The case of clinical trials for convalescent plasma during COVID-19 illustrates important lessons for realizing public sector approaches to biomedical research and development. These lessons, centering on mission, transparency, and spillover effects, can be translated to wider efforts to develop a “public option” for clinical trials.

Anydomainofscientificresearchhasitssustainingorthodoxy. Thatis, research on a problem, whether in astronomy, physics, or biology, is con- ducted against a backdrop of broadly shared assumptions. It is these as- sumptionsthatguideinquiryandprovidethecanonofwhatisreasonable-- of what "makes sense." And it is these shared assumptions that constitute a framework for the interpretation of research results. Research on the problem of how we see is likewise sustained by broadly shared assump- tions, where the current orthodoxy embraces the very general idea that the business of the visual system is to (...) create a detailed replica of the visual world, and that it accomplishes its business via hierarchical organization and by operatingessentiallyindependently of other sensorymodalitiesas well as independently of previous learning, goals, motor planning, and motor execution. (shrink)

A t first glance you might not noorder, which afflicts about 0.5 percent of tice anything odd on meeting a American children. Neither researcher young boy with autism. But if had any knowledge of the other’s work, you try to talk to him, it will and yet by an uncanny coincidence each quickly become obvious that gave the syndrome the same name: autism, something is seriously wrong. He may not which derives from the Greek word autos, make eye contact with (...) you; instead he may meaning “self.” The name is apt, because avoid your gaze and fidget, rock his body the most conspicuous feature of the disorto and fro, or bang his head against the der is a withdrawal from social interacwall. More disconcerting, he may not be tion. More recently, doctors have adopted able to conduct anything remotely resemthe term “autism spectrum disorder” to bling a normal conversation. Even though make it clear that the illness has many rehe can experience emotions such as fear, lated variants that range widely in severity rage and pleasure, he may lack genuine but share some characteristic symptoms. empathy for other people and be oblivious Ever since autism was identified, reto subtle social cues that most children searchers have struggled to determine would pick up effortlessly. what causes it. Scientists know that sus- In the 1940s two physicians—Americeptibility to autism is inherited, although.. (shrink)

Unethical employee behavior (UEB), an important organizational phenomenon, is dynamic and multi-faceted. Recent renewed interest in the role of emotion in ethical decision-making (EDM) suggests that unethical behaviors are neither always rationally derived nor deliberately undertaken. This study explores how to integrate the conscious and nonconscious dimensions of unethical decision-making. By broadening the scope of inquiry, we explore how integral affect—the emotion tied to anticipated decision outcomes for the employee engaging in misconduct—can shed light on UEB. We review related literature (...) on affect and EDM and propose a model in which we assert that at a decision point, an employee experiences multiple integral affects that are either persuasive or dissuasive toward UEB. We further posit that among these integral affects, a dominant integral affect (DIA) emerges, determining the nature and direction of unethical behavior. In addition, our model considers the role of affective residue and the influence of other factors, such as incidental affect, disposition, context, and retrospection, to derive propositions. Our DIA model can help managers gain a comprehensive understanding of how affect, characterized by its locus (self or other orientation) and valence (enhancing or harming), determines the characteristics of UEB. (shrink)

(1) The induced colours led to perceptual grouping and pop-out, (2) a grapheme rendered invisible through ‘crowding’ or lateral masking induced synaesthetic colours — a form of blindsight — and (3) peripherally presented graphemes did not induce colours even when they were clearly visible. Taken collectively, these and other experiments prove conclusively that synaesthesia is a genuine percep- tual phenomenon, not an effect based on memory associations from childhood or on vague metaphorical speech. We identify different subtypes of number–colour synaesthesia (...) and propose that they are caused by hyperconnectivity between col- our and number areas at different stages in processing; lower synaesthetes may have cross-wiring (or cross-activation) within the fusiform gyrus, whereas higher synaesthetes may have cross-activation in the angular gyrus. This hyperconnec- tivity might be caused by a genetic mutation that causes defective pruning of con- nections between brain maps. The mutation may further be expressed selectively (due to transcription factors) in the fusiform or angular gyri, and this may explain the existence of different forms of synaesthesia. If expressed very diffusely, there may be extensive cross-wiring between brain regions that represent abstract concepts, which would explain the link between creativity, metaphor and synaesthesia (and the higher incidence of synaesthesia among artists and poets). Also, hyperconnectivity between the sensory cortex and amygdala would explain the heightened aversion synaesthetes experience when seeing numbers printed in the ‘wrong’ colour. Lastly, kindling (induced hyperconnectivity in the temporal lobes of temporal lobe epilepsy [TLE] patients) may explain the purported higher incidence of synaesthesia in these patients. We conclude with a synaesthesia-based theory. (shrink)

Subjects perceived touch sensations as arising from a table (or a rubber hand) when both the table (or the rubber hand) and their own real hand were repeatedly tapped and stroked in synchrony with the real hand hidden from view. If the table or rubber hand was then ‘injured’, subjects displayed a strong skin conductance response (SCR) even though nothing was done to the real hand. Sensations could even be projected to anatomically impossible locations. The illusion was much less vivid, (...) as indicated by subjective reports and SCR, if the real hand was simultaneously visible during stroking, or if the real hand was hidden but touched asynchronously. The fact that the illusion could be significantly diminished when the real hand was simultaneously visible suggests that the illusion and associated SCRs were due to perceptual assimilation of the table (or rubber hand) into one’s body image rather than associative conditioning. These experiments demonstrate the malleability of body image and the brain’s remarkable capacity for detecting statistical correlations in the sensory input. (shrink)

Almost everyone who has a limb amputated will experience a phantom limb--the vivid impression that the limb is not only still present, but in some cases, painful. There is now a wealth of empirical evidence demonstrating changes in cortical topography in primates following deafferentation or amputation, and this review will attempt to relate these in a systematic way to the clinical phenomenology of phantom limbs. With the advent of non-invasive imaging techniques such as MEG (magnetoencephalogram) and functional MRI, topographical reorganization (...) can also be demonstrated in humans, so that it is now possible to track perceptual changes and changes in cortical topography in individual patients. We suggest, therefore, that these patients provide a valuable opportunity not only for exploring neural plasticity in the adult human brain but also for understanding the relationship between the activity of sensory neurons and conscious experience. We conclude with a theory of phantom limbs, some striking demonstrations of phantoms induced in normal subjects, and some remarks about the relevance of these phenomena to the question of how the brain constructs a 'body image.'. (shrink)

Neurological syndromes in which consciousness seems to malfunction, such as temporal lobe epilepsy, visual scotomas, Charles Bonnet syndrome, and synesthesia offer valuable clues about the normal functions of consciousness and ‘qualia’. An investigation into these syndromes reveals, we argue, that qualia are different from other brain states in that they possess three functional characteristics, which we state in the form of ‘three laws of qualia’. First, they are irrevocable: I cannot simply decide to start seeing the sunset as green, or (...) feel pain as if it were an itch; second, qualia do not always produce the same behaviour: given a set of qualia, we can choose from a potentially infinite set of possible behaviours to execute; and third, qualia endure in short-term memory, as opposed to non-conscious brain states involved in the on-line guidance of behaviour in real time. We suggest that qualia have evolved these and other attributes because of their role in facilitating non-automatic, decision-based action. We also suggest that the apparent epistemic barrier to knowing what qualia another person is experiencing can be overcome by using a ‘bridge’ of neurons; and we offer a hypothesis about the relation between qualia and one's sense of self. (shrink)

Patients with right parietal lesions often deny their paralysis , but do they have "tacit" knowledge of their paralysis? I devised three novel tests to explore this. First, the patients were given a choice between a bimanual task vs a unimanual one . They chose the former on 17 of 18 trials and, surprisingly, showed no frustration or learning despite repeated failed attempts. I conclude that they have no tacit knowledge of paralysis . Second, I used a "virtual reality box" (...) to convey the optical illusion to the patient that she was moving her paralyzed left hand up and down to the rhythm of a metronome, and yet she showed no sign of surprise. Third, I irrigated patient BM′s left ear canal with cold water, a procedure that is known to shift that patient′s spatial frame of reference by stimulating the vestibular system. Surprisingly, this allowed her "repressed" memory of paralysis to come to the surface; she said she had been paralyzed continuously for several days. I suggest that the vestibular stimulation produces these remarkable effects by mimicking REM sleep. These patients also emply a whole arsenal of grossly exaggerated Freudian "defense mechanisms" to account for their paralysis. To explain this, I propose that in normal individuals the left hemisphere ordinarily deals with small, local anomalies by trying to impose consistency but, when the anomaly exceeds threshold, an interaction with the right hemisphere forces a "paradigm shift". A failure of this process, in patients with right hemisphere damage, might partially account for anosognosia. Finally, I present a new conceptual framework that may help link several psychological and neurological phenomena such as Freudian defense mechanisms, vestibular stimulation, anosognosia, memory repression, visual illusions, anterograde amnesia, REM sleep, dreaming, and humor. (shrink)

This article supplements our earlier paper on synaesthesia published in JCS (Ramachandran & Hubbard, 2001a). We discuss the phenomenology of synaesthesia in greater detail, raise several new questions that have emerged from recent studies, and suggest some tentative answers to these questions.

We studied two otherwise normal, synaesthetic subjects who `saw' a speci¢c colour every time they saw a speci¢c number or letter. We conducted four experiments in order to show that this was a genuine perceptual experience rather than merely a memory association. (i)The synaesthetically induced colours could lead to perceptual grouping, even though the inducing numerals or letters did not. (ii)Synaesthetically induced colours were not experienced if the graphemes were presented peripherally. (iii)Roman numerals were ine¡ective: the actual number grapheme was (...) required. (iv)If two graphemes were alternated the induced colours were also seen in alternation. However, colours were no longer experienced if the graphemes were alternated at more than 4 Hz. We propose that grapheme colour synaesthesia arises from `cross-wiring' between the `colour centre' (area V4 or V8)and the `number area', both of which lie in the fusiform gyrus. We also suggest a similar explanation for the representation of metaphors in the brain: hence, the higher incidence of synaesthesia among artists and poets. (shrink)

The mechanism by which humans perceive others differs greatly from how humans perceive inanimate objects. Unlike inanimate objects, humans have the distinct property of being “like me” in the eyes of the observer. This allows us to use the same systems that process knowledge about self-performed actions, self-conceived thoughts, and self-experienced emotions to understand actions, thoughts, and emotions in others. The authors propose that internal simulation mechanisms, such as the mirror neuron system, are necessary for normal development of recognition, imitation, (...) theory of mind, empathy, and language. Additionally, the authors suggest that dysfunctional simulation mechanisms may underlie the social and communicative deficits seen in individuals with autism spectrum disorders. (shrink)

An interview with Anthony Freeman, in which one of the original authors of ‘The Science of Art’ [JCS, 6, No. 6/7, 1999] responds to to ongoing commentary.

Neurological syndromes in which consciousness seems to malfunction, such as temporal lobe epilepsy, visual scotomas, Charles Bonnet syndrome, and synesthesia offer valuable clues about the normal functions of consciousness and ‘qualia’. An investigation into these syndromes reveals, we argue, that qualia are different from other brain states in that they possess three functional characteristics, which we state in the form of ‘three laws of qualia ’ based on a loose analogy with Newton’s three laws of classical mechanics. First, they are (...) irrevocable: I cannot simply decide to start seeing the sunset as green, or feel pain as if it were an itch; second, qualia do not always produce the same behaviour: given a set of qualia, we can choose from a potentially infinite set of possible behaviours to execute; and third, qualia endure in short-term memory, as opposed to non-conscious brain states involved in the on-line guidance of behaviour in real time. We suggest that qualia have evolved these and other attributes (e.g. they are ‘filled in’) because of their role in facilitating non-automatic, decision-based action. We also suggest that the apparent epistemic barrier to knowing what qualia another person is experiencing can be overcome simply by using a ‘bridge ’ of neurons; and we offer a hypothesis about the relation between qualia and one’s sense of self. (shrink)

Summary Apotemnophilia, or body integrity image disorder (BIID), is characterised by a feeling of mismatch between the internal feeling of how one’s body should be and the physical reality of how it actually is. Patients with this condition have an often overwhelming desire for an amputation- of a specific limb at a specific level. Such patients are not psychotic or delusional, however, they do express an inexplicable emotional abhorrence to the limb they wish removed. It is also known that such (...) patients show a left-sided preponderance for their desired amputation. Often they take drastic action to be rid of the offending limb. Given the left-sided bias, emotional rejection and specificity of desired amputation, we suggest that there are clear similarities to be drawn between BIID and somatoparaphrenia. In this rare condition, which follows a right parietal stroke, the patient rejects (usually) his left arm as ‘‘alien’’. We go on to hypothesis that a dysfunction of the right parietal lobe is also the cause of BIID. We suggest that this leads to an uncoupling of the construct of one’s body image in the right parietal lobe from how one’s body physically is. This hypothesis would be amenable to testing by response to cold-water vestibular caloric stimulation, which is known to temporarily treat somatoparaphrenia. It could also be investigated using functional brain imaging and skin conductance response. If correct our hypothesis not only suggests why BIID arises, but also, in caloric stimulation a therapeutic avenue for this chronic and essentially untreatable condition. (shrink)

Jones and Coleman are among a handful of otherwise normal as a child and the number 5 was red and 6 was green. This the- people who have synesthesia. They experience the ordinary ory does not answer why only some people retain such vivid world in extraordinary ways and seem to inhabit a mysterious sensory memories, however. You might _think _of cold when you no-man’s-land between fantasy and reality. For them the sens- look at a picture of an ice cube, (...) but you probably do not feel es—touch, taste, hearing, vision and smell—get mixed up in- cold, no matter how many encounters you may have had with stead of remaining separate. ice and snow during your youth. Modern scientists have known about synesthesia since Another prevalent idea is that synesthetes are merely being 1880, when Francis Galton, a cousin of Charles Darwin, pub- metaphorical when they describe the note C flat as “red” or say lished a paper in _Nature _on the phenomenon. But most have that chicken tastes “pointy”—just as you and I might speak of brushed it aside as fakery, an artifact of drug use (LSD and a “loud” shirt or “sharp” cheddar cheese. Our ordinary lan- mescaline can produce similar effects) or a mere curiosity. guage is replete with such sense-related metaphors, and perhaps About four years ago, however, we and others began to un- synesthetes are just especially gifted in this regard. cover brain processes that could account for synesthesia. Along We began trying to find out whether synesthesia is a gen- the way, we also found new clues to some of the most mysteri- uine sensory experience in 1999. This deceptively simple ques- ous aspects of the human mind, such as the emergence of ab- tion had plagued researchers in this field for decades. One nat- stract thought, metaphor and perhaps even language. ural approach is to start by asking the subjects outright: “Is this A common explanation of synesthesia is that the affected just a memory, or do you actually see the color as if it were right people are simply experiencing childhood memories and asso- in front of you?” When we tried asking this question, we did ciations.. (shrink)

Apotemnophilia, a disorder that blurs the distinction between neurology and psychiatry, is characterized by the intense and longstanding desire for amputation of a speci¢c 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..

Edited proceedings of an interdisciplinary symposium on consciousness held at the University of Cambridge in January 1978. Includes a foreword by Freeman Dyson. Chapter authors: G. Vesey, R.L. Gregory, H.C. Longuet-Higgins, N.K. Humphrey, H.B. Barlow, D.M. MacKay, B.D. Josephson, M. Roth, V.S. Ramachandran, S. Padfield, and (editorial summary only) E. Noakes. A scanned pdf is available from this web site (philpapers.org), while alternative versions more suitable for copying text are available from https://www.repository.cam.ac.uk/handle/1810/245189. -/- Page numbering convention for the pdf (...) version viewed in a pdf viewer is as follows: 'go to page n' accesses the pair of scanned pages 2n and 2n+1. Applicable licence: CC Attribution-NonCommercial-ShareAlike 2.0. (shrink)

Here we outline a simple method of using two mirrors which allows one to stand outside oneself. This method demonstrates that registration of vision with touch and proprioception is crucial for the perception of the corporeal self. Our method may also allow the disassociation of taste from touch, proprioception, and movement.

