This article describes a new low-cost rapid microfabrication technology for high-density interconnects and passive devices on flexible substrates for sensing applications. Silver nanoparticles with an average size of 80 nm were used to create a conductive SU-8 mixture with a concentration of wt 25%. The patterned structures after hard baking have a sheet resistance of 11.17 Ω/☐. This conductive SU-8 was used to pattern planar inductors, capacitors and interconnection lines on flexible Kapton film. The conductive SU-8 structures were used as a seed layer for a subsequent electroplating process to increase the conductivity of the devices. Examples of inductors, resistor-capacitor (RC) and inductor-capacitor (LC) circuits, interconnection lines and a near-field communication (NFC) antenna are presented as a demonstration. As an example of high-resolution miniaturization, we fabricated microinductors having line widths of 5  Composite materials exhibit properties that cannot be found with metals, polymers or ceramics alone. In particular, metallic nanoparticles embedded in polymers have become increasingly popular because of their ability to maintain the electrical properties in the metallic range while maintaining the flexibility and some unique properties of polymers such as bio-compatibility, chemical resistivity, optical transparency, photo-sensitivity, etc. These composites materials do not have the drawbacks of pure metals such as high density, low chemical resistance and complex manufacturing process.Photoresists are good candidates to be mixed with these metallic particles; they are chemically inert, mechanically stable and can be easily spin coated. Photoresists, such as epoxy-based SU-8 , have a The electrical conductivity of these composite materials depends strongly on the type of filler and the proportion and average size of the particles. As outlined by , the larConductive SU-8 can be obtained by mixing silver nanoparticles ,4, carboOne of the main limitations of the addition of metal nano-particles in SU-8 is the increase of light absorbance, reducing the photo-polymerization depth. In this work, silver was selected as metallic filler for its low absorption in the near UV range, as outlined in , allowinSome of the reported applications of conductive SU-8 include strain sensors ,15, presIn this article, we present a new fabrication approach to create planar passive devices and circuit interconnects with the possibility of miniaturization, and how this technique can lead to obtain highly conductive lines as small as 5  such as . We alsoTypically, the number of passive components in a printed circuit board (PCB) is higher than the number of active components such as operational amplifiers and integrated circuits; therefore, a high number of electrical interconnections are needed to wire these devices together, sometimes needing multiple layers for a proper connection. Embedded passive components can be fabricated between these layers to simplify the design and reduce the footprint. Further advantages include higher reliability, better electrical performance, decreased number of electrical interconnections and low cost . PerhapsBecause of their unique mechanical properties after curing, SU-8 has been widely used as structural material for the fabrication of MEMS devices , allowinBeing able to spin deposit and photo-pattern at high resolution conductive areas is of special interest for the microfabrication community, as it increases the flexibility in the fabrication process in areas of microelectromechanical systems (MEMS) and microfluidics, where temperature-sensitive materials and processes are used and they would be otherwise incompatible with conventional metal deposition processing. Moreover, adhesion of metals to polymers is poor, requiring adhesion promoters to be used prior to metal deposition .Modern electronics often require surface mounted elements to be attached to flexible circuits. The current flexible electronics industry allows circuits to be built using interconnection lines as small as 25 en lines . These pen lines .Guided by the results obtained in ,4, a forThe silver nanoparticles were gradually introduced into the SU-8 while a high-speed mixer was used to evenly disperse the particles and minimize silver aggregation. This agitation process created unwanted air bubbles, which were later removed by immersing the sample in an ultrasound bath for 30 min. To avoid any silver to sediment at the bottom of the vial, a spin bar and a magnetic stirrer at moderate speed was used to maintain a good dispersion of the particles in the sample prior spin coating. Some research groups use pre-treated silver nanoparticles to enhance dispersion in the mixture .The addition of silver nanoparticles into the SU-8 increases the viscosity of the mixture, increasing the expected film thickness. For example, the film thickness of ordinary SU-8 2005 spun at 1000 RPM on a silicon wafer was 7.2 Several experiments were performed by varying the concentration of silver in the SU-8 with increments of 5%, where the percolation threshold was detected to be around 20%. After experimentation, we noticed some variation in the conductivity of the patterned traces in different locations of the same sample. We mitigated this phenomenon by using a slightly higher concentration of silver nanoparticles of 25% in the mixture. As a consequence, the conductivity became much more controllable, especially for fine traces; nevertheless, the minimum patterned features increased in size as well as the required exposure dose. Initial experiments revealed a standard variation in the sheet resistance of ±8.2 Ω/☐ when a concentration of 20% was used. After the concentration was increased to 25%, the standard variation in the sheet resistance dropped to ±5.8 Ω/☐. When the concentration of silver was 60%, it was not possible to achieve any patterned traces on the substrate even when high UV doses were used; at this point, the concentration of nanoparticles was so high that that the UV light could not penetrate the entire thickness of the layer so it could be adhered to the substrate.For the fabrication of planar inductors and capacitors, a piece of Kapton film  with a thickness of 137 The photomask design was exposed using a maskless lithographic system SF-100 Xpress from Intelligent Micropatterning  with 0.6 rding to , enhanciAfter exposure, the sample was post-exposure baked for five additional minutes and then developed for 1 min in an SU-8 developer in a gentle agitation environment. A short rinse in acetone and isopropanol helped to remove silver residues from the substrate. In preliminary work, we noticed that, by spinning and baking a layer of ordinary SU-8 2005 before depositing the conductive SU-8 improved the adhesion of the fabricated devices, it also allowed us to achieve a smaller gap between features since the silver residues were able to be washed away more easily.In order to calculate the sheet resistance of our conductive SU-8 films, we used a cloverleaf design following . A four-ained by .We fabricated planar resistors and capacitors using our functionalized SU-8 on Kapton films. The last step in our fabrication process is to hard bake the patterned features at 200 °C for 2 h to increase the conductivity of the traces as described in . We succPassive filters fabricated as planar devices are becoming increasingly popular for flexible circuits as an alternative of soldering surface-mounted devices.We designed an RC array to be used as a low-pass filter built on a piece of Kapton film. The final resistor and capacitor are shown in We connected the RC circuit to act as a low-pass filter, a sinusoidal voltage with an amplitude of 10 V was used as input. The frequency response of the system is shown in To assess the silver particle distribution, we obtained dark-field images of unexposed conductive SU-8 in different regions of a sample, including the center and areas close to the edges. The silver particle density in the image was estimated using image processing techniques from , where tConductive traces patterned using functionalized SU-8 can be used as a seed layer during an electroplating process to increase the electrical conductivity of the devices. To monitor the copper growth, we patterned a line with functionalized SU-8 measuring 100 As it was mentioned before, a copper electroplating process allowed us to decrease the electrical resistivity of planar inductors fabricated with functionalized SU-8. A low series resistance is necessary to create inductors with high quality factors. The electroplating time and current intensity allows the tuning to the desired conductance.As an example of this fabrication approach, we replicated the design of a commercially available NFC microantenna  using ouThe topography of the inductor traces was measured using a white light interferometer . The electrical impedance of the antenna was measured using an impedance analyzer Agilent E4294A . As an example of miniaturization, we successfully fabricated a microinductor comparable in size with a commercial chip microinductor . It has This minimum limit of 5 antennas , where aThe proposed fabrication process can be used to pattern high-density interconnection lines comparable to those in the flexible PCB industry . Figure The average electrical resistivity between the center connections and the external terminals was 35 kΩ; after electroplating the sample for 1.5 h maintaining a current of 1mA, the average resistivity was decreased to 31 Ω. Based on the resistivity values, equivalent interconnections fabricated in gold and platinum would have a resistance 9.4 Ω and 40.7 Ω, respectively, meaning that the resistivity of our electroplated SU-8 