“I awoke to consciousness in a hospital-tent. I got hold of my own identity in a moment or two, and was suddenly aware of a sharp cramp in my left leg. I tried to get at it to rub it with my single arm, but, finding myself too weak, hailed an attendant. “Just rub my left calf,” said I, “if you please.”
Calf?” said he. “You ain’t none. It’s took off.”
“I know better,” said I. “I have pain in both legs.”
“Wall, I never!” said he. “You ain’t got nary leg.”
As I did not believe him, he threw off the covers, and, to my horror, showed me that I had suffered amputation of both thighs, very high up.
“That will do,” said I, faintly. “ From The Case of George Dedlow, S. Wier Mitchell, 1866.
Silas Wier Mitchell’s account of the injuries suffered by the titular Dedlow in the American civil war was a work of fiction, yet the sensation and pain associated with amputated limbs is all too real. Commonly referred to as ‘phantom limb sensation’, it is estimated that 80% of amputees suffer from pain which they believe to come from the no-longer present limb. While the phenomenon was first described by the French surgeon Ambroise Paré in the 16th century, it took the popular account of Dedlow by Wier Mitchell in 19th century to truly establish the phenomenon within western medicine. While almost 150 years have passed since its publication, treatments for phantom limb pain are still for the most part unsuccessful, hampered no doubt by the slow realization that, instead of focusing on the peripheral vestiges of the vanished limb, the key to unlocking phantom phenomenology lies not in the body, but in the brain.
To understand the genesis of phantom sensation it is useful to appreciate something of the neuroscience underlying brain development; namely, how does the growing brain ‘know’ how to wire itself up? The human brain is estimated to contain 100 thousand million neurons (the number 1 followed by eleven zeros). Because a typical neuron forms ~1,000 synaptic connections to other neurons, the total number of synapses in the brain is estimated to be 100 trillion (the number 1 followed by 14 zeros). In the late 1970s, faced with the complexity of adult neuronal connectivity, the French neuroscientist John-Paul Changeux stated that it would be impossible for the brain to develop if it was forced to rely on genetic information – there simply wasn’t enough in the genome to specify the myriad of wiring that makes the mature mind. In a memorable comparison, he estimated that the spermatozoa would need to be the size of a golf ball to carry all the extra information needed – a situation that would cause some problems to the continuation of Homo Sapiens. Summarizing the work of a number of philosophers, psychologists and neuroscientists before him, Changeux recognized the need for a marriage between nature and nurture: nature could supply the building materials, but the architectural plans must come from nurture. This general idea was gradually refined by experimental work: general principles of development resided in the genome, and specified a chemical landscape of trails and paths that growing fibres could use to pathfind to their targets. Yet the problem of connectivity remained: upon arrival, how would a given axon (cable through which neuron connect to one another) know to connect to a given dendrite (protrusions on neurons cell bodies, contacted by neurotransmitters emitted from axons)? One solution, initially proposed by theoreticians, was to ensure that growing fibers connected to a multitude of targets, and use the environment, through its interactions with the brain via the senses, to ensure that the most useful connections remain whilst others wither and die. Thus nature, through genetics, is taught by nurture, via the environment. While this simple relating of the nature/nurture debate does not do justice to its incredible sophistication, this general principle that more connections are created by the developing brain that survive into adulthood is generally agreed upon – and thus the environment plays a significant part in the initial wiring of the brain. That it could also play a significant part in changing adult brain connectivity is a notion that has only gained prominence in the last twenty years, and continues to court controversy.
To return to phantoms: before suggesting how the sensation of a missing part of the body might be experienced, it is worthwhile to briefly discuss how information from our bodies is processed by the brain normally. Like other sources of sensory information like sound and vision, somesthesis relies upon energy acting upon a specialized sense organ, or receptor, with the energy being transduced into a form that the organism can use. All nervous systems use electrochemical mechanisms for communication (although some species use electrical synapses as well) and so share basic features. Mammals, however, rarely rely on a single sensory modality. Each of these senses may have a number of receptor sub-classes, each of which in turn may use different transduction mechanisms, or produce a different response from the organism. Whether the energy is photons, sound waves, or pressure on a touch receptor, ALL information is transformed into these signals. It is also noteworthy to remember that we are only able to sense something in the outside world if there is a receptor available or tuned to it – as the great german physicist and experimental psychologist Helmholtz stated, ‘ the character of our perceptions is conditioned as much by our senses themselves as by external things’.
Figure 1: Physiology of the somatosensory system. Left: Positions of receptors in the periphery, showing both touch and muscle/joint receptors. Right: The path from the periphery to the brain, showing ascending information from the body terminating in primary somatosensory cortex.
