Brain, Vol. 125, No. 6, 1256-1264,
June 2002
© 2002 Guarantors of Brain
Spatial acuity after digit amputation
1 Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland, USA
Correspondence to: Dr F. Vega-Bermudez, 338 Krieger Hall, Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA E-mail: fvega{at}jhu.edu
Received June 28, 2001. Revised December 18, 2001. Accepted January 9, 2002.
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Digit amputation in human and non-human primates results in reorganization of somatosensory cortex in which the representations of adjacent, intact digits expand to fill the cortical region previously devoted to the amputated digits. Whether this expanded representation results in improved sensory performance has not been determined. Consequently, we measured the ability to recognize small objects (raised letters) with a digit adjacent to the amputation and the same digit on the normal, contralateral hand in 15 amputees. The same digits were also tested in 15 age-matched, amputation-free subjects. There was no significant difference in recognition scores between digits in the amputees or between amputees and control subjects. More detailed analyses of specific confusion patterns and of the improvement with practice showed no significant differences. As far as we could determine, the cortical expansion that is presumed to accompany digit amputation had no effect on tactile pattern recognition performance.
Keywords: amputation; plasticity; somatosensory; tactile acuity; touch perception
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
A number of interventions, including amputations, can produce changes in the somatotopic maps of the postcentral gyrus. In a landmark experiment, Merzenich and colleagues (Merzenich et al., 1984
) showed that digit amputation in a monkey results in increased cortical representation of the adjacent digits. In addition, the neurones in the expanded representation have smaller receptive fields. The authors suggested that these cortical rearrangements result in increased tactile acuity in the skin areas adjacent to the amputation.
Amputation in humans produces similar changes in somatotopic representation (Knecht et al., 1996; Borsook et al., 1998; Flor et al., 1998; Moore et al., 2000). The majority of humans with digit amputations also have phantom limb sensations. There is a strong suggestion that these phantom limb sensations result from the cortical reorganization that follows amputation (Ramachandran et al., 1992; Flor et al., 1995; Knecht et al., 1998). What is less clear is whether the increased neural representation of digits adjacent to an amputation results in increased tactile acuity in those digits as Merzenich and colleagues suggested (Merzenich et al., 1984).
Several studies have addressed this question in limb amputees but the results are contradictory. Teuber et al. (1949) showed that two-point thresholds in the stump of above-the-knee amputees were lower than comparable skin regions in the contralateral, intact limb. Haber (1958) likewise showed improved two-point discrimination, point localization and touch thresholds at the stump and nearby skin regions in above-elbow amputees relative to the comparable intact, contralateral skin regions. In contrast, recent studies have found no improvement in performance. Flor et al. (1998) found no difference in two-point thresholds when comparing the stump and adjacent skin regions with the intact contralateral corresponding skin region of above-elbow amputees. A similar experiment (Grusser et al., 2001) found no differences in two-point, electrical and thermal thresholds between the stump and intact contralateral skin areas, and, furthermore, no correlation between any of these measures and cortical expansion. Similarly, Braune and Schady (1993) measured vibration thresholds, force thresholds and two-point discrimination in subjects with nerve injury (median or ulnar) and digit amputations, and found no statistical difference between skin regions adjacent to denervated sites and the corresponding contralateral skin areas.
These contradictory results may have been due to the sensory tests that were used, the skin areas that were tested, or failure to control for tactile learning. Both the two-point discrimination and point localization tests are flawed as measures of spatial acuity. A single point evokes a more intense neural discharge than two points, and therefore two points can be discriminated from one point without recourse to spatial neural information (Vega-Bermudez and Johnson, 1999; Craig and Johnson, 2000). When subjects begin to learn this, their performance becomes very variable and the two-point threshold declines rapidly (Dressler, 1894; Milerian and Tkachenko, 1963; Johnson et al., 1994). This accounts for the fact that two-point limen values return to normal or even better than normal in a skin region affected by nerve injury, even though the region remains partially anaesthetic (Karas et al., 1990; Van Boven and Johnson, 1994). Point localization thresholds are subject to the same criticisms. They are very variable within and between studies (Braune and Schady, 1993; Stevens and Choo, 1996); improvement, as in the two-point limen test, may be accounted for by learning and attention (Moore et al., 1999). Furthermore, like two-point limen thresholds, point localization thresholds frequently return to normal in skin regions that are severely affected by nerve injury (Braune and Schady, 1993).
