The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees

doi:10.1016/S0306-4522(00)00491-7

Neuroscience

Volume 102, Issue 2, 15 January 2001, Pages 263-272

https://doi.org/10.1016/S0306-4522(00)00491-7 Get rights and content

Abstract

In this study 16 unilateral upper extremity amputees participated in a comprehensive psychophysiological examination that included the assessment of painful and non-painful phantom and stump sensations, thermal and electric perception as well as two-point discrimination thresholds, the detailed analysis of referred sensation and the measurement of reorganizational changes in primary somatosensory cortex using neuroelectric source imaging. Reorganization of the primary somatosensory cortex was associated with increased habitual phantom limb pain, telescoping, non-painful stump sensations and painful referred sensation induced by painful stimulation. It was unrelated to non-painful phantom sensations, non-painful referred sensation elicited by painful or non-painful stimulation, painful referred sensation elicited by non-painful stimulation, perception thresholds and stump pain.

These data substantiate the hypothesis that painful and non-painful phantom phenomena are mediated by different neural substrates.

Section snippets

Participants

Sixteen unilateral upper extremity amputees, 14 male and two female, were studied. Their mean age was 57.5 years (S.D.=10.68, range 39–74). Thirteen participants were right-handed, three had no clear hand preference, and none was left-handed. Mean age at the time of the amputation was 21.83 years (S.D.=10.95, range 2–47). The average time since amputation was 50.33 years (S.D.=15.14, range 15–65). The mean stump length was 33.38 cm (S.D.=18.67, range 0–54). Forty-four per cent of the sample had

Painful and non-painful phantom phenomena and cortical reorganization

Eleven of the 16 amputees in the study suffered from phantom limb pain. They showed a significantly larger amount of reorganization of primary somatosensory cortex as assessed with the Euclidean distance measure (M=20.25 mm, S.D.=5.15) than the remaining five amputees without phantom limb pain [M=3.36 mm, S.D.=2.87; t(14)=6.79, P<0.001]. Phantom limb pain as assessed by the MPI Pain Intensity Scale was highly correlated with cortical reorganization (r₁₆=0.91, P<0.001).

Non-painful phantom

Painful and non-painful phantom sensations

Cortical reorganization in primary somatosensory cortex was positively associated with phantom limb pain, and this phenomenon seems to be very stable.1., 5., 6., 22., 27. Non-painful phantom sensations were not consistently related to these plastic cortical changes. When a significant correlation was found, it was entirely mediated by phantom limb pain. We assume that other cortical areas, for example, the posterior parietal cortex and SII, may be involved in the subjective awareness of a still

Conclusions

The data of this study suggest that reorganizational changes in SI appear to be mainly related to spontaneously occurring or induced phantom limb pain, whereas no significant relationship was found with non-painful phantom phenomena and perception thresholds. The stable relationship between phantom limb pain and cortical reorganization1., 5., 6., 16., 22., 27. and our present findings suggest that plastic changes in the primary somatosensory cortex may be an important neural correlate of

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (Fl 156/16).

References (40)

C.D Gilbert
Rapid dynamic changes in adult cerebral cortex
Curr. Opin. Neurobiol.
(1993)
R.D Kerns et al.
The West Haven Multidimensional Pain Inventory (MPI)
Pain
(1985)
R Melzack
Phantom limbs and the concept of a neuromatrix
Trends Neurosci.
(1990)
R.C Oldfield
The assessment and analysis of handedness: the Edinburgh Inventory
Neuropsychologia
(1971)
R.A Sherman et al.
Chronic phantom and stump pain among American veterans: results of a survey
Pain
(1984)
R.A Sherman
Stump and phantom limb pain: mechanisms and syndromes
Neurol. Clin.
(1989)
N Birbaumer et al.
Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization
J. Neurosci.
(1997)
D Borsook et al.
Acute plasticity in the human somatosensory cortex following amputation
NeuroReport
(1998)
B Cronholm
Phantom limbs in amputees
Acta Psychiatr. Scand. Suppl.
(1951)
T Elbert et al.
Extensive reorganization of the somatosensory cortex in adult humans after nervous system injury
NeuroReport
(1994)

H Flor et al.

