- Cogito ergo sum, I think therefore I am. Rene Descartes' famous proposition relies upon a logic that assumes the preeminence of a rational mind that primarily thinks, but in this age, we increasingly appreciate that we also feel, experience, perceive the world. For instance, how many times do we hear people express their views by feeling? I feel you're mistaken, my feeling is that this is true, or false. Opinions are often expressed as feelings, and indeed, the stronger the view, the stronger is the feeling with which it's associated, the stronger the conviction with which it's held. Our mental domains, thoughts, mood, sensation, perception, cognition, attention, memory, and insight, how we view ourselves, all contribute to how we view the world, how we see ourselves, gauge our place within that world, the apparent reality of that world, as well as the reality of ourselves, and the boundaries between ourselves and that outside world. All of these domains work together to guide our behaviors, so if any of these complex functions break down and fail to act in a coordinated way, behavior can become disturbed. In this lecture, I will present evidence that supports an alternative or embellished view from that of Descartes, that, in fact, our minds do not assume rationality by default, but rational thought and logical judgment is a development, a transformation built upon a mind that is by default illogical, irrational, a mind that can be regarded as psychotic. Psychosis as the default mental state may seem a strange proposal to many, we're used to thinking that we are intrinsically logical, purposeful, and capable of sound judgment. I do not challenge the belief that we are so capable, but that to achieve such a state of rationality requires great effort, largely inhibitory on that natural tendency to be disordered and chaotic. In developing the argument, I intend present some evidence within the following outline: what do we mean by psychosis, what is clinical psychosis, I'll present epidemiological evidence that psychotic phenomena are prevalent in the general population, I'll give examples of naturally occurring psychosis, such as hypnagogic and hypnopompic hallucinations, what occurs during sensory deprivation, and delusions, I'll explore what science might tell us about how these psychotic phenomena arise, with reference to the neuroscience of sensory input, perception, and attentional cognitive inhibition, I'll briefly ask why we have the capacity to have strange beliefs, with reference to vigilance and paranoia, and finally, highlight some implications of these ideas for health and society, before concluding. So what do we mean by psychosis? Psychosis is a fragmentation of the psyche where connections between mental domains become distorted or disconnected such that mental activity becomes disturbed. We can define psychosis as a mental state where people experience a different world, different from what most of us may experience, a world which is perhaps mysterious, strange, where the so-called normal coordinates and tangible features of a world familiar to most of us seem unfamiliar, a world that may seem perplexing and perhaps unfathomable, a world populated with experiences like hallucinations that arise unbidden and outside our control, a frightening world. In concert with hallucinations are delusions, thoughts and beliefs that defy our understanding, that appear unlikely, or odd, or bizarre, but that are held with complete conviction and unaltered by evidence to the contrary. I'll now describe some features of clinical psychosis seen in patients, and later, will attempt to persuade you that at least some of these features lie very close to the surface of our conscious awareness. Fortunately, we've moved a long way from what some people may still see as madness. The German psychiatrist Kurt Schneider described features characteristic of schizophrenia as first-rank symptoms. Hallucinations are commonly experienced, such as seeing things or hearing voices when there's no outside source. Another common feature of psychosis is paranoia. Paranoia is where the person interprets the outside world as pointing at or observing the person, and this is only happening to that person, no one else. This is often accompanied by discomfort or overt fear, they may become convinced that they are being monitored or subject to a sinister plot against them that's unique to them. These thoughts can assume a delusional intensity, absolute conviction in the absence of objective evidence. Sometimes, if someone is depressed, their thinking may be unduly negative about themselves and their place in the world. They may, for instance, think their life isn't worth living, and that the world is better off without them. And if this reaches delusional intensity, they may think they're personally responsible for all the ills of the world. At the other extreme, if manic, they may become grandiose and think that they have special powers to control the Sun or Moon, for instance. Some people may find it difficult to communicate in language, and insight is lost, the ability to look at these symptoms objectively and put them down to an illness that requires help or treatment. As psychiatrists, we learn from our patients, so perhaps the best way to exemplify psychosis is from the descriptions people give us when in that state. And here, I pay tribute to the artist Bryan Charnley, who had the courage to paint a series of self-portraits as he descended into psychosis. The paintings by Bryan Charnley provide poignant examples of links between what the artist refers to and these clinical descriptions. This