structures lies in the same order of magnitude as common metallic materials used for interconnections .We tested the performance of a fully electroplated LC resonator circuit shown in r, where d is the thickness of the substrate [Planar devices on flexible substrates are subjected to repeated bending. When a sheet is bent, the outer surface experiences tensile stress and the inner surface compressive stress, while a plane inside the sheet  experiences no stress at all. When films are very thin relative to the substrate the simple approximation below describes the relationship between film strain ubstrate ,r=d2ε.Y and the coated film has a higher value than the substrate, the neutral plane is shifted toward the film reducing the strain by a factor specified in Equation (2) of [In the case of a film deposited on a substrate, then n (2) of .Given the process parameters of our samples, we considered a maximum strain of less than 2% for our calculations based on the results of . A correis 0.944 , 4.5 mm To measure the effects of repetitive bending, we created a similar fixture as in  shown inThe sample was bent at 15, 10, 5 and 4.5 mm radii for 1, 10, 100 and 1000 times. The average variation in the inductance stayed below 1% from its initial value. For a bending radius below 3 mm, tensile stress caused the conductive tracks to fracture.As a complimentary experiment, we tested the effects of compressive stress; we bent the LC circuit sample presented in The Kapton film used as substrate shrinks by 0.35% when heated to 200 °C; this low shrinkage percentage on the substrate produced no delamination nor evident damage on the patterned SU-8 layers even after bending; nevertheless, attention is required should substrates with higher shrinkage percentage be used as they might compromise the minimum achievable resolution of patterns; for instance, high-density polyethylene (HDPE) and thermoplastic elastometers (TPE) films exhibit shrinkage rates beyond 2.5%.It is important to mention that the presented fabrication approach is not limited to flexible substrates; some of the example devices shown were also fabricated on rigid substrates (silicon wafers and glass slides).We presented the successful fabrication of planar passive devices and circuit interconnects on a flexible piece of Kapton using conductive SU-8 with silver nanoparticles embedded at a concentration of wt 25%. Such components can be the building blocks of more complex sensing schemes such as filters and wireless sensors. To the best of the author’s knowledge, this is the first report of functionalized SU-8 used to fabricate such planar devices and the first on flexible substrates. A demonstration of a miniature inductor design was presented, where conductive line traces as small as 5 It is worth mentioning that all of the fabricated devices presented in this paper do not have a protective layer on top and are directly exposed to air. The minimum bending radius could potentially be further reduced by adding a protective layer such as parylene or SU-8, thereby enhancing the adhesion of the conductive traces to the substrate. An extra advantage is that these components can easily be manufactured in the inner layers of flexible substrates, occupying less footprint where space is critical in sensing applications.For future work, we plan a hybrid integration of planar devices fabricated with functionalized SU-8, off-the-shelf components and die elements mounted on flexible substrates. As preliminary work, we were able to solder a surface-mounted capacitor between two electroplated tracks on functionalized SU-8 as shown in In summary, this article is meant to highlight the novelty of using conductive SU-8 and electroplating for the fabrication of passive elements and circuit interconnects on flexible substrates. Conductive SU-8 can be used as an alternative to metal deposition when the substrate is sensitive to the environment of metal evaporators and sputtering systems; moreover, functionalized SU-8 can be used as electrical connections for elements that do not require a high electrical conductivity such as capacitive devices. A UV mask aligner was the only required piece of equipment inside a cleanroom to pattern conductive tracks and so it allowed us to continue with the electroplating step in a conventional laboratory using a simple and inexpensive electroplating system, representing a potential reduction in the fabrication costs.


To the editor: Indeed, the similarities between the cases reported by Fraaij et al. from the Netherlands [herlands  and our herlands  are someherlands . In our herlands , we alsoWe share all the concerns raised by the Authors of the Letter to the editor . In partIn addition, we support the suggestion for follow-up investigations in patients with a documented SIV infection, a task that might not be easy to achieve. As far as our recent experience is concerned, at a follow-up telephone visit on 7 February 2017 [Finally, we would like to emphasise that swine influenza monitoring programmes at the Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna (IZSLER) have been in place since the late 1990s, especially in northern Italy where more than 75% of the Italian swine industry is located. These programmes (further improved since 2009) are mainly based on genome detection, virus isolation and sequencing of all respiratory forms and revealing continuous circulation of H1N1, H3N2 and H1N2 SIVs as well as the isolation of influenza A(H1N1)pdm09 viruses in pigs.European Surveillance Network for Influenza in Pigs  which are aimed at expanding our knowledge on European SIV epidemiology [Moreover, surveillance of SIV circulating in European pigs is carried out in many countries, mainly in western Europe, involving the networks emiology . However


High temperatures have substantial impacts on mortality and, with growing concerns about climate change, numerous studies have developed projections of future heat-related deaths around the world. Projections of temperature-related mortality are often limited by insufficient information to formulate hypotheses about population sensitivity to high temperatures and future demographics.The present study derived projections of temperature-related mortality in New York City by taking into account future patterns of adaptation or demographic change, both of which can have profound influences on future health burdens.We adopted a novel approach to modeling heat adaptation by incorporating an analysis of the observed population response to heat in New York City over the course of eight decades. This approach projected heat-related mortality until the end of the 21st century based on observed trends in adaptation over a substantial portion of the 20th century. In addition, we incorporated a range of new scenarios for population change until the end of the 21st century. We then estimated future heat-related deaths in New York City by combining the changing temperature–mortality relationship and population scenarios with downscaled temperature projections from the 33 global climate models (GCMs) and two Representative Concentration Pathways (RCPs).The median number of projected annual heat-related deaths across the 33 GCMs varied greatly by RCP and adaptation and population change scenario, ranging from 167 to 3,331 in the 2080s compared with 638 heat-related deaths annually between 2000 and 2006.These findings provide a more complete picture of the range of potential future heat-related mortality risks across the 21st century in New York City, and they highlight the importance of both demographic change and adaptation responses in modifying future risks.Petkova EP, Vink JK, Horton RM, Gasparrini A, Bader DA, Francis JD, Kinney PL. 2017. Towards more comprehensive projections of urban heat-related mortality: estimates for New York City under multiple population, adaptation, and climate scenarios. Environ Health Perspect 125:47–55; http://dx.doi.org/10.1289/EHP166 High temperatures have long been recognized to have substantial impacts on mortality, and with growing concerns about climate change, numerous studies have projected future heat-related mortality due to climate change in recent years . Some stProjections of temperature-related mortality are, unfortunately, often limited by insufficient understanding of the population adaptation to heat. To date, relatively few heat-health impact studies have considered future adaptation. Some studies have used temperature–mortality curves from “analogue cities” that currently experience temperatures similar to those projected to occur in the future at a location of interest  or tempeAn important question to consider is whether the future population response to high temperatures should be projected based on observations from the present and/or the recent past. Cities are complex adaptive systems  capable In addition to future changes in climate and population adaptation to heat, future demographics are important determinants of health impacts . UtiliziWe start by developing heat adaptation models that project the population response to heat until the year 2100 based on eight decades of historical daily temperature and mortality data. The approach is particularly suitable for New York City, which is among the largest cities in the world and has retained a relatively consistent urban shape over the entire historical period covered by this study. We then develop demographic scenarios that characterize potential changes in the city population during the study period. Finally, we calculate future heat-related deaths by combining the derived temperature–mortality relationships and population scenarios with the downscaled temperature projections from the 33 global climate