[MUSIC] Good morning, my name is Kenneth Hugdahl, I'm a professor of Biological Psychology at the University of Bergen in Norway. I also hold a position as a researcher at the Haukeland University Hospital, also in Bergen, Norway. Today, I will talk with you about my research on auditory hallucinations and also brain asymmetry and using different methods. And the details of these lectures will be apparent as we move along through the lectures. I will start with the first lecture, which will be on auditory hallucinations as a symptom in schizophrenia. And we will be looking at a series of slides, also, as I go through my lecture. Before going into the details of what an auditory hallucination is, let me provide a kind of roadmap for you. Which is also always important when one are doing research on mental phenomena. All mental phenomena manifest themselves on, what I have called in a different context, levels of explanation. And that means that they manifest themselves from a cultural level all the way down to the genetics at the molecular level. In between there, we have a clinical level, we have cognitive level, we have the brain level, we have cellular levels. And all of them have their own specifics and details. And it is important that we are clear on which level we are actually dealing with when you hear researchers come and present the research. So the two levels that I will be primarily occupied with here today you see now on the screen with the marks. That will be on the cognitive level and on the brain level. So we will be talking about the cognitive aspects of a auditory hallucination. We will also be looking into where in the brain do they occur? And how can we understand how this very remarkable phenomenon can occur? Which means hearing a voice that, in essence, actually does not exist. I will also, at the end, come down to the cellular level. And we will talk a little about the chemistry or the neurochemistry about also hallucination. So that's the kind of roadmap that I will follow through my first lecture here now. Starting with the topic what is the characteristics of auditory hallucinations? Auditory hallucinations is a major symptom of the most severe mental disorders that we know of, namely schizophrenia. In a majority of the patients, up to 70 to 80% of them, who have a diagnosis of schizophrenia experience this auditory hallucination which is in the form of hearing a voice. They'll communicate and they are in dialogue with individuals, persons, voices. Which in the objective sense, it does not exist, but the subjectively or phenomenologically for the patient is very real. Now, anti-psychotic medication helps, and is helping a good deal of the patient. But all antipsychotics has unwanted side effects, and about 30 to 40% percent of the patients are also resistant to medications. And this is a real clinical problem that we are encountering. So understanding what is going on and trying to explain what an auditory hallucination is an important aspect also from a clinical level of explanation. Now referring back to my first slide, an hallucination is a conviction. Or from the patient perspective, being convinced of perceiving a real voice in the absence of a corresponding external auditory or linguistic source that could explain that experience. That means that we cannot measure in the airwaves hitting the airs. Which would then be an explanation for setting in motion a set of neuronal events that lead to the subjective perception of a voice, which will be the normal phenomenon. Which is what you as an audience is actually now hearing, my voice. Now, if you had been a real audience, we could have actually measured the airwaves hitting your ears. Now, the remarkable phenomenon about an hallucination is the same phenomenological or subjective perception without that other source to explain the phenomenon. So the big question is then, of course, where do these experiences come from? There are three main dimensions of hallucinations. And I will go through all of these three now and show how research has tried to elucidate each of these dimension. The first I mention is what I call a perceptual dimension. That translates into a subjective experience from the patient point of view, which you can see on the slide here in brackets, that is, the voice is speaking to me. Then we see cognitive dimension, which translates phenomenologically into the patient's mind that the voice is controlling me. That means that when the voices are coming on, they start commenting, commanding. They say things like, why are you here, you're an idiot, shut up, why do you dress like that, you're worthless, you're nothing. And these commands cannot be cognitively suppressed or inhibited by the patient. So it is like these voices are cognitively controlling the patient rather than the other way around, which would be the natural, Phenomena. Then the third dimension is the emotional dimension. The emotional dimension has to do with if the voices are emotionally negative or positive. And for a very clear majority of patients, they are negative. And that translates phenomenologically into a sentence of being the voice is evil, the voice is hurting me, the voice want bad things to happen to me. So we have these three dimensions, and now we'll go through them and start with the perception dimension. But before that, let me address the more basic phenomenological, Question that how can a perceptual experience of a voice which is in a way a linguistic problem occur without an external source? Where in the brain would a thing like that happen or occur? And the logic we have been following in our research over the years is as follows and you see it on the slide and I will also read it for you. If an auditory hallucination or auditory hallucinations or experience that someone speaking to me as I said in the perceptual dimension, it would follow that they could have an origin in the same brain regions that encode normal speech perception. And we know where normal speech perception and language is encoded in the brain. We have known that for 100 years. The normal speech perception is encoded in the left posterior temporal lobe. And you see that in the red, in the area in the brain in the temporal lobe encircled by the red circle. Now, there are two anatomically distinct areas seen in the circle and that is the transverse gyrus work, which is called the Heschl's gyrus. And there's the primary auditory cortex that there's the primary auditory area in the brain where the brain is kind of picking up any auditory sensations. And just behind that, a triangular shaped small area and that's called the planum temporale area. And on the left side of the brain in the left temporal lobe, that area is the main speech perception area. In the neurological terms, that's called the Wernicke's area. And that's where normal speech perception is encoded. So we hypothesized then that auditory hallucinations or speech perceptual phenomena that are mis-attributed to an external agent, that does not exist. And it caused by neuronal hyper-excitation or over-activation of the neurons of the nerve cells in this region of the brain, which is in the posterior temporal lobe region. This region is also anatomically part of what is called the superior temporal gyrus, which is abbreviated STG. I will also