Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI
Open accessAbstract
BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes. While considerable work has been done in humans and rats to understand the HRF, much less is known in mice. As a prerequisite to investigate mechano-sensory processing and BOLD fMRI data in male and female mice, we (1) designed a rotating stimulator that allows application of two different mechanical modalities, including innocuous von Frey and noxious pinprick stimuli and (2) determined and statistically compared HRFs across 30 brain structures and experimental conditions, including sex and, stimulus modalities. We found that mechanical stimulation lead to brain-wide BOLD signal changes thereby allowing extraction of HRFs from multiple brain structures. However, we did not find differences in HRFs across all brain structures and experimental conditions. Hence, we computed a whole-brain mouse HRF, which is based on 88 functional scans from 30 mice. A comparison of this mouse-specific HRF with our previously reported rat-derived HRF showed significantly slower kinetics in mice. Finally, we detected pronounced differences in cerebral BOLD activation between male and female mice with mechanical stimulation, thereby exposing divergent processing of noxious and innocuous stimuli in both sexes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Convolving theta-band power with a double-gamma HRF noticeably strengthened its correlation with idYFP and shifted the cross-correlation peak to zero lag.
“Convolving theta-band power with this HRF noticeably strengthened its correlation with idYFP and shifted the cross-correlation peak to zero lag.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [42]
The Materials and methods sections describe convolving a stimulation paradigm with a double-gamma HRF to model mouse BOLD signals. The Results discuss BOLD activation, but the passages found for theta-band power, idYFP, and cross-correlation do not address whether their correlation strengthened or its peak shifted to zero lag. No passage in our copy verifies the attributed result. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Statistical Parametric Mapping: The Analysis of Functional Brain Images
Penny, W. D., Friston, K. J., Ashburner, J., Kiebel, S. J., & Thomas, N. (2007) · UCL Discovery (University College London) · Cited by 3,339 · see citing works
Methods Used to Evaluate Pain Behaviors in Rodents
Deuis, J. R., Dvorakova, L. S., & Vetter, I. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00284 · Cited by 1,269 · cited 1× · see citing works
“The withdrawal response to von Frey filaments (blunt, rather innocuous) is the current gold standard for measuring mechanical hypersensitivity in rodent pain models and hence, is frequently used (Deuis et al., 2017; Segelcke et al., 2019) and enables detection of relevant sex differences in rodents (Segelcke et al.”
BackgroundFunctional Data Analysis with R and MATLAB
Ramsay, J. O., Hooker, G., & Graves, S. B. (2009) · Springer eBooks · doi:10.1007/978-0-387-98185-7 · Cited by 912 · cited 1× · see citing works
“To examine whether there were significant differences between HRFs of two modalities or brain structures, we performed functional t-tests (Ramsay et al., 2009) as previously described (Lambers et al.”
MethodFemale mice liberated for inclusion in neuroscience and biomedical research
Prendergast, B. J., Onishi, K. G., & Zucker, I. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.01.001 · Cited by 788 · see citing works
Wind-up of spinal cord neurones and pain sensation: much ado about something?
Herrero, J. F., Laird, J. M. A., & Lopez-Garcia, J. A. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00051-9 · Cited by 714 · see citing works
Qualitative sex differences in pain processing: emerging evidence of a biased literature
Mogil, J. S. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0310-6 · Cited by 691 · cited 1× · see citing works
“While growing evidence shows that female individuals have greater sensitivity to pain in humans and animals compared to their male counterparts (Mogil, 2020), the behavioral or phenotypic manifestation of these differences may be subtle and dependent on the number of subjects used.”
BackgroundNonlinear event‐related responses in fMRI
Friston, K. J., Josephs, O., Rees, G. E., & Turner, R. (1998) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910390109 · Cited by 629 · cited 1× · see citing works
“It is frequently combined with a general-linear-model (GLM) -based analysis to detect BOLD responses, which uses the convolution of the hemodynamic response function (HRF) with the stimulus paradigm for statistical analysis of fMRI data (Friston et al., 1998; Henson and Friston, 2007).”
MethodMODIFICATION OF THE OESTROUS CYCLE OF THE MOUSE BY EXTERNAL STIMULI ASSOCIATED WITH THE MALE
Whitten, W. K. (1956) · Journal of Endocrinology · doi:10.1677/joe.0.0130399 · Cited by 563 · see citing works
The case for the inclusion of female subjects in basic science studies of pain
Mogil, J. S., & Chanda, M. L. (2005) · Pain · doi:10.1016/j.pain.2005.06.020 · Cited by 376 · cited 1× · see citing works
“In fact, differences in heat thresholds have been reported in naïve male and female mice with group sizes of approximately n = 4,000 (Mogil and Chanda, 2005).”
BackgroundNeely, G. G., Heß, A., Costigan, M., Keene, A. C., Goulas, S., Langeslag, M., Griffin, R. S., Belfer, I., Dai, F., Smith, S. B., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.047 · Cited by 310 · see citing works
Spontaneous pseudopregnancy in mice.