models (GCMs) and the two Representative Concentration Pathways (RCPs), RCP4.5 and RCP8.5, developed in support of the Intergovernmental Panel on Climate Change (IPCC)’s Fifth Assessment Report (AR5) .http://freepages.genealogy.rootsweb.ancestry.com/~gfli/). Annual numbers of deaths calculated from these records were compared with the numbers published in the New York City Department of Health’s annual Summary of Vital Statistics reports. Annual calculated numbers of deaths were between 0.02% and 4.94% (median 0.95%) higher than those reported in the annual Summary of Vital Statistics reports  . There wWe used the distributed lag nonlinear model (DLNM) module in R  to charaE(ty)] = α + f + s + g + Σ6p= 1δpIp(td) [1]log[whereE(ty) is the expected number of deaths at day tf is the function modeling the association with x, a moving average of temperature over a lag of 3 days (lag 0–3), with parameters βs is the function of time t modeling the long-term trend with parameters γg is the function of the day of the year j modeling the seasonal trend with parameters ηpI is a series of indicators modeling the association with day of the week d with parameters δp.f as a cross-basis composed of a quadratic spline with 4 degrees of freedom with 2 knots at equally spaced percentiles of temperature distribution for the exposure–response function, and a natural spline with 2 degrees of freedom with 2 knots for the lag–response function. The functions s and g were defined as natural cubic splines with 7 degrees of freedom per decade and with 4 degrees of freedom for day in year, respectively.Although longer lags have been found to be appropriate in modeling heat-mortality impacts in the beginning of the 20th century because of some immediate partial harvesting following exposure to heat, shorter lags have been found to adequately capture heat effects in recent decades . Thus, aThe methods used here have been described by Projections are provided for two RCPs . The patThe two RCPs used in this analysis were RCP4.5 and RCP8.5, which are the most frequently used RCPs among the climate modeling community. These two scenarios represent relatively low (4.5) and high (8.5) greenhouse gas projections/radiative forcing through the end of the century. Under RCP4.5, stabilization of greenhouse gas concentrations occurs shortly after 2100 as a product of emissions reduction before that time. RCP8.5 is a scenario with increasing emissions through the century, associated with an energy-intensive future and limited use of green technologies .To develop daily temperature projections, the monthly output from the climate models for the 1/8° grid box corresponding to New York City  was used to develop change factors for each calendar month based on the difference between a 30-year future average for that calendar month and the same model’s 30-year baseline average for that same calendar month . The monThe combination of 33 models and 2 RCPs yielded 66 synthetic future temperature projections for daily mean temperature from 2010 to 2099 that are based on three 30-year time slices, defined as the 2020s (2010–2039), the 2050s (2040–2069) and the 2080s (2070–2099).A comprehensive set of population projections for New York State until 2040 and a detailed methodology were previously derived by the Cornell Center for Applied Demographics .Projections were developed for this study by establishing a range of assumptions regarding the components of the basic demographic equation based on the Cohort Component model :whereatPOP is the city population age a in at point t in timeaPOP0 is the population age a at the beginning of the projection according to the Decennial Census 2010. See 2010 Census Summary File 1  and the number of people moving out .This set of equations was set up separately by sex.We defined five different scenarios for projecting future New York City populations by altering the parameters of the above-mentioned equations. The “baseline” scenario assumed that all parameters of the model remained constant; that is, age-specific fertility and mortality rates and age characteristics of migration were all held constant, but the population aged forward. The “decreased mortality” scenario assumed a decrease in age-specific mortality rates such that the values reached 2/3 of the 2010 values in 2100. Life expectancy at birth would increase by 6 years over time under this scenario, which is in line with the mortality assumptions in the recent Census Bureau projections . The thip-value < 0.001), suggesting rapid adaptation since the 1970s   .Because we did not have mortality data from the 1950s and 1960s, we could not verify the precise onset of the adaptation process (as indicated by the downward shift in the trend for RRs). However, if we assume that access to air conditioning was the major driving force behind heat adaptation, it is plausible to define three stages in the population response to heat: before the introduction of domestic air conditioning, during air conditioning penetration, and after air conditioning penetration levels reach a steady state. Because 84% of surveyed households in New York City in 2003 already had air conditioning in their homes , compareFuture heat-related mortality relative risks at each degree Celsius (°C) were derived for temperatures ≥ 25°C using the temperature-specific relative risk estimates from the historical decades as described above. Decade-specific temperature curves were linearly extrapolated for temperatures ≤ 41°C, the highest projected temperature, using the last four temperature data points of each curve. We chose a sigmoid function to model the decadal change in the heat-mortality response because it permits an accurate approximation of the three stages in the adaptation process:MAXRR) at each temperature was determined by selecting the mean relative risk from the first part of the 20th century, corresponding to the preadaptation part of the sigmoid curve. The RANGERR was derived as the difference between the MAXRR and MINRR, where MINRR is the minimum relative risk for a given temperature or the value to which the sigmoidal curve converges. We developed two future adaptation scenarios in addition to a no-adaptation scenario: a scenario of high adaptation where the projected MINRR in 2100 is 80% lower than the RR observed at the same temperature during the 2000s, and a scenario of moderate adaptation where the projected MINRR in 2100 is 20% lower than the corresponding observed RR during the 2000s. Y represents the year for which ADAPTRR is calculated, and Y0 represents the half decay point, or the year in which MAXRR drops by half of the RANGERR. The steepness of the transition between the periods of no adaptation and complete adaptation is determined by the coefficient α. Both α and Y0 were subjected to nonlinear least squares optimization using the data points for the last four decades. We are not proposing a scenario assuming 100% adaptation because sub-populations of vulnerable individuals without access to air conditioning or other means of heat relief are likely to continue to exist in the future; thus, heat-related mortality may not be completely avoidable.The initial level of temperature-specific relative risk  for which no historical mortality data exist. This extrapolation may underestimate mortality impacts at such very high temperatures, particularly during the initial exposures of the populations to temperatures that they have not previously experienced. Studies of mortality responses in unacclimatized populations would be particularly useful in characterizing heat impacts at very high temperatures. Finally, we acknowledge that the assumptions underlying the two adaptation scenarios developed for this study were arbitrary, but we believe that they capture a reasonable range of potential future adaptation, from modest (20%) to substantial (80%). More data over a longer time period will be needed to determine which end of this range is most realistic.Although we believe that the assumptions of the demographic models developed for this work are reasonable, they are based on historical trends that may or may not continue. Population projections are rarely developed beyond several decades, particularly on a fine, city-level geographical scale. Given the increasing importance of projecting population health impacts under a changing climate, additional work focused on developing and validating long-term population projections will be of critical importance for improving the accuracy of projecting heat-related mortality and other health impacts. Nevertheless, by including five different population scenarios, our study is among the first to examine sensitivity to this important assumption.The methods and findings of this study may be particularly relevant to estimating heat-related mortality in cities currently experiencing heat impacts and increasing urbanization with or without population growth. Because the choice of adaptation scenario substantially affected the number of projected heat-related deaths, improved understanding of heat adaptation is necessary in order to refine projections. Nonetheless, the substantial reduction of heat-related mortality, particularly under the high-adaptation scenario, provides evidence of the importance of public policy measures leading to continuous heat adaptation. Finally, the number of median annual heat-related deaths calculated across all models under RCP8.5 was in many instances more than twice as high as the number of deaths projected under RCP4.5. This difference highlights the magnitude of the potential public health benefit associated with reducing greenhouse gas concentrations in the atmosphere.(319 KB) PDFClick here for additional data file.


Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24 hr gluing manipulation in which the right index and right middle fingers (digits 2 and 3) were adjoined with surgical glue. Somatotopic representations, assessed with two 7 tesla fMRI protocols, revealed rapid off-target reorganisation in the non-manipulated fingers following gluing, with the representation of the ring finger (digit 4) shifted towards the little finger (digit 5) and away from the middle finger (digit 3). These shifts were also evident in two behavioural tasks conducted in an independent cohort, showing reduced sensitivity for discriminating the temporal order of stimuli to the ring and little fingers, and increased substitution errors across this pair on a speeded reaction time task.DOI:http://dx.doi.org/10.7554/eLife.17280.001 The areas of the brain that receive inputs from our senses have a map-like structure. In an area called the visual cortex this map represents our field of vision; in the auditory cortex, it represents the range of different tones we can hear. The sense of touch is processed in the somatosensory cortex: an area of the brain that is organised around a map of the body, with adjacent regions of the cortex representing adjacent regions of the body. The clear structure of these brain regions makes them ideal for exploring how the organisation of the brain changes over time.How quickly can changes to the touch inputs that the brain receives cause the map in the somatosensory cortex to reorganise? Can these effects be produced in just 24 hours? And would this remapping affect how we perceive touch? To investigate these questions, Kolasinski et al. glued together the right index and right middle fingers of healthy human volunteers. This separated the middle and ring fingers: a pair that usually move together due to the anatomical structure of the hand.Functional magnetic resonance imaging of the brain’s activity revealed that within 24 hours of the gluing, the brain’s representation of the ring finger moved away from that of the middle finger, and towards the representation of the little finger. A perceptual judgment task mirrored this finding: after 24 hours of gluing, the participants became better at distinguishing between the middle and ring fingers and worse at distinguishing between the ring and little fingers. This is a powerful demonstration of the human brain’s potential to adapt and reorganise rapidly to changes to sensory inputs.The sense of touch declines gradually with age and may also be reduced as a result of disease such as stroke. A long-term challenge is to understand how the sensory regions of the brain change during this loss of sensation. Further research could then investigate how to maintain the structure of the cortical map to prolong or restore high quality touch sensation.DOI:http://dx.doi.org/10.7554/eLife.17280.002 Evidence for experience-dependent plasticity in the adult mammalian brain exists across a variety of sensory modalities . The ordIn the human brain, there has also been evidence of experience-dependent remapping in SI. Considerable emphasis has been placed upon cross-sectional differences in the cortical organisation of SI observed in specialist populations, such as musicians, or patients with sensorimotor dysfunction, such as focal dystonia . HoweverUsing a well-validated paradigm of single-subject fMRI mapping of human SI at 7 tesla , we askeF = 13.412, p<0.0005, η2:0.626)  = 23.379, p<0.0005; Pairwise Sidak-corrected p<0.05) and a significant increase in the overlap of D4-D5  = 13.384, p<0.0005; Pairwise Sidak-corrected p<0.05) in the glued condition compared with both control sessions  . This wasessions . No signsessions . No shifsessions  or the osessions . No systsessions .10.7554/To further explore the observed change in inter-digit overlap with no change in overall cortical surface area of each digit representation, the fMRI representations of digit 4 used to calculate the cortical overlap metrics (Dice coefficients) were visualised for each participant and session . This daRepresentational similarity analysis conducted on the block design fMRI data also implicated changes in the representation of digit 4 . These dGiven the fMRI data were strongly suggestive of changes in cortical overlap outside of the glued digit pair (D2-D3), we sought to more fully investigate the observed pattern of short-term reorganisation by assessing the behavioural correlates of the gluing manipulation. The same experimental design and gluing manipulation were applied in a separate cohort. Instead of an fMRI scan, nine participants undertook behavioural psychophysics tasks during each session. The first task involved temporal order judgment (TOJ), where pairs of rapid vibrotactile stimuli were applied to adjacent digit pairs of the right hand at varying interstimulus intervals. Participants judged which digit was stimulated first. A psychometric function was fitted to the resulting accuracy data, from which a metric of tactile discrimination ability was calculated for each adjacent digit pair (Just Noticeable Difference: JND). Greater values of JND are associated with poorer discrimination across an adjacent digit pair . We aske2 > 0.4). A two-way repeated measures ANOVA indicated a significant interaction between session and digit pair on tactile discrimination (JND)  = 14.613, p<0.0005, η2:0.676). This was driven by a significant reduction in JND across D3-D4  = 14.631, p<0.0005; Pairwise Sidak-corrected p<0.05), and a significant increase in the JND across D4-D5  = 10.578, p=0.002; Pairwise Sidak-corrected p<0.05) in the gluing condition compared with both control sessions . Instead, we saw changes in cortical overlap, and corresponding change in behavioural performance, for the other digit pairs. Specifically, we saw a shift of D4 away from D3 and towards D5. These findings reject our hypothesis of increased tactile synchronisation driving an increase in cortical overlap. Instead, these data support the alternative hypothesis that compensatory behaviour in other digits during the 24 hr manipulation drives off-target effects.In light of the considerable dexterous abilities specific to the human hand  and the The two fMRI datasets showed independent evidence of a shift in the digit 4 representation during the gluing manipulation: away from digit 3, and towards digit 5  and 3, rA shift in the cortical representation of digit 4 , rather What mechanism drives the observed change in cortical overlap? In vivo studies in rodent barrel cortex demonstrate that a 24 hr period of altered sensory input can induce increases in synaptic density in the corresponding cortical representation . This coThe consistent cortical changes at the flanks of the digit 4 representation  in the aGiven the increasingly recognised contribution of motor efference information to activity patterns in somatosensory cortex , 2013, iThe rapidity of cortical changes shown herein supports further investigation of rapid and targeted therapeutic interventions in conditions such as focal dystonia, where maladaptive changes in somatotopy have previously been reported . The mecAll data were acquired in accordance with local central university research ethics committee approval (University of Oxford MSD-IDREC-C2-2013-05). Eighteen participants were recruited , leaving the tips and pads of the digits exposed. The mixture octyl- and butyl-cyanoacrylates in this glue were selected for their combination of strength and flexibility. Participants were able to flex and extend the two attached digits and were instructed to go about the day-to-day routine as normal.Functional MRI data were acquired using a Siemens 7T Magnetom system with a 32-channel head coil. Blood oxygenation level dependent (BOLD) fMRI was acquired using a T2*-weighted multislice gradient echo planar imaging (EPI), with true axial slices centered on the left anatomical hand knob in the z-axis . One single volume contrast matched EPI acquisition of the same resolution was also acquired for registration purposes. fMRI data acquisition, task and data preprocessing have been detailed previously .Structural MRI data were acquired using a 3T Siemens Trio system during one of the scan sessions with a multi-echo magnetisation prepared rapid acquisition gradient echo (MEMPRAGE) sequence   to digit 5 (D5: little) inclusive. The digits involved in the gluing manipulation were released prior to any scan. During the tasks, participants made individual movements of D2, D3, D4 and D5 in the form of button presses on an MRI-compatible button-box (in-house manufactured) placed on the right thigh of the participant. Instructions were delivered via a visual display projected into the scanner bore. Four white circles were presented, representing the four fingers of the right