Tactile localization
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Background: Activation of cannabinoid receptor 1 (CB1R) in the nervous system modulates the processing of acute and chronic pain. CB1R activity is regulated by desensitization and internalization. SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1) inhibits the internalization of CB1R. This causes increased and prolonged association of the desensitized receptor with G protein-coupled receptor kinase 3 (GRK3) and beta-arrestin on the cell membrane and results in decreased activation of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Genetic deletion of SGIP1 in mice leads to altered CB1R-related functions, such as decreased anxiety-like behaviors, modified cannabinoid tetrad behaviors, reduced acute nociception, and increased sensitivity to analgesics. In this work, we asked if deletion of SGIP1 affects chronic nociception and analgesic effect of Δ9-tetrahydrocannabinol (THC) and WIN 55,212-2 (WIN) in mice. Methods: We measured tactile responses of hind paws to increasing pressure in wild-type and SGIP1 knock-out mice. Inflammation in the paw was induced by local injection of carrageenan. To determine the mechanical sensitivity, the paw withdrawal threshold (PWT) was measured using an electronic von Frey instrument with the progression of the applied force. Results: The responses to mechanical stimuli varied depending on the sex, genotype, and treatment. SGIP1 knock-out male mice exhibited lower PWT than wild-type males. On the contrary, the female mice exhibited comparable PWT. Following THC or WIN treatment in male mice, SGIP1 knock-out males exhibited PWT lower than wild-type males. THC treatment in SGIP1 knock-out females resulted in PWT higher than after THC treatment of wild-type females. However, SGIP1 knock-out and wild-type female mice exhibited similar PWT after WIN treatment. Conclusions: We provide evidence that SGIP1, possibly by interacting with CB1R, is involved in processing the responses to chronic pain. The absence of SGIP1 results in enhanced sensitivity to mechanical stimuli in males, but not females. The antinociceptive effect of THC is superior to that of WIN in SGIP1 knock-out mice in the carrageenan-induced model of chronic pain.
- MeSH
- benzoxaziny * farmakologie MeSH
- hyperalgezie * genetika MeSH
- morfoliny farmakologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované * MeSH
- myši MeSH
- naftaleny MeSH
- nocicepce účinky léků MeSH
- receptor kanabinoidní CB1 * genetika metabolismus MeSH
- tetrahydrokanabinol * farmakologie MeSH
- zánět * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The perception of a voice in the absence of an external auditory source-an auditory verbal hallucination-is a characteristic symptom of schizophrenia. To better understand this phenomenon requires integration of findings across behavioural, functional, and neurochemical levels. We address this with a locally adapted MEGA-PRESS sequence incorporating interleaved unsuppressed water acquisitions, allowing concurrent assessment of behaviour, blood-oxygenation-level-dependent (BOLD) functional changes, Glutamate + Glutamine (Glx), and GABA, synchronised with a cognitive (flanker) task. We acquired data from the anterior cingulate cortex (ACC) of 51 patients with psychosis (predominantly schizophrenia spectrum disorder) and hallucinations, matched to healthy controls. Consistent with the notion of an excitatory/inhibitory imbalance, we hypothesized differential effects for Glx and GABA between groups, and aberrant dynamics in response to task. Results showed impaired task performance, lower baseline Glx and positive association between Glx and BOLD in patients, contrasting a negative correlation in healthy controls. Task-related increases in Glx were observed in both groups, with no significant difference between groups. No significant effects were observed for GABA. These findings suggest that a putative excitatory/inhibitory imbalance affecting inhibitory control in the ACC is primarily observed as tonic, baseline glutamate differences, rather than GABAergic effects or aberrant dynamics in relation to a task.
- MeSH
- cingulární gyrus metabolismus patofyziologie MeSH
- dospělí MeSH
- GABA * metabolismus MeSH
- glutamin metabolismus MeSH
- halucinace * metabolismus patofyziologie MeSH
- kognice * fyziologie MeSH
- kyselina glutamová * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- psychotické poruchy * metabolismus patofyziologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) diminishes auditory hallucinations (AHs). The aims of our study were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). METHODS: Nineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n = 10) or sham (n = 9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. RESULTS: AHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40 % vs 12 %; p = 0.01). sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group. LIMITATIONS: Limitations to our study included the small group sizes, and the disability of LORETA to assess subcortical neuronal activity. CONCLUSIONS: LF-rTMS attenuated AHs and induced a decrease of higher frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.