Van Der Lee, S., & Lm, B. (1955) · PubMed · Cited by 268 · see citing works
Gender differences in pain modulation by diffuse noxious inhibitory controls: a systematic review
Popescu, A., LeResche, L., Truelove, E. L., & Drangsholt, M. T. (2010) · Pain · doi:10.1016/j.pain.2010.05.013 · Cited by 265 · cited 1× · see citing works
“A likely mechanism for different cerebral processing could involve the descending pain inhibition, which exerts different effects in male and female volunteers (Popescu et al., 2010), and which has also been replicated in animal fMRI studies (Silva et al.”
ResultMéziane, H., Ouagazzal, A., Aubert, L., Wietrzych, M., & Krężel, W. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00249.x · Cited by 260 · cited 1× · see citing works
“Furthermore, different phases of the estrous cycle did not affect sensory perception/nociception in C57BL/6J female mice (Meziane et al., 2007).”
BackgroundArcourt, A., Gorham, L., Dhandapani, R., Prato, V., Taberner, F. J., Wende, H., Gangadharan, V., Birchmeier, C., Heppenstall, P. A., & Lechner, S. G. (2016) · Neuron · doi:10.1016/j.neuron.2016.11.027 · Cited by 213 · see citing works
Deciphering laminar-specific neural inputs with line-scanning fMRI
Yu, X., Qian, C., Chen, D.-Y., Dodd, S. J., & Koretsky, A. P. (2013) · Nature Methods · doi:10.1038/nmeth.2730 · Cited by 173 · cited 1× · see citing works
“, 2021) or line-scanning BOLD fMRI (Yu et al., 2014; Albers et al., 2018; Choi et al., 2022).”
Estrus-Inducing Pheromone of Male Mice: Transport by Movement of Air
Whitten, W., Bronson, F., & Greenstein, J. A. (1968) · Science · doi:10.1126/science.161.3841.584 · Cited by 169 · see citing works
Neurovascular coupling is brain region-dependent
Devonshire, I. M., Papadakis, N. G., Port, M., Berwick, J., Kennerley, A. J., Mayhew, J. E. W., & Overton, P. G. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.09.050 · Cited by 140 · see citing works
Buerkle, H., & Yaksh, T. L. (1998) · British Journal of Anaesthesia · doi:10.1093/bja/81.2.208 · Cited by 128 · see citing works
Dhandapani, R., Arokiaraj, C. M., Taberner, F. J., Pacifico, P., Raja, S., Nocchi, L., Portulano, C., Franciosa, F., Maffei, M., Hussain, A. F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04049-3 · Cited by 127 · see citing works
Effect of Exteroceptive Factors on the Œstrous Cycle of Mice
WHITTEN, M. K. (1957) · Nature · doi:10.1038/1801436a0 · Cited by 124 · see citing works
Kahn, I., Desai, M., Knoblich, U., Bernstein, J., Henninger, M., Graybiel, A. M., Boyden, E. S., Buckner, R. L., & Moore, C. I. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0007-11.2011 · Cited by 122 · cited 1× · see citing works
“, 2022), and optogenetic stimulation (Kahn et al., 2011; Salvan et al., 2021; Wank et al., 2021).”
BackgroundThe power of using functional fMRI on small rodents to study brain pharmacology and disease
Jonckers, E., Shah, D., Hamaide, J., Verhoye, M., & der Linden, A. V. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00231 · Cited by 120 · cited 1× · see citing works
“Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) has become a prevalent method to study evoked neuronal circuits in rodent disease models (Jonckers et al., 2015; Xu et al., 2022).”
MethodSchroeter, A., Schlegel, F., Seuwen, A., Grandjean, J., & Rudin, M. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.01.046 · Cited by 110 · cited 3× · see citing works
“, 2020) and anesthesia (Schroeter et al., 2014; Schlegel et al., 2015) are known to modulate the HRF significantly and, together with brain structures, are likely to be more critical factors for the HRF than the stimulus modality per se.”
BackgroundMethodHenderson, L. A., Gandevia, S. C., & Macefield, V. G. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.10.045 · Cited by 108 · cited 1× · see citing works
“Moreover, investigating muscle and cutaneous pain in humans, Henderson and colleagues found increased activation of mid-cingulate cortex and dorsolateral PFC in naïve female compared to male human volunteers, while the overall pain intensity rating was not affected (Henderson et al., 2008).”
BackgroundMesoscopic and microscopic imaging of sensory responses in the same animal
Boido, D., Rungta, R. L., Osmanski, B.-F., Roche, M., Tsurugizawa, T., Bihan, D. L., Ciobanu, L., & Charpak, S. (2019) · Nature Communications · doi:10.1038/s41467-019-09082-4 · Cited by 103 · cited 1× · see citing works
“, 2021), visual, olfactory or auditory (Niranjan et al., 2016, 2017; Blazquez Freches et al., 2018; Boido et al., 2019; Chen et al., 2020; Dinh et al., 2020; Komaki et al., 2020; Zhao et al., 2020; Pradier et al., 2021; Lungu et al., 2022), and optogenetic stimulation (Kahn et al.”
BackgroundSex similarities and differences in pain-related periaqueductal gray connectivity
Linnman, C., Beucke, J., Jensen, K. B., Gollub, R. L., & Kong, J. (2011) · Pain · doi:10.1016/j.pain.2011.11.006 · Cited by 101 · cited 1× · see citing works
“Other examples for divergent BOLD activation following noxious stimuli in human volunteers have also been observed following noxious visceral and thermal stimulation using fMRI (Linnman et al., 2012; Wang et al., 2019).”
