Interareal projections typically connect topographically matched subregions across areas. Because matched subregions process the same stimulus, their interaction is central to many computations. Here, we ask how topographically matched subregions of primary and secondary vibrissal somatosensory cortices (vS1 and vS2) interact during active touch. Volumetric calcium imaging in mice palpating an object with two whiskers revealed a sparse population of highly responsive, broadly tuned touch neurons especially pronounced in layer 2 of both areas. These rare neurons exhibited elevated synchrony and carried most touch-evoked activity in both directions. Lesioning the subregion of either area responding to the spared whiskers degraded touch responses in the unlesioned area, with whisker-specific vS1 lesions degrading whisker-specific vS2 touch responses. Thus, a sparse population of broadly tuned touch neurons dominates vS1-vS2 communication in both directions, and topographically matched vS1 and vS2 subregions recurrently amplify whisker touch activity.

Oscillatory Responses to Tactile Stimuli of Different Intensity.

Tactile perception encompasses several submodalities that are realized with distinct sensory subsystems. The processing of those submodalities and their interactions remains understudied. We developed a paradigm consisting of three types of touch tuned in terms of their force and velocity for different submodalities: discriminative touch (haptics), affective touch (C-tactile touch), and knismesis (alerting tickle). Touch was delivered with a high-precision robotic rotary touch stimulation device. A total of 39 healthy individuals participated in the study. EEG cluster analysis revealed a decrease in alpha and beta range (mu-rhythm) as well as theta and delta increase most pronounced to the most salient and fastest type of stimulation. The participants confirmed that slower stimuli targeted to affective touch low-threshold receptors were the most pleasant ones, and less intense stimuli aimed at knismesis were indeed the most ticklish ones, but those sensations did not form an EEG cluster, probably implying their processing involves deeper brain structures that are less accessible with EEG.

Effects of skin moisturization on various aspects of touch showing differences with age and skin site.

The human body is encompassed by a thin layer of tissue, the skin, which is heterogenous and highly specialized to protect the body and encode interactions with the external world. There is a fundamental scientific drive to understand its function, coupled with the need to preserve skin as we age, which impacts on our physiological and psychological well-being. In the present study, we aimed to define differences in touch perception between age groups and with skin cream application. We investigated touch on the finger, the forearm and cheek in younger (20-28 years, n = 22) and older (65-75 years, n = 22) females. We measured skin hydration, touch detection, finger spatial discrimination, forearm tactile pleasantness together with electrodermal activity, and perceptual ratings about cream use, skin dryness, and cosmetic habits. Glabrous finger skin became drier and touch performance was impaired with age, but these aspects were preserved in hairy skin. Skin moisturization immediately increased hydration levels, but did not significantly change touch perception. We also found that touch appreciation increased with age. We conclude that reduced finger capacity may impact self-evaluation of the skin and that long-term skin care strategies should focus on hydrating the hand to preserve touch capacities.

Role of medial prefrontal cortex and primary somatosensory cortex in self and other-directed vicarious social touch: a TMS study.

Conflicting evidence points to the contribution of several key nodes of the 'social brain' to the processing of both discriminatory and affective qualities of interpersonal touch. Whether the primary somatosensory cortex (S1) and the medial prefrontal cortex (mPFC), two brain areas vital for tactile mirroring and affective mentalizing, play a functional role in shared representations of C-tactile (CT) targeted affective touch is still a matter of debate. Here, we used offline continuous theta-burst transcranial magnetic stimulation (cTBS) to mPFC, S1 and vertex (control) prior to participants providing ratings of vicarious touch pleasantness for self and others delivered across several body sites at CT-targeted velocities. We found that S1-cTBS led to a significant increase in touch ratings to the self, with this effect being positively associated to levels of interoceptive awareness. Conversely, mPFC-cTBS reduced pleasantness ratings for touch to another person. These effects were not specific for CT-optimal (slow) stroking velocities, but rather they applied to all types of social touch. Overall, our findings challenge the causal role of the S1 and mPFC in vicarious affective touch and suggest that self- vs other-directed vicarious touch responses might crucially depend on the specific involvement of key social networks in gentle tactile interactions.

Infants' sex affects neural responses to affective touch in early infancy.

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.

On the Correlation Between Tactile Stimulation and Pleasantness.

Several studies in the affective haptics research field showed the potential of using haptic technology to convey emotions in remote communications. In this context, it is of interest to simplify the haptic feedback without altering the informative content of the stimulus, with a two-fold advantage. On one side, it would allow the development of affective haptic devices whose technological complexity is limited, hence more compatible with wearability and portability requirements. On the other side, having a simplified set of stimuli would decrease the amount of data to be transmitted, thus improving the overall quality of remote haptic interactions. In this work, we investigated the correlation between the parameters regulating a caress-like stimulation and the perceived pleasantness. This was done by means of two experiments, in which we asked subjects to adjust the temperature and the motion velocity of a set of stimuli in order to find the most pleasant combination. Results indicated that subjects preferred different values of temperature and velocity of the stimulus depending on the proposed tactile stimulation. A small difference in the pleasantness ratings was observed between caresses provided with linear movements and those given as discrete sequences of taps. In particular, participants preferred linear movements set at 34.5 °C and 3.4 cms-1. As regards caress-like stimuli provided with discrete sequences of taps, the preferred temperature and velocity were 33.2 °C and 2.9 cms-1, respectively. The presence of vibration had a little effect on the perceived pleasantness.

