Editor's evaluation: Complex pattern of facial remapping in somatosensory cortex following congenital but not acquired hand loss

Abstract

Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Appendix 1 Data availability References Decision letter Author response Article and author information Metrics Abstract Cortical remapping after hand loss in the primary somatosensory cortex (S1) is thought to be predominantly dictated by cortical proximity, with adjacent body parts remapping into the deprived area. Traditionally, this remapping has been characterised by changes in the lip representation, which is assumed to be the immediate neighbour of the hand based on electrophysiological research in non-human primates. However, the orientation of facial somatotopy in humans is debated, with contrasting work reporting both an inverted and upright topography. We aimed to fill this gap in the S1 homunculus by investigating the topographic organisation of the face. Using both univariate and multivariate approaches we examined the extent of face-to-hand remapping in individuals with a congenital and acquired missing hand (hereafter one-handers and amputees, respectively), relative to two-handed controls. Participants were asked to move different facial parts (forehead, nose, lips, tongue) during functional MRI (fMRI) scanning. We first confirmed an upright face organisation in all three groups, with the upper-face and not the lips bordering the hand area. We further found little evidence for remapping of both forehead and lips in amputees, with no significant relationship to the chronicity of their phantom limb pain (PLP). In contrast, we found converging evidence for a complex pattern of face remapping in congenital one-handers across multiple facial parts, where relative to controls, the location of the cortical neighbour – the forehead – is shown to shift away from the deprived hand area, which is subsequently more activated by the lips and the tongue. Together, our findings demonstrate that the face representation in humans is highly plastic, but that this plasticity is restricted by the developmental stage of input deprivation, rather than cortical proximity. Editor's evaluation This fundamental work substantially advances our understanding of cortical remapping in people with congenital or acquired missing hands. The evidence supporting the idea that remapping may not follow cortical proximity but instead functional rules as to how the effector is used are compelling, with rigorous univariate and multivariate analyses applied to functional Magnetic Resonance Imaging data. Importantly, the authors suggest this is mostly the case for one-handers but not for amputees for who the reorganization seems more limited in general. https://doi.org/10.7554/eLife.76158.sa0 Decision letter Reviews on Sciety eLife's review process Introduction Our brains capacity to adapt, known as cortical plasticity, is integral to our successful functioning in daily life, as well as rehabilitation from injury. A key model for exploring the extent, and consequences of, cortical plasticity is upper-limb loss (via amputation or congenital absence). Here, the cortical hand territory in the primary somatosensory cortex (hereafter S1), suffers an extreme loss of sensory input in tandem with dramatic alterations of motor behaviour (Makin et al., 2013a; Muret and Makin, 2021). The functional and perceptual correlates of amputation-related plasticity are currently debated (Makin and Bensmaia, 2017; Ortiz-Catalan, 2018). In particular, it is not clear whether functional cortical reorganisation is restricted to early life development or can also occur in adults. Traditionally, research assessing cortical plasticity after upper-limb loss has followed the tenet that neighbouring body parts of the missing hand, and the lower face in particular, shift and encroach into the deprived hand area. This emphasis on the lip representation stems from early electrophysiological work in non-human primates, where numerous studies demonstrated an ‘upside-down’ facial somatotopy, with the lower face immediately neighbouring the hand (Dreyer et al., 1975; Merzenich et al., 1978; Sur et al., 1982; Cusick et al., 1986; Lin and Sessle, 1994; Manger et al., 1995; Manger et al., 1996; Jain et al., 2001; Cerkevich et al., 2014). Here, the lips and/or chin inputs have been shown to remap into the deprived hand area after sensory loss (Pons et al., 1991; Jain et al., 1997), leading to the well-accepted assumption that remapping is determined by cortical proximity (Buonomano and Merzenich, 1998; Nardone et al., 2013). Thereafter, human measurement of topographic shifts has tended to focus on that of the lips, where researchers have reported that shifted lip representation towards and into the deprived hand area is significantly associated with phantom limb pain (PLP) intensity (Flor et al., 1995; Birbaumer et al., 1997; Lotze et al., 2001; Grüsser