BackgroundHenson, R. N., & Friston, K. J. (2007) · Elsevier eBooks · doi:10.1016/b978-012372560-8/50014-0 · Cited by 99 · see citing works
High field BOLD response to forepaw stimulation in the mouse
Adamczak, J. M., Farr, T. D., Seehafer, J. U., Kalthoff, D., & Hoehn, M. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.02.083 · Cited by 99 · cited 1× · see citing works
“Since investigation of sensory processing is vital to many brain disorders, different fMRI task (stimulus) modalities have been developed and applied to mouse fMRI studies; these include electrical or heat stimulation of the glabrous paw skin (Nair and Duong, 2004; Adamczak et al., 2010; Neely et al., 2010; Schroeter…”
BackgroundSensory evoked fMRI paradigms in awake mice
Chen, X., Tong, C., Han, Z., Zhang, K., Bo, B., Feng, Y., & Liang, Z. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116242 · Cited by 93 · cited 2× · see citing works
“, 2021), visual, olfactory or auditory (Niranjan et al., 2016, 2017; Blazquez Freches et al., 2018; Boido et al., 2019; Chen et al., 2020; Dinh et al., 2020; Komaki et al., 2020; Zhao et al., 2020; Pradier et al., 2021; Lungu et al., 2022), and optogenetic stimulation (Kahn et al.”
BackgroundFunctional Connectivity of the Brain Across Rodents and Humans
Xu, N., LaGrow, T. J., Anumba, N., Lee, A., Zhang, X., Yousefi, B., Bassil, Y., Clavijo, P. G., Sharghi, V. K., Maltbie, E. A., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.816331 · Cited by 91 · see citing works
Prefrontal cortex lesions and sex differences in fear extinction and perseveration
Baran, S. E., Armstrong, C. E., Niren, D. C., & Conrad, C. D. (2010) · Learning & Memory · doi:10.1101/lm.1778010 · Cited by 90 · cited 1× · see citing works
“Despite overall sex differences in cerebral processing in small animals and humans (Levin et al., 1998; Baran et al., 2010; Dumais et al., 2017; Bloch et al., 2021), only a few studies have systematically investigated sex differences in the temporal progression of the BOLD response or parameters of the hemodynamic res…”
BackgroundShim, H., Jung, W. B., Schlegel, F., Lee, J., Kim, S., Lee, J., & Kim, S. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.04.062 · Cited by 86 · cited 1× · see citing works
“Since investigation of sensory processing is vital to many brain disorders, different fMRI task (stimulus) modalities have been developed and applied to mouse fMRI studies; these include electrical or heat stimulation of the glabrous paw skin (Nair and Duong, 2004; Adamczak et al., 2010; Neely et al., 2010; Schroeter…”
BackgroundSchlegel, F., Schroeter, A., & Rudin, M. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.05.013 · Cited by 82 · see citing works
Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI
Moon, H. S., Jiang, H., Vo, T. T., Jung, W. B., Vazquez, A. L., & Kim, S. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab068 · Cited by 80 · cited 1× · see citing works
“Since investigation of sensory processing is vital to many brain disorders, different fMRI task (stimulus) modalities have been developed and applied to mouse fMRI studies; these include electrical or heat stimulation of the glabrous paw skin (Nair and Duong, 2004; Adamczak et al., 2010; Neely et al., 2010; Schroeter…”
BackgroundDesjardins, M., Kılıç, K., Thunemann, M., Matéo, C., Holland, D., Ferri, C. G. L., Cremonesi, J. A., Li, B., Cheng, Q., Weldy, K. L., et al. (2018) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2018.12.002 · Cited by 78 · see citing works
Hayward, N., Tuunanen, P. I., Immonen, R. J., Ndode‐Ekane, X. E., Pitkänen, A., & Gröhn, O. H. J. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.67 · Cited by 77 · see citing works
Fiber-optic implant for simultaneous fluorescence-based calcium recordings and BOLD fMRI in mice
Schlegel, F., Sych, Y., Schroeter, A., Stobart, J. L., Weber, B., Helmchen, F., & Rudin, M. (2018) · Nature Protocols · doi:10.1038/nprot.2018.003 · Cited by 74 · see citing works
Characteristics of fMRI responses to visual stimulation in anesthetized vs. awake mice
Dinh, T. N. A., Jung, W. B., Shim, H., & Kim, S. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117542 · Cited by 72 · see citing works
Bosshard, S. C., Baltes, C., Wyss, M. T., Mueggler, T., Weber, B., & Rudin, M. (2010) · Pain · doi:10.1016/j.pain.2010.08.025 · Cited by 67 · cited 1× · see citing works
“This is consistent with previous reports showing no change in the temporal progression of BOLD responses following mechanical or electrical stimulation of the paw skin at noxious and innocuous intensities (Bosshard et al., 2010; Schlegel et al., 2015; Amirmohseni et al., 2016; Lambers et al., 2020).”
ResultSex differences in response to red and blue light in human primary visual cortex: a bold fMRI study
Cowan, R. L., Frederick, B. D. B., Rainey, M., Levin, J. M., Maas, L. C., Bang, J., Hennen, J., Lukas, S. E., & Renshaw, P. F. (2000) · Psychiatry Research: Neuroimaging · doi:10.1016/s0925-4927(00)00074-3 · Cited by 65 · cited 1× · see citing works
“It is important to mention that our study did not compare BOLD response amplitudes, which differ in men and women (Levin et al., 1998; Cowan et al., 2000; Kaufmann et al., 2001).”