is his self-portrait before he became unwell, and after some days, he says he feels very paranoid,"The person upstairs was reading my mind"and speaking back to me"to keep me in a sort of ego crucifixion."The large rabbit ear is because I was confused"and extremely sensitive to human voices,"like a wild animal." So he tells us that he's more acutely aware of voices and experiences auditory-verbal hallucinations. Kurt Schneider described these as first-rank symptoms, hearing voices, referring to the person in the third person, making a running commentary on their actions, or hearing their own thoughts. The state of paranoia is experienced as though the world refers to the person with special personal significance, so-called salience, in a way that's often persecutory in nature, and this is frequently accompanied by extreme anxiety. Here, Bryan Charnley expresses paranoia, when he says,"I feel like a target for people's cruel remarks."The nails in my eyes express that I cannot see,"whereas other people seem to have extrasensory perception,"and I am blind in this respect." Other first-rank symptoms include delusional perception, where a normal perception becomes linked with a delusional interpretation, for example, a red traffic light is interpreted as meaning that the person is being followed. And there are abnormalities of thought possession, as in thought insertion, other people's thoughts are beamed into my head, thought withdrawal, where my thoughts are taken out of my head, and thought broadcast, where my personal thoughts are broadcast out loud, like on a radio. Bryan Charnley tells us about these effects on his mood, and he describes thought broadcasting. He says, "The blue of the portrait is there"because I felt depressed"through cutting back on the antidepressants."I was pleased I was able to express"such a purely mental concept as thought broadcasting"by the simple device of turning the brain into a mouth." And here he describes paranoia again,"People laughed at me when this happened,"or let me know it was for real by acute remarks." He refers to the effect on his social life, as he says,"I continued my retreat from social contact." And here he says,"My mind seemed to be thought broadcasting very severely"and it was beyond my will to do anything about it."I summed this up by painting my brain as an enormous mouth"acting independently of me." He goes on to say,"The eggs have been emptied"like a head stripped of its contents."It has nothing left in it, no more secrets,"they went to satisfy somebody's appetite,"somebody that has power over me." So he's beginning to feel a loss of self, all of which makes him more depressed, as he says,"Needless to say, I feel suicidal,"so I painted in van Gogh's crows"from his final suicide picture of the 'Wheat Field.'"Birds come from eggs,"so the crows can also be like my thoughts flying away," thought withdrawal."All of this gossip increases my fears." Finally, Kurt Schneider describes special types of delusion where the person is no longer in control of self, experienced as made feelings, my feelings are made by others, made impulses, if I do something, it's not my will to do it, and made actions, my actions are controlled directly by someone else. And these symptoms are exemplified by Bryan Charnley, who says this is,"An extremely complicated picture,"as I feel I'm closing in"on the essential image of my schizophrenia."I am transparent,"I make crazy attempts at some sort of control"over what's become an impossible situation,"the man with the control stick," in the middle of the picture."My brain, my ego is transfixed by nails"as the Christ who couldn't move freely on the cross"without severe pain."I realize that the fear caused by the anger,"symbolized by the red, tied beast, muzzled,"is because the anger arises"through not being able to reply to the abuse heaped on me."My senses are being bent by fear into hallucinations." At the end, he refers to anger, and perhaps describes

"He's mad at you, he's mad,"is cause of fear,"the anger being in a latent, unconscious state,"but giving rise to paranoia,"which in turn gives rise to characteristic"schizophrenic hallucinations and symptoms." These are his final words

"The cards are no good that I'm holding,"unless they are from another world." Having given examples of clinical psychosis, let us now consider how common similar psychotic symptoms are in the general population. An extensive meta-analysis of 47 from 2,442 screened papers reported the prevalence of psychotic phenomena in healthy populations, and here we see that these phenomena are actually relatively common, more so as one moves criteria from strict psychosis, 3%, to psychotic experiences, 8%. And worldwide health surveys, shown here, report psychotic experiences in up to a third of nonclinical samples. For instance, this is a sample of 1,777 young male and female students, you see the demographics here, and in this sample, when asked, have you ever felt as if thoughts in your head are being taken away from you, nearly 20% reported at least sometimes, when asked, have you ever felt as if you're under the control of some force or power other than yourself, nearly 20% said at least sometimes, and 25% experienced auditory-verbal hallucinations. Each of these phenomena qualify as first-rank symptoms of schizophrenia. That means that psychiatrists regard them as significant to make a diagnosis of this condition. So psychotic symptoms occur in the general population, and everyone has the potential to become psychotic. Factors that determine what tips people over the edge from psychotic experiences to psychosis is a combination