In all studies, except that of Braune and Schady (1993), tactile function was investigated on or around the amputees’ upper arm or leg stump. These areas may be poor choices for investigating the relationship between cortical representation and spatial acuity because cortical representation and spatial acuity are not tightly linked in these areas. It might be, for example, that the cortex representing these areas is devoted more to detecting the presence of a stimulus than to determining its spatial form. In that case, a change in cortical representation might have little, if any, effect on spatial acuity.
Another factor that varied between studies was whether subjects had worn prostheses and, if so, how long they had worn them. In the study by Haber (1958), for example, 18 out of 24 subjects wore prostheses for an unspecified length of time. This exposed the stump and the remaining limb to motor and tactile training not available to the contalateral intact limb used for comparison. Weiss et al. (1999) have shown that the use of a functional prosthesis decreases phantom pain; they hypothesize that this results from use-dependent cortical plasticity. Thus, differences between studies, between subjects, and between the stump and the contralateral skin surface discussed earlier may have also reflected differences in tactile training (Vega-Bermudez et al., 1991; Sathian and Zangaladze, 1997; Van Boven et al., 2000).
We have attempted to correct these confounding factors. We used a letter recognition task to test the fingertip of the digit next to amputated finger(s) and we compared it with the same digit in the intact contralateral hand. Tactile letter recognition provides an objective test of tactile spatial acuity and a detailed characterization of spatial pattern recognition performance that is highly repeatable within and between subjects. It also provides a measure of acuity that is consistent with measures provided by other well controlled methods (Johnson and Phillips, 1981; Vega-Bermudez et al., 1991; Vega-Bermudez and Johnson, 2001). A number of clinical studies suggest that patients with cortical lesions involving the hand area of somatosensory cortex (Roland, 1976; Bender et al., 1982; Kim and Choi-Kwon, 1996) or hand dystonia (Bara-Jimenez et al., 1998, 2000; Elbert et al., 1998) are most affected in tactile tasks that depend on spatial acuity. Therefore, any changes in somatosensory function or somatotopy associated with finger amputation would probably be reflected in tactile spatial acuity changes.
Sensory function was measured at the fingertips adjacent to an amputated finger for three reasons. First, when a finger is amputated there is normally no reason to believe that the innervation of the adjacent finger is affected. Any change in performance can reasonably be assigned to changes in the central nervous system. Secondly, the effects of finger amputation on cortical reorganization have been studied directly and the effects are well known (Merzenich et al., 1984; Manger et al., 1996). Thirdly, the fingertips are specialized for spatial acuity as indicated by their dense mechanoreceptive innervation (Johansson and Vallbo, 1979; Darian-Smith and Kenins, 1980) and their large cortical representations (Merzenich et al., 1978; Sur et al., 1980). Therefore, any change in the central mechanisms serving the fingertips is likely to have an effect on spatial acuity.
Neither the amputees nor controls had any prior experience with tactile letter recognition. Tactile acuity was measured by presenting letters to the finger next to the amputation and to the same finger of the contralateral hand on alternate trial so any learning opportunity would be distributed equally between the two hands.
We report the results of our experiments and discuss their implication for changes in function associated with plasticity.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Fifteen subjects with amputated digits and 15 age-matched control subjects participated in the psychophysical experiments. Subjects were recruited from the Curtis Hand Center of Union Memorial Hospital and from Johns Hopkins University. The committee on clinical investigation of Johns Hopkins University and the committee on clinical investigation of the Union Memorial Hospital approved the protocol. Consent was obtained according to the principles in the Declaration of Helsinki. All subjects were screened for neuropathy or calluses affecting the distal pads of the fingers used for testing, and for a history of learning disorders.