et al., 2001; Foell et al., 2014). PLP is a neuropathic pain syndrome experienced in the missing, amputated limb by the majority of amputees (Limakatso et al., 2019). This condition is commonly thought to arise from maladaptive cortical plasticity in S1 (although see Makin, 2021), specifically from a signal mismatch between the missing hand representation and the remapped inputs of the lips in the deprived hand area (Ramachandran and Hirstein, 1998). The research focus on lip cortical remapping in amputees is based on the assumption that the lips neighbour the hand representation. However, this assumption goes against the classical upright orientation of the face in S1 (Penfield, 1950; Schwartz et al., 2004; Roux et al., 2018; Sato et al., 2005; Willoughby et al., 2020), as first depicted in Penfield’s Homunculus and in later intracortical recordings and stimulation studies (Penfield, 1950; Schwartz et al., 2004; Roux et al., 2018; Sato et al., 2005), with the upper-face (i.e. forehead) bordering the hand area. Furthermore, neuroimaging studies in humans studying face topography provided contradictory evidence for the past 30 years. While a few neuroimaging studies provided partial evidence in support of the traditional upright face organisation (Willoughby et al., 2020), other studies supported the inverted (or ‘upside-down’) somatotopic organisation of the face, similar to that of non-human primates (Yang et al., 1993; Servos et al., 1999). Other studies suggested a segmental organisation (Moulton et al., 2009), or even a lack of somatotopic organisation (Iannetti et al., 2003; Nguyen et al., 2004; Kopietz et al., 2009), whereas many studies provided inconclusive or incomplete results (Mogilner et al., 1994; Hoshiyama et al., 1996; Disbrow et al., 2003; Nevalainen et al., 2006). Together, the available evidence does not successfully converge on face topography in humans. In line with the upright organisation originally suggested by Penfield, recent work reported that the shift in the lip representation towards the missing hand in amputees was minimal (Makin et al., 2015; Raffin et al., 2016), and likely to reside within the face area itself. Surprisingly, there is currently no research that considers the representation of other facial parts, in particular the upper-face (e.g. the forehead), in relation to plasticity or PLP. Detailed mapping of the upper and lower face is therefore needed to assess typical topography of facial sensorimotor organisation, as well as remapping after limb loss. More recent electrophysiological studies in monkeys demonstrated that much of the face remapping observed in the primary sensorimotor cortex following upper-limb deafferentation does not result from cortico-cortical plasticity, but instead arises from plasticity in the brainstem (Florence and Kaas, 1995; Kambi et al., 2014). This important finding also highlights the limited explanatory power of local activity increase that has been historically used to infer changes to the representational features of a given brain. Does it reflect a gain modulation of input coming from the brainstem, or increase of local processing of the face input in the hand area? While it remains challenging to dissociate these two contributions, alternative analysis tools are becoming increasingly popular for mining richer information of the processing underlying activity in a given cortical region. Multivariate analyses are sensitive to more subtle changes in representational content, that are not accessible with the traditional univariate approach. In the context of facial remapping, if the deprived hand area updates its local processing to include facial information (and does not just display more facial activity), we would expect it to show greater information about representational features relevant to different facial parts. Remapping after upper-limb loss has also been documented in individuals born without a hand (hereafter one-handers), who do not experience PLP (Makin et al., 2013b). Here, it has been shown that the representation of multiple body parts, including the residual arm, legs and lips, remapped into the missing hand territory (Hahamy et al., 2017; Hahamy and Makin, 2019). Importantly, cortical remapping in this group does not depend on cortical proximity. With regard to the lips, a recent transcranial magnetic stimulation (TMS) study has reported functionally relevant lip activity in the deprived hand area of one-handers (Amoruso et al., 2021), showcasing that reported remapping may also be functional. It was proposed that the observed remapping of various body parts could have been shaped by compensatory behaviour (Hahamy et al., 2017), as these body parts are all used by one-handers to compensate for their missing hand function, but this hypothesis awaits validation. Here, we conducted a mapping of face cortical organisation to determine facial orientation (upright versus inverted) in the