of genes and environment. When people who've reported psychotic experiences are followed up over three years, the risk of developing the disorder is estimated to be about a factor of 25, And at a group level, one can consider population A and population B. The proportion of those exceeding the psychosis threshold in population A is shown in red, but population B has a genetic predisposition, and many stressful life events, that push a greater proportion of them past the psychosis threshold, which is showed in the blue, hatched area. Thus, in summary, according to these studies, up to a third of healthy people have symptoms that psychiatrists regard as indicative of a psychotic illness. It doesn't mean that these individuals have the illness as such, as they appear not to be so affected by psychotic experiences to seek professional help, however, it does indicate that a high proportion of people have the tendency to develop and exhibit psychotic symptoms. And these symptoms are not necessarily benign, and often associated with significant distress. I give one example of this distress here, this is a structural MRI brain scan of a person who was so distressed by their hallucinations they tried to gouge out their brain with a knife, leaving the tip of the knife blade in their skull, and you can see the effect of that at the top of the scan. So when are healthy people most susceptible to psychotic phenomena, and why? Here I turn to the example of hypnagogic and hypnopompic hallucinations. Many people have transient hallucinations on falling asleep and on waking, so-called hypnagogic and hypnopompic hallucinations, and as we've seen, hallucinations occur in those in a clinical psychotic state. These experiences in otherwise healthy people may not be as vivid as in those with a clinical condition, but they are commonly experienced. Studies report prevalence rates of hypnagogic and hypnopompic hallucinations in up to a third of the healthy population, and lifetime prevalence up to two thirds. These can be experienced in any sensory modality, as shown here. And further, to exemplify their commonality, we have many examples from literature and art through the centuries. Common example include the incubus, witch pressing, and the mare, or hag. The incubus and mare can be seen here in "The Nightmare," by Henry Fuseli. Goya alludes to psychotic content in his painting "The Sleep of Reason Produces Monsters." Edvard Munch describes how even a normal scene in full wakefulness provokes, in his words,"an endless scream passing through nature." And Salvador Dali paints a dramatic scene full of psychotic symbolism in that transient moment between sleep and waking up, a hypnopompic hallucination. So these hallucinations occur while the higher cognitive control of the brain is asleep, but on waking, becomes aware of current experience, and before the brain starts to fully process external sensory input, hence this transient window of semi-wakefulness is when we are aware, consciously, of the messages sent from the default brain. These hallucinate occur not only during transient periods of falling asleep or waking, but also in full wakefulness, for example seeing ghosts or apparitions, that I'll mention later. Perhaps the condition that provides the most natural environment within which to observe the default brain is one of complete sensory deprivation. Without any external input, the brain relies completely upon its own self-generated activity for any thinking or experience. So what happens under these circumstances? It is of course extremely difficult to create such an environment, divest of all sensory inputs, except in carefully controlled experimental conditions, conditions that, when prolonged, are extremely unpleasant. In the 1950s and 1960s, a number of experimental studies were performed to investigate the mental state changes consequent upon such deprivation. The Canadian psychologist Donald Hebb invited participants to spend time a soundproofed environment, surrounded by pillows to minimize sound, wearing translucent visors, and cotton gloves, and cardboard cuffs to prevent sensory stimulation. Within minutes, many became anxious and disturbed, and experienced distressing hallucinations. These were described as points of light evolving into formed shapes and forms such as squirrels marching with sacks over their heads, dogs, babies, or eyeglasses processing down the street. They heard music, felt sensations of being shot in the arm, and electric shocks. And importantly for providing a evidence of the default mental state, is their statements that they had little control over these experiences. Hebb wrote that, "The results were very unsettling to us,"to find, in your own laboratory,"that merely taking away"the usual sights, sounds, and bodily context"from a healthy university student for a few days"can shake him right down to the base." Was he referring to what we could now consider the default mental state? More recent experimental evidence of the psychotogenic effects of sensory deprivation come from a recent study by Daniel and Mason. They selected 24 high-hallucination-prone versus 22 low-hallucination-prone people and measured hallucinations before and after only 25 minutes of complete auditory and visual sensory deprivation in an anechoic chamber. Even after this short period of sensory deprivation, psychotic experiences increased, especially in those who were prone to hallucinations. Psychotic experiences are shown in this graph on the y-axis, and you see they increase after only 25 minutes of sensory deprivation, particularly in those who are prone to hallucinations, shown in the blue line. We also learn from these experiments that participants developed attentional techniques to control the hallucinations, and that, in addition to hallucinations, they lost touch with reality, an area I'll return to. And we have examples from the real world for the reason that sensory deprivation is so unpleasant, it's been used as a means of torture, used for centuries, before, during the time of Thomas Gresham, and to the present day, We have, for instance, firsthand accounts from prisoners kept in solitary confinement about the terrors they experienced at the hands of their own brains' unfettered activity, unconstrained by external stimulation, which we all need to keep ourselves sane. Accounts from those subjected to solitary isolation include that from Sarah Shourd, accused of spying and kept in solitary confinement for over a year. She described how her mind began to slip after about two months, she heard phantom footsteps, and saw flashing lights, and spent most of her day crouched on all fours, listening through a gap in the door."In the periphery of my vision," she said,"I began to see flashing lights,"only to jerk my head around"to find that nothing was there." And we don't have to look hard for other real-life examples of the adverse effect of sensory deprivation on our mental state, for example, the trapped Chilean miners in 2010, some of whom began to hallucinate, and the effects of isolation during the COVID pandemic that increased paranoia. So in order to explain these phenomena, perhaps we need to look at examples of how we perceive or misperceive the world around us under normal conditions, and here I give the example of illusions, where the brain generates a reality, making inferences about the external world that differs from objective reality. These illusions can be quite robust and instantiated in the brain, for instance, the Herring Illusion, these red lines are parallel, but we see them as bulging in the middle, and the Ebbinghaus Illusion, the orange disk appears larger when surrounded by smaller, gray discs. And the extent to which we may experience the Ebbinghaus Illusion may relate to our underlying brain matter. This study, for instance, correlated the amount of gray matter in the visual cortex, shown in red, with the intensity with which the Ebbinghaus Illusion was perceived, shown underneath. The less the volume of visual cortical gray matter, the more the illusion was perceived, implying that the less brain substance we have to process the outside world, the more likely we are to perceive an illusory world. The McGurk Illusion exemplifies how consistently our brain gets it wrong even in full non-psychotic consciousness. I invite you to listen to the lady's voice first with your eyes open, and then close your eyes, and see what you hear.- Okay, here we go. Da-da, da-da, da-da, da-da, da-da.- [Peter] Now close your eyes.- Ba-ba, ba-ba, ba-ba, ba-ba.- [Peter] And open them again.- Da-da- You're actually hearing ba-ba, but when you see the lips move, you actually hear something else,'cause the brain gets it wrong. Our brains, that provide the substrate for all our mental life, also provide a bias, which we may be unaware of. So here, in my Sheffield research laboratory, we showed, using neuroimaging, how our brain gives priority to the female over the male voice. Irrespective of whether you are male or female listener, female voices activate our brains more than male voices. So we see, on the left, the yellow area is the area in the hearing part of the brain that is more activated by female voices than male voices, taking account of obvious confounders like volume and pitch. And of course, this is one reason why familiar announcements, you see on the right, such as this one, use a female voice,'cause that's what gets our attention. And to demonstrate that we hear what we expect to hear, we performed an experiment of imaging people while listening to identical sound under two visual conditions, on seeing a tranquil beach scene and a non-tranquil motorway scene. People heard the beach as softer than the motorway, and the hearing systems of the brain were more connected to areas considered to be those related to meditation or tranquility, despite the auditory input being identical in both conditions. This is the motorway scene, and this is what we hear.(engines hum) And the beach scene, this is what you hear.(waves crash) Identical auditory input, but because of the different visual context, the brain areas differ, and here, these represent those in the hearing cortex that are more connected to areas associated with meditation and tranquility across the brain. So even when fully conscious in a normal environment, our brains can mislead us by giving us perceptions that differ from external reality. So how might these phenomena arise? And here, we turn to the neuroscience of sensory processing and cognitive inhibition. If we return to the example of auditory hallucinations, we're told by people who experience them that they're heard like we hear external voices. Neuroimaging studies show us that when people hear auditory hallucinations, they activate the same parts of the brain that normally process external speech. And in the first functional magnetic imaging study of its kind, we reported that hearing hallucinations activated the same part of the brain that perceives voices from outside the head, shown here in red. So the person was actually experiencing auditory hallucinations in the scanner, and the red area is the same part of the brain that you normally use to process external speech. And along the bottom here, along the blocks, you see the periods of hallucinations, and the signal in the auditory cortex above shows it increases coincident with the experience of hallucinations, and drops down when the hallucinations stop. And here we scanned a group of patients actively hallucinating voices and examined the brain's response to externally presented speech, and the same group re-scanned after recovery, and we found that when people are actively hallucinating voices, the brain's response to external speech was actually less than when they had no hallucinations. So while they're hallucinating, external speech is less than when they're not hallucinating. And this phenomenon we explained as the saturation hypothesis, where auditory hallucinations compete with external speech for common neurophysiological resources, so when people are actively hallucinating voices, the presentation of external speech actually lessens the brain's response to the hallucinations. And this is consistent with coping strategies patients adopt to alleviate their hallucinations, activities like listening to music, talking to themselves, or shouting, activity that is going to stimulate the auditory cortex and inhibit their hallucinations. And the saturation hypothesis can be regarded as a feedback mechanism, whereby external speech and the brain signal responsible for auditory hallucinations compete with each other for the brain processing capacity, illustrated here. We have the temporal lobe, which is the hearing part of the brain, activated, leading to hallucinations, driven by hallucination signal from the brain and also external speech, and there's a negative feedback between the two. But the model presupposes that the hearing apparatus of the brain generates intrinsic signal, which we also demonstrated using functional MRI. The colored areas show spontaneous brain activity in the hearing cortex during acoustic silence. These observations support the notion that the brain generates its own signal responsible for hallucinations, and that the signal is inhibited by external sensory input. So perhaps external sensory input is needed to inhibit the natural tendency for hallucinations, as we saw in those who were sensorially deprived. But we're not passive recipients of signals from the environment, we attend to features of interest to us, a common example is the cocktail party effect, whereby we can hone in on conversations of interest, and attention actually enhances brain activity in the relevant sensory processing region. And I illustrate this with two neuroimaging studies, one showing how attending to one visual field enhances brain activity in the visual cortex, so here we're looking at the back of the brain, the visual cortex, and if you attend to the left visual field, it activates the right visual cortex, if you attend to the right visual field, it activates the left visual cortex, and this is an effect of attention, not just the sensory input. And this is a similar study we performed using functional MRI, and when we presented people with auditory and visual stimuli, and the task was to either attend to what they heard or attend to what they saw, and in this series of brain scans, you see, in one individual, that the slices through the auditory cortex, in the top row, and identical slices in the bottom row, and when they had to attend to what they heard, you see that, in yellow, there's more activity in the auditory cortex than when they attended to what they saw. And this is despite the fact there's an identical input of auditory signal in both conditions, we're seeing the direct effect of attention enhancing the hearing apparatus of the brain. And these observations fit with the clinical descriptions from patients, who find that they can alter their hallucinations by concentrating on them. And this attentional enhancement was also seen in healthy participants who developed hallucinations due to sensory deprivation, where their hallucinations increased when they attended to them. And so we can further develop the hallucination model. Here, the hallucinations result from activity in the hearing cortex, the temporal lobe of the brain, the spontaneous brain activity drives the hallucination signal whilst inhibited by external speech, as we've seen before, attention, shown as A, sets the threshold at which the system is activated and leads to the overall auditory perception. And as we know, the largely inhibitory cerebral cortex, comprising 80% of brain gray matter, these ideas can be summarized by Kenneth Hugdahl's paper, entitled "Auditory Hallucinations"as Failure of Top-down Cortical Inhibitory Control"of Bottom-up Intrinsic Perceptual Processes," the bottom-up perceptual processes being the default brain. Does neuroscience tell us something about how the brain controls our decisions? We saw in the painting of Bryan Charnley how he felt controlled by the outside agency, the man with the control stick controlling his actions, so this leads the question, are we free to make decisions? I give one example of this neuroimaging study that follows the idea of Benjamin Libet that our brains make decisions for us before we're aware of making them. And this was a functional neuroimaging study where the task was to move the right or left index finger and indicate the moment that decision was made. The red vertical line shows the moment of decision, and we can see significant brain activity, indicated in green, four to five seconds before the person is aware of having made the decision, so the activity you can see in green to the left of the red vertical line, where the decision was made. And this contrasts with activity