Tactile acuity was measured using a tactile letter recognition task as described previously (Vega-Bermudez et al., 1991). Subjects were seated comfortably with their hands placed through a screen that blocked any view of their hands, the experimenter and the stimuli. The subject’s hands rested palm down on a foam pad 5 mm thick, with a 60 x 40 mm aperture under the finger used to palpate the letters. The tactile stimuli comprised upper-case Helvetica, sans serif letters, 6 mm high, embossed (0.5 mm relief) on a smooth plastic plate.
Subjects scanned the letters with repeated, smooth, continuous left-to-right movements (lifting the finger for the return right-to-left movement) using whatever scanning force and velocity they liked (Vega-Bermudez et al., 1991). Trials in which the subjects used any other motion were discarded. Subjects were allowed as many scans as they liked; the average was five.
Subjects were told that all 26 letters of the alphabet were equally likely on each trial and that there would be repeats. After each presentation subjects were required to name one of the 26 letters of the alphabet (forced-choice design); responses such as ‘I don’t know’ were not allowed. Subjects were given no feedback. Amputees were tested on the finger next to the amputation (designated ipsilateral) and on the same finger of the opposite hand (designated contralateral). When there were whole fingers on both sides of the amputation, the finger closer to the thumb was chosen for testing. Each control subject matched an amputee in age (±3 years) and sex, and was tested on the same fingers as the matching amputee. Each finger was tested with 78 trials (26 letters x three presentations per letter). The ipsi- and contralateral fingers were tested in parallel by choosing the finger and the letter to be tested by a randomization algorithm. Testing with 156 trials (26 letters x three presentations per letter x two fingers) was completed in a single 1–2 h session.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Fifteen subjects with digit amputations participated in the experiment as shown in Table 1. They were all male, right-handed, and ranged in age from 32 to 67 years (mean 48 years). Eleven subjects were tested 1 year after amputation, and the remaining four were tested at 11 months, 1.4 years, 1.6 years and 2 years, as shown in Table 1. Ten amputations involved a single finger and all but one of those had lost at least two distal phalanges; the other five were missing one or more phalanges from each of two adjacent fingers. Performance data for 15 control subjects matched for age, sex and handedness are shown in Table 2.
|
|
There was no performance difference between the digit next to the amputation and the same digit of the intact contralateral hand (43.8 versus 43.2% correct; P = 0.93, t test), nor between the left and right hands of the control subjects (42.7 versus 42.9% correct; P = 0.98, t test). Performance scores for individual amputees and control subjects are shown in Fig. 1. If a 0.05 significance criterion was used for single amputees, one (Subject A15) would have been significant, but the probability of one subject among 15 exceeding 0.05 is 0.54; no amputee was close to significance after applying the Bonferroni correction for multiple comparisons. The mean recognition scores for the controls and amputees were almost identical (42.8 versus 43.5% correct) and there was no difference in the distribution of scores between the two groups (P = 0.92, Kolmogorov–Smirnov).
|
There was no clear performance difference between amputees with left or right hand amputations and no relationship with the number of missing phalanges. There was, however, a general decline in performance with age (Stevens and Choo, 1996
). After pooling the amputees and controls, subjects less than the median age (46 years old) averaged 48% correct, whereas older subjects averaged 37% correct identifications (P = 0.02, t test). The previous analysis demonstrates that amputation has no effect on the accuracy of spatial pattern recognition with fingers adjacent to the amputation. However, it is also clear from many previous studies that the central pathways carrying the information from the adjacent fingers are strongly affected by amputation. Therefore, we analysed the pattern recognition behaviour more closely. Two possibilities are examined here. One is that the cortical reorganization might have affected spatial information processing in some negative way but the amputees have learned to compensate for the deficit. If this is so, the deficit might be manifested as some change in the details of pattern recognition behaviour, e.g. in the errors that subjects make. Another possibility is that the reorganization has endowed the amputees with some greater capacity but they have not learned to use it. They might, for example, learn tactile letter recognition more rapidly with fingers adjacent to the amputation. Both of these possibilities are tested below.