primary sensorimotor cortex in 22 two-handed controls, 17 amputees, and 21 one-handers using an active functional MRI paradigm, where participants were visually instructed to move their forehead, nose, lips or tongue. This paradigm was chosen because it enabled simultaneous bilateral activation of S1 within individual participants, providing a within-participants control design. We also explored the representation of multiple facial movements, which have not been previously studied in the context of deprivation-triggered brain plasticity. To measure the extent of cortical remapping of the upper (forehead) and lower (lips) face in relation to the deprived (or non-dominant) hand area across all groups, we used surface-based topographic comparisons. For this purpose, we employed up-to-date methodology to harvest traditional measures, that is winner-takes-all assessment of surface coverage in the hand and face areas, followed by cortical (geodesic) distances, and similarity analysis of selectivity maps. Furthermore, to go beyond the gross topographic properties of face representation, we used multivariate representational similarity analysis (RSA). This approach allows us to characterise more subtle alterations in the relationship between facial activity patterns (forehead, nose, lips, tongue) in the deprived hand and the face areas. We found that, in line with Penfield’s original description, facial topography was arranged in an upright manner, with the forehead (i.e. upper-face) bordering the hand area across all groups. Contrary to traditional theories (Flor et al., 2006), we did not find evidence for facial remapping of either the lips or the (cortically neighbouring) forehead, into the deprived hand area of amputees. We did, however, observe significant remapping of multiple face parts (upper and lower face) in the one-handers group, validating our methodology as suitable for identifying remapping effects. Interestingly, remapping of the cortical neighbour (upper-face) within the one-handers group was away from the missing hand area, while the lips and tongue representations shifted towards the deprived cortex, hinting that the underlying mechanism of remapping is more complex than simple cortical proximity. Results The cortical neighbour of the hand representation is the forehead We first visualised the average group activity resulting from active movements with each of the facial parts (versus rest), within a broad sensorimotor mask. When looking at gross facial organisation at the group-level, we found qualitatively similar activity maps across groups (see Figure 1), highlighting a robust somatotopy of the face with preserved symmetry across the two hemispheres. These facial maps also indicate an upright orientation of the face in S1, with the forehead located closest to the hand area, followed by the nose, lips, and the tongue located laterally, across all groups. The facial somatotopy presented here therefore suggests that the hand’s cortical neighbour is the forehead (or upper-face), highlighting the need to reassess the often-cited, traditional lip-to-hand marker of cortical remapping in amputees and one-handers. However, conclusions based on threshold-dependant group averages may be misleading as they ignore inter-individual differences. Figure 1 Download asset Open asset Group-level activity maps for each facial movement versus rest. Group average activity for the forehead (red), nose (yellow), lips (blue) and tongue (green) movements, contrasted to rest, in the (A) deprived/non-dominant and (B) intact/dominant hemisphere of controls (n=22), amputees (n=17), and one-handers (n=21). All clusters were created using a threshold-free cluster enhancement procedure with a sensorimotor pre-threshold mask (defined using the Harvard Cortical Atlas; outlined in darker grey), and thresholded at p<0.01. The hand and face regions of interest (ROIs) are outlined in purple and orange respectively, and the central sulcus is denoted with a white arrow. One-handers, but not amputees, show lip remapping in the deprived cortex based on univariate topographic mapping To account for inter-individual differences in functional topography and brain topology, we calculated for each participant a winner-takes-all map across facial parts within a (combined) hand and face S1 region of interest (ROI). Focusing on the centre of gravity (CoG) of the lips cluster, we first explored changes in the cortical (geodesic) distance between the lips and an anatomical landmark (~1 cm lateral to the hand knob) of amputees and controls. Here we found no statistically significant main effects or group x hemisphere interaction (F(1,36)=0.019, p=0.890, n2p=0.001, BF10=0.297; controlled for brain size volume; Figure 2B), indicating that the lip area in amputees is not located differently to that of controls. We also measured the proportion of the deprived hand ROI occupied by the lip-winner surface area (relative