ResultEarly fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow
Jung, W. B., Im, G. H., Jiang, H., & Kim, S. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023265118 · Cited by 64 · see citing works
The effect of medetomidine, an α2-adrenoceptor agonist, in various pain tests
Pertovaara, A., Kauppila, T., & Tukeva, T. A. (1990) · European Journal of Pharmacology · doi:10.1016/0014-2999(90)90172-3 · Cited by 60 · cited 1× · see citing works
“Following a subcutaneous route of administration—at a concentration very similar to the one used in our study—the analgesic effects of MED coincide with the impairment of motor performance (Pertovaara et al., 1990; Idanpaan-Heikkila et al., 1994), making the estimation of its analgesic effect virtually impossible.”
BackgroundA Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice
Wiesmann, M., Zerbi, V., Jansen, D., Haast, R., Lütjohann, D., Broersen, L. M., Heerschap, A., & Kiliaan, A. J. (2016) · Neural Plasticity · doi:10.1155/2016/6846721 · Cited by 60 · see citing works
Mouse BOLD fMRI at ultrahigh field detects somatosensory networks including thalamic nuclei
Jung, W. B., Shim, H., & Kim, S. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.03.063 · Cited by 59 · cited 1× · see citing works
“Because the HRF is affected by numerous factors, including species, anesthetic regimen, or stimulation protocol, many studies used custom-made HRF for GLM analysis (Schroeter et al., 2014; Jung et al., 2019; Lambers et al., 2020; Pradier et al., 2021; You et al., 2021).”
MethodSex Differences in Blood-Oxygenation-Level-Dependent Functional MRI With Primary Visual Stimulation
Levin, J. M., Ross, M. H., Mendelson, J. H., Mello, N. K., Cohen, B. M., & Renshaw, P. F. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.3.434 · Cited by 57 · cited 2× · see citing works
“Despite overall sex differences in cerebral processing in small animals and humans (Levin et al., 1998; Baran et al., 2010; Dumais et al., 2017; Bloch et al., 2021), only a few studies have systematically investigated sex differences in the temporal progression of the BOLD response or parameters of the hemodynamic res…”
BackgroundResultMarumo, K., Takizawa, R., Kawakubo, Y., Onitsuka, T., & Kasai, K. (2008) · Neuroscience Research · doi:10.1016/j.neures.2008.10.012 · Cited by 56 · cited 1× · see citing works
“, 2021), only a few studies have systematically investigated sex differences in the temporal progression of the BOLD response or parameters of the hemodynamic response in humans (Marumo et al., 2009; Squair et al., 2020) or rats (Lambers et al.”
BackgroundLambers, H., Segeroth, M., Albers, F., Wachsmuth, L., van Alst, T. M., & Faber, C. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116446 · Cited by 56 · cited 10× · see citing works
“The calculation of mouse-specific HRFs was conducted similar to a procedure described earlier for rats (Lambers et al., 2020).”
BackgroundMethodResultInfluentialSelf-citationGonzález‐Cano, R., Montilla‐García, Á., Ruiz‐Cantero, M. C., Bravo‐Caparrós, I., Tejada, M. A., Nieto, F. R., & Cobos, E. J. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.004 · Cited by 56 · cited 1× · see citing works
“To investigate these mechanisms, withdrawal of the paw in response to a noxious thermal or mechanical stimulus is typically measured in rodents to assess pain-related behavior (González-Cano et al., 2020).”
BackgroundEcho‐planar BOLD fMRI of mice on a narrow‐bore 9.4 T magnet
Nair, G., & Duong, T. Q. (2004) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20158 · Cited by 55 · see citing works
Pawela, C. P., Hudetz, A. G., Ward, B. D., Schulte, M. L., Li, R., Kao, D. S., Mauck, M. C., Cho, Y. R., Neitz, J., & Hyde, J. S. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.02.022 · Cited by 54 · cited 1× · see citing works
“, 2018), visual (Pawela et al., 2008; Bailey et al., 2013) and olfactory stimulation (Chen et al.”
BackgroundAnesthesia differentially modulates neuronal and vascular contributions to the BOLD signal
van Alst, T. M., Wachsmuth, L., Datunashvili, M., Albers, F., Just, N., Budde, T., & Faber, C. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.03.057 · Cited by 53 · see citing works
Self-citationHypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice
Wiesmann, M., Zerbi, V., Jansen, D., Lütjohann, D., Veltien, A. A., Heerschap, A., & Kiliaan, A. J. (2017) · Theranostics · doi:10.7150/thno.18509 · Cited by 52 · see citing works
Location Matters: Navigating Regional Heterogeneity of the Neurovascular Unit
Bernier, L., Brunner, C., Cottarelli, A., & Balbi, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.696540 · Cited by 49 · cited 1× · see citing works
“, intrinsic optical imaging, arterial spin labeling (ASL), immunohistochemistry) suggest differences in blood flow dynamics and blood vessel density in different brain structures, including cortex, hippocampus and thalamus (Hayward et al., 2011; Wiesmann et al., 2016, 2017; Bernier et al., 2021).”