hand. The circles flashed individually at a frequency of 1 Hz, instructing movements of a specific digit at that rate. During each visit , a blockThe task followed a phase-encoding design, involving continuous button presses with no rest periods. The task involved 8 s blocks of movement of each digit. A phase-encoding forward task cycled through blocks of D2, D3, D4 and D5, with a total of eight repetitions of the cycle. A phase-encoding backward task cycled through blocks of D5, D4, D3 and D2, with a total of eight repetitions of the cycle. The total duration of task fMRI acquisition was 8 min 50 s.A block design task was undertaken involving the same cued movements of a given digit in blocks of 12 s, contrasted with 12 s blocks of rest. Blocks of movement for each digit were repeated four times, giving a total of 16 movement blocks and 16 rest blocks. The total duration of the task was 6 min 30 s. Block order was counterbalanced, and different orders used across the different visits, counterbalanced across participants.fMRI data were processed using tools from the FMRIB Software Library . All fMRThe phase-encoding fMRI data were used to map representations of individual digits in S1; using these representations, it is possible to derive a measure of overlap between the representations of adjacent digits. The phase-encoding task fMRI analysis has been outlined fully elsewhere . The trar-value maps for the lags of each digit were averaged to yield three-dimensional digit maps  for the phase-encoding forward and backward tasks in each participant, in each session. These maps were resampled into the participant’s high-saturation EPI space from the corresponding session using FSL FLIRT. The forward and backward r-value maps were then averaged to yield a digit representation for each participant in each session. A corresponding z-statistic map was calculated for each of the four digit representations in each participant, in each session.Each iteration of the model was assigned to a specific digit based on the position of the ‘on’ period in the digit cycle. The Digit maps from all sessions were resampled into the contrast matched EPI space of the control 0 habituation scan using FSL FLIRT  6 degre , and binarised for subsequent overlap analysis.Cortical surface reconstructions were derived from MEMPRAGE images using FreeSurfer . The z-sorkbench . Once prA measure of cortical overlap between adjacent digits  was calculated from the binarised digit representations for each participant and session using the Dice coefficient . The metz-statistic for each digit within the FreeSurfer-derived SI region of interest. The geodesic distance between adjacent digit peaks was subsequently calculated   . Parametlboxes/) .Nine healthy adult volunteers participated in this experiment, none of whom participated in experiment one. Participants attended four behavioural testing sessions in total. These sessions were scheduled in the same way as the scans the fMRI Experiment , with anParticipants performed a temporal order judgment (TOJ) task on vibrotactile stimuli presented on the distal pad of digits 2, 3, 4 and 5 of the right hand. This is a standard task used previously to study hand representation . ParticiParticipants performed a two alternative forced choice task following instructions on a laptop screen positioned at eye level at a distance of 56 cm. Participants performed three runs of this task, one for each digit pairing . Each run of the task was composed of 192 trials. During each trial, participants received one stimulus to each of the two digits and were asked to judge whether the left or right stimulus came first by pressing with the corresponding digit. Participants were cued on the screen with ‘Ready’ to alert of an oncoming stimulus, ‘Response’ to cue a choice and ‘No response’ in cases of failure to press respond within 2 s of the stimuli. Participants were instructed to fixate on a central fixation cross present on the screen at all times; monitoring was in place to ensure participants’ eyes remained open at all times. The inter stimulus intervals (ISIs) were +400,–400,+250,–250,+180,–180,+120,–120,+70,–70,+30 or 30 ms where, by convention, a positive ISI denotes that the right digit was stimulated first. For each digit pair, the 12 ISIs were presented 16 times in a randomly assigned order.2 < 0.4), threshold selected from earlier study . The task was delivered in the same testing environment as the TOJ task. Movements were cued every 700 ms, in blocks of 210 button presses, separated by a 20-s rest period, with a total of four blocks acquired in each session. The order of button presses was pseudorandomised, and the same button press was not repeated twice consecutively; the overall sequence in each block included an equal number of all possible adjacent digit pairings, including both neighbouring digits (e.g. D2 D3) and non-neighbouring digits (e.g. D3 D5). Participants were instructed to respond as quickly and accurately as possible to each cue and to not correct any perceived errors through double presses.Data were analysed including only responses within the 700-ms response window. Responses were categorised as correct or incorrect; for the latter, the digit used to make the response was recorded.Statistical analyses and graphing used JMP  and Statistics Package for the Social Sciences . The within-subjects data applied for the fMRI and psychophysics data were interrogated with independent two-way repeated measures ANOVAs, selected on the basis of data normality (Shapiro-Wilk confirmed). Significant interactions were further interrogated with analysis of simple main effects; full statistical outputs are provided in  In the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.eLife. Your article has been reviewed by three peer reviewers, and the evaluation has been overseen by Rich Ivry, the Reviewing Editor, and Sabine Kastner as the Senior Editor. The following individual involved in review of your submission has agreed to reveal their identity: Hubert Dinse (Reviewer #1).Thank you for submitting your article "Rapid remapping of human somatosensory cortex" for consideration by The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission.Summary:Three reviewers have evaluated the paper. We all find the paper intriguing with the potential to make a nice addition to the literature on short-term plasticity in the human somatosensory system. The converging evidence from fMRI and psychophysics has the potential to make a compelling story. However, there are a number of substantive issues that must be addressed in a revision to make the case more convincing.Essential Revisions:1) The main issues concern the analyses.1A) We take it that your key findings, namely that the main reorganization effects are observed in the untreated fingers, were unexpected – that you had anticipated observing changes in the representation of the treated fingers (perhaps in addition to the untreated fingers). Granted, one has to follow the data. However, the situation is puzzling. You report no change in the peak locations, representational areas of all fingers, and overlap of D2-D3 (treated fingers). You do find changes in overlap of D3-D4  and D4-D5 (greater overlap). If we put this all together, the results indicate that there is a change in the flank of D4 such that the region near D3 shifts to the other side (near D5). That is, with no change in peak of D4 or its overall area, there should be some sort of marked asymmetry in representation of D4, with much larger flank on side towards D5 (with corresponding reduction in flank on D3 side to keep area constant). Is this correct? Or does the significant overlap shift emerge as a consequence of non-significant changes in finger peaks, areas, etc.? We would like to see a graphical depiction to better understand this puzzling pattern, perhaps some pre-post variant on the graph you show in 1B) We would like a sense of the variability of individual somatotopic maps. Two measures to consider here. First, a measure of goodness-of-fit between the phase-encoding model and brain activity . Second, a quantitative evaluation of inter-subject stability, perhaps performed by calculating Cronback's α  to measure the correlation between the spatial patterns of digit representations of each subject.1C) Other authors have shown that the representational structure of the fingers may depict the invariant organization of the somatosensory cortex better than the exact spatial distribution of the finger clusters . Such measures are not prone to some of the problems of the measurements of cortical overlap used here  can be computed and compared between sessions, allowing an assessment of the distance between the brain activity patterns related to each digit before and after gluing. This