to the intact hand area; Laterality index). We did not find a significant remapping of the lips (i.e., greater surface coverage) in the missing hand ROI for amputees when compared to controls (U=141.000, p=0.197, rb = 0.246, BF10=0.579; Figure 2C) or to zero (W=91.000, p=0.245, rb=0.338, BF10=0.472; Figure 2C), though here the Bayes Factors did not provide conclusive evidence. Together, these results suggest, contrary to popular theories on brain plasticity in amputees (Flor et al., 2006), that the lips do not remap into the deprived hand area. We next compared the lips laterality index between those individuals who reported suffering from PLP (n=11) and those who no longer experienced chronic PLP (n=6) and found no significant differences (U=27.000, p=0.295, rb = 0.182, BF10=0.629). Figure 2 Download asset Open asset Characterisation of lip (re)mapping in the primary somatosensory cortex. (A) Group-level consistency map for the lips clusters resulting from the individual winner-takes-all maps in the S1 ROI (defined by combining the hand and face areas). The colour gradient represents participant agreement for the lips ‘winning’ that particular voxel, relative to other face movements. Please note that the individual-participant winner-takes-all maps are minimally thresholded, and thus produce an inherently different spatial distribution relative to the group contrast maps presented in Figure 1. The hand ROI is outlined in purple and central sulcus denoted by the white arrow. (B) Cortical geodesic distances from the lip CoG to the anatomical landmark (~1 cm lateral to the hand knob) are plotted for amputees (n=17), controls (n=22), and one-handers (n=21). Distances in the intact/dominant hemisphere are plotted in light blue, and distances in the deprived/non-dominant hemisphere are plotted in darker blue (in amputees and one-handers/controls, respectively). Positive distances indicate the lips CoG is located medial to the anatomical landmark, and negative distances indicate the lips CoG is located lateral to that landmark. The anatomical landmark itself equates to a geodesic distance of zero. For main effects of comparison between amputees and one-handers versus controls, see Figure 2—source data 1–2. (C) Laterality indices for the proportion of surface area coverage of the lips in the hand ROI for all groups (amputees, controls and one-handers). Positive values indicate greater surface area coverage in the deprived/non-dominant hemisphere relative to the intact/dominant hemisphere (in amputees and one-handers/controls, respectively), and negative values reflect greater surface area coverage in the intact/dominant hemisphere relative to the deprived/non-dominant hemisphere. Standard error bars and all individual data-points are plotted in grey and uncorrected for brain size. Amputees with PLP (yes/no) are plotted in orange. ** p<0.01; coloured asterisk’s indicate values are significantly different from zero. Figure 2—source data 1 Main effects and interaction for comparison of geodesic distances between amputees and controls for the lips. https://cdn.elifesciences.org/articles/76158/elife-76158-fig2-data1-v2.docx Download elife-76158-fig2-data1-v2.docx Figure 2—source data 2 Main effects and interaction for comparison of geodesic distances of the lips between one-handers and controls. https://cdn.elifesciences.org/articles/76158/elife-76158-fig2-data2-v2.docx Download elife-76158-fig2-data2-v2.docx Figure 2—source data 3 Raw data for cortical geodesic distances of the lips for amputees, controls, and one-handers. https://cdn.elifesciences.org/articles/76158/elife-76158-fig2-data3-v2.xlsx Download elife-76158-fig2-data3-v2.xlsx Figure 2—source data 4 Raw data for laterality indices of the lips for amputees, controls, and one-handers. https://cdn.elifesciences.org/articles/76158/elife-76158-fig2-data4-v2.xlsx Download elife-76158-fig2-data4-v2.xlsx When visualising the average lip activity within the one-handers group, however, we did note a slight qualitative shift in the location, and spread, of the lip activity within the deprived hemisphere (Figure 1A). This is further supported by a visible shift of the one-handers lip-winner consistency map towards the deprived hand area (Figure 2A). These qualitative changes in the lip representation resulted in a significant group x hemisphere interaction for the lips cortical distance to the anatomical landmark in one-handers and controls (F(1,40)=4.352, p=0.043, n2p=0.098; controlling for brain size; Figure 2B). Confirmatory comparisons indicated no statistically significant shifts of the lip CoG in the deprived hemisphere when compared to the controls non-dominant hemisphere (t(40)=-1.178, p=0.246,~d = −0.395, ~BF10=0.148; corrected alpha = 0.025; uncorrected p-values reported; Figure 2B). Although when compared to their intact hemisphere, shorter distances from the lips to the hand area were found in the deprived hemisphere of