Touch is one of the primary communication tools. Interestingly, the sensation of touch can also be experienced when observed in another person. Due to the system of mirror neurons, it is, in fact, being mapped on the somatosensory cortex of the observer. This phenomenon can be triggered not only by observing touch in another individual, but also by a mirror reflection of the contralateral limb. Our study aims to evaluate and localize changes in the intracerebral source activity via sLORETA imaging during the haptic stimulation of hands, while modifying this contact by a mirror illusion. A total of 10 healthy volunteers aged 23-42 years attended the experiment. The electrical brain activity was detected via scalp EEG. First, we registered the brain activity during resting state with open and with closed eyes, each for 5 min. Afterwards, the subjects were seated at a table with a mirror reflecting their left hand and occluding their right hand. The EEG was then recorded in 2 min sequencies during four modifications of the experiment (haptic contact on both hands, stimulation of the left hand only, right hand only and without any tactile stimuli). We randomized the order of the modifications for each participant. The obtained EEG data were converted into the sLORETA program and evaluated statistically at the significance level of p ≤ 0.05. The subjective experience of all the participants was registered using a survey. A statistically significant difference in source brain activity occurred during all four modifications of our experiment in the beta-2, beta-3 and delta frequency bands, resulting in the activation of 10 different Brodmann areas varying by modification. The results suggest that the summation of stimuli secured by interpersonal haptic contact modified by mirror illusion can activate the brain areas integrating motor, sensory and cognitive functions and further areas related to communication and understanding processes, including the mirror neuron system. We believe these findings may have potential for therapy.
- Publikační typ
- časopisecké články MeSH
Social touch may modulate emotions, but the neurobehavioral correlates are poorly understood. Here, we investigated neural responses to a picture of a deceased close person and if neural activity and connectivity are modulated by social touch from one's romantic partner. Using functional magnetic resonance imaging, we found altered reactivity in several brain areas including the anterior cingulate cortex (ACC) and the anterior insula in response to the personal picture compared to a picture of an unfamiliar person. Hand holding with the romantic partner, compared to being alone, reduced reactivity in the ACC and cerebellum and provided subjective comfort. To separate physical touch from the emotional effect of partner presence, we evaluated hand holding with the partner relative to a stranger and found reduced reactivity in the anterior insula. Connectivity between the anterior insula and the ACC was reduced during partner touch, and the connectivity strength was negatively related to attachment security, with higher reported partner security associated with weaker connectivity. Overall, holding hands with one's partner attenuates reactivity in emotional brain areas and reduces between-region connectivity.
- MeSH
- cingulární gyrus fyziologie MeSH
- dospělí MeSH
- emoce fyziologie MeSH
- hmat MeSH
- hmatová percepce fyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku metody MeSH
- mozek fyziologie MeSH
- mozková kůra fyziologie MeSH
- sexuální partneři psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Reaching to target locations on the body has been studied little despite its importance for adaptive behaviors such as feeding, grooming, and indicating a source of discomfort. This behavior requires multisensory integration given that it involves coordination of touch, proprioception, and sometimes vision as well as action. Here we examined the origins of this skill by investigating how infants begin to localize targets on the body and the motor strategies by which they do so. Infants (7-21 months of age) were prompted to reach to a vibrating target placed at five arm/hand locations (elbow, crook of elbow, forearm, palm, and top of hand) one by one. To manually localize the target, infants needed to reach with one arm to the other. Results suggest that coordination increases with age in the strategies that infants used to localize body targets. Most infants showed bimanual coordination and usually moved the target arm toward the reaching arm to assist reaching. Furthermore, intersensory coordination increased with age. Simultaneous movements of the two arms increased with age, as did coordination between vision and reaching. The results provide new information about the development of multisensory integration during tactile localization and how such integration is linked to action.
- MeSH
- hmat fyziologie MeSH
- hmatová percepce fyziologie MeSH
- kojenec MeSH
- lidé MeSH
- pohyb fyziologie MeSH
- propriocepce fyziologie MeSH
- psychomotorický výkon fyziologie MeSH
- vývoj dítěte fyziologie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Infant development of reaching to tactile targets on the skin has been studied little, despite its daily use during adaptive behaviors such as removing foreign stimuli or scratching an itch. We longitudinally examined the development of infant reaching strategies (from just under 2 to 11 months) approximately every other week with a vibrotactile stimulus applied to eight different locations on the face (left/right/center temple, left/right ear, left/right mouth corners, and chin). Successful reaching for the stimulus uses tactile input and proprioception to localize the target and move the hand to it. We studied the developmental progression of reaching and grasping strategies. As infants became older the likelihood of using the hand to reach to the target - versus touching the target with another body part or surface such as the upper arm or chair - increased. For trials where infants reached to the target with the hand, infants also refined their hand postures with age. As infants became older, they made fewer contacts with a closed fist or the dorsal part of the hand and more touches/grasps with the fingers or palm. Results suggest that during the first year infants become able to act more precisely on tactile targets on the face.