A more detailed analysis of the sensory behaviour is obtained by analysing the responses to the individual letters. Stimulus–response matrices (confusion matrices) for the amputees’ ipsi- and contralateral hands are shown in Fig. 2. The number in row I, column J represents the number of times the Ith letter was identified as the Jth letter. The confusion matrices were used to analyse the true and false identification rates for individual letters.
|
Figure 3A shows recognition rates for individual letters. In no case was the recognition rate with the ipsilateral finger significantly different from the contralateral finger. The greatest disparity among the amputees was for the letter R, where the recognition rates were 58% (26/45 correct) and 40% (18/45) on the finger next to the amputation and the contralateral finger. Differences greater than that occur by chance with probability 0.23. Since there were no differences between ipsi- and contralateral fingers, recognition rates for the amputees’ two fingers were pooled for comparison with control subjects (Fig. 3B). A two-way ANOVA (analysis of variance) with letter and group (finger next to amputation, contralateral finger, control right hand, control left hand) shows that there were no significant differences between groups [F(3,25) = 0.119, P = 0.948].
|
Thus far, our analysis has not shown any differences in tactile sensory function between the finger adjacent to the amputation and the homologous finger in the opposite hand, or with age-matched controls. A possibility that we explore next is that the lack of a demonstrable difference is due to a lack of prior experience with such a task. In that case, the cortical changes that are presumed to have followed amputation may have conferred an increased potential for tactile spatial pattern recognition that is manifested as an increased learning rate.
There was a small but significant improvement in performance within the single testing session in both groups. This was analysed by dividing the 78 presentations to each finger into six blocks of 13 letters each. The means for each block and regressions are shown in Fig. 4. The regression slopes were 1.8, 3.0, 1.5 and 1.1% increase per block for the amputee hand, the contralateral hand, and the right and left hands of control subjects, respectively. The slopes were not significantly different from one another [F(3,16) = 0.69, P = 0.43]. Overall, the learning slope was 0.12% per trial and this was significantly different from zero (P < 0.0001). Our testing was limited to a single 2-h session. We cannot rule out the possibility that testing over a longer period might have shown a difference.
|
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
We investigated tactile pattern recognition ability using digits next to amputated digits because of the direct evidence in non-human primates (Merzenich et al., 1984
) and the indirect evidence in humans (Knecht et al., 1996; Borsook et al., 1998; Flor et al., 1998; Moore et al., 2000) that amputation causes an expansion of the cortical representation of the adjacent digits. The present investigation shows that there are no differences in tactile spatial pattern recognition between these digits, the homologous digits in the intact contralateral hand or digits in normal subjects. Even detailed analysis of the confusion matrices and learning rates during the 2-h training period failed to show any differences. There are several possible explanations for our results: (i) there is no significant cortical reorganization 1 year after amputation; (ii) there is significant reorganization with functional significance, but our spatial acuity and pattern recognition tasks failed to detect it; and (iii) there is significant reorganization but it has no effect on sensory capacity. These possibilities are discussed below.
(i) There may have been no significant reorganization 1 year after amputation
Data on the primary somatosensory area cortical representation of digits adjacent to amputated digits suggest that there is an immediate, significant enlargement followed by a decline. Merzenich et al. (1984) showed that, following amputation of one or two digits in four owl monkeys, the cortical representations of the adjacent digits nearly doubled (average 80% enlargement) within 2 months; the cortical representation in one monkey tested again at 8.5 months declined slightly to 
60% enlargement. Manger et al. (1996) mapped the hand representation of a macaque monkey with a 2-year-old amputation of the index finger and found the representations of the adjacent digits to be enlarged (no quantitative estimate). Thus, it seems certain that there was enlargement of the cortical representation of the adjacent digits in our subjects. Furthermore, experimental data from monkeys suggest that the enlargement following amputation is comparable to that following training in a tactile discrimination task. Tactile learning experiments show representational enlargements of 1.4 to 3.4 times for the skin surface used in the learned task (Recanzone et al., 1992; Xerri et al., 1999). Digit amputation results in enlargement ranging from 1.3 to 2.2 times control values (Merzenich et al., 1984). Therefore, the enlargement following amputation is similar to that which follows extensive tactile training.