in the motor cortex, shown in orange, that occurs after the decision was made. So whatever the default brain is doing, it's doing it before we're aware of making our own decisions, so are we under our brain's control without being aware of it, does the unconscious default brain prime our decision making? And we don't need to look at science, but T.S. Eliot hinted at this gap between cognitive awareness and behavior in his poem. Here, the poet talks about the shadow between intention and action, the gap where the default brain could intervene,"Between the idea and the reality,"between the motion and the act"falls the shadow."Between the conception and the creation,"between the emotion and the response"falls the shadow." So far, then, I've proposed psychotic experiences are common, we all have the capacity for psychosis. While asleep and during sensory deprivation, unimpeded by our higher cortical inhibitions, our experiences share features with psychosis, hallucinations, and what we perceive depends on what our brains expect, illusions, or give attention to, hearing female voices or tranquil scenes, and we've seen the default brain may prime our decisions. So what about other characteristics of psychosis, delusions? We all have the capacity for strange beliefs, and this was eloquently said by Francis Bacon 400 years ago:"The human understanding is not composed of dry light,"but is subject to influence from the will and emotions,"a fact that creates fanciful knowledge."Man prefers to believe what he wants to be true." We have countless examples of strange beliefs, and to harbor beliefs without objective evidence could even be said to be an intrinsic part of our make-up. For instance, some still ask the question, is the Earth flat, and try and explain why images appear to show it's spherical, studies indicate that many people have seen ghosts, and also believe in their existence in the outside world, ghosts exist according to several YouGov polls, 30% of the British, and in a sample of 1,293 American adults, 40% of the North American public believe in ghosts. Seeing ghosts is not universal, but common, and occurs usually under certain conditions. If one imagines spending a dark, blustery night in an old, creaky house, alone, it's easy to understand how odd sounds of creaking beams or flickering lights can be misinterpreted as a presence, particularly if there's a history of such phenomena. Sometimes, such visual or auditory perceptions can be misinterpretations of actual objects or hallucinations in the absence of such a stimulus. We may be susceptible to these experiences when anxious and in high arousal as our autonomic nervous system can prime us to be hypervigilant, and so more easily misinterpret events in our environment. It's easy to conclude that these reactions may have had an evolutionary advantage to alert us to predatory threats, and indeed, may alert us today to a potential attack, but in the absence of such an external threat, can prime our brains to overreact, and perhaps generate a threat that doesn't exist in external space. Which all leads to the big question, what is reality? Even hard science physicists question how we think. In quantum mechanics, we change the nature of matter by the very fact of observing it. That leads to the question posed on the front page of "The New Scientist," is there an objective reality at all? If the brain creates its own reality, then is there an evolutionary advantage to thinking in certain ways, and I take the example of vigilance as a possible precursor of paranoia. Over 1.5 million years of evolution, Homo sapiens has needed to be vigilant to survive predators. Now, it's essential to avoid being mugged or run over by a car, we have unconscious autonomic alerting systems, the fight and flight reaction to direct attention, but limited cognitive attentional resources. As social animals, we can share these, so others alert us to danger while we can perform different tasks. And I'll give one example of the advantage of how we cooperate to conserve vigilance. Gomes and Semin studied people during a task requiring attention to a central target whilst also remaining vigilant to a peripheral threat. The results showed that in the presence of another person, vigilance to the external threat was less and attention to the central task more, hence, when alone, we're more vigilant, and when with other, cooperative people, less vigilant, so we can concentrate on other useful tasks. We've evolved to focus our attentional resources and to share the need for vigilance to maximize our group safety from predators, so perhaps the cost of vigilance is the potential to be paranoid. What then are the implications of these observations for health? In summary, we can say psychotic experiences are common, they may be associated with the risk of psychosis. It's important to identify and detect psychotic experiences early, as these may indicate risk factors that need assessment and treatment. Loneliness and isolation is now considered a major mental and public health issue. A better understanding of the balance of vulnerability versus resilience to psychosis could help reorientate how we prioritize clinical care to those who need it most. So in conclusion, thinking is assumed as rational, and awareness that we think insight as evidence of sanity, but we are subjective, human beings, we all perceive things differently, and fundamental to our make-up is the capacity to believe in things beyond reason. In psychosis, the mind loses the natural assumptions we may make about the world we experience, and hence may experience a different world. The