would allow you to confirm that the representational structure of the digits is modified in the post-gluing session only, and not in the control conditions.1D) Please clarify how binary images were obtained to calculate the Dice coefficient. Did the binary maps obtained through different thresholds show the same patterns of overlap across conditions  Methods suggest that the individual maps of correlation coefficients were averaged and the z-score was calculated on the group level map. Would it be better to transform the single-subject maps to z-scores before averaging them?1F) Not clear if you have averaged across positive and negative BOLD signals. Would analyzing negative and positive BOLD separately reveal a different picture of the changes?2) While the psychophysics is impressive, the temporal order task seems to provide an indirect way to assess change in overlap representation. A spatial localization task would provide a more direct test , as well as add to null results of no change in confusions for D2 and D3. This experiment would further bolster your conclusions, especially important here given that the imaging results are unexpected.3) The methods section is difficult to sort through. A few of us came away from text assuming you had done before/after contrasts, with one contrast Baseline vs. Control and the other Baseline vs. Gluing. Your design figure suggests that you may have planned things this way for decided there were concerns with the first session (familiarity with scanner environment?) and thus developed a different set of pairings. As such, one contrast is separated by 24 hours and the other by 4 weeks. We recognize that, by counterbalancing things, this is not a confound. Indeed, one could say it is even more impressive that there is little change between Control 1 and 2 given that the time between scans is much greater for this contrast  compared to between (one of the) control scans and Gluing scan. However, we do think it important to report if there is an effect of delay. That is, do you get more stability when the control scans are separated by 24 hours vs. 4 weeks . The n will be quite small (4 vs. 5) in an analysis of order but we think the order issue should be addressed. Given that the small n may lack power in a statistical test, we would also like to see a supplemental figure with the fMRI data for the two orders.4) While appreciating the novelty of your design, we do believe that there is a substantial body of literature, both human and non-human, on short-term plasticity. You cite the Pleger et al. '03 paper which is most similar to the current work. There are other uncited papers that seem relevant to the discussion, some using fMRI and some using other methods. Please consider relevance of Pleger et al. 2001 (PNAS), Dinse et al. 2003 (Science), Hodzik et al. 2004 (J Neurosci), Tegenthoff et al. 2005 (PLoS Biol), Lissek et al. 2009, Kalisch et al. 2009, and Mogilner et al. 1993 (PNAS).5) Your method is similar to that used by Merzenich and colleagues in the late 80's. They, of course, looked at long-term changes and observed dramatically different results. A (slightly) expanded discussion of these differences and possible mechanisms would better situate your paper in the somatosensory reorganization literature. […]Essential Revisions:1) The main issues concern the analyses.1A) We take it that your key findings, namely that the main reorganization effects are observed in the untreated fingers, were unexpected – that you had anticipated observing changes in the representation of the treated fingers (perhaps in addition to the untreated fingers). Granted, one has to follow the data. However, the situation is puzzling. You report no change in the peak locations, representational areas of all fingers, and overlap of D2-D3 (treated fingers). You do find changes in overlap of D3-D4  and D4-D5 (greater overlap). If we put this all together, the results indicate that there is a change in the flank of D4 such that the region near D3 shifts to the other side (near D5). That is, with no change in peak of D4 or its overall area, there should be some sort of marked asymmetry in representation of D4, with much larger flank on side towards D5 (with corresponding reduction in flank on D3 side to keep area constant). Is this correct? Or does the significant overlap shift emerge as a consequence of non-significant changes in finger peaks, areas, etc.? We would like to see a graphical depiction to better understand this puzzling pattern, perhaps some pre-post variant on the graph you show in As the reviewers suggest, the pattern of changes was unexpected in light of previous work in non-human primates. However, we feel that while the results were not perhaps those we might have expected, it should be emphasised that human hand use differs considerably in terms of the dexterous abilities. This could in turn drive compensatory strategies in humans, which were not seen in monkeys: for example, adapting usage patterns of different non-glued digits to achieve the daily tasks. As such, the triggers for reorganization in this study may be different from those in primate studies.While unexpected, our findings have been bolstered by both additional analysis of independent fMRI data (point 1C), as well as complementary evidence from psychophysics, including additional data and analysis (point 2).Following the reviewers’ suggestion, we have now provided additional figures exploring the shift in digit 4 at the level of individual participants . In brieWe have included additional references to the figure in the main text, and refined our discussion of the results to explain in qualitative terms the nature of an expansion and contraction at the flanks of the representation of digit 4, and the likely mechanistic underpinnings of such a change. We have also included details of how the peaks were defined, and the distances between these peaks were calculated.Results:“In order to more fully explore the observed change in inter-digit overlap with no change in overall cortical surface area of each digit representation, the fMRI representations of digit four used to calculate the degree of cortical overlap between adjacent digits (Dice coefficients) were visualized for each participant, at each session . This daDiscussion:“The observation of a cortical shift in the digit 4 , rather Methods: Phase-encoding fMRI analysis: inter-digit overlapz-statistic for each digit within the FreeSurfer-derived SI region of interest. The geodesic distance between adjacent digit peaks was subsequently calculated  We would like a sense of the variability of individual somatotopic maps. Two measures to consider here. First, a measure of goodness-of-fit between the phase-encoding model and brain activity .We are happy to provide a measure of the goodness of fit between the phase-encoding models and the BOLD fMRI signal within the FDR thresholded digit representations of each participant acquired in each session. These cross-correlations represent the goodness of fit between the model and BOLD signal across 181 TRs (TR = 1500 ms). This data is provided in In brief, we demonstrate that there is no systematic change in the goodness of fit across the different sessions, therefore discounting the possibility of this account for the observed changes in the glued condition.Results:“No systematic difference in the fit between the phase-encoding models and fMRI signal were observed across sessions .”Second, a quantitative evaluation of inter-subject stability, perhaps performed by calculating Cronback's α  to measure the correlation between the spatial patterns of digit representations of each subject.We understand from this comment that the reviewers would like to see some quantification of the degree of inter-individual variability in spatial distribution of digit maps across individual participants. As we recently demonstrated using the same phase-encoding mapping technique and scan parameters , the degree of intra-individual variability in the digit maps across time is low, however there is a considerable degree of variability in the spatial distribution of digit representations across different participants. While some individuals show a high concordance in the representation of the same digits, the majority do not. This is supported by evidence of striking variability in the morphology and angle of activation patterns across different participants  Other authors have shown that the representational structure of the fingers may depict the invariant organization of the somatosensory cortex better than the exact spatial distribution of the finger clusters . Such measures are not prone to some of the problems of the measurements of cortical overlap used here  can be computed and compared between sessions, allowing an assessment