one-handers (t(40)=-3.374, p=0.002,~d = −0.621), indicating evidence for lip remapping. These shifts in the deprived hemisphere were also reflected in significantly greater surface area coverage of the lips in the hand ROI when compared to controls (t(41)==-2.762, p=0.009, d=−0.843; Figure 2C), which was significantly different from zero (W=1098.000, p=0.006, rb = 0.426). This converging evidence of lip remapping is in line with previous work in one-handers (Hahamy et al., 2017; Amoruso et al., 2021). One-handers, and to a lesser extent also amputees, show forehead remapping away from the hand area in the deprived cortex As we note a qualitative upright orientation of the face (see Figure 1), the question remains as to whether the neighbour to the hand – the forehead – would reorganise after limb loss in amputees, as hypothesised by traditional theories (Flor et al., 2006). Again, we found no significant evidence for cortical remapping of the neighbouring forehead in amputees when assessing changes in cortical distances (group x hemisphere: F(1,36)=1.338, p=0.255, n2p=0.036, BF10=0.695; controlled for brain size volume; Figure 3B). But a significant difference was found for reduced forehead surface area coverage in the deprived hand ROI when compared to controls (t(37)=2.236, p=0.031, d=0.722; Figure 3C). Interestingly, the direction of this effect indicates less, not more, remapping of the forehead in the deprived hand ROI of amputees. However, note that this decrease of surface area coverage was not significantly different from zero (t(16)=-1.86, p=0.082, d=−0.451, BF10=1.012; Figure 3C). When comparing the forehead laterality index for amputees with and without PLP, no significant differences were found (t(15)=-0.729, p=0.761, d=−0.370, BF10=0.291). Taken together, these results suggest that if remapping of the cortical neighbour – the forehead – does occur, this occurs away from the hand area, and is not related to PLP. Figure 3 Download asset Open asset Characterisation of forehead (re)mapping in the primary somatosensory cortex. All annotations are as in Figure 2. For main effects of cortical geodesic distance comparison between amputees and one-handers versus controls, see Figure 3—source data 1–2. Distances in the intact/dominant hemisphere are plotted in pink and deprived/non-dominant hemisphere in red. (B) # p<0.05; * p<0.025 (corrected alpha); (C) * p<0.05; ** p<0.01; *** p<0.001; coloured asterisk’s indicate values are significantly different from zero. Figure 3—source data 1 Main effects and interaction for comparison of geodesic distances between amputees and controls for the forehead. https://cdn.elifesciences.org/articles/76158/elife-76158-fig3-data1-v2.docx Download elife-76158-fig3-data1-v2.docx Figure 3—source data 2 Main effects and interaction for comparison of geodesic distances between one-handers and controls for the forehead. https://cdn.elifesciences.org/articles/76158/elife-76158-fig3-data2-v2.docx Download elife-76158-fig3-data2-v2.docx Figure 3—source data 3 Raw data for cortical geodesic distances of the forehead for amputees, controls, and one-handers. https://cdn.elifesciences.org/articles/76158/elife-76158-fig3-data3-v2.xlsx Download elife-76158-fig3-data3-v2.xlsx Figure 3—source data 4 Raw data for laterality indices of the forehead for amputees, controls, and one-handers. https://cdn.elifesciences.org/articles/76158/elife-76158-fig3-data4-v2.xlsx Download elife-76158-fig3-data4-v2.xlsx When looking at the one-handers group we did find significant evidence of forehead remapping with a group x hemisphere interaction (F(1,40)=7.437, p=0.009, n2p=0.157; controlled for brain size volume; Figure 3B). Confirmatory comparisons indicated a positive trend for shorter distances of the foreheads’ CoG to the anatomical landmark in the deprived hemisphere when compared to their intact hemisphere (t(40)=2.085, p=0.043,~d = 0.435,~BF10=1.18; corrected alpha = 0.025; trend defined as p<.05; uncorrected p-values reported) and significantly shorter distances when compared to the controls non-dominant hemisphere (t(40)=2.580, p=0.014,~d = 0.774). As the forehead’s CoG tended to be located above the anatomical landmark (see Figure 3A), these results indicate a significant shift of forehead activity away from the deprived hand ROI. This is further supported by a significant decrease of surface area coverage for the forehead in the deprived hand ROI when compared to controls (t(41)=3.676, p<.001, d=1.122), which was significantly different from zero (t(20)=-3.57, p=0.002, d=−0.779; Figure 3C). Remapping of the cortical neighbour in one-handers, therefore, manifests in a shifting away of the upper-face from the deprived hand area, possibly due to increases in activity of other facial movements, for example lips. Tongue movements produce different topographic maps across groups We also assessed changes in the tongue representation, which is not an immediate neighbour