Body signals come from the skin, and the muscles and joints. They pass through the spinal cord, connect with a relay point within the cord, pass through a deep blob of cell bodies in the brain called the thalamus, and then project upwards to the cerebral cortex, to an area called the primary somatosensory cortex (SI). What makes things particularly fascinating is the mature order of terminations of information from the body to area SI is not random – neighbourhood relationships are maintained, such that nerve cells (neurons) that receive information from the middle finger lie in close proximity to those that are ‘wired’ to receive information from both the index and ring fingers. While there are discontinuities (the ‘hand’ area of this map abuts the ‘face’ area, which will become significant below), to all intents and purposes area SI contains a ‘map’ of the body’s surface. The discovery of these maps in audition, vision and touch was one of the greatest achievements of sensory neuroscience in the 20th century, as they explained a wealth of clinical observations: from the gradual ‘walk’ of an epileptic fit from the periphery to the centre of the body; to the remarkable spatial preciseness of visual loss secondary to damage to the visual map.
Figure 2. The ‘mapping’ of stimulus features from the receptor organs to the brain. From Schreiner and Dinse, 2003.
We say that the parts of the brain that contain such maps contain topographic mappings of the world – however, these maps are not simple point to point representations where information along a given dimension (with touch this is position of stimulation on the body, while with audition it relates, more abstractly, to the frequency of the sound itself), as even at this early stage the maps contain specializations. For example, because the fingertips contain the most touch receptors (and are correspondingly extremely sensitive), a larger amount of the brain is needed to process this incoming information. Thus the area of SI which is sensitive to information coming from the hand is far larger than the physical size of the hands would suggest. Conversely, the trunk region has only sparse touch receptor density when compared to other regions, and so it is relatively small within SI (see Figure 3).
Figure 3. The ‘sensory homunculus’, or the relative amounts of primary somatosensory cortex given over to information coming from parts of the body. Note the relative difference between the amount of cortex used to represent the face and hands verses the trunk.
In 1981 the seizing of a group of macaque monkeys from the laboratories of Edward Taub (due to alleged animal cruelty charges, subsequently quashed in court) provided a unique opportunity to study how the brain reacted to the loss of input from a limb. Due to ongoing legal issues, Taub’s monkeys, who had all had the peripheral nerves from their forelimbs cut, were not studied again until roughly ten years later. After such a long time it was assumed that areas of SI that previously received information from the ‘silent’ limb would too be silent at best and shrunken and lifeless at worst. Instead, using recording electrodes to listen to neuronal activity within this area, it was found that these regions were responsive when the animals were stimulated in the region of the chin and cheek. Such an example of change in the adult brain was startling. The disconnected region did not remain disconnected: the brains of the monkeys had undergone ‘reorganisation’, either through the activity of previously-existing ‘weak’ connections or through the growth of new ones. And while the monkeys couldn’t report on whether they felt any phantoms to go with their reorganization, it seemed something of a coincidence that the very areas that could now evoke activity in the silent, limbless, zone lay next next-door to it in SI. Could human phantom sensations be due to a similar reorganization?
Yet a problem remained in linking the animal work to the reports of human amputees: invasive brain mapping of the type carried out in the monkeys is rarely, if ever, used on normal human volunteers. It was therefore somewhat surreptitious that the 1991 publication of the Silver Spring follow-up study dove-tailed with the increasing use of non-invasive technologies to map human brains, in particular, with a study by VS Ramachandran and colleagues that linked phantom limb sufferer’s phenomenological perceptions with the remapping of their sensory cortices. Using magnetoencephalography (MEG), Ramachandran was able to show that stimulating areas of the face and upper arm activated regions in somatosensory cortex that would previously have received input from the missing limb. It is common to use terms such as ‘invaded’ to describe how face and arm cortex have managed to activate the hand, yet it is equally plausible that previously weak connections (less an invasion – more a fifth column) from arm and face to the hand area actually underlies this effect.
Ramachandran’s data showed that it was possible to show a correlation between phantom sensations and activity within specific areas of the brain. While the exact relationship between this remapping of sensory cortex and phantom pain has remained the subject of active study (see Flor et al., 1995, for an example), this study proved that the phantom experience had an organic basis; and, furthermore, that it seemed to be best explained by a change in sensory experience (the loss of the arm) having an effect centrally. The phantom was an example of the brain’s ability in adult life to adapt and change according to the environment around it – a process which is usually known as plasticity.
Plasticity was first coined by the great American psychologist, the brother of the great American novelist Henry James, William James, in 1890. In his massive, sprawling opus The Principles of Psychology James defined plasticity as ‘the possession of a structure weak enough to yield an influence but strong enough not to yield all at once’. Structures with the potential for change, in other words, but with the good sense to wait for the appropriate moment. Modern neurophysiology has updated James’ terms and supplied mechanistic explanations (see Hebb’s The Organisation of Behaviour), yet his explanation remains near definitive. The experimental confirmation that endogenous neuronal plasticity underlies phantom sensations (and, it is currently thought, phantom pain) bodes well for the use of novel therapeutic measures to reverse such pathological plasticities, and exorcise the phantoms for good.he phenomenon of the post-amputation ‘phantom limb’ was first described medically by the French military surgeon Paré in the 16th Century, and continues to attract both public interest and empirical study in the 21st. In this talk I will outline a history of studies and observations of the ‘phantom menace’, focusing on the recent use of non-invasive neuroimaging techniques to provide unique descriptions of the neurobiological mechanisms underlying it.