of the distance between the brain activity patterns related to each digit before and after gluing. This would allow you to confirm that the representational structure of the digits is modified in the post-gluing session only, and not in the control conditions.We agree with the reviewers that multivoxel pattern analysis approaches, including analysis using representational spaces, do offer many benefits in terms of assessing the representational structural of a given cortical region. We feel that this is specifically true here, given the strong hypotheses we have regarding remapping from the phase-encoding fMRI and TOJ psychophysics results. Ejaz et al. 2015 have shown this approach to be effective in the assessment of digit representations in S1. We have therefore included an additional analysis using a similar representational similarity analysis (RSA) approach to assess the representational distances between different digit representations across the three experimental sessions under study.This analysis uses block-design task fMRI data acquired during each session of the experiment. It therefore provides a valuable replication of the observed remapping, independent of the previously discussed analysis of phase-encoding task fMRI data.Below we have provided the additional descriptions of RSA methods, analysis, and results in the manuscript. In brief, we first find that RSA yields representational dissimilarity matrices comparable to those previously presented by Ejaz et al. 2015 in S1, showing greater representational similarity of adjacent digits, specifically of digits which show common synergistic usage patterns. Analysis of the distance metrics between adjacent digit pairs  across the three experimental sessions reveals a significant increase in the representational distance between D3 and D4, and a significant reduction in the representational distance between D4 and D5 . No chanMethods:“Block design task”A block task was undertaken involving the same cued movements of a given digit in blocks of 12 seconds, contrasted with 12-second blocks of rest. Blocks of movement for each digit were repeated four times, giving a total of 16 movement blocks and 16 rest blocks. The total duration of the task was 6 minutes 30 seconds. Block order was counterbalanced, and different orders used across the different visits, counterbalanced across participants.“Block task fMRI: representational similarity analysisMultivariate analysis was conducted using block task data in order to compare the representational structure of digit maps in the glued versus control sessions. Block task fMRI data were analysed at the single-subject level using a standard GLM approach using FSL FEAT , with an individual regressor for movement of each digit , with a γ-HRF boxcar (four 12-second blocks of activity per digit during the task). […] For visualization purposes, the individual participant representational distance matrices (RDMs) for each session was subjected to classical multidimensional scaling (MDS). Within each session, the result of the MDS for each participant was subject to procrustes alignment and correct of standard errors, as described previously .”Results:“Representational similarity analysis conducted on independent block-design fMRI data acquired during each session also implicated changes in the representation of digit 4 . These d1D) Please clarify how binary images were obtained to calculate the Dice coefficient.z-statistic image was projected from 3D volumetric space onto the 2D cortical surface reconstruction of the specific participant. Once projected to the cortical surface, the 2D maps of each digit for each participant and each session were subject to thresholding using FDR (α=0.01). The resulting thresholded z-statistic 2D maps were then binarised, and used in the calculation of Dice coefficients. We have clarified this as follows in the Methods section:We apologise that this process was not sufficiently clear in the Methods section, and have clarified this in the main text. In summary, for each participant and each session, a Methods: Phase-encoding fMRI analysis: inter-digit overlap“Cortical surface reconstructions were derived from MEMPRAGE images using FreeSurfer . […] Where A and B are the area of the two digit representations, the Dice Coefficient is expressed as:”Did the binary maps obtained through different thresholds show the same patterns of overlap across conditions ; Figure 6). We feel that given the same scan parameters and analysis were applied here, a consistent approach to thresholding is justified. More stringent thresholds (e.g. FDR α=0.001) do not yield any overlap between adjacent representations. We have re-run the analysis with a more lenient threshold (FDR α=0.05), which shows the same general pattern of change, but with an expected increase in variance.1E) Methods suggest that the individual maps of correlation coefficients were averaged and the z-score was calculated on the group level map. Would it be better to transform the single-subject maps to z-scores before averaging them?r-value maps for each participant and session were then used to construct z-statistic maps of individual digit representations for that participant and session. At no point were the r-value maps averaged across participants or across sessions (i.e. at the group level). We have clarified this approach in the text as follows:We have attempted to clarify this point in the Methods section. Consistent with previous applications of phase-encoding cross-correlation analysis  for each participant’s data in each session, we averaged the r-value maps from the forward and backward variants of the phase-encoding task, to avoid order effects on the resulting activation . The resulting Methods: Phase-encoding fMRI analysis: inter-digit overlapr-value maps were then averaged to yield a digit representation for each participant in each session. A corresponding z-statistic map was calculated for each of the four digit representations in each participant, in each session.”“Each iteration of the model was assigned to a specific digit based on the position of the ‘on’ period in the digit cycle. […] The forward and backwardMethods: MRI Data Preprocessing“fMRI data were processed using tools from the FMRIB Software Library . All fMRI data were analysed at the level of individual participants and sessions; no group averaging was undertaken across session or across participants.”1F) Not clear if you have averaged across positive and negative BOLD signals. Would analyzing negative and positive BOLD separately reveal a different picture of the changes?The analysis herein has not considered the positive and negative components of the BOLD signals independently. Modelling of negative BOLD considers signal changes relative to baseline. The phase-encoding fMRI task does not have periods of baseline, and it modelled with a travelling wave, rather than a GLM. As such, this data is not suited to extracting specific information regarding changes in the negative BOLD signal. Similarly, the representational similarity analysis (point 1C above), also does not independent consider changes in negative and positive BOLD signals.While considering changes in negative BOLD independently could provide complementary information in this manuscript, we feel that this analysis is outside the scope of the main hypothesis, and would not provide an easily interpretable additional measure in this case. We are concerned that by including this analysis, particularly in a short report manuscript, the focus of the work may become unclear to potential readers, particularly given the focus of negative BOLD in studies of motor rather than somatosensory cortex. We therefore feel that this would be best addressed separately in our future work. However, given the broadening interest in negative BOLD in sensorimotor cortex , we do feel that this should be mentioned as an area of potential interest. We have included a reference to this in the Discussion as follows:Discussion:“The recent observation of somatotopic information in the negative BOLD signal in primary motor cortex also raises questions regarding the mechanisms maintaining cortical topographic organisation, and whether such signals show the same propensity for plastic change as seen in this study , though the negative BOLD signal was not considered independently herein.”2) While the psychophysics is impressive, the temporal order task seems to provide an indirect way to assess change in overlap representation. A spatial localization task would provide a more direct test , as well as add to null results of no change in confusions for D2 and D3. This experiment would further bolster your conclusions, especially important here given that the imaging results are unexpected.We agree that it is