BackgroundSex differences in the structure and function of rat middle cerebral arteries
Wang, S., Zhang, H., Liu, Y., Li, L., Guo, Y., Jiao, F., Fang, X., Jefferson, J. R., Li, M., Gao, W., et al. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00722.2019 · Cited by 48 · cited 1× · see citing works
“However, several studies indicate that the HRF differs across experimental factors, including anesthesia, stimulation modalities, brain structures, sexes, and species, and hence might strongly affect the outcome of BOLD analyses (Duque et al., 2017; Lambers et al., 2020; Wang et al., 2020).”
BackgroundRoles of gender and gonadectomy in pilocarpine and clonidine analgesia in rats
Kiefel, J. M., & Bodnar, R. J. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90075-q · Cited by 47 · cited 1× · see citing works
“While clonidine has been shown to have greater analgesic properties in males compared to female rats (Kiefel and Bodnar, 1992), tizanidine did not exert different analgesic properties in naïve male and female rats (Rodríguez-Palma et al.”
BackgroundfMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI
Niranjan, A., Christie, I. N., Solomon, S. G., Wells, J. A., & Lythgoe, M. F. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.06.015 · Cited by 47 · see citing works
Kaufmann, C., Elbel, G. K., Gössl, C., Pütz, B., & Auer, D. P. (2001) · Human Brain Mapping · doi:10.1002/hbm.1039 · Cited by 45 · cited 1× · see citing works
“It is important to mention that our study did not compare BOLD response amplitudes, which differ in men and women (Levin et al., 1998; Cowan et al., 2000; Kaufmann et al., 2001).”
ResultYou, T., Im, G. H., & Kim, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-92582-5 · Cited by 45 · cited 5× · see citing works
“Therefore, the determination of species or even data-specific HRF has been acknowledged to be important and is increasingly applied in animal fMRI studies (Schroeter et al., 2014; Jung et al., 2019, 2021; Dinh et al., 2020; You et al., 2021).”
BackgroundMethodInfluentialSharp, P. S., Shaw, K., Boorman, L. W., Harris, S., Kennerley, A. J., Azzouz, M., & Berwick, J. (2015) · Scientific Reports · doi:10.1038/srep12621 · Cited by 43 · see citing works
Characterization of incisional and inflammatory pain in rats using functional tools of MRI
Amirmohseni, S., Segelcke, D., Reichl, S. U., Wachsmuth, L., Görlich, D., Faber, C., & Pogatzki-Zahn, E. M. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.11.052 · Cited by 41 · cited 3× · see citing works
“Since we only used a 10 s-stimulation period consistent with our previous experiments in rats (Amirmohseni et al., 2016; Just et al., 2020), we cannot estimate the effect of stimulus duration on the BOLD response.”
BackgroundMethodResultSelf-citationSex differences in functional brain activation during noxious visceral stimulation in rats
Wang, Z., Guo, Y., Bradesi, S., Labus, J. S., Maarek, J. I., Lee, K. C., Winchester, W. J., Mayer, E. A., & Holschneider, D. P. (2009) · Pain · doi:10.1016/j.pain.2009.05.025 · Cited by 40 · cited 1× · see citing works
“Other examples for divergent BOLD activation following noxious stimuli in human volunteers have also been observed following noxious visceral and thermal stimulation using fMRI (Linnman et al., 2012; Wang et al., 2019).”
BackgroundAlbers, F., Schmid, F., Wachsmuth, L., & Faber, C. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.12.059 · Cited by 40 · cited 1× · see citing works
“, 2021) or line-scanning BOLD fMRI (Yu et al., 2014; Albers et al., 2018; Choi et al., 2022).”
Self-citationPradier, B., Wachsmuth, L., Nagelmann, N., Segelcke, D., Kreitz, S., Heß, A., Pogatzki-Zahn, E. M., & Faber, C. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118626 · Cited by 38 · cited 8× · see citing works
“This anesthetic regimen produces a stable brain state, functional connectivity and reliable BOLD activation in mice (Pradier et al., 2021).”
BackgroundMethodInfluentialSelf-citationDumais, K. M., Kulkarni, P. P., Ferris, C. F., & Veenema, A. H. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.04.003 · Cited by 34 · cited 1× · see citing works
“Despite overall sex differences in cerebral processing in small animals and humans (Levin et al., 1998; Baran et al., 2010; Dumais et al., 2017; Bloch et al., 2021), only a few studies have systematically investigated sex differences in the temporal progression of the BOLD response or parameters of the hemodynamic res…”
BackgroundIdänpään-Heikkilä, J. J., Kalso, E. A., & Seppälä, T. T. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24012-5 · Cited by 33 · cited 1× · see citing works
“Following a subcutaneous route of administration—at a concentration very similar to the one used in our study—the analgesic effects of MED coincide with the impairment of motor performance (Pertovaara et al., 1990; Idanpaan-Heikkila et al., 1994), making the estimation of its analgesic effect virtually impossible.”
BackgroundSilva, J. T. D., Zhang, Y., Asgar, J., Ro, J. Y., & Seminowicz, D. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.04.055 · Cited by 33 · cited 1× · see citing works
“, 2010), and which has also been replicated in animal fMRI studies (Silva et al., 2018).”