(ii) There may have been significant reorganization and improved function but our pattern recognition tasks failed to detect it
A potential weakness of this study is that only one aspect of tactile function (spatial acuity) was tested and, therefore, our conclusions may be restricted to that single aspect of tactile function. However, we used tactile letter recognition to study sensory function in the amputees because we believe that the ability to recognize complex spatial stimuli is the sensory capacity most likely to be affected by a change in the cortical representation of a digit. Tactile letter recognition provides an effective measure of both pattern recognition behaviour and acuity (Johnson and Phillips, 1981; Vega-Bermudez et al., 1991). The cortical area devoted to a unit area of the sensory surface (cortical magnification) is strongly correlated with spatial acuity in both the visual and somatosensory systems (Cowey and Rolls, 1974; Sur et al., 1980); therefore, if the enlargement of the cortical representation affects spatial acuity it will be manifested as a change in the accuracy of letter recognition. Furthermore, clinical studies suggest that patients with cortical lesions are most affected in tactile tasks that depend on spatial information (Roland, 1976; Bender et al., 1982; Kim and Choi-Kwon, 1996). An example of this is the finding that dystonic patients who have been shown to have disrupted somatotopic representations (Bara-Jimenez et al., 1998; Elbert et al., 1998) also have deficits in tactile spatial acuity (Bara-Jimenez et al., 2000). Thus, although we cannot state that other sensory functions are unaltered, that would seem to be the most likely and parsimonious hypo thesis. For example, Grusser et al. (2001) have shown that non-painful electrical and thermal sensations are unaffected by the cortical reorganization that accompany amputation.
(iii) There may have been significant reorganization without increased sensory capacity
There are two possible explanations for our results in which the cortex undergoes significant reorganization with no effect on sensory capacity. The first is that there is significant expansion of the afferent projections to the cortex and that the neurones in the deafferented cortex have become responsive to the adjacent digits, but that the sensory function of the cortex is unaltered. That is, the regions once driven by the amputated digits continue to serve their old sensory function, not the sensory function of the adjacent digits. According to this hypothesis, the subject’s sensory capacity in the digits adjacent to the amputation is unaltered because it depends on the same afferent projections as it did before the amputation. The effect of the expanded projections from the digits adjacent to the amputation is to induce sensations appropriate to the original function of the cortex newly driven by the adjacent digits (i.e. sensations in the missing digits).
Phantom limb sensations, which were reported by 13 of the 15 subjects in this study, are evidence that the function of the denervated cortex is unaltered. Experiments on upper-limb amputees show that stimulation of body parts with cortical representations adjacent to the cortical region that normally represent the limb (proximal stump and face) cause phantom sensations (reviewed by Ramachandran and Hirstein, 1998). Moore and Schady (2000) have provided direct evidence of this by stimulating single nerve fascicles proximal to the site of nerve transection in 10 subjects. Even though the cortex previously driven by the body parts innervated by these transected nerves had been remodelled, the microstimulation produced the same sensations as in normal subjects.
Thalamic stimulation in humans undergoing implantation of a thalamic stimulator for treatment of intractable pain supports the same idea (Davis et al., 1998; Lenz et al., 1998). Thalamic neurones in the region originally representing the missing limb have receptive fields in the stump area, as shown previously in monkeys (Merzenich et al., 1984; Manger et al., 1996). However, when these same neurones are stimulated with electrical stimuli they elicit sensations in the missing limb. The discrepancy between projective and receptive fields suggests that the cortex formerly connected to the missing limb still represents it perceptually. Neurones in the deafferented cortex may have new receptive fields but the same old perceptual functions. By analogy, the cortical machinery serving sensory function in the intact limbs may be unchanged.