- Publikační typ
- časopisecké články MeSH
This study focuses on how the body schema develops during the first months of life, by investigating infants' motor responses to localized vibrotactile stimulation on their limbs. Vibrotactile stimulation was provided by small buzzers that were attached to the infants' four limbs one at a time. Four age groups were compared cross-sectionally (3-, 4-, 5-, and 6-month-olds). We show that before they actually reach for the buzzer, which, according to previous studies, occurs around 7-8 months of age, infants demonstrate emerging knowledge about their body's configuration by producing specific movement patterns associated with the stimulated body area. At 3 months, infants responded with an increase in general activity when the buzzer was placed on the body, independently of the vibrator's location. Differentiated topographical awareness of the body seemed to appear around 5 months, with specific responses resulting from stimulation of the hands emerging first, followed by the differentiation of movement patterns associated with the stimulation of the feet. Qualitative analyses revealed specific movement types reliably associated with each stimulated location by 6 months of age, possibly preparing infants' ability to actually reach for the vibrating target. We discuss this result in relation to newborns' ability to learn specific movement patterns through intersensory contingency. Statement of contribution what is already known on infants' sensorimotor knowledge about their own bodies 3-month-olds readily learn to produce specific limb movements to obtain a desired effect (movement of a mobile). infants detect temporal and spatial correspondences between events involving their own body and visual events. what the present study adds until 4-5 months of age, infants mostly produce general motor responses to localized touch. this is because in the present study, infants could not rely on immediate contingent feedback. we propose a cephalocaudal developmental trend of topographic differentiation of body areas.
- MeSH
- chování kojenců fyziologie MeSH
- fyzikální stimulace MeSH
- hmatová percepce fyziologie MeSH
- kojenec MeSH
- končetiny fyziologie MeSH
- lidé MeSH
- pohyb fyziologie MeSH
- průřezové studie MeSH
- vibrace MeSH
- vývoj dítěte fyziologie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Sensorimotor integration is essential for successful motor control and the somatosensory modality has been shown to have strong effects on the execution of motor plans. The primary (SI) and the secondary somatosensory (SII) cortices are known to differ in their neuroanatomical connections to prefrontal areas, as well as in their involvement to encode cognitive aspects of tactile processing. Here, we ask whether the area-specific processing architecture or the structural neuroanatomical connections with prefrontal areas determine the efficacy of sensorimotor integration processes for motor control. In a system neurophysiological study including EEG signal decomposition (i.e., residue iteration decomposition, RIDE) and source localization, we investigated this question using vibrotactile stimuli optimized for SI or SII processing. The behavioral data show that when being triggered via the SI area, inhibitory control of motor processes is stronger as when being triggered via the SII area. On a neurophysiological level, these effects were reflected in the C-cluster as a result of a temporal decomposition of EEG data, indicating that the sensory processes affecting motor inhibition modulate the response selection level. These modulations were associated with a stronger activation of the right inferior frontal gyrus extending to the right middle frontal gyrus as parts of a network known to be involved in inhibitory motor control when response inhibition is triggered over SI. In addition, areas important for sensorimotor integration like the postcentral gyrus and superior parietal cortex showed activation differences. The data suggest that connection patterns are more important for sensorimotor integration and control than the more restricted area-specific processing architecture.
- MeSH
- analýza rozptylu MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- evokované potenciály fyziologie MeSH
- inhibice (psychologie) * MeSH
- lidé MeSH
- mapování mozku * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pohybová aktivita fyziologie MeSH
- psychomotorický výkon fyziologie MeSH
- shluková analýza MeSH
- somatosenzorické korové centrum anatomie a histologie fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA) to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC50 concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP) ion channels. In contrast, lidocaine and tetrodotoxin (TTX) reduce CGRP release by 53-75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC). Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC) NaV1.9, but not NaV1.8 or NaV1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes NaV1.7 and NaV1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics.
- MeSH
- ciguatera metabolismus MeSH
- ciguatoxiny chemie farmakologie MeSH
- ELISA MeSH
- hyperalgezie chemicky indukované MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lidokain farmakologie MeSH
- membránové potenciály účinky léků MeSH
- mořské toxiny farmakologie MeSH
- myši transgenní MeSH
- myši MeSH
- napětím řízený sodíkový kanál, typ 1 účinky léků MeSH
- napětově řízený sodíkový kanál typ 11 účinky léků MeSH
- napěťově řízený sodíkový kanál, typ 9 účinky léků MeSH
- peptid spojený s genem pro kalcitonin účinky léků MeSH
- receptory peptidu se vztahem ke genu kalcitoninu účinky léků MeSH
- tetrodotoxin farmakologie MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH