Neuroimaging characteristics of pruritus induced by eczema: An fMRI study

doi:10.21203/rs.3.rs-3224681/v1

Download PDF

Article

Neuroimaging characteristics of pruritus induced by eczema: An fMRI study

https://doi.org/10.21203/rs.3.rs-3224681/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objective: To explore the neuroimaging characteristics of eczema-induced pruritus with resting-state functional Magnetic Resonance Imaging (rs-fMRI).

Methods: 42 patients with eczema were recruited in the PE group, and 42 healthy participants were included in the HC group. The Visual Analogue Score (VAS), 12-Item Pruritus Severity Scale (12-PSS), Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety Scale (SAS) were recorded in the PE group. The different values of fraction Amplitude of Low Frequency Fluctuation (fALFF) and functional connectivity(FC) were compared after rs-fMRI scanning.

Results: Compared with the HC group, the fALFF values of the left precentral gyrus, left postcentral gyrus, left supplementary motor area (SMA) and left midcingulate cortex in the PE group were increased. The FC values between the left precentral gyrus and bilateral superior temporal gyrus, bilateral hippocampus, left inferior occipital gyrus in the PE group were decreased. The FC values between left SMA and bilateral superior temporal gyrus in the PE group were decreased. The 12-PSS score was positively correlated with fALFF value of the left precentral gyrus and left postcentral gyrus.

Conclusion: Pruritus caused increased spontaneous activity in given cerebral regions, involving the perception of itch, control of scratching movements, and expression of itch-related emotions. Simultaneously, the aberrant fALFF values result in corresponding alterations in networks, primarily characterized by a bilateral decrease in the symmetry of FC values such as the superior temporal gyrus and the hippocampus. Meanwhile, there is a correlation between fALFF values of given cerebral regions and clinical scales, which provided potential neurobiological markers for the future study of pruritus.

Biological sciences/Neuroscience/Diseases of the nervous system

Health sciences/Signs and symptoms/Pruritus

eczema

pruritus

functional Magnetic Resonance Imaging(fMRI)

fraction Amplitude of Low Frequency Fluctuation (fALFF)

Functional Connectivity(FC)

Eczema is a common chronic, pruritic, inflammatory skin disease that can cause disruption in the epidermal barrier^[1]. In addition to cutaneous symptoms, patients with eczema often complain of neurological and psychiatric dysfunctions^[2], such as headaches, insomnia, depression, or anxiety^{[3, 4]}. Severe pruritus caused by eczema, in particular can cause an uncomfortable sensation similar to pain^{[5, 6]}. Pruritus is defined as an uncomfortable sensation that induces the urge to scratch. It is not only the cardinal symptom of eczema but also a common symptom associated with various disorders, such as renal failure^{[7, 8]} and liver disease^{[9, 10]}, however, the central mechanism that activates neurons associated with pruritus remains largely unknown. The effect of pruritus on the central nervous system (CNS) has long been the focus of research with previous studies simulating the sensation of pruritus via mechanical (e.g. brush) ^{[11, 12]}or chemical (e.g. histamine, lathyrus sativus, and capsaicin) methods on animal models or humans^[13–17], to observe the responses within the CNS, including changes in various neurotransmitters or metabolites^[18]. Nevertheless, these methods often fail to provide insights into the persistent effects of pruritus on the brain, especially the functional plasticity in neural circuits related to pruritus^{[19, 20]}.

Resting-state functional magnetic resonance imaging (rs-fMRI) is based on the blood oxygen level-dependent (BOLD) signal^[21] and is a non-invasive approach for analyzing the characteristics of CNS, which can be used to observe the changes in neural activity in real-time^[22]. Through indicators, including fraction amplitude of low-frequency fluctuation (fALFF)^[23] and functional connectivity (FC)^[24], neuronal activities and networks caused by pruritus could be observed. Previous fMRI studies have shown that a pruritic stimuli elicited a significant activation pattern in specific regions within the brain^[25], including the primary somatosensory cortical (S1), the secondary somatosensory cortex (S2), and supplementary motor areas (SMA)^[26]. Areas involved in emotional processing and evaluation (e.g. cingulate and insula)^{[16, 27]} were also activated during itching and scratching^[28]. Similar to yawning, pruritus is a kind of socially contagious behavior and is prevalent in humans and highly social animals^[29]. Particularly, several areas within the brain associated with pruritus, including the S1, S2, SMA, and thalamus, were activated when the subjects were shown videos where a character demonstrated scratching behaviors^[30]. Interestingly, a similar finding has also been demonstrated in mice^[31]. C-FOS is commonly used as a biomarker of neuronal activity. The mice that displayed the contagious scratching behavior exhibited a significant increase in c-Fos expression in the suprachiasmatic nucleus (SCN), the nucleus accumbens, the caudate, the putamen, and in the amygdala^[32]. Moreover, the above brain regions interacted with each other and established neural circuits, which indicated that the neuroplasticity in patients who suffered from pruritus was significantly altered^[33].

These varied findings for both humans and animals may be affected by methodologies and sample selections. Moreover, regional and circuit changes within the brain may indicate an association with different clinical symptoms of patients with pruritus^[34]. While the relationship between regional and network functional changes remains unclear, specific regions or networks may potentially be used as biomarkers and therapeutic targets for pruritus. Therefore, the purpose of this study was to conduct fMRI studies on patients who suffer from pruritus and explore the relationship between the changes in cerebral activities and clinical manifestations. Based on the above research background, we first hypothesized that brain function changes in response to pruritus are different at the regional or network levels; secondly, the activity changes in a given brain regions may be correlated with the clinical data of patients.

2.1. Participants

42 patients with eczema were enrolled in the PE group. 42 healthy controls, who matched for age, gender, years of education, and handedness with the PE group, were recruited from the community as the HC group. All subjects completed fMRI scans between July 2022 and October 2022 from Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine. All experimental protocols were approved by the Institutional Review Board of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine(Approve Number: 2022-1168-105-01). Their personal data were kept confidential, and they were allowed to withdraw at any time during the prospective study. “Informed consent was obtained from all subjects and/or their legal guardian(s)”.

2.2. Inclusion/Exclusion Criteria.

Diagnostic criteria for eczema:

(1) Multiform skin lesions with intensely pruritic, erythema and edema as the essential features. (2) Erythematous papules and vesicles with exudation, crusting, erosion, blisters and oozing. (3) Center of the lesion is more severe, with scattered papules and vesicles in the periphery, the boundary is unclear.

Inclusion criteria for PE group:

(1) Clinically consistent with the manifestations of eczema, with the first onset and the course of disease within 6 weeks. (2) Between the ages of 18 and 55. (3) Right-handed; High school education or above; (4) Agree to participate in the study and sign the informed consent.

Inclusion criteria for HC group

(1) Previous good health, no history of eczema or pruritus within half a year; (2) Between the ages of 18 and 55; (3) Right-handed; High school education or above; (4) Agree to participate in the study and sign the informed consent.

Exclusion criteria for PE & HC groups

(1) have had other types of eczema or primary and secondary diseases that can cause pruritus, such as seborrheic dermatitis, urticaria, cholestasis, uremia, diabetes, multiple sclerosis; (2) Complicated with cardiovascular and cerebrovascular diseases, liver and kidney insufficiency, hematopoietic system and mental diseases; (3) Pregnant or lactating women; (4) Oral administration of antihistamines, steroids and other immunosuppressive agents within 1 week before enrollment; (5) Patients with conditions that are not suitable for MRI examination, such as hearing aid implantation, cardiac pacemaker, claustrophobia, etc.

2.3. Clinical Evaluations Scale

Demographic data were collected for all participants. The Visual Analogue Score (VAS), 12-Item Pruritus Severity Scale (12-PSS), Pittsburgh Sleep Quality Index (PSQI), and Self-rating Anxiety Scale (SAS) were recorded for the PE group after rs-fMRI scanning. All instruments were conducted by a trained clinician under strict guidelines and protocols.

2.4. Rs-fMRI scanning

Rs-MRI images were acquired by using a 3.0-Tesla scanner (Siemens MAGNETOM Skyra platform) with a 16-channel flexible head coil. A sponge-built head holder was used to prevent head movements. The parameters were set as follows: 3D-T1WI sequence structural imaging was performed with a magnetization-prepared rapid gradient echo(MP-RAGE). TR = 7.2ms, TE = 3.1ms, thickness = 1mm, flip angle = 10 °, FOV = 256mm × 256mm, 192 slices. BOLD-fMRI images were acquired with a single-shot gradient recalled echo planar imaging (EPI) sequence. TR = 2000ms, TE = 30ms, thickness = 3.5mm, flip angle = 90 °, FOV = 224mm × 224mm, 33 slices, matrix = 64 × 64. BOLD-fMRI scan lasted for 8 minutes, with a total of 240 time points. Participants were instructed to relax with their eyes closed during the scanning process.

2.5. Data processing of rs-fMRI

Image preprocessing was performed by SPM 12 (https://fil.ion.ucl.ac.uk/spm) based on Matlab2019b (mathworks.com) platform, and the data involving the following main steps: (1) The first 10 volumes of each scan were removed to avoid instability due to T1-related relaxation effect. (2) Slice timing corrections: the time difference between data at each point in time and obtain the head motion parameters of the subject in the scanning time series. (3) Realigning: the data at all time points were spatially aligned with the data collected at the first time point to obtain the head motion parameters of the subject in the scanning time series. (4) Coregister and Normalization: all the collected data were resampled according to the Montreal Neurological Institute (MNI) standard template space with a 3 × 3 × 3 mm voxel size for spatial normalization. (5) Voxel-wise detrending: mean signals from white matter and CSF were regressed out, leaving the gray matter signal for denoising. (6) Filtering: the band-pass filtering range was set at 0.01–0.08 Hz to physiological and high-frequency noise. (7) Smooth: a Gaussian kernel of 6 mm full width at half-maximum (FWHM) was used to smooth the images.

The whole-brain fALFF and FC values were conducted by Data Processing & Analysis of Brain Imaging (DPABI, http://rfmri.org/dpabi). The fALFF was the ratio of the power spectrum in the low-frequency band (0.01–0.08 Hz) to the entire frequency range. The fALFF value of each voxel was divided by the global mean fALFF value for each participant to reduce the global effects. For FC analysis, the regions of interest (ROI) based on the comparison results of fALFF values between PE group and HC group were selected. The time series of all voxels in the ROI of each participant were averaged, and the Pearson correlation coefficient between the ROI time series of each participant and the time series of all voxels in the whole brain was calculated to obtain the z-score graph of FC.

2.6. Statistical analysis

Statistical analysis was performed using SPSS 25.0 version (http://www.spss.com). The results were expressed as mean ± standard deviation. The demographic data and clinical variables (except for gender) were compared using independent-sample t-test, and gender was compared using chi-square test. P < 0.05 were considered to indicate statistical significance. The fALFF statistical across groups were performed using a voxel-based, independent-sample t-test with FDR corrections (P < 0.001, cluster size > 50). Brain regions that exhibited differences between the two groups were further elected as ROIs for FC analysis. Mean FC values were extracted within each of these ROIs for further analysis. Furthermore, Pearson correlation coefficients were computed between the extracted fALFF and FC values within these ROIs and the clinical assessments of patients, the significance level was set at P < 0.05 (two-tailed).

3.1. Demographic and clinical characteristics of participants

A total of 84 participants (PE group = 42; HC group = 42) were recruited in the final data analysis. All participants completed the fMRI scanning, and no significant difference in age, sex ratio, and years of education was identified between both groups (P > 0.05). Demographic data for all the participants are shown in Table 1.

Table 1

Demographic and clinical characteristics of participants
	PE group(n = 42)	HC group(n = 42)	P value
Age(year)	36.81 ± 12.12	34.82 ± 9.96	0.41^a
Gender(male/female)	14/28	16/26	0.77^b
Education(year)	14.67 ± 2.26	14.27 ± 2.86	0.48^a
VAS	6.43 ± 1.21	NA	—
12-PSS	13.33 ± 3.45	NA	—
PSQI	7.57 ± 4.26	NA	—
SAS	50.02 ± 15.93	NA	—

a: Independent-sample test. b: Chi-square test. NA: not applicable; VAS: Visual Analogue Score; 12-PSS: 12-Item itch Severity Scale, PSQI: Pittsburgh Sleep Quality Index; SAS: Self-rating Anxiety Scale; PE group: patients with eczema; HC group: healthy controls.

3.2. Comparison of fALFF and FC results between the two groups.

Compared with the HC group, the fALFF values of the left precentral gyrus, left postcentral gyrus, left supplementary motor area(SMA) and left midcingulate cortex(MCC) in the PE group were increased, while no significant decrease in brain was found (Table 2, Fig. 1A).

The selected FC seeds were based on the fALFF results (left precentral gyrus, left postcentral gyrus, left SMA, and left MCC). Compared with the HC group, the FC values between left precentral gyrus and bilateral inferior temporal gyrus, bilateral hippocampus, left inferior occipital gyrus in the PE group were decreased (Table 2, Fig. 1B). The FC values between left SMA and bilateral inferior temporal gyrus in the PE group were decreased (Table 2, Fig. 1C). There was no significant difference in FC values between the left postcentral gyrus, the left MCC and the whole brain.

Table 2

Differences in fALFF and FC values between PE and HC groups.
Brain Area	MNI coordinates			Voxels	T-value*
Brain Area	X	Y	Z	Voxels	T-value*
fALFF
left precentral gyrus	-42	-6	51	95	3.93
left postcentral gyrus	-42	-23	49	68	3.66
left supplementary motor area	-9	-9	66	96	4.14
left midcingulate cortex	-4	35	14	55	3.63
FC(seed based in Left precentral gyrus)
left superior temporal gyrus	-33	6	-24	58	-5.92
right superior temporal gyrus	36	9	-24	61	-6.10
left hippocampus	-25	-21	-10	72	-5.66
righ hippocampus	29	-20	-10	85	-5.19
left inferior occipital gyrus	-39	-90	-15	74	-5.03
FC(seed based in SMA.L)
left superior temporal gyrus	-39	3	-24	57		-6.76
right superior temporal gyrus	36	6	-24	70		-7.50

*: voxel-based, independent-sample t-test with FDR corrections (P < 0.001, cluster size > 50).

3.3. Correlation analysis between fMRI results and clinical scale data.

The fALFF values of the left precentral gyrus (r = 0.59, P < 0.01) and the left postcentral gyrus (r = 0.52, P < 0.01) in the PE group were positively correlated with 12-PSS score(Fig. 2).

4.1 The fMRI study and cerebral regional activity characteristic in patients of itch.

For this study, a special group of patients was selected in the clinic. The selected patients were Koreans without a prior history of eczema in South Korea, however developed eczema accompanied by different degrees of pruritus after living in China for a period of time. The pruritus in these patients was not simulated for experimental purposes which made them the ideal subjects as their pruritus was long standing. Similar to other senses such as pain, temperature, and touch, pruritus was considered to be an independent sensory form that evokes a desire to scratch which is initiated in a particular dermatome and transmitted to the CNS^{[25, 35]}. While given that there are particular cerebral regions are responsible for processing pruritus, the actual circuits and interconnecting networks related to it in the human brain remains largely unexplored.

Pruritus consists of sensory, emotional, and motivational components^[36]. In this fMRI study, we observed that the fALFF values of left MCC, left precentral gyrus, left postcentral gyrus, and left SMA in the PE group were increased. The postcentral gyrus is a critical cortical region for the sensory component of pruritus processing^[37]. According to previous brain imaging study, subjects showed significant activation of the postcentral gyrus in response to pruritic stimuli induced by a histamine or saline injection^[38]. Additionally, participants who were shown video clips of scratching also demonstrated activation in similar cerebral regions^[39]. The precentral gyrus, SMA, and cingulate cortex depicts a motor intention from the urge to scratch, particularly, the precentral gyrus and MCC play a key role in driving scratching behavior and are activated by both pruritus and pain^[40]. Numerous studies have shown that cingulate cortex can be activated in both acute and pain and is related to emotional expressions such as anxiety and depression in the process of pain^[41]. Pruritus and pain share many common targets and neurophysiological bases in terms of regulatory mediators and pathogenesis, such as protease-activated receptor 2 (PAR2)^[42], transient receptor potential (TRP) ^[18]and nerve growth factor (NGF)^[43] activation of peripheral nerve endings, which are the pathological mechanisms of pruritus and pain^[44]. Therefore, we speculate that the abnormal activation of MCC may be related to the experience of itch-induced anxiety. Considering that the subjects were all right-handed and all of the activated brain areas were in the left hemisphere, we speculate that the changes may be related to scratching caused by pruritus, and suggested that itch could lead to increased spontaneous activity of the dominant cerebral hemisphere.

4.2 The influence of cerebral regional functional changes on the network in patients with pruritus.

Previous brain imaging studies in healthy subjects have revealed that many brain regions, such as SMA, prefrontal cortex(PFC), insula, thalamus, and cingulate cortex are involved in the perception and processing of pruritus^{[17, 20, 29]}. Prior to this study, it was unclear whether there were regional changes caused by the over stimulation from pruritus and if this lead to alterations in neural networks. In our study, functional connectivity analysis based on the fALFF results showed widespread decreased FC, mainly involving the superior temporal gyrus, hippocampus and the inferior occipital gyrus, which provided evidence for the impaired cortical functional in patients with pruritus and implied that regional function alterations exerted considerable effects on network function. The superior temporal gyrus exhibits diverse functions, encompassing higher-order perception and cognition, as well as visual-auditory integration. It is closely associated with emotion recognition, facial expression processing, memory, and attention regulation^[45–47].

The hippocampus is involved in spatial orientation, in addition to its well-established role in memory and learning^[48]. Furthermore, the hippocampus exhibits close associations with the brain's reward circuitry, and the act of scratching, which serves to alleviate or suppress pruritus, engages the activation or suppression of the reward system. Previous studies have demonstrated the activation of motor-related regions and reward circuitry^[49], including the supplementary motor area (SMA), prefrontal cortex (PFC), and cingulate cortex, during both pruritus and itch-scratching tasks. Conversely, pruritus-induced scratching has been found to inhibit the activity of the temporal lobe and hippocampus^[50]. The inferior occipital gyrus is a vital component of the default mode network. It is implicated in the regulation of cognitive control, emotional experiences, encoding and integration of memories, as well as self-awareness and bodily perception^[51]. Itch sensation is associated with negative emotion(e.g. stress, anxiety, depress). The reported inferior occipital gyrus may be associated with visual memory and attention deficits in depression^[52], coupled to increased attention and response in expression towards sadness^[53]. The decreased FC values in the above brain areas may ultimately point to the remodeling or inhibition of neural function in the itch-related brain area and the reward system. In order to explore the potential relationship between the clinical manifestations of pruritus and regional/network function alterations, fALFF and FC values of significant brain areas were extracted and correlated with pruritus-related scales. We found positive correlation between fALFF of the left precentral gyrus, left postcentral gyrus and 12-PSS, which suggested that increased fALFF was correlated with the manifestation of pruritus. The direct relationship between regional cerebral function and the pruritus index strengthens the hypothesis of neuroplasticity. Therefore, our study suggests that higher cognitive abilities such as learning, memory, spatial orientation and facial recognition may be affected in patients with pruritus. Although we found various regional and network abnormalities with increases or decreases in brain functional changes by fMRI in eczema patients with pruritus, there are still some limitations that should be considered in this study. Firstly, this cross-sectional study hardly reflect the dynamic functional abnormalities during the progression of pruritus. Secondly, there were more female participants than males both in PE and HC group may bias our results with more female features. Finally, we did not take into account the confounding effects on brain activity from medications. A larger sample sizes with more homogenous gender ratios and a longitudinal study, including a comparison before and after treatment, as well as a variety of pruritus-related serological indicators are needed in future studies to display the progression of brain alterations in patients with itch^[54].

In conclusion, this study revealed that there was a decrease in spontaneous activity in particular regions within the brain that were affected by itch and there were cerebral functional network connection changes based on the findings from fALFF and FC. There was an abnormal amount of increased regional activity mostly involved in sensorimotor and MCC. Network alterations with widespread FC decrease involved in temporal lobes, occipital lobes and hippocampus. Our results showed that pruritus affects the spontaneous activity of the sensorimotor cortex in patients with eczema, resulting in extensive imbalances in the functional connectivity of brain regions such as the temporal, occipital and hippocampus. These findings enhanced our understanding of the neural circuit mechanisms underlying pruritus.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author contributions

Xiang-yu Wei was responsible for the recruitment of healthy controls, data interpretation, preparation of the tables and figures, manuscript writing and review; The authors would like to thank Larissa Tao for her valuable support in polishing the manuscript language; Tae-eun Kim and Xiang-yu Wei were responsible for the arrangement of all subjects' data and recruitment of patients with eczema; Tae-eun Kim and Wei-dong Shen were responsible for funding support. All authors contributed to the discussion of the data and the manuscript.

Data Availability

The data which support the conclusions of our study is included within the article.

Ethical Standards

The study compliances with the ethical standards of the responsible committee on human experimentation (Shuguang Hospital affiliated to Shanghai University of traditional Chinese Medicine; Approve Number: 2022-1168-105-01) and with the Helsinki Declaration of 1975, as revised in 2005. "Informed consent was obtained from all subjects and/or their legal guardian(s)".

Acknowledgments

Not applicable.

Funding support

This research was supported by:

1, National Natural Science Foundation of China (grant No. 82205267)

2, Shanghai Committee of Science and Technology (grant No. 20Y21902900)

3, Shanghai University of Traditional Chinese Medicine budget project(grant No.2021LK078)

David BW, Tarbox JA, Tarbox MB. Atopic Dermatitis: Pathophysiology. Adv Exp Med Biol 2017, 1027: 21–37.
Kim J, Kim BE, Leung D. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc 2019, 40: 84–92.
Buske-Kirschbaum A, Trikojat K, Tesch F, Schmitt J, Roessner V, Luksch H, et al. Altered hypothalamus-pituitary-adrenal axis function: A relevant factor in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder? Psychoneuroendocrinology 2019, 105: 178–186.
Cabanillas B, Brehler AC, Novak N. Atopic dermatitis phenotypes and the need for personalized medicine. Curr Opin Allergy Clin Immunol 2017, 17: 309–315.
Anzelc M, Burkhart CG. Pain and Pruritus: a study of their similarities and differences. Int J Dermatol 2020, 59: 159–164.
Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci 2019, 20: 667–685.
Scherer JS, Combs SA, Brennan F. Sleep Disorders, Restless Legs Syndrome, and Uremic Pruritus: Diagnosis and Treatment of Common Symptoms in Dialysis Patients. Am J Kidney Dis 2017, 69: 117–128.
Mettang T, Kremer AE. Uremic pruritus. Kidney Int 2015, 87: 685–691.
Yoshikawa S, Asano T, Morino M, Matsumoto K, Kashima H, Koito Y, et al. Pruritus is common in patients with chronic liver disease and is improved by nalfurafine hydrochloride. Sci Rep 2021, 11: 3015.
Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet 2015, 386: 1565–1575.
Hill RZ, Loud MC, Dubin AE, Peet B, Patapoutian A. PIEZO1 transduces mechanical itch in mice. Nature 2022, 607: 104–110.
Stumpf A, Burgmer M, Schneider G, Heuft G, Schmelz M, Phan NQ, et al. Sex differences in itch perception and modulation by distraction–an FMRI pilot study in healthy volunteers. PLoS One 2013, 8: e79123.
Khasabov SG, Truong H, Rogness VM, Alloway KD, Simone DA, Giesler GJ. Responses of neurons in the primary somatosensory cortex to itch- and pain-producing stimuli in rats. J Neurophysiol 2020, 123: 1944–1954.
Pavlenko D, Funahashi H, Sakai K, Hashimoto T, Lozada T, Yosipovitch G, et al. IL-23 modulates histamine-evoked itch and responses of pruriceptors in mice. Exp Dermatol 2020, 29: 1209–1215.
Pan H, Fatima M, Li A, Lee H, Cai W, Horwitz L, et al. Identification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch. Neuron 2019, 103: 1135–1149.
Zhang TT, Guo SS, Wang HY, Jing Q, Yi X, Hu ZH, et al. An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice. Neurosci Bull 2022.
Vierow V, Forster C, Vogelgsang R, Dorfler A, Handwerker HO. Cerebral Networks Linked to Itch-related Sensations Induced by Histamine and Capsaicin. Acta Derm Venereol 2015, 95: 645–652.
Moore C, Gupta R, Jordt SE, Chen Y, Liedtke WB. Regulation of Pain and Itch by TRP Channels. Neurosci Bull 2018, 34: 120–142.
Chen XJ, Liu YH, Xu NL, Sun YG. Multiplexed Representation of Itch and Mechanical and Thermal Sensation in the Primary Somatosensory Cortex. J Neurosci 2021, 41: 10330–10340.
Chen XJ, Sun YG. Central circuit mechanisms of itch. Nat Commun 2020, 11: 3052.
Kim SG, Ogawa S. Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab 2012, 32: 1188–1206.
Ugurbil K. Development of functional imaging in the human brain (fMRI); the University of Minnesota experience. Neuroimage 2012, 62: 613–619.
Zou QH, Zhu CZ, Yang Y, Zuo XN, Long XY, Cao QJ, et al. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods 2008, 172: 137–141.
Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 1995, 34: 537–541.
Sutaria N, Adawi W, Goldberg R, Roh YS, Choi J, Kwatra SG. Itch: Pathogenesis and treatment. J Am Acad Dermatol 2022, 86: 17–34.
Dong X, Dong X. Peripheral and Central Mechanisms of Itch. Neuron 2018, 98: 482–494.
Li X, Yao J, Hu KH, Wu B, Sui JF, Gao J, et al. Differential roles of prelimbic and anterior cingulate cortical region in the modulation of histaminergic and non-histaminergic itch. Behav Brain Res 2021, 411: 113388.
Liu X, Miao XH, Liu T. More than Scratching the Surface: Recent Progress in Brain Mechanisms Underlying Itch and Scratch. Neurosci Bull 2020, 36: 85–88.
Mu D, Deng J, Liu KF, Wu ZY, Shi YF, Guo WM, et al. A central neural circuit for itch sensation. Science 2017, 357: 695–699.
Schut C, Grossman S, Gieler U, Kupfer J, Yosipovitch G. Contagious itch: what we know and what we would like to know. Front Hum Neurosci 2015, 9: 57.
Yu YQ, Barry DM, Hao Y, Liu XT, Chen ZF. Molecular and neural basis of contagious itch behavior in mice. Science 2017, 355: 1072–1076.
Ehling S, Butler A, Thi S, Ghashghaei HT, Baumer W. To scratch an itch: Establishing a mouse model to determine active brain areas involved in acute histaminergic itch. IBRO Rep 2018, 5: 67–73.
Setsu T, Hamada Y, Oikawa D, Mori T, Ishiuji Y, Sato D, et al. Direct evidence that the brain reward system is involved in the control of scratching behaviors induced by acute and chronic itch. Biochem Biophys Res Commun 2021, 534: 624–631.
Sanders KM, Akiyama T. The vicious cycle of itch and anxiety. Neurosci Biobehav Rev 2018, 87: 17–26.
Darsow U, Pfab F, Valet M, Tolle TR, Ring J. Itch and eczema. Chem Immunol Allergy 2012, 96: 81–88.
Silverberg JI. Comorbidities and the impact of atopic dermatitis. Ann Allergy Asthma Immunol 2019, 123: 144–151.
Spiegel DR, Pattison A, Lyons A, Ansari U, Mccroskey AL, Luehrs E, et al. The Role and Treatment Implications of Peripheral and Central Processing of Pain, Pruritus, and Nausea in Heightened Somatic Awareness: A Review. Innov Clin Neurosci 2017, 14: 11–20.
Woo S, Kim YR, Bak MS, Chung G, Kim SJ, Kim SK. Multiplexed Representation of Itch and Pain and Their Interaction in the Primary Somatosensory Cortex. Exp Neurobiol 2022, 31: 324–331.
Najafi P, Ben SD, Carre JL, Misery L, Dufor O. Functional and anatomical brain connectivity in psoriasis patients and healthy controls: a pilot brain imaging study after exposure to mentally induced itch. J Eur Acad Dermatol Venereol 2020, 34: 2557–2565.
Kakigi R, Mochizuki H. [Mechanisms of intracerebral pain and itch perception in humans]. Brain Nerve 2011, 63: 987–994.
Lu YC, Wang YJ, Lu B, Chen M, Zheng P, Liu JG. ACC to Dorsal Medial Striatum Inputs Modulate Histaminergic Itch Sensation. J Neurosci 2018, 38: 3823–3839.
Mollanazar NK, Smith PK, Yosipovitch G. Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out? Clin Rev Allergy Immunol 2016, 51: 263–292.
Indo Y. Nerve growth factor, pain, itch and inflammation: lessons from congenital insensitivity to pain with anhidrosis. Expert Rev Neurother 2010, 10: 1707–1724.
Forster C, Handwerker HO. Central Nervous Processing of Itch and Pain. 2014.
Yu M, Song Y, Liu J. The posterior middle temporal gyrus serves as a hub in syntactic comprehension: A model on the syntactic neural network. Brain Lang 2022, 232: 105162.
Chang EF, Raygor KP, Berger MS. Contemporary model of language organization: an overview for neurosurgeons. J Neurosurg 2015, 122: 250–261.
Lin YH, Young IM, Conner AK, Glenn CA, Chakraborty AR, Nix CE, et al. Anatomy and White Matter Connections of the Inferior Temporal Gyrus. World Neurosurg 2020, 143: e656-e666.
Burgess N, Maguire EA, O'Keefe J. The human hippocampus and spatial and episodic memory. Neuron 2002, 35: 625–641.
Mochizuki H, Papoiu A, Nattkemper LA, Lin AC, Kraft RA, Coghill RC, et al. Scratching Induces Overactivity in Motor-Related Regions and Reward System in Chronic Itch Patients. J Invest Dermatol 2015, 135: 2814–2823.
Kim HJ, Park JB, Lee JH, Kim IH. How stress triggers itch: a preliminary study of the mechanism of stress-induced pruritus using fMRI. Int J Dermatol 2016, 55: 434–442.
Sellal F. Anatomical and neurophysiological basis of face recognition. Rev Neurol (Paris) 2022, 178: 649–653.
Couvy-Duchesne B, Strike LT, de Zubicaray GI, McMahon KL, Thompson PM, Hickie IB, et al. Lingual Gyrus Surface Area Is Associated with Anxiety-Depression Severity in Young Adults: A Genetic Clustering Approach. eNeuro 2018, 5.
Palejwala AH, Dadario NB, Young IM, O'Connor K, Briggs RG, Conner AK, et al. Anatomy and White Matter Connections of the Lingual Gyrus and Cuneus. World Neurosurg 2021, 151: e426-e437.
Wang Z, Jiang C, Yao H, Chen O, Rahman S, Gu Y, et al. Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition. Brain 2021, 144: 665–681.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Neuroimaging characteristics of pruritus induced by eczema: An fMRI study

Status:

Version 1

Abstract

Figures

1. Introduction

2. Materials and methods

2.1. Participants

2.2. Inclusion/Exclusion Criteria.

2.3. Clinical Evaluations Scale

2.4. Rs-fMRI scanning

2.5. Data processing of rs-fMRI

2.6. Statistical analysis

3. Results

3.1. Demographic and clinical characteristics of participants

3.2. Comparison of fALFF and FC results between the two groups.

3.3. Correlation analysis between fMRI results and clinical scale data.

4. Discussion

4.1 The fMRI study and cerebral regional activity characteristic in patients of itch.

4.2 The influence of cerebral regional functional changes on the network in patients with pruritus.

Declarations

References

Additional Declarations

Status:

Version 1