BackgroundKawamata, T., Omote, K., Yamamoto, H., Toriyabe, M., Wada, K., & Namiki, A. (2003) · Anesthesiology · doi:10.1097/00000542-200306000-00027 · Cited by 32 · see citing works
Segelcke, D., Fischer, H. K., Hütte, M., Dennerlein, S., Benseler, F., Brose, N., Pogatzki-Zahn, E. M., & Schmidt, M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110152 · Cited by 32 · see citing works
Self-citationDesensitization to the Behavioral Effects of α2-Adrenergic Agonists in Rats
Hayashi, Y., Guo, T., & Maze, M. (1995) · Anesthesiology · doi:10.1097/00000542-199504000-00019 · Cited by 31 · cited 11× · see citing works
“The first task fMRI experiment started 50 min after initial MED bolus injection.”
BackgroundInfluentialEklund, A., Andersson, M., & Knutsson, H. E. (2011) · International Journal of Biomedical Imaging · doi:10.1155/2011/627947 · Cited by 30 · cited 1× · see citing works
“, 2020)2 using 10,000 permutations (Eklund et al., 2011).”
Advances in assessment of pain behaviors and mechanisms of post-operative pain models
Segelcke, D., Pradier, B., & Pogatzki-Zahn, E. M. (2019) · Current Opinion in Physiology · doi:10.1016/j.cophys.2019.07.002 · Cited by 30 · cited 1× · see citing works
“The withdrawal response to von Frey filaments (blunt, rather innocuous) is the current gold standard for measuring mechanical hypersensitivity in rodent pain models and hence, is frequently used (Deuis et al., 2017; Segelcke et al., 2019) and enables detection of relevant sex differences in rodents (Segelcke et al.”
BackgroundSelf-citationAnalysis of Time and Space Invariance of BOLD Responses in the Rat Visual System
Bailey, C. J., Sanganahalli, B. G., Hermán, P., Blumenfeld, H., GJEDDE, A. H., & Hyder, F. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs008 · Cited by 28 · cited 1× · see citing works
“, 2018), visual (Pawela et al., 2008; Bailey et al., 2013) and olfactory stimulation (Chen et al.”
BackgroundNeural correlates of hyperalgesia in the monosodium iodoacetate model of osteoarthritis pain
Abaei, M., Sagar, D. R., Stockley, E. G., Spicer, C. H., Prior, M. J. W., Chapman, V., & Auer, D. P. (2016) · Molecular Pain · doi:10.1177/1744806916642445 · Cited by 28 · see citing works
Respiratory plasticity after perinatal hypercapnia in rats
Bavis, R. W., Johnson, R. A., Ording, K. M., Otis, J. P., & Mitchell, G. S. (2005) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2005.09.002 · Cited by 26 · cited 1× · see citing works
“This is also in line with previous reports that did not detect differences in blood gas composition in male and female rats (Bavis et al., 2006).”
ResultGil, R., Fernandes, F. F., & Shemesh, N. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117446 · Cited by 25 · cited 2× · see citing works
“Yet, they were not identical, and it is plausible that these differences between both modeled signals could significantly affect GLM analysis if the BOLD signals had higher amplitudes or were acquired with faster image acquisition schemes as it is used for single-slice GE-EPI (Gil et al., 2021) or line-scanning BOLD f…”
BackgroundBOLD-fMRI in the mouse auditory pathway
Freches, G. B., Chavarrías, C., & Shemesh, N. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.10.027 · Cited by 24 · see citing works
Vollert, J., Trewartha, N., Kemkowski, D., Cremer, A. F., Zahn, P. K., Segelcke, D., & Pogatzki-Zahn, E. M. (2022) · European Journal of Pain · doi:10.1002/ejp.2014 · Cited by 24 · cited 1× · see citing works
“However, these results are not entirely consistent, especially not in more recent studies in human volunteers (Vollert et al., 2022) and need further investigation.”
ResultSelf-citationNetwork analysis identifies consensus physiological measures of neurovascular coupling in humans
Squair, J. W., Lee, A. H. X., Sarafis, Z. K., Chan, F., Barak, O. F., Dujić, Ž., Day, T. A., & Phillips, A. A. (2019) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x19831825 · Cited by 20 · cited 3× · see citing works
“, 2021), only a few studies have systematically investigated sex differences in the temporal progression of the BOLD response or parameters of the hemodynamic response in humans (Marumo et al., 2009; Squair et al., 2020) or rats (Lambers et al.”
BackgroundResultKomaki, Y., Debacker, C., Djemai, B., Ciobanu, L., Tsurugizawa, T., & Bihan, D. L. (2020) · PLOS ONE · doi:10.1371/journal.pone.0228759 · Cited by 20 · see citing works
Salvan, P., Lazari, A., Vidaurre, D., Mandino, F., Johansen‐Berg, H., & Grandjean, J. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109954 · Cited by 20 · see citing works
Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI
Choi, S., Zeng, H., Chen, Y., Sobczak, F., Qian, C., & Yu, X. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab497 · Cited by 18 · cited 1× · see citing works
“, 2021) or line-scanning BOLD fMRI (Yu et al., 2014; Albers et al., 2018; Choi et al., 2022).”
