Hypnosis: The day my mind was ‘possessed’

I am lying on my back and trapped in a gleaming white tunnel, the surface barely six inches from my nose. There is a strange mechanical rumbling in the background, and I hear footsteps padding around the room beyond. In my mounting claustrophobia, I ask myself why I am here – but there is no way out now. A few moments later, the light dims, and as the man speaks, my thoughts begin to fade.

“The engineer has developed a way of taking control of your thoughts from the inside. He does this because he is fascinated by mind control, and wants to apply the most direct method of controlling your thoughts. He is doing this to advance his research into mind control. You will soon be aware of the engineer inserting his thoughts.”

A strange serenity descends as I realise that soon, my will won’t be my own. Then the experiment begins. I am about to be possessed.

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New study discovers biological basis for magic mushroom ‘mind expansion’

Psychedelic drugs such as LSD and magic mushrooms can profoundly alter the way we experience the world but little is known about what physically happens in the brain. New research, published in Human Brain Mapping, has examined the brain effects of the psychedelic chemical in magic mushrooms, called psilocybin, using data from brain scans of volunteers who had been injected with the drug.

The study found that under psilocybin, activity in the more primitive brain network linked to emotional thinking became more pronounced, with several different areas in this network - such as the hippocampus and anterior cingulate cortex - active at the same time. This pattern of activity is similar to the pattern observed in people who are dreaming. Conversely, volunteers who had taken psilocybin had more disjointed and uncoordinated activity in the brain network that is linked to high-level thinking, including self-consciousness.

Psychedelic drugs are unique among other psychoactive chemicals in that users often describe ‘expanded consciousness,’ including enhanced associations, vivid imagination and dream-like states. To explore the biological basis for this experience, researchers analysed brain imaging data from 15 volunteers who were given psilocybin intravenously while they lay in a functional magnetic resonance imaging (fMRI) scanner. Volunteers were scanned under the influence of psilocybin and when they had been injected with a placebo.

“What we have done in this research is begin to identify the biological basis of the reported mind expansion associated with psychedelic drugs,” said Dr Robin Carhart-Harris from the Department of Medicine, Imperial College London.  “I was fascinated to see similarities between the pattern of brain activity in a psychedelic state and the pattern of brain activity during dream sleep, especially as both involve the primitive areas of the brain linked to emotions and memory. People often describe taking psilocybin as producing a dream-like state and our findings have, for the first time, provided a physical representation for the experience in the brain.”    

The new study examined variation in the amplitude of fluctuations in what is called the blood-oxygen level dependent (BOLD) signal, which tracks activity levels in the brain. This revealed that activity in important brain networks linked to high-level thinking in humans becomes unsynchronised and disorganised under psilocybin. One particular network that was especially affected plays a central role in the brain, essentially ‘holding it all together’, and is linked to our sense of self.

In comparison, activity in the different areas of a more primitive brain network became more synchronised under the drug, indicating they were working in a more co-ordinated, ‘louder’ fashion. The network involves areas of the hippocampus, associated with memory and emotion, and the anterior cingulate cortex which is related to states of arousal.

Lead author Dr Enzo Tagliazucchi from Goethe University, Germany said: “A good way to understand how the brain works is to perturb the system in a marked and novel way. Psychedelic drugs do precisely this and so are powerful tools for exploring what happens in the brain when consciousness is profoundly altered. It is the first time we have used these methods to look at brain imaging data and it has given some fascinating insight into how psychedelic drugs expand the mind. It really provides a window through which to study the doors of perception.”

Dr. Carhart-Harris added: “Learning about the mechanisms that underlie what happens under the influence of psychedelic drugs can also help to understand their possible uses. We are currently studying the effect of LSD on creative thinking and we will also be looking at the possibility that psilocybin may help alleviate symptoms of depression by allowing patients to change their rigidly pessimistic patterns of thinking. Psychedelics were used for therapeutic purposes in the 1950s and 1960s but now we are finally beginning to understand their action in the brain and how this can inform how to put them to good use.”

The data was originally collected at Imperial College London in 2012 by a research group led by Dr Carhart-Harris and Professor David Nutt from the Department of Medicine, Imperial College London. Initial results revealed a variety of changes in the brain associated with drug intake. To explore the data further Dr. Carhart-Harris recruited specialists in the mathematical modelling of brain networks, Professor Dante Chialvo and Dr Enzo Tagliazucchi to investigate how psilocybin alters brain activity to produce its unusual psychological effects.

As part of the new study, the researchers applied a measure called entropy. This was originally developed by physicists to quantify lost energy in mechanical systems, such as a steam engine, but entropy can also be used to measure the range or randomness of a system. For the first time, researchers computed the level of entropy for different networks in the brain during the psychedelic state. This revealed a remarkable increase in entropy in the more primitive network, indicating there was an increased number of patterns of activity that were possible under the influence of psilocybin. It seemed the volunteers had a much larger range of potential brain states that were available to them, which may be the biophysical counterpart of ‘mind expansion’ reported by users of psychedelic drugs.