A second possible explanation for our results, in which the cortex undergoes significant reorganization with no effect on sensory capacity, is that the circuits reorganize in a functionally useful way but there is no evident increase in sensory performance because the factors limiting sensory performance lie elsewhere, either more peripheral or more central than the somatosensory regions that are reorganized following amputation. Indeed, it has been argued that the capacity for tactile spatial resolution in typical human subjects may be limited by the peripheral afferent innervation density (Johnson and Phillips, 1981). However, a recent study of tactile acuity in blind Braille readers has shown that there is enormous room for improvement (Van Boven et al., 2000). Van Boven and colleagues showed that the mean grating orientation discrimination threshold in a group of 15 blind Braille readers was 0.80 mm in the finger used for Braille reading; the comparable mean threshold in an age-matched, sighted control group was 1.46 mm. Thus, a peripheral limit can be ruled out unless the blind subjects had a substantially higher innervation density than the sighted subjects. However, a more central limit cannot be ruled out.
Previous studies
Previous studies suggest that there is no simple correlation between tactile function and measures of changes in cortical representation. For example, increased cortical representation of fingertip surfaces has been observed in monkeys trained in a tactile task (Recanzone et al., 1992; Xerri et al., 1999), in Braille readers (Pascual-Leone and Torres, 1993), and in guitar players (Elbert et al., 1995). Braille readers have also been shown to have better than average tactile spatial acuity (Van Boven et al., 2000). However, improved spatial acuity has also been associated with no change in cortical representation; Braille readers have better than average spatial acuity in fingers adjacent to the dominant reading finger and also better than average spatial acuity on the contralateral hand (Van Boven et al., 2000), even though the evidence suggests that these skin regions do not have increased cortical representations (Pascual-Leone and Torres, 1993). Further more, improved function has been associated with a decrease in cortical representation as shown by Spengler et al. (1997), even though the same tactile paradigm leads to increased cortical representations measured in anaesthetized monkeys after 4–6 weeks of training (Wang et al., 1995). Finally, changes in cortical representation are highly dependent on the subject’s state of attention (Braun et al., 2000).
Conclusion
There is evidence that digit amputation causes expansion of the cortical representation of the adjacent digits, yet our results show that sensory performance in the adjacent digits is unaltered. This suggests there is no obligatory relationship between changes in cortical representation and sensory performance.
|
Acknowledgements |
|---|
We would like to thank Dr Shaw Wilgas and the Curtis Hand Center at the Union Memorial Hospital for their outstanding support which made this work possible. This work was supported by a fellowship from the Robert Wood Johnson Foundation (grant no. 037213) and by NIH grants NS 18787 and NS 38034.
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Bara-Jimenez W, Catalan MJ, Hallett M, Gerloff C. Abnormal somatosensory homunculus in dystonia of the hand. Ann Neurol 1998; 44: 828–31.[Web of Science][Medline]
Bara-Jimenez W, Shelton P, Hallett M. Spatial discrimination is abnormal in focal hand dystonia. Neurology 2000; 55: 1869–73.
Bender MB, Stacy C, Cohen J. Agraphesthesia. A disorder of directional cutaneous kinesthesia or a disorientation in cutaneous space. J Neurol Sci 1982; 53: 531–5.[Web of Science][Medline]
Borsook D, Becerra L, Fishman S, Edwards A, Jennings CL, Stojanovic M, et al. Acute plasticity in the human somatosensory cortex following amputation. Neuroreport 1998; 9: 1013–7.[Web of Science][Medline]
Braun C, Schweizer R, Elbert T, Birbaumer N, Taub E. Differential activation in somatosensory cortex for different discrimination tasks. J Neurosci 2000; 20: 446–50.
Braune S, Schady W. Changes in sensation after nerve injury or amputation: the role of central factors. J Neurol Neurosurg Psychiatry 1993; 56: 393–9.
Cowey A, Rolls ET. Human cortical magnification factor and its relation to visual acuity. Exp Brain Res 1974; 21: 447–54.[Web of Science][Medline]
Craig J, Johnson KO. The two-point threshold: not a measure of tactile spatial resolution. Curr Dir Psychol Sci 2000; 9: 29–32.
Darian-Smith I, Kenins P. Innervation density of mechanoreceptive fibres supplying glabrous skin of the monkey’s index finger. J Physiol (Lond) 1980; 309: 147–55.
Davis KD, Kiss ZH, Luo L, Tasker RR, Lozano AM, Dostrovsky JO. Phantom sensations generated by thalamic microstimulation. Nature 1998; 391: 385–7.[Medline]
Dressler FB. Studies in the psychology of touch. Am J Psychol 1894; 6: 313–68.