Bosshard, S. C., Stuker, F., von Deuster, C., Schroeter, A., & Rudin, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126513 · Cited by 16 · see citing works
Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception
Reimann, H. M., Hentschel, J., Marek, J., Huelnhagen, T., Todiraş, M., Kox, S., Waiczies, S., Hodge, R., Bäder, M., Pohlmann, A., et al. (2016) · Scientific Reports · doi:10.1038/srep17230 · Cited by 16 · cited 1× · see citing works
“Since investigation of sensory processing is vital to many brain disorders, different fMRI task (stimulus) modalities have been developed and applied to mouse fMRI studies; these include electrical or heat stimulation of the glabrous paw skin (Nair and Duong, 2004; Adamczak et al., 2010; Neely et al., 2010; Schroeter…”
BackgroundCerebrovascular Hemodynamics in Women
Duque, C., Feske, S. K., & Sorond, F. A. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1608881 · Cited by 14 · cited 2× · see citing works
“While sex differences are probably involved in the BOLD response through the interaction of, for example, estrogen with the sympathetic nervous system resulting in vasoconstriction (Duque et al., 2017), studies with large human cohorts (n > 100) did not detect differences in parameters of the hemodynamic response (Squ…”
BackgroundZhao, F., Meng, X., Lu, S. X., Hyde, L. A., Kennedy, M. E., Houghton, A. K., Evelhoch, J. L., & Hines, C. D. G. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116725 · Cited by 14 · cited 2× · see citing works
“, 2021), visual, olfactory or auditory (Niranjan et al., 2016, 2017; Blazquez Freches et al., 2018; Boido et al., 2019; Chen et al., 2020; Dinh et al., 2020; Komaki et al., 2020; Zhao et al., 2020; Pradier et al., 2021; Lungu et al., 2022), and optogenetic stimulation (Kahn et al.”
BackgroundLeacy, J. K., Johnson, E. M., Lavoie, L., Macilwraith, D. N., Bambury, M., Martin, J. A., Lucking, E. F., Linares, A. M., Saran, G., Sheehan, D. P., et al. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00292.2021 · Cited by 14 · cited 2× · see citing works
“This is also consistent with humans, where studies with larger cohorts did not detect sex differences in temporal progression of the BOLD response (Squair et al., 2020; Leacy et al., 2022).”
BackgroundResultRodríguez-Palma, E. J., Castelo-Flores, D. G., Caram‐Salas, N. L., Salinas-Abarca, A. B., Centurión, D., la Luz-Cuellar, Y. E. D., & Granados‐Soto, V. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174855 · Cited by 12 · cited 1× · see citing works
“While clonidine has been shown to have greater analgesic properties in males compared to female rats (Kiefel and Bodnar, 1992), tizanidine did not exert different analgesic properties in naïve male and female rats (Rodríguez-Palma et al., 2022).”
BackgroundWank, I., Pliota, P., Badurek, S., Kraitsy, K., Kaczanowska, J., Griessner, J., Kreitz, S., Heß, A., & Haubensak, W. E. (2021) · Communications Biology · doi:10.1038/s42003-021-02262-3 · Cited by 11 · see citing works
Just, N., Segelcke, D., Sandbrink, M., Pogatzki-Zahn, E. M., & Faber, C. (2019) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2019.2936571 · Cited by 8 · cited 3× · see citing works
“Since we only used a 10 s-stimulation period consistent with our previous experiments in rats (Amirmohseni et al., 2016; Just et al., 2020), we cannot estimate the effect of stimulus duration on the BOLD response.”
BackgroundMethodSelf-citationBrain-wide sensory aberrations in a Parkinson’s Disease mouse model revealed by functional MRIPreprint
Lungu, R., Fernandes, F. F., Outeiro, T. F., & Shemesh, N. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.06.487227 · Cited by 7 · cited 1× · see citing works
“, 2021), visual, olfactory or auditory (Niranjan et al., 2016, 2017; Blazquez Freches et al., 2018; Boido et al., 2019; Chen et al., 2020; Dinh et al., 2020; Komaki et al., 2020; Zhao et al., 2020; Pradier et al., 2021; Lungu et al., 2022), and optogenetic stimulation (Kahn et al.”
BackgroundSegelcke, D., Linnemann, J., Pradier, B., Kronenberg, D., Stange, R., Richter, S. H., Görlich, D., Baldini, N., Pompo, G. D., Verri, W. A., Jr., et al. (2023) · Cancers · doi:10.3390/cancers15051565 · Cited by 6 · see citing works
Self-citationBloch, S., Rinker, J. A., Smith, A. C. W., Shiromani, P. J., Wheeler, D. G., Azevedo, R., Gandhi, S., Hoffman, M., & Mulholland, P. J. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.19.444869 · Cited by 4 · cited 1× · see citing works
“Despite overall sex differences in cerebral processing in small animals and humans (Levin et al., 1998; Baran et al., 2010; Dumais et al., 2017; Bloch et al., 2021), only a few studies have systematically investigated sex differences in the temporal progression of the BOLD response or parameters of the hemodynamic res…”
BackgroundMalheiros, J. M., Andreeta, M. B., Polli, R. S., Paiva, F. F., Tannús, A., Guinsburg, R., & Covolan, L. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14948 · Cited by 3 · cited 1× · see citing works
“Using manganese-enhanced MRI, the authors found increased activation of S1, M1, CPu and amygdala in female compared to male rats (Malheiros et al., 2021).”