mind is beset with hallucinations and delusions, we refer to people with psychosis as being out of touch with reality. But in the absence of external sensory input, the default brain approximates to clinical psychosis, psychosis that needs external sensory input and cognitive inhibition to inhibit its natural expression. Perhaps we should realize that we're all in a dynamic, delicate equilibrium that keeps us in a balance between psychosis and rationality and that as we understand more about perception, cognition, and human behavior, we should consider that rational thought is fragile, and be aware that the motivation for our thinking, by default, is irrational. We may not be aware of it, but our default mental state affect our whole experience of the world, hence our propensity to believe weird things, or things that don't seem weird, but have no basis in rational thought, but which are held with absolute conviction without objective evidence. Sometimes it's apparent that our brains make incorrect assumptions, illusions, but we seem unaware of our default mental state, except perhaps on waking or falling asleep, or in the unusual situation of complete sensory deprivation. Even in science, we try to make sense of the world through the refraction of our thoughts and senses that often conflict with each other and may not make sense. Hence I put to you examples of psychotic thinking are commonplace in everyday life, that we do not think completely rationally, but we are basically psychotic by default, but that tendency to psychosis is inhibited to a greater or lesser degree, hence it is of some societal relevance to register how thin the boundary is between sanity and madness, to understand the factors that lead from one to the other, and to appreciate the frailty of rational thought. And perhaps, then, rather than ask why do people develop psychosis, we should ask ourselves why don't we all develop psychosis. And with this, I leave the final words to those of Bryan Charnley,"because, after all,"we are all victims of insanity." Thank you very much.(audience applauds)- Thank you very much, Professor Woodruff, for a really fascinating lecture. We've got lots of questions online, and no doubt there are quite a few in the hall too. I'm going to kick off with one of the online questions here,

"There is a genetic link in some cases,"as schizophrenia often runs in families."The onset is often puberty,"could there be a hormonal cause,"such as the flight or fight hormones being out of control?"- The answer's always yes, these things are possible, and of course we are subject to the influence of our hormones as much as we are by our environments, our upbringing, genes, of course, and genes and environment interact from the moment we're conceived right through to the end of life, and our brain is changing minute by minute, all our brains will be different at the end of this lecture than they were at the beginning because our synapses have made new connections, new memories, et cetera, and it's all under the influence of our body's milieu, hormones being very important in that. There is evidence that, actually, one reason why schizophrenia develops later, and is generally more benign in females than males, is because of estrogen, which is considered to be a protective hormone for the brain. So I think the answer is yes, and it's extremely complicated, and there's a dynamic interaction between genes, and the enzymes, and hormones that are coded for genes with our environment throughout life, and of course that affects our brain and our behavior.- First, thank you very much for a very insightful lecture, we appreciate. I want to refer to a particular point, and ask a question regarding the qualification of a clinical state of psychosis for hearing voices. If we look to the wider science, we know about quantum physics, we know there are people who are able to hear electricity, because electricity is waves, and they are seriously affected. We know, in the boson theory, that everything around us is moving. So my question is, why do you quantify hearing voices as determined as being psychosis as a clinical state rather than something which we might not be able to understand or hear? Because if someone else is not able to hear, it doesn't mean that the other person is clinically sick. And we know that, in the world, there are animals with different types of capabilities, so our limitation of knowledge, would it be enough to quantify that the other person doesn't hear certain voices, or things, or sounds, my question is.- I suppose we have to start somewhere, and we start with what we commonly regard as the limits of human ability, or the limits of our own range of perceptions. Our hearing has a range which is not as high as dogs, so dogs can hear things which we can't because they have a much more acute hearing at a higher frequency than we do. But I think we understand the spectrum of certain measures of human activity and human abilities, and so I think that's where we start from. And I guess those who have other experiences, I guess you're implying that maybe they have abilities which most of us don't have, which may be the case, but I think, whatever they are, every thought, and experience, and perception is instantiated in our brains,'cause without brains, we have no life, so if only we knew what the correlate was, we'd be able to measure it.