Elbert T, Pantev C, Wienbruch C, Rockstroh B, Taub E. Increased cortical representation of the fingers of the left hand in string players. Science 1995; 270: 305–7.
Elbert T, Candia V, Altenmuller E, Rau H, Sterr A, Rockstroh B, et al. Alteration of digital representations in somatosensory cortex in focal hand dystonia. Neuroreport 1998; 9: 3571–5.[Web of Science][Medline]
Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 1995; 375: 482–4.[Medline]
Flor H, Elbert T, Muhlnickel W, Pantev C, Wienbruch C, Taub E. Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees. Exp Brain Res 1998; 119: 205–12.[Web of Science][Medline]
Grusser SM, Winter C, Muhlnickel W, Denke C, Karl A, Villringer K, et al. The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees. Neuroscience 2001; 102: 263–72.[Web of Science][Medline]
Haber WB. Reaction to loss of limb: physiological and psychological aspects. Ann NY Acad Sci 1958; 74: 14–24.
Johansson RS, Vallbo AB. Tactile sensibility in the human hand: relative and absolute densities of four types of mechanoreceptive units in glabrous skin. J Physiol 1979; 286: 293–300.
Johnson KO, Phillips JR. Tactile spatial resolution. I. Two-point discrimination, gap detection, grating resolution, and letter recognition. J Neurophysiol 1981; 46: 1177–92.
Johnson KO, VanBoven RW, Hsiao SS. The perception of two points is not the spatial resolution threshold. In: Bovie J, Hansson P, Lindblom U, editors. Touch Temperature and Pain in Health and Disease: Mechanisms and Assessments. Progress in Pain Research and Management, Vol. 3. Seattle: IASP Press; 1994. p. 389–404.
Karas ND, Boyd SB, Sinn DP. Recovery of neurosensory function following orthognathic surgery. J Oral Maxillofac Surg 1990; 48: 124–34.[Web of Science][Medline]
Kim JS, Choi-Kwon S. Discriminative sensory dysfunction after unilateral stroke. Stroke 1996; 27: 677–82.
Knecht S, Henningsen H, Elbert T, Flor H, Hohling C, Pantev C, et al. Reorganizational and perceptional changes after amputation. Brain 1996; 119: 1213–9.
Knecht S, Henningsen H, Hohling C, Elbert T, Flor H, Pantev C, et al. Plasticity of plasticity? Changes in the pattern of perceptual correlates of reorganization after amputation. Brain 1998; 121: 717–24.
Lenz FA, Gracely RH, Baker FH, Richardson RT, Dougherty PM. Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury. J Comp Neurol 1998; 399: 125–38.[Web of Science][Medline]
Manger PR, Woods TM, Jones EG. Plasticity of the somatosensory cortical map in macaque monkeys after chronic partial amputation of a digit. Proc R Soc Lond B Biol Sci 1996; 263: 933–9.[Medline]
Merzenich MM, Kaas JH, Sur M, Lin CS. Double representation of the body surface within cytoarchitectonic areas 3b and 1 in ‘SI’ in the owl monkey (Aotus trivirgatus). J Comp Neurol 1978; 181: 41–73.[Web of Science][Medline]
Merzenich MM, Nelson RJ, Stryker MP, Cynader MS, Schoppmann A, Zook JM. Somatosensory cortical map changes following digit amputation in adult monkeys. J Comp Neurol 1984; 224: 591–605.[Web of Science][Medline]
Milerian EA, Thachenko VG. The effects of exercise upon the space threshold of tactile differentiation. Sov Psychol Psychiatry 1963; 1: 3–8.
Moore CE, Schady W. Investigation of the functional correlates of reorganization within the human somatosensory cortex. Brain 2000; 123: 1883–95.
Moore CE, Partner A, Sedgwick EM. Cortical focusing is an alternative explanation for improved sensory acuity on an amputation stump. Neurosci Lett 1999; 270: 185–7.[Web of Science][Medline]
Moore CI, Stern CE, Dunbar C, Kostyk SK, Gehi A, Corkin S. Referred phantom sensations and cortical reorganization after spinal cord injury in humans. Proc Natl Acad Sci USA 2000; 97: 14703–8.