Phantom limb pain as a perceptual correlate of cortical reorganization

Nature

(1995)

H Flor et al.

Cortical reorganization and phantom phenomena in congenital and traumatic upper extremity amputees

Expl Brain Res.

(1998)

H Flor et al.

A neural substrate for nonpainful phantom limb phenomena

NeuroReport

(2000)

Flor H. (2000) The functional organization of the brain in chronic pain. In Nervous System Plasticity and Pain:...

C.C Gallen et al.

Neuromagnetic mapping of brain function

Radiology

(1993)

P.E Garraghty et al.

NMDA Receptors and plasticity in adult primate somatosensory cortex

J. comp. Neurol.

(1996)

P.W Halligan et al.

Thumb in cheek? Sensory reorganization and perceptual plasticity after limb amputation

NeuroReport

(1993)

W.B Haber

Effects of loss of limb on sensory functions

J. Psychol.

(1955)

T.S Jensen et al.

Immediate and long-term phantom limb pain in amputees: incidence, clinical characteristics and relationship to pre-amputation limb pain

Pain

(1983)

J.H Kaas

Plasticity of sensory and motor maps in adult mammals

A. Rev. Neurosci.

(1991)

Cited by (155)

Reassessing referral of touch following peripheral deafferentation: The role of contextual bias
2023, Cortex
Some amputees have been famously reported to perceive facial touch as arising from their phantom hand. These referred sensations have since been replicated across multiple neurological disorders and were classically interpreted as a perceptual correlate of cortical plasticity. Common to all these and related studies is that participants might have been influenced in their self-reports by the experimental design or related contextual biases. Here, we investigated whether referred sensations reports might be confounded by demand characteristics (e.g., compliance, expectation, suggestion). Unilateral upper-limb amputees (N = 18), congenital one-handers (N = 19), and two-handers (N = 22) were repeatedly stimulated with computer-controlled vibrations on 10 body-parts and asked to report the occurrence of any concurrent sensations on their hand(s). To further manipulate expectations, we gave participants the suggestion that some of these vibrations had a higher probability to evoke referred sensations. We also assessed similarity between (phantom) hand and face representation in primary somatosensory cortex (S1), using functional Magnetic Resonance Imaging (fMRI) multivariate representational similarity analysis. We replicated robust reports of referred sensations in amputees towards their phantom hand; however, the frequency and distribution of reported referred sensations were similar across groups. Moreover, referred sensations were evoked by stimulation of multiple body-parts and similarly reported on both the intact and phantom hand in amputees. Face-to-phantom-hand representational similarity was not different in amputees' missing hand region, compared with controls. These findings weaken the interpretation of referred sensations as a perceptual correlate of S1 plasticity and reveal the need to account for contextual biases when evaluating anomalous perceptual phenomena.
Facilitatory Effect of Intermittent Repetitive Transcranial Magnetic Stimulation on Perceptual Distortion of the Face
2022, Journal of Pain
Orofacial pain patients often report that the painful facial area is “swollen” without clinical signs - known as perceptual distortion (PD). The neuromodulatory effect of facilitatory repetitive transcranial magnetic stimulation (rTMS) on PD in healthy individuals was investigated, to provide further support that the primary somatosensory cortex (SI) is involved in facial PD. Participants were allocated to active (n = 26) or sham (n = 26) rTMS group in this case-control study. PD was induced experimentally by injecting local anesthesia (LA) in the right infraorbital region. PD was measured at baseline, 6 min after LA, immediately, 20 and 40 min after rTMS. Intermittent theta-burst stimulation (iTBS) as active rTMS and sham rTMS was applied to the face representation area of SI at 10 min after LA. The magnitude of PD was compared between the groups. The magnitude of PD significantly increased immediately after iTBS compared with sham rTMS (P = .009). The PD was significantly higher immediately after iTBS compared to 6 min after LA (P = .004) in the active rTMS group, but not in the sham rTMS group (P = .054). iTBS applied to a somatotopic-relevant cortical region appears to facilitate facial PD further supporting the involvement of SI in the processing of one´s own face and PD.
This study provides information on neural substrate responsible for processing of perceptual distortion of the face which is speculated to contribute to the chronification of orofacial pain. The findings of this study may aid in mechanism-based management of the condition in orofacial pain disorders and possibly other chronic pain states.
The Prevalence and Characteristics of Phantom Limb Pain and Non-Painful Phantom Phenomena in a Nationwide Survey of 3,374 Unilateral Limb Amputees
2022, Journal of Pain
The experience of phantom limb pain (PLP) is a common consequence of limb amputation, resulting in severe impairments of the affected person. Previous studies have shown that several factors such as age at or site of amputation are associated with the emergence and maintenance of PLP. In this cross-sectional study we assessed the presence of several phantom phenomena including PLP and other amputation-related information in a sample of 3,374 unilateral upper and lower limb amputees. Clinical and demographic variables (age at amputation, level of amputation) explained 10.6% of the variance in PLP and perceptual variables (intensity of phantom limb sensation [PLS], referred sensations, intensity of telescoping, residual limb pain [RLP] intensity) explained 16.9% of the variance. These variables were specific for PLP and not for RLP. These results suggest that distinct variables are associated with PLP (age at amputation, level of amputation, PLS intensity, referred sensations, intensity of telescoping, RLP intensity) and RLP (PLP intensity) and point at partly different mechanisms for the emergence and maintenance of PLP and RLP.
Clinical/demographic variables as well as perceptual variables are 2 major components related to PLP and explain ∼11% and ∼17% of the variance. These results could potentially help clinicians to understand which factors may contribute to chronic phantom limb pain.
Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations.
2020, Psychiatry Research - Neuroimaging
The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.
Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain
2020, Clinical Neurophysiology
Citation Excerpt :
Cortical representation changes are frequently observed in PLP patient studies; however, mixed results are observed. The cortical remapping theory states that after limb amputation, the central control area of the amputated limb becomes deafferented, and the potential unmasking of previously silent connections leads to functional and cortical reorganization (Flor et al., 1995, Grüsser et al., 2001, Montoya et al., 1998, Ramachandran et al., 1992). In this regard, Flor et al. (1995) and Raffin et al. (2016) showed that cortical changes (maladaptive reorganization) were closely associated with PLP: they reported a shift of nearby lip representation area into the deafferented hand region in upper-limb amputees.
The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity.
Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging.
We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04).
There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity.
These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.
5.42 - Phantom Limb Pain
2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
When put into the context of sensory experience and perception, the phenomenon of phantom limb pain may seem puzzling at first. The term describes the feeling of pain in a body part that has been lost in an accidental or clinical amputation. In amputees with phantom limb pain, the sensation of pain exists in ostensible absence of a painful stimulus. At first sight, this seems to fulfill the definition of a hallucination, as there is a perceptual sensation without any object or other stimulus in the physical world to elicit it. However, as this chapter will show, the sensation of phantom limb pain is more complicated and much more akin to normative perception than to hallucinatory experiences.