- You focused a lot on brain scans in the PowerPoint, and I was wondering, we hear a lot about certain parts of the brain being switched on when certain things happen, and I was wondering, the whole brain, people who have been active doing something, what is it that we mean when we say a part of the brain is switched on? Is it electrical activity, is it chemical activity? And the different experiments, will they all have been looking for the same kind of activity? Does being switched on in one experiment mean the same thing as a region of the brain being switched on in another experiment? Does that make sense?- Yes, sure. Each technique has its own measures, you're correct. The one with the visual attention was actually more an electrical map of the brain activity, most of the others were functional magnetic resonance imaging, which is related to brain activity that is correlated with differences in blood flow to different parts of the brain. When we have a particular network of the brain that's more active, there's more blood flow to that region, and so there's a difference in the ratio between oxygenated and deoxygenated hemoglobin, which has different magnetic properties, and that what's being picked up by the scan. So there are different techniques, but broadly speaking, they have different resolutions for timing, and so on, but I was just trying to keep it relatively non-technical.- There's a very interesting question online here, which asks,"The samples underlying the statistics you've presented"are for Western developed nations."What is known about psychosis"in the developing world nations?"- One of the studies which was there in the world literature was one from the Middle East, which is relatively recent, and I think the results from that are fairly consistent with the findings of psychotic experiences found in the Western cultures. But yes, most of the research is done in the West, and we need to do more research in other countries and in other cultures,'cause, obviously, the cultural context that people live in will affect their experiences. I would say, though, that I think, generally speaking, brains are biological systems that are fairly consistent across Homo sapiens as a whole, that's how we've evolved for over 1 1/2 million years, the capacity to be psychotic is probably there across all cultures. What differs, depending on culture and upbringing, will be the content more than the actual form of the experience, I would propose.- [Questioner] Given the changing view of so-called psychotic experiences over the last thousands, even hundreds of years, do you think there's potential for the increased medicalization, even prejudicial relationship with so-called psychotic experiences, to have changed the intensity of those psychotic experiences, something in line with the social model of disability?- I think perhaps what you're referring to is stigma, is that right? Stigma is a huge problem for people with mental illness, the a fear of mental illness, perhaps because we don't understand it as much as we do with other medical illnesses, can prevent people from seeking help early on. And I think one of the implications I mentioned at the end is these psychotic experiences, although they don't indicate clinical psychosis and people needing treatment, they are risk factors for clinical psychosis, and so maybe understanding the profile of them in the general population may help us be more aware of them, de-stigmatize them, and make people feel easier, and more able, and more confident in seeking help without any kind of judgment, this is what I think is important for psychiatry, that we raise the profile of mental illness in the population and de-stigmatize it. There's no shame in being ill, there's no shame in having these experiences, they happen, and they need to be taken seriously.- Related to the question that you had online about cultural differences, and how human beings, we develop differences biologically across different cultures and ethnicities, some people are shorter, taller, so we develop differences biologically, so I wonder about whether the brain develops differently, biologically, influenced by the social factors around them? So things like people running amok, how that's accepted in cultures as not psychotic, that's normal, whereas we would often understand that to be a psychotic experience, things like witch doctors, it's more accepted, and I'm thinking of my Irish family, who, when death is around somebody, and they hear the banshee wailing because somebody's dying, so a lot of it is about how people express what they believe rather than difference in brain functioning. And it can be quite difficult to differentiate between what people are expressing and what is happening in their brain.- Yeah, sure, of course. I don't think there's any inconsistency between trying to understand things have a biological basis, have a psychological basis, have a social and cultural context-- [Questioner] But psychiatry's often tried to funnel it down into more of a narrow concept.- I would argue that, of all medical specialties, psychiatry is the most open-minded and psychologically-minded, and actually, we lead the way in medicine of being the psychologically-minded experts, and that's why we talk about the bio-psycho-social model. We're not limited to biological understanding, we're very much trying to put an understanding in the context of people's social and cultural background, which I think relates to your question, that we take this very seriously, and we're the only medical specialty that makes that our business.- So ladies and gentlemen, the next lecture in our neuroscience series is actually on Wednesday the 16th of March at 6 p.m., Professor Guy Leschziner will be speaking about the neuroscience of sleep and its disorders. But for now, thank you very much, Professor Woodruff.(audience applauds)