BackgroundHigh temporal resolution BOLD responses to visual stimuli measured in the mouse superior colliculus
Niranjan, A., Siow, B. M., Lythgoe, M. F., & Wells, J. A. (2017) · Matters · doi:10.19185/matters.201701000001 · Cited by 2 · see citing works
Characteristics of fMRI responses to visual stimulation in anesthetized vs. awake mice
Dinh, T. N. A., Jung, W. B., Shim, H.-J., & Kim, S.-G. (2020) · doi:10.1101/2020.08.17.253500 · Cited by 1
Flagged first, then by citations
Research works printed but not linked: 1
- Franklin K. Paxinos G. (2008). The mouse brain in stereotaxic coordinates, compact. 3rd Edn Academic Press Available at: https://www.elsevier.com/books/the-mouse-brain-in-stereotaxic-coordinates-compact/franklin/978-0-12-374244-5.
Cited by
Sorted by citations
Yin, X., Zeng, X., Lin, J., Xu, W., Cui, K.-Y., Guo, X., Li, W., & Xu, S. (2025) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2025.01.006 · Cited by 8 · see citing works
Elucidating hemodynamics and neuro-glio-vascular signaling using rodent fMRI
Zhou, X. A., Jiang, Y., Gomez-Cid, L., & Yu, X. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2024.12.010 · Cited by 7 · see citing works
How spinal GABAergic circuits modulate cerebral processing of postsurgical pain
Pradier, B., Segelcke, D., Just, N., Augustin, M., Nagelmann, N., Faber, C., & Pogatzki-Zahn, E. M. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107609 · Cited by 9 · see citing works
Self-citationKreitz, S., Pradier, B., Segelcke, D., Amirmohseni, S., Heß, A., Faber, C., & Pogatzki-Zahn, E. M. (2024) · Current Research in Neurobiology · doi:10.1016/j.crneur.2024.100142 · Cited by 5 · see citing works
“We developed a mechanical stimulator for rats (Amirmohseni et al., 2016; Just et al., 2020) and mice (Chen et al., 2023) to compare activation of mechanosensitive A β , A δ and C-fibers (Zimmermann et al., 2009) with electrical stimulation and study their effects on pain (hyper-) sensitivity.”
Self-citationPlagwitz, L., Choi, S., Yu, X., Segelcke, D., Lambers, H., Pogatzki-Zahn, E., Varghese, J., Faber, C., & Pradier, B. (2024) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2024.106136 · Cited by 3 · see citing works
Self-citationSegelcke, D., Jolmes, J., Pradier, B., Rosenberger, D. C., Macháček, P. A., Bakker, R., Ritte, A., Kartscher, A., Graw, C., Jurr, H., et al. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106422 · Cited by 4 · see citing works
Self-citationEnergy paradox in REM sleep: balancing supply and consumption in brain metabolism
Takahashi, Y., Ikoma, Y., & Matsui, K. (2026) · Communications Biology · doi:10.1038/s42003-026-10646-6 · Cited by 1 · see citing works
Systematic evaluation of adhesives for implant fixation in multimodal functional brain MRI
Szinyei, A. Z., Maus, B., Schmid, J. Q., Klimek, M., Segelcke, D., Pogatzki-Zahn, E. M., Pradier, B., & Faber, C. (2025) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-024-01220-4 · Cited by 1 · see citing works
Self-citationLee, D., Kim, D. Y., To, X. V., Nasrallah, F. A., & Lee, H. K. (2025) · Scientific Reports · doi:10.1038/s41598-025-18556-z · Cited by 1 · see citing works
“In fact, the use of low-dose medetomidine has several advantages for sensory study such as sedation 57 preservation of sensory processing 18,58 less impairment of motor function 12,59 reduced cardiovascular and respiratory effects 60 and longitudinal study facilitation 61 .”
Understanding Brain-Wide Network by Combining Optogenetics with Genetic and Connectivity Atlases
Chuang, K. (2026) · Neuromethods · doi:10.1007/978-1-0716-5178-0_14
Shedding Light on Brain Activity: How to Fuse Optical Signals with BOLD fMRI
Pradier, B., Wachsmuth, L., & Faber, C. (2026) · Neuromethods · doi:10.1007/978-1-0716-5178-0_5
Self-citationLawen, A., Succi, I., Lichtman, D., Peterka, D. S., Abdus-Saboor, I., & Kahn, I. (2026) · Science Advances · doi:10.1126/sciadv.aed0935
“…learning-related changes in hemodynamic responses benefits from prior work showing that the mouse HRF differs systematically from the canonical human HRF, typically exhibiting faster temporal dynamics and substantial variability across acquisition and physiological conditions ( 44 – 47 ).”
- Authors
- Chen, H.-F., Lambers, H., Nagelmann, N., Sandbrink, M., Segelcke, D., Pogatzki-Zahn, E., Faber, C., & Pradier, B.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Pradier, Bruno
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2023-08-28
- Volume
- 17
- Pages
- 1187328-1187328
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC10493293
- OpenAlex
- W4386223516
- Cited by
- 12
- References
- 95
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- URN:NBN Resolver for Germany & Switzerland (German National Library) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Universitäts- und Landesbibliothek Münster (cc-by)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- hemodynamic response function, sex differences, mechanosensing, BOLD fMRI, mice, rodent pain models
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
