How everyday sounds can trigger strong emotions: ASMR, misophonia and the feeling of wellbeing.

We propose that synesthetic cross-activation between the primary auditory cortex and the anatomically adjacent insula may help explain two puzzling conditions-autonomous sensory meridian response (ASMR) and misophonia-in which quotidian sounds involuntarily trigger strong emotional responses. In ASMR the sounds engender relaxation, while in misophonia they trigger an aversive response. The insula both plays an important role in autonomic nervous system control and integrates multiple interoceptive maps representing the physiological state of the body to substantiate a dynamic representation of emotional wellbeing. We propose that in ASMR cross-activation of the map for affective (sensual) touch leads to an increase in subjective wellbeing and parasympathetic activity. Conversely, in misophonia the effect of the cross-activation is to decrease emotional wellbeing and increase sympathetic activity. Our hypothesis also illuminates the connection between hearing and wellbeing more broadly and helps explain why so many people experience decreased wellbeing from modern urban soundscapes.

Can Vestibular Stimulation be Used to Treat Obesity?: Vestibular stimulation targeting the otoliths could rebalance energy homeostasis to trigger a leaner body habitus and thus treat metabolic syndrome.

It is hypothesized that repeated, non-invasive stimulation of the vestibular (balance) system, via a small electrical current to the skin behind the ears, will cause the brain centers that control energy homeostasis to shift the body toward a leaner physique. This is because these centers integrate multiple inputs to, in effect, fix a set-point for body fat, which though difficult to alter is not immutable. They will interpret repeated stimulation of the parts of the vestibular system that detect acceleration as a state of chronic activity. During such a physiologically challenging time it is preferable, from an energy homeostasis viewpoint, to both utilize fat reserves, and reduce the volume of these reserves and thus the energy cost of carrying them around. Hence, this type of vestibular stimulation could potentially be a therapeutic option for metabolic syndrome disorders such as obesity. This hypothesis is eminently testable via a clinical trial.

Primary somatosensory cortex hand representation dynamically modulated by motor output.

The brain's primary motor and primary somatosensory cortices are generally viewed as functionally distinct entities. Here we show by means of magnetoencephalography with a phantom-limb patient, that movement of the phantom hand leads to a change in the response of the primary somatosensory cortex to tactile stimulation. This change correlates with the described conscious perception and suggests a greater degree of functional unification between the primary motor and somatosensory cortices than is currently realized. We suggest that this may reflect the evolution of this part of the human brain, which is thought to have occurred from an undifferentiated sensorimotor cortex.

The appearance of new phantom fingers post-amputation in a phocomelus.

We report the unusual case of a woman with right upper limb phocomelia who, post-amputation of her right hand following trauma, sprouted a phantom hand that contained five digits, including a phantom thumb and index finger that had been absent since her birth. These two phantom digits were initially half normal size, however, more than three decades later, with mirror visual feedback treatment, she was able to elongate them to normal length. This suggests that a hardwired representation of a complete hand had always been present in her brain, but inhibited by the presence of afferents from the phocomelic hand. Amputation of the phocomelic hand then led to disinhibition of this dormant representation, and the emergence of a phantom hand with five fingers, which was then further enhanced by false visual feedback from a mirror. The case powerfully demonstrates the interaction of nature and nurture in creating and sustaining body image.

Xenomelia: a new right parietal lobe syndrome.

BACKGROUND: Damage to the right parietal lobe has long been associated with various disorders of body image. The authors have recently suggested that an unusual behavioural condition in which otherwise rational individuals desire the amputation of a healthy limb might also arise from right parietal dysfunction. METHODS: Four subjects who desired the amputation of healthy legs (two right, one left and one, at first, bilateral and then left only) were recruited and underwent magnetoencephalography (MEG) scans during tactile stimulation of sites above and below the desired amputation line. Regions of interest (ROIs) in each hemisphere (superior parietal lobule (SPL), inferior parietal lobule, S1, M1, insula, premotor cortex and precuneus) were defined using FreeSurfer software. RESULTS: Analysis of average MEG activity across the 40-140 ms post-stimulation timeframe was carried out using an unpaired t test. This revealed significantly reduced activation only in the right SPL ROI for the subjects' affected legs when compared with both subjects' unaffected legs and that of controls. CONCLUSIONS: The right SPL is a cortical area that appears ideally placed to unify disparate sensory inputs to create a coherent sense of having a body. The authors propose that inadequate activation of the right SPL leads to the unnatural situation in which the sufferers can feel the limb in question being touched without it actually incorporating into their body image, with a resulting desire for amputation. The authors introduce the term 'xenomelia' as a more appropriate name than apotemnophilia or body integrity identity disorder, for what appears to be an unrecognised right parietal lobe syndrome.

Anti-diabetic effect of vestibular stimulation is mediated via AMP-activated protein kinase.

There is abundant animal evidence that vestibular stimulation, particularly of the otolith organs, can trigger a shift in body mass composition towards a leaner physique. One way of non-invasively stimulating the otolith organs is via a small electrical current applied to the skin behind the ears. This technique is called vestibular nerve stimulation, or VeNS, and is believed to have a good safety profile. Thus, it has previously been argued that VeNS could be used in human health as a means of treating the complications of metabolic syndrome, such as obesity and type 2 diabetes mellitus. Weight loss itself is known to improve diabetic control, however, tantalizing evidence is now emerging that the improvements seen in the glycemic control of type 2 diabetics who undergo repeated vestibular stimulation are significantly better than would be expected on the basis of weight loss alone. As vestibular stimulation has been shown to increase levels of an anti-inflammatory protein, called sirtuin 1, we hypothesize here that VeNS will increase levels of an associated enzyme called AMP-activated protein kinase (AMPK). AMPK plays an important role in glucose and fat metabolism and is activated by exercise, as well as being a known target for certain anti-diabetic drugs. This hypothesis is readily amenable to clinical testing as specific assays for testing human AMPK are available. If substantiated, then this hypothesis could prove an important clinical insight and potentially offer a new treatment avenue for patients with type 2 diabetes; a condition which remains a major cause of morbidity and premature mortality worldwide.

Size reduction using Mirror Visual Feedback (MVF) reduces phantom pain.

Following limb amputation patients continue to feel the vivid presence of a phantom limb. A majority of patients also experience pain in the phantom and sometimes (as in our case DS) the pain is severe. Remarkably we find that optically 'resurrecting' the phantom with a mirror and using a lens to make the phantom appear to shrink caused the pain to 'shrink' as well.

Does cortical reorganisation explain the enduring popularity of foot-binding in medieval China?

In the past, it used to be taught that neural connections were essentially fixed and unchangeable from birth. However, in recent years it has become clear that, in fact, the brain possesses a tremendous degree of latent plasticity, and significant reorganisation can occur in response to changes in the body. This is clearly demonstrated by the phenomenon of phantom limbs--the vivid sensation of a limb still being present despite its amputation. After removal of a limb, the region of the somatosensory cortex that is deafferented is "taken over" by afferents that normally innervate the adjacent areas of cortex. This cross-activation between the different areas of the somatosensory cortex plays a large role in creating these phantom sensations. The same is also true of the motor cortex. After amputation of a limb, the deprived area of motor cortex does not remain nonfunctional but instead becomes active in the control of adjacent non-amputated muscle groups. It is notable that the genital area of the somatosensory cortex and the pelvic floor muscle area of the motor cortex are dislocated and in both cases lie adjacent to the foot area. Foot-binding of Chinese girls started around the 10th Century AD and for the next millennium was an extremely prevalent and popular custom. Mothers would tightly wrap their daughters' feet from about the age of six years, thus preventing the feet from maturing normally. The aim of the process was to create as small feet as possible, since this would greatly enhance a girl's matrimonial prospects. Historians of the period have noted that Chinese men viewed foot-binding as conducive to better sexual intercourse because they believed that women with bound feet had vaginas that were more highly muscled and sensitive. We hypothesise that since foot-binding kept a girl's feet small and atrophic, this resulted in underutilisation of the foot areas of her somatosensory and motor cortices. This resulted in cross-activation between the redundant foot cortex and the adjacent genital areas in her brain. Hence women with bound feet devoted a disproportionately large area of the sensory and motor cortices of their brains to their genitalia and pelvic floor musculature, which made them more sensitive and pleasurable lovers. This caused Chinese men to prefer their sexual partners to have bound feet, which resulted in the enduring popularity of foot-binding in China over the last millennium.

Occurrence of phantom genitalia after gender reassignment surgery.

Transsexuals are individuals who identify as a member of the gender opposite to that which they are born. Many transsexuals report that they have always had a feeling of a mismatch between their inner gender-based "body image" and that of their body's actual physical form. Often transsexuals undergo gender reassignment surgery to convert their bodies to the sex they feel they should have been born. The vivid sensation of still having a limb although it has been amputated, a phantom limb, was first described by Weir Mitchell over a century ago. The same phenomenon is also occurs after amputation of the penis or a breast. Around 60% of men who have had to have their penis amputated for cancer will experience a phantom penis. It has recently been shown that a significant factor in these phantom sensations is "cross-activation" between the de-afferented cortex and surrounding areas. Despite this it also known that much of our body image is innately "hard-wired" into our brains; congenitally limbless patients can still experience phantom sensations. We hypothesise that, perhaps due to a dissociation during embryological development, the brains of transsexuals are "hard-wired" in manner, which is opposite to that of their biological sex. We go on to predict that male-to-female transsexuals will be much less likely to experience a phantom penis than a "normal" man who has had his penis amputated for another reason. The same will be true of female-to-male transsexuals who have had breast removal surgery. We also predict that some female-to-male transsexuals will have a phantom penis even although there is not one physically there. We believe that this is an easily testable hypothesis, which, if correct, would offer insights into both the basis of transsexuality and provide farther evidence that we have a gender specific body image, with a strong innate component that is "hard-wired" into our brains. This would furnish us with a better understanding the mechanism by which nature and nurture interact to link the brain-based internal body image with external sexual morphology. We would emphasise here that transsexuality should not be regarded as "abnormal" but instead as part of the spectrum of human behaviour.