View all citing articles on Scopus

^*: Corresponding author

View full text

The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees

Abstract

Section snippets

Participants

Painful and non-painful phantom phenomena and cortical reorganization

Painful and non-painful phantom sensations

Conclusions

Acknowledgements

Curr. Opin. Neurobiol.

Pain

Trends Neurosci.

Neuropsychologia

Pain

Neurol. Clin.

Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization

J. Neurosci.

Acute plasticity in the human somatosensory cortex following amputation

NeuroReport

Phantom limbs in amputees

Acta Psychiatr. Scand. Suppl.

Extensive reorganization of the somatosensory cortex in adult humans after nervous system injury

NeuroReport

Phantom limb pain as a perceptual correlate of cortical reorganization

Nature

Cortical reorganization and phantom phenomena in congenital and traumatic upper extremity amputees

Expl Brain Res.

A neural substrate for nonpainful phantom limb phenomena

NeuroReport

Neuromagnetic mapping of brain function

Radiology

NMDA Receptors and plasticity in adult primate somatosensory cortex

J. comp. Neurol.

Thumb in cheek? Sensory reorganization and perceptual plasticity after limb amputation

NeuroReport

Effects of loss of limb on sensory functions

J. Psychol.

Immediate and long-term phantom limb pain in amputees: incidence, clinical characteristics and relationship to pre-amputation limb pain

Pain

Plasticity of sensory and motor maps in adult mammals

A. Rev. Neurosci.