Pascual-Leone A, Torres F. Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers. Brain 1993; 116: 39–52.
Ramachandran VS, Hirstein W. The perception of phantom limbs. The D. O. Hebb lecture. [Review]. Brain 1998; 121: 1603–30.
Ramachandran VS, Rogers-Ramachandran D, Stewart M. Perceptual correlates of massive cortical reorganization [letter]. Science 1992; 258: 1159–60.
Recanzone GH, Merzenich MM, Jenkins WM, Grajski KA, Dinse HR. Topographic reorganization of the hand representation in cortical area 3b of owl monkeys trained in a frequency-discrimination task. J Neurophysiol 1992; 67: 1031–56.
Roland E. Astereognosis: tactile discrimination after localized hemispheric lesions in man. Arch Neurol 1976; 33: 543–50.
Sathian K, Zangaladze A. Tactile learning is task specific but transfers between fingers. Percept Psychophys 1997; 59: 119–28.[Web of Science][Medline]
Spengler F, Roberts TP, Poeppel D, Byl N, Wang X, Rowley HA, et al. Learning transfer and neuronal plasticity in humans trained in tactile discrimination. Neurosci Lett 1997; 232: 151–4.[Web of Science][Medline]
Stevens JC, Choo KK. Spatial acuity of the body surface over the life span. Somatosens Mot Res 1996; 13: 153–66.[Web of Science][Medline]
Sur M, Merzenich MM, Kaas JH. Magnification, receptive-field area, and ‘hypercolumn’ size in areas 3b and 1 of somatosensory cortex in owl monkeys. J Neurophysiol 1980; 44: 295–311.
Teuber HL, Kreiger HP, Bender MB. Reorganization of sensory function in amputation stumps: two-point discrimination. Fed Proc 1949; 8: 156.
Van Boven RW, Johnson KO. A psychophysical study of the mechanisms of sensory recovery following nerve injury in humans. Brain 1994; 117: 149–67.
Van Boven RW, Hamilton RH, Kauffman T, Keenan JP, Pascual-Leone A. Tactile spatial resolution in blind Braille readers. Neurology 2000; 54: 2230–6.
Vega-Bermudez F, Johnson KO. Surround suppression in the responses of primate SA1 and RA mechanoreceptive afferents mapped with a probe array. J Neurophysiol 1999; 81: 2711–9.
Vega-Bermudez F, Johnson KO. Differences in spatial acuity between digits. Neurology 2001; 56: 1389–91.
Vega-Bermudez F, Johnson KO, Hsiao SS. Human tactile pattern recognition: active versus passive touch, velocity effects, and patterns of confusion. J Neurophysiol 1991; 65: 531–46.
Wang X, Merzenich MM, Sameshima K, Jenkins WM. Remodelling of hand representation in adult cortex determined by timing of tactile stimulation. Nature 1995; 378: 71–5.[Medline]
Weiss T, Miltner WH, Adler T, Bruckner L, Taub E. Decrease in phantom limb pain associated with prosthesis-induced increased use of an amputation stump in humans. Neurosci Lett 1999; 272: 131–4.[Web of Science][Medline]
Xerri C, Merzenich MM, Jenkins W, Santucci S. Representational plasticity in cortical area 3b paralleling tactual-motor skill acquisition in adult monkeys. Cerebr Cortex 1999; 9: 264–76.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. D. Marasco, A. E. Schultz, and T. A. Kuiken Sensory capacity of reinnervated skin after redirection of amputated upper limb nerves to the chest Brain, June 1, 2009; 132(6): 1441 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Hunter, J. Katz, and K. D. Davis Dissociation of phantom limb phenomena from stump tactile spatial acuity and sensory thresholds Brain, February 1, 2005; 128(2): 308 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Goldreich and I. M. Kanics Tactile Acuity is Enhanced in Blindness J. Neurosci., April 15, 2003; 23(8): 3439 - 3445. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||