to the hand in S1 (Figure 4A). We did find evidence for significant shifts in the tongue’s CoG towards the anatomical landmark in amputees when compared to controls (group x hemisphere: F(1,36)=4.859, p=0.034, n2p=0.119; controlled for brain size volume; Figure 4B). Confirmatory comparisons indicated significantly shorter distances in the deprived hemisphere of amputees when compared to their intact hemisphere (t(36)=-2.595, p=0.014,~d = 0.678) but not to the controls non-dominant hemisphere (t(36)=1.690, p=0.100,~d = 0.454,~BF10=1.211; corrected alpha = 0.025; uncorrected p-values reported). The tongue showed only a trend for greater surface area coverage in the deprived hand ROI of amputees when compared to controls (t(37)=-2.011, p=0.052, d=−0.650, BF10=1.48; Figure 4C), and tended to be different to zero (t(16)=-1.93, p=0.072, d=−0.467). As tongue remapping is not reflected consistently across analyses, and due to the lack of pre-existing hypotheses, this preliminary result should be interpreted with caution. However, it does indicate that some level of cortical remapping may occur in amputees after limb loss. Figure 4 Download asset Open asset Characterisation of tongue (re)mapping in the primary somatosensory cortex. Distances in the intact hemisphere are plotted in light green and distances in the deprived hemisphere in dark green. For main effects of cortical geodesic distance comparison between amputees and one-handers versus controls, see Figure 4—source data 1–2. (B) * p<0.025 (corrected alpha); *** p<0.001; (C) # p<0.1; * p<0.05; coloured asterisk’s indicate values are significantly different from zero. All other annotations are as in Figure 2. Figure 4—source data 1 Main effects and interaction for comparison of geodesic distances between amputees and controls for the tongue. https://cdn.elifesciences.org/articles/76158/elife-76158-fig4-data1-v2.docx Download elife-76158-fig4-data1-v2.docx Figure 4—source data 2 Main effects and interaction for comparison of geodesic distances between one-handers and controls for the tongue. https://cdn.elifesciences.org/articles/76158/elife-76158-fig4-data2-v2.docx Download elife-76158-fig4-data2-v2.docx Figure 4—source data 3 Raw data for cortical geodesic distances of the tongue for amputees, controls, and one-handers. https://cdn.elifesciences.org/articles/76158/elife-76158-fig4-data3-v2.xlsx Download elife-76158-fig4-data3-v2.xlsx Figure 4—source data 4 Raw data for laterality indices of the tongue for amputees, controls, and one-handers. https://cdn.elifesciences.org/articles/76158/elife-76158-fig4-data4-v2.xlsx Download elife-76158-fig4-data4-v2.xlsx We next explored whether this trend for an increase in tongue activity within the deprived hand ROI, as captured by the laterality index of amputees, was related to PLP (Figure 4C), and found a non-significant difference (U=28.000, p=0.325, rb = 0.152, BF10=0.589). These results suggest, along with an inconclusive Bayes Factor, that amputees with PLP may not report greater instances of tongue remapping, when compared to amputees without PLP. When repeating the same analysis in one-handers, we also found a significant group x hemisphere interaction (F(1,40)=8.536, p=0.006, n2p=0.176; controlled for brain size volume; Figure 4B) for the cortical distance between the tongue’s CoG and the anatomical landmark. Confirmatory comparisons indicated significantly shorter distances to the anatomical landmark in the deprived hemisphere compared to the intact hemisphere (t(40)=-3.794, p<.001, ~d = −0.677), as well as when compared to the controls’ non-dominant hemisphere (t(40)=-2.380, p=0.022, ~d = −0.751). This was also reflected in greater surface area coverage of the tongue in the deprived hand ROI (see Figure 4A) that was significantly different from zero (W=162.000, p=0.035, rb = 0.543) and from controls (t(41)=-2.534, p=0.015, d=−0.773; Figure 4C). These results suggest that cortical remapping in one-handers extends to tongue movements. Nose movements produce similar topographic maps across groups Similar analyses were performed to assess changes in the nose representation (see Appendix 1—figure 1). We did not find evidence for either CoG shifts (p values ≥ 0.829, BF10 ≤0.337) nor differences in surface area coverage (p values ≥ 0.174, BF10 ≤0.664) in both amputees and one-handers compared to controls (see Appendix 1—figure 1). These results suggest that the nose representation remains unaffected in both amputees and one-handers, with conclusive Bayes Factors for one-handers indicating evidence for the null. Amputees’ topographic maps are more similar to the maps of controls than of one-handers Finally, we wanted to investigate whether amputees’ facial maps in the deprived hemisphere were more similar to those of controls or to one-handers. To provide a summary measure of univariate facial maps, we performed a Jaccard similarity analysis. This analysis quantifies the degree of sim