refer to that later in my talk. So I'm just mentioning to here now. So how could we then empirically test out if this hypothesis has any validity or not? And that can be done by a method which is called functional Magnetic Resonance Imaging or fMRI for short. And you see, Two pictures of the environment of an MRI scanner. And in the upper, Image, you see the actual scanner, which is a so-called 3 Tesla scanner. It has a very strong magnetic field in the tunnel where the patient is then moved into when we start to scanning. And in the lower image, you see the cockpit where the MRI technicians is sitting and they from there running the scanner and what is happening there. What are we measuring with this method of functional magnetic resonance imaging? You see the left here an example of one nerve cell, a neuron. Now, neurons communicate. Brain consisted by the 100 billions of these neurons and they communicate with each other through electrochemical impulses. They send electrical impulses along and you see that in the pink fiber along the nerve fiber called an axon. And when the impulse comes to the end of that axon, it elicits a chemical substances called transmitter substances. And they literally move over the cleft and the gap onto and make contact with the next neuron and the dendrite which is the fiber leading the electrical impulse further on. And that's how neurons communicate. And when they do that, that needs energy. And neurons, as other cells takes their energy or to put it very simply, they need fuel like your car engine needs a constant fueling to work. The neurons needs constant fueling to work and that is supplied through the blood. And there are blood vessels that runs across and around every aspect of the brain. You see that to the right in the picture here. That's the the blood vessel system. Now in the blood, there are components being transported and among them, oxygen glucose are important component for refueling system for the neurons. And we are in our fMRI method. We are measuring the concentration of oxygen in certain regions of the brain. Because when neurons in a particular region are more active, they need more energy exactly like your car engine. When it has to take the car up the hill, it needs more energy and it needs more fueling, the same with the neurons. And oxygenated blood, blood rich in oxygen has a different magnetic property than blood which is not rich in oxygen called deoxygenated blood. And that difference in signal intensity from the MRI scanner, we can take that information and we convert it. And it comes out and that we can then color code areas and regions in the brain. And the more orange and yellow it gets, it means these areas are where neurons have been particularly active during a particular task or a particular period. And they have then consumed more oxygen. So that's the basic logic of our method. Now, let's look at what we then have been finding with regard to auditory hallucinations. The first finding which is called or I have called it a classic finding instead. If you look to the image to the right now first, and we see the red spot is exactly that area where the speech perception area and where speech perception is supposed to occur. If we take a horizontal slice through that area and we move that slice over to the left as you can see, and I put it down and so the nose is pointing upwards. You see the marked red spot on the left side, which is the spontaneous activation that these patients are showing when they are hallucinating in the scanner. So we have an evidence here that there is hyper Excitability or hyperactivity going on at the neuronal level in this particular region of the brain in the temporal lobe when they are experienced hearing a voice. So this is probably or most likely the area where hallucinate things are starting in the brain. That led to what I've called a paradoxical finding, which was the second finding that we made. I had thought then that if the brain were spontaneously hyperactivated in that area caused by the inner voices, what would happen if one put headphones on patients? And they now had also voices coming from the outside, outer voices, meaning they heard speech sounds through these headphones. I had thought originally that what happened what that active would be that the activation would be much larger. It would double or whatever because now they had two sources, one inner source, one outer source, and they would add together. What happened is what you see to the right here and that is marked in blue. It was a deactivation. Activation in these areas actually went down. So the inner voices was kind of blocking the outer voices to reach into that area or it might have been a cognitive effect. So that the patients were unable to attend to the real voices coming from the outside. So the same area in the brain and that was the paradox. The same area could be both hyperactivated or overactivated caused by the inner voices. And then they were hypo-activated or underactivated when we also added an outer voice coming into the same areas into the brain. And we will take, come back to this findings later in my talk. This points to kind of imbalance model where excitatory, and that's the word for overactivation and inhibitory is then dampening activation. Forces are either in or out of phase when hallucinations are going on. So when hallucinations come and go, these forces might be either in a phase or they go out of phase. And then they could come in to phase again, which is the kind of basic perceptual understanding of where auditory hallucination is starting in the brain. So that led to a theoretical model that we developed and published. I think the first publication, you see it at the bottom of the slide here was around ten years ago. And we call that the VOICE model. The VOICE model now says and as you can see, if we start in a temporal lobe now with the light blue area down to the right, we have the hyperactivated, which is called a bottom-up perceptual system. It is bottom-up because the system is driven by the stimulus element of the hallucinations. Then we have in the frontal areas in the, Of the brain, the hypo-activated top-down, also called executive control. The cognitive system is underactivated. It's hypo-activated. It doesn't engage. It is not engaged to suppress or inhibit the overactivation in the temporal lobe. It is like when the voices start coming on because of the spontaneous neuronal firing, the voices start living their own life. And they are not cognitively controlled from other areas of the brain, in particular the frontal lobes. That leads to a clinical challenge. The VOICE model of a hyper-activated bottom-up system and the hypo-activated top-down system not inhibiting the bottom-up system needs the clinical challenge. And that challenge could be framed as a question. So how could the temporal hyper-activation now be inhibited or suppressed? How could we dampen the temporal lobe activation and at the same time excite or enhance the underactivated frontal lobe system, the top-down system? And that is what I will return to or come back to in my second lecture. And we have had two different approaches to that and you can see examples of that on the right hand side of this slide. And this will be the topic of my next lecture. Thank you.