How the brain constructs one's inner sense of gender iden-tity is poorly understood. On the other hand, the phenomenon of phantom sensations-- the feeling of still having a body-part after amputation--has been much studied. Around 60% of men experience a phantom penis post-penectomy. As transsexuals report a mismatch between their inner gender identity and that of their body, we won-dered what could be learnt from this regarding innate gender-specific body image. We surveyed male-to-female transsexuals regarding the incidence of phantoms post-gender (...) reassignment surgery. Addition-ally, we asked female-to-male transsexuals if they had ever had the sensation of having a penis when there was not one physically there. In post-operative male-to-female transsexuals the incidence of phan-tom penises was significantly reduced at 30%. Remarkably, over 60% of female-to-male transsexuals also reported phantom penises. We explain the absence/presence of phantoms here by postulating a mis-match between the brain's hardwired gender-specific body image and the external somatic gender. Further studies along these lines may provide penetrating insights into the question of how nature and nur-ture interact to produce our brain-based body image. (shrink)

First Published on: 21 June 2007 To cite this Article: Ramachandran, Vilayanur S., McGeoch, Paul D., Williams, Lisa and Arcilla, Gerard (2007) 'Rapid Relief of Thalamic Pain Syndrome Induced by Vestibular Caloric Stimulation', Neurocase, 13:3, 185 - 188 To link to this article: DOI: 10.1080/13554790701450446 URL: http://dx.doi.org/10.1080/13554790701450446..

This article reviews the potential use of visual feedback, focusing on mirror visual feedback, introduced over 15 years ago, for the treatment of many chronic neurological disorders that have long been regarded as intractable such as phantom pain, hemiparesis from stroke and complex regional pain syndrome. Apart from its clinical importance, mirror visual feedback paves the way for a paradigm shift in the way we approach neurological disorders. Instead of resulting entirely from irreversible damage to specialized brain modules, some of (...) them may arise from short-term functional shifts that are potentially reversible. If so, relatively simple therapies can be devised—of which mirror visual feedback is an example—to restore function. (shrink)

��Grapheme-color synaesthesia is a neurological phenomenon in which particular graphemes, such as the numeral 9, automatically induce the simultaneous perception of a particular color, such as the color red. To test whether the concurrent color sensations in graphemecolor synaesthesia are treated as meaningful stimuli, we recorded event-related brain potentials as 8 synaesthetes and 8 matched control subjects read sentences such as ‘‘Looking very clear, the lake was the most beautiful hue of 7.’’ In synaesthetes, but not control subjects, congruous graphemes, (...) compared with incongruous graphemes, elicited a more negative N1 component, a less positive P2 component, and a less negative N400 component. Thus, contextual congruity of synaesthetically induced colors altered the brain response to achromatic graphemes beginning 100 ms postonset, affecting pattern-recognition, perceptual, and meaning-integration processes. The results suggest that grapheme-color synaesthesia is automatic and perceptual in nature and also suggest that the connections between colors and numbers are bidirectional. (shrink)

Summary 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.. (shrink)

The NIH-Moderna mRNA COVID-19 vaccine’s steep price increase raises concerns that this will be the new anchor for continued price hikes and underscores the need for upstream government intervention to enable greater accountability and stewardship of public biomedical research investment.

Several recent lines of inquiry have pointed to the amygdala as a potential lesion site in autism. Because one function of the amygdala may be to produce autonomic arousal at the sight of a significant face, we compared the responses of autistic children to their mothers’ face and to a plain paper cup. Unlike normals, the autistic children as a whole did not show a larger response to the person than to the cup. We also monitored sympathetic activity in autistic (...) children as they engaged in a wide range of everyday behaviours. The children tended to use self-stimulation activities in order to calm hyper-responsive activity of the sympathetic (`fight or flight’) branch of the autonomic nervous system. A small percentage of our autistic subjects had hyporesponsive sympathetic activity, with essentially no electrodermal responses except to self-injurious behaviour. We sketch a hypothesis about autism according to which autistic children use overt behaviour in order to control a malfunctioning autonomic nervous system and suggest that they have learned to avoid using certain processing areas in the temporal lobes. (shrink)

Summary 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 visualkinaesthetic 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. (shrink)