Differences in intracortical responses following non-noxious and noxious stimulation in anaesthetized rats.

Cortical responses have been proposed as a source for the extraction of unique and non-subjective sensory information. The present study aimed to investigate if it is possible to distinguish between non-noxious and noxious cortical responses with two different types of anesthesia. Sixteen rats were randomly allocated to receive either Hypnorm/Dormicum (HD) or isoflurane (ISO) anesthesia. Each animal had a custom-made microelectrode array implanted in the primary somatosensory cortex to record the local field potentials and a cuff electrode implanted around the sciatic nerve to deliver electrical stimulations. Three stimulation intensities were applied: 1x movement threshold (MT) (i.e., non-noxious activation), 5x MT (low intensity noxious activation), and 10x MT (high intensity noxious activation). The evoked potentials were assessed by extracting three features: 1) the negative peak (NP), 2) the positive peak (PP), and 3) the peak-to-peak (PtP) amplitudes. Our results showed that it was possible to distinguish between three levels of stimulation intensities based on the NP, PP, and PtP features for the HD group, whereas it was only possible to make the same differentiation with the use of PP and PtP when applying ISO. This work is believed to contribute to a basic understanding of how the cortical responses change in the hyperacute phase of pain and which cortical features may be suitable as objective measures of nociception.

Depression severity is associated with reduced pleasantness of observed social touch and fewer current intimate touch experiences.

Depression is associated with loss of pleasure in previously enjoyed activities and withdrawal from social interactions. Depression alters the perception of social cues, but it is currently unclear whether this extends to social touch. In the current cross-sectional study, we explored the association between depression severity, perceived pleasantness of observed social touch, and general longing for touch. For observed touch, we contrasted videos of slow touch (1-10cm/s), which optimally activates C tactile afferent nerve fibres and generally feels pleasant, with 'non-CT-optimal' touch (i.e., outside the 1-10cm/s range, commonly rated more neutral). We predicted that greater depression severity would be related to lower pleasantness ratings specifically for CT-optimal touch, and less longing for touch. N = 226 adults completed self-report measures of depression severity and longing for touch, and rated touch pleasantness for six videos depicting social touch at three velocities (3cm/s in the CT-optimal range, 0.5 and 30cm/s outside this range) and at two locations varying in CT innervation (palm vs. arm). We controlled for general anhedonia and individual differences in touch experiences and attitudes. Across touch locations, greater depression severity was associated with lower perceived pleasantness of touch, especially for the fastest non-CT-optimal (rather than the CT-optimal) velocity, contrary to our prediction. However, when grouping participants into probable vs. no/minimal depression, the probable depression group rated both the fastest non-CT-optimal and the CT-optimal velocity as less pleasant than did the no/minimal depression group. Overall, while depression was associated with perceived pleasantness of observed touch, this was not specific to CT-optimal touch. Furthermore, touch longing was not associated with depression severity. Instead, variance in depression symptoms was better explained by reduced levels of current intimate touch. Though the direction of causality is unclear, greater depression severity is related to lower pleasantness of observed social touch, and lower levels of current intimate touch.

[Characterization of brain deactivations elicited by transient painful and tactile stimuli using functional MRI].

The aim of the present study was to explore the specific pattern of brain deactivation elicited by painful stimuli, in contrast with that elicited by tactile stimuli. Functional magnetic resonance imaging (fMRI) data were collected from 62 healthy subjects under painful and tactile stimuli with varying intensities. The brain deactivations under different conditions were identified using the general linear model. Two-way analysis of variance (ANOVA) was performed to test whether there was a significant interaction between perceived stimulus intensity (factor 1: high intensity, low intensity) and stimulus modality (factor 2: pain, touch) on the brain deactivations. The results showed that there were significant interactions between stimulus intensity and stimulus modality on the deactivations of left medial superior frontal gyrus, left middle occipital gyrus, left superior frontal gyrus and right middle occipital gyrus (P < 0.05, Cluster-level FWE). The deactivations induced by painful stimuli with low perceived intensity (ß = -3.38 ± 0.52) were significantly stronger than those induced by painful stimuli with high perceived intensity (ß = -1.22 ± 0.54) (P < 0.001), whereas the differences between the deactivations induced by tactile stimuli with different perceived intensities were not statistically significant. In addition, there were no significant differences between the deactivations elicited by painful and tactile stimuli with the same stimulus intensities. These results suggest that there is a specific relationship between the deactivations induced by painful stimuli in multiple brain regions (such as the left medial superior frontal gyrus) and the stimulus intensity, providing evidence for a deeper understanding of the brain mechanisms underlying pain perception.