Can vestibular caloric stimulation be used to treat Dejerine-Roussy Syndrome?

Dejerine-Roussy Syndrome (thalamic pain syndrome) is characterised by the development of chronic, severe pain in the contralateral half of the body after a thalamic stroke. It is often largely refractory to treatment. In this paper we draw together a number of disparate pieces of knowledge to propose a novel therapy for this condition. There is already substantial evidence from neurological disease that the brain's left hemisphere serves to "smooth over" discrepancies in sensory input in order to impose order and maintain the existing view of the world around us. Conversely the right hemisphere acts on discrepant sensory input to cause a re-evaluation of one's world view. Based on this, it was proposed by Harris that pain is an organism's response to discrepancy. It is already known that cold water vestibular caloric irrigation of the ear leads to activation of a number of areas in the contralateral hemisphere - including the insular cortex. Indeed it is known that - presumably because it also activates the right parietal lobe - this technique can be used to treat anosognosia, somatoparaphrenia and neglect. In addition to being activated by vestibular stimulation, it has been shown that the posterior insula has a somatotopic map of the body for painful stimuli. We speculate that phylogenetically, close anatomical proximity between the pain and vestibular areas of the brain makes sense; as it would allow modulation of otherwise disabling chronic pain, when the organism makes a sudden movement to avoid a predator. Given Harris's theory we propose that post stroke thalamic pain may represent a pathological amplification of the thalamic posterior insular response to pain due to discrepant sensory input. Based on all the above we go on to hypothesise that cold vestibular caloric stimulation will be effective in treating Dejerine-Roussy Syndrome and we present provisional evidence from two patients which supports this conclusion. If our hypothesis is correct this will be the first time in clinical neurology that a chronic disorder, long considered refractory to treatment, is relieved by a simple non-invasive procedure.

Apraxia, metaphor and mirror neurons.

Ideomotor apraxia is a cognitive disorder in which the patient loses the ability to accurately perform learned, skilled actions. This is despite normal limb power and coordination. It has long been known that left supramarginal gyrus lesions cause bilateral upper limb apraxia and it was proposed that this area stored a visual-kinaesthetic image of the skilled action, which was translated elsewhere in the brain into the pre-requisite movement formula. We hypothesise that, rather than these two functions occurring separately, both are complementary functions of chains of "mirror neurons" within the left inferior parietal lobe. We go on to propose that this neural mechanism in the supramarginal gyrus and its projection zones, which originally evolved to allow the creation of a direct map between vision and movement, was subsequently exapted to allow other sorts of cross-domain mapping and in particular those sorts of abstract re-conceptualisation, such as metaphor, that make mankind unique.

Dynamic reorganization of referred sensations by movements of phantom limbs.

After amputation of an arm the sensory map of the body changes radically, causing the sensory input from face to 'invade' the original hand area in the brain. As a result, touching the face of the amputee evokes tactile sensations on the phantom. These sensory referrals from the face to phantom hand occur in a stable, topographically organized manner. We now find that volitional movements of the phantom cause striking, systematic shifts in the map along the direction of movement. We conclude that the reorganization of maps is based partly on reversible inhibition of ordinarily silent synapses, not entirely on new anatomical connections. This finding further highlights the dynamic nature of the brain on remarkably short-time scales.

Sexual and food preference in apotemnophilia and anorexia: interactions between 'beliefs' and 'needs' regulated by two-way connections between body image and limbic structures.

Apotemnophilia straddles the boundary between neurology and psychiatry. It is a condition in which individuals experience the strong and specific desire for amputation of a healthy limb. Research suggests this disorder may be of neurological origin, specifically that the body image centers of the brain lack a cortical representation for a particular limb. A curious aspect of this condition is that sufferers often report an attraction to amputees in addition to desiring their own limb be removed. We postulate that sexual 'aesthetic preference' for certain body morphology is dictated in all individuals in part by the cortical representation of one's body image.

Apotemnophilia: a neurological disorder.

Apotemnophilia, a disorder that blurs the distinction between neurology and psychiatry, is characterized by the intense and longstanding desire for amputation of a specific limb. Here we present evidence from two individuals suggestive that this condition, long thought to be entirely psychological in origin, actually has a neurological basis. We found heightened skin conductance response to pinprick below the desired line of amputation. We propose apotemnophilia arises from congenital dysfunction of the right superior parietal lobule and its connection with the insula.

Rapid relief of thalamic pain syndrome induced by vestibular caloric stimulation.

Central post-stroke pain syndrome develops in a minority of patients following a stroke. The most usual causative lesion involves the lateral thalamus. The classic presentation is of severe, unrelenting pain that involves the entire contralateral half of the body. It is largely refractory to current treatments. We found that in two patients with this condition their pain was substantially improved by vestibular caloric stimulation, whereas placebo procedures had no effect. We proposed that this is because vestibular stimulation activates the posterior insula, which in turn inhibits the generation of pain in the anterior cingulate.