important to support our imaging results with sound behavioural results. We selected the temporal order judgment task because it engages the representations of two adjacent digit representations in the cortex, and therefore provides a window on the extent of their shared territory, which is highly comparable to the measures of interest from our imaging results.A spatial localisation task, in which participants are asked to judge the location of a tactile stimulus, could provide a complementary behavioural measure. We would hypothesise that the gluing manipulation would induce more mislocalisations between the digits where cortical overlap has increased.However, we have concerns regarding the feasibility of a spatial localisation task for this study. The duration of testing required to record a relatively small number of errors made such a task undesirable . We feel that this task is perhaps better suited in patient populations, where the number of mislocalisations is expected to be increased due to somatosensory dysfunction. We instead used an active task, which invited a greater number of errors.In this work we posit that usage-dependent plasticity is responsible for the observed shift in the representation of digit 4, as it is freed from anatomical enslavement to digit 3, and free to function even more synergistically with digit 5. We have now included additional data acquired as part of the behavioural experiment, which speaks to the question of mislocalisation from a motor perspective. Specifically, after the gluing manipulation, is there evidence for an increased synergy in digit 4 and 5, in the form of increased confusion in movements between them? We acquired data during a rapidly-cued button-press task, which could address to the concept of mislocalisation.We have included details of the task, analysis, and results below. In brief, we find that in keeping with our hypothesis, there is an increased level of confusion of movements between digit 4 and digit 5 after the gluing manipulation, compared with the two control conditions. No such reduction is observed between digit 3 and digit 4. Nonetheless, we feel that this provides corroborative behavioural evidence supporting the observed pattern of remapping. Moreover, in contrast to a sensory localisation task, we feel that this provides additional insight to data from the TOJ task, demonstrating potential differences in movement synergies after the glued manipulation that may explain the somatosensory changes observed.Methods:“Motor confusion taskA motor confusion task was undertaken to behaviourally assess whether the gluing manipulation induced changes in motor function, which aligned with the observed patterns of somatosensory remapping in experiment 1, and any tactile perceptual changes from the temporal order judgment task. […] Analysis was conducted on the number of mis-presses made across adjacent digit pairs in either direction .”Results:“In other words, after the gluing manipulation, tactile discrimination was improved across D3-D4, and was diminished across D4-D5, with no change in the glued digits D2-D3. […] Data from this task demonstrated an increase in the level of confusion between digits 4 and 5 after the gluing manipulation compared with the control conditions .”3) The methods section is difficult to sort through. A few of us came away from text assuming you had done before/after contrasts, with one contrast Baseline vs. Control and the other Baseline vs. Gluing. Your design figure suggests that you may have planned things this way for decided there were concerns with the first session (familiarity with scanner environment?) and thus developed a different set of pairings.We have attempted to clarify the Methods section to explain these important elements of the experimental design. We hope that by adding this detail, the Methods section will with be easier to follow. The study design figure has been modified to reflect the fact that control 0 was not included in any analysis, and rather acted as a habituation scan as the reviewers suggest, due to the frequent presence of excessive motion during this scan session, attributed to the novel scanner environment at 7 tesla.Methods: fMRI experiment“Nine healthy adult volunteers participated in this experiment, in line with the closest previous studies of longitudinal remapping in human SI . […] The order in which the participants undertook the control and gluing condition was counterbalanced across the group.”As such, one contrast is separated by 24 hours and the other by 4 weeks. We recognize that, by counterbalancing things, this is not a confound. Indeed, one could say it is even more impressive that there is little change between Control 1 and 2 given that the time between scans is much greater for this contrast  compared to between (one of the) control scans and Gluing scan. However, we do think it important to report if there is an effect of delay. That is, do you get more stability when the control scans are separated by 24 hours vs. 4 weeks . The n will be quite small (4 vs. 5) in an analysis of order but we think the order issue should be addressed. Given that the small n may lack power in a statistical test, we would also like to see a supplemental figure with the fMRI data for the two orders.As requested, we have included a summary of the data presented in 4) While appreciating the novelty of your design, we do believe that there is a substantial body of literature, both human and non-human, on short-term plasticity. You cite the Pleger et al. '03 paper which is most similar to the current work. There are other uncited papers that seem relevant to the discussion, some using fMRI and some using other methods. Please consider relevance of Pleger et al. 2001 (PNAS), Dinse et al. 2003 (Science), Hodzik et al. 2004 (J Neurosci), Tegenthoff et al. 2005 (PLoS Biol), Lissek et al. 2009, Kalisch et al. 2009, and Mogilner et al. 1993 (PNAS).Thank you for providing these additional citations. As this manuscript was initially prepared as a short report, we were conscious of limiting the depth of our discussion. However, given the suggested publications would improve the context of the reported findings, we are of course happy to provide a further discussion of this work, and how it relates to our findings herein. We have integrated these citations across the Introduction and Discussion, as follows:Introduction:“In the human brain there has also been evidence of experience dependent remapping in SI. […] However, only limited longitudinal evidence exists that directly investigates remapping at the level of human SI, either in response to altered hand usage patterns , or more intensive Hebbian co-activation paradigms delivering specific patterns of tactile stimulation to the fingertips .”Discussion:“The observation of a cortical shift in the digit 4 , rather 5) Your method is similar to that used by Merzenich and colleagues in the late 80's. They, of course, looked at long-term changes and observed dramatically different results. A (slightly) expanded discussion of these differences and possible mechanisms would better situate your paper in the somatosensory reorganization literature.We agree that given the contrast between our short time findings, and the longer-term remapping studies of Merzenich and colleagues, a short additional discussion of the possible mechanisms would be warranted. We have modified the original Discussion to better integrate content on Merzenich’s work, as well as more recent work that may shed light on the likely underlying mechanisms of plasticity.Discussion:“The 24-hour manipulation in this study may have promoted more adaptive behavioural strategies using unaffected digits, particularly in humans, whose hand usage and dexterous repertoire both exceed those of new world monkeys . […]While BOLD fMRI is unable to map at a comparable spatial resolution to such studies, it is conceivable that the observed changes in cortical activation could be underpinned by shifts in population receptive fields at the boundary of cortical digit representations , or even changes in multidigit receptive fields .”“The question remains: what drives the observed changes in the cortex? Given the potential role for adaptive or compensatory behaviour as a driving force for the observed cortical remapping, bottom-up signals are likely to play a significant role in any receptive field changes that underpin remapping. […] The recent observation of somatotopic information in the negative BOLD signal in primary motor cortex also raises questions regarding the mechanisms maintaining cortical topographic organisation, and whether such signals show the same propensity for plastic change as seen in this study , though the negative BOLD signal was not considered independently in this study.”