Previous research has suggested that there may be an optimal number of dynamic networks active in the brain, neither too many nor too few. This may provide evolutionary advantages in terms of optimising the balance between the stability and flexibility of consciousness. The mind works best at a critical point when there is a balance between order and disorder and the brain maintains this optimal number of networks. However, when the number goes above this point, the mind tips into a more chaotic regime where there are more networks available than normal. Collectively, the present results suggest that psilocybin can manipulate this critical operating point.

Noninvasive brain control

Optogenetics, a technology that allows scientists to control brain activity by shining light on neurons, relies on light-sensitive proteins that can suppress or stimulate electrical signals within cells. This technique requires a light source to be implanted in the brain, where it can reach the cells to be controlled.

MIT engineers have now developed the first light-sensitive molecule that enables neurons to be silenced noninvasively, using a light source outside the skull. This makes it possible to do long-term studies without an implanted light source. The protein, known as Jaws, also allows a larger volume of tissue to be influenced at once.

This noninvasive approach could pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders, the researchers say, although much more testing and development is needed. Led by Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, the researchers described the protein in the June 29 issue of Nature Neuroscience.

Optogenetics, a technique developed over the past 15 years, has become a common laboratory tool for shutting off or stimulating specific types of neurons in the brain, allowing neuroscientists to learn much more about their functions.

The neurons to be studied must be genetically engineered to produce light-sensitive proteins known as opsins, which are channels or pumps that influence electrical activity by controlling the flow of ions in or out of cells. Researchers then insert a light source, such as an optical fiber, into the brain to control the selected neurons.

Such implants can be difficult to insert, however, and can be incompatible with many kinds of experiments, such as studies of development, during which the brain changes size, or of neurodegenerative disorders, during which the implant can interact with brain physiology. In addition, it is difficult to perform long-term studies of chronic diseases with these implants.

Mining nature’s diversity

To find a better alternative, Boyden, graduate student Amy Chuong, and colleagues turned to the natural world. Many microbes and other organisms use opsins to detect light and react to their environment. Most of the natural opsins now used for optogenetics respond best to blue or green light.

Boyden’s team had previously identified two light-sensitive chloride ion pumps that respond to red light, which can penetrate deeper into living tissue. However, these molecules, found in the bacteria Haloarcula marismortui and Haloarcula vallismortis, did not induce a strong enough photocurrent — an electric current in response to light — to be useful in controlling neuron activity.

Chuong set out to improve the photocurrent by looking for relatives of these proteins and testing their electrical activity. She then engineered one of these relatives by making many different mutants. The result of this screen, Jaws, retained its red-light sensitivity but had a much stronger photocurrent — enough to shut down neural activity.

“This exemplifies how the genomic diversity of the natural world can yield powerful reagents that can be of use in biology and neuroscience,” says Boyden, who is a member of MIT’s Media Lab and the McGovern Institute for Brain Research.

Using this opsin, the researchers were able to shut down neuronal activity in the mouse brain with a light source outside the animal’s head. The suppression occurred as deep as 3 millimeters in the brain, and was just as effective as that of existing silencers that rely on other colors of light delivered via conventional invasive illumination.

A key advantage to this opsin is that it could enable optogenetic studies of animals with larger brains, says Garret Stuber, an assistant professor of psychiatry and cell biology and physiology at the University of North Carolina at Chapel Hill.

“In animals with larger brains, people have had difficulty getting behavior effects with optogenetics, and one possible reason is that not enough of the tissue is being inhibited,” he says. “This could potentially alleviate that.”

Restoring vision

Working with researchers at the Friedrich Miescher Institute for Biomedical Research in Switzerland, the MIT team also tested Jaws’s ability to restore the light sensitivity of retinal cells called cones. In people with a disease called retinitis pigmentosa, cones slowly atrophy, eventually causing blindness.

Friedrich Miescher Institute scientists Botond Roska and Volker Busskamp have previously shown that some vision can be restored in mice by engineering those cone cells to express light-sensitive proteins. In the new paper, Roska and Busskamp tested the Jaws protein in the mouse retina and found that it more closely resembled the eye’s natural opsins and offered a greater range of light sensitivity, making it potentially more useful for treating retinitis pigmentosa.

This type of noninvasive approach to optogenetics could also represent a step toward developing optogenetic treatments for diseases such as epilepsy, which could be controlled by shutting off misfiring neurons that cause seizures, Boyden says. “Since these molecules come from species other than humans, many studies must be done to evaluate their safety and efficacy in the context of treatment,” he says.

Boyden’s lab is working with many other research groups to further test the Jaws opsin for other applications. The team is also seeking new light-sensitive proteins and is working on high-throughput screening approaches that could speed up the development of such proteins.

Brain fills gaps to produce a likely picture

Researchers at Radboud University use visual illusions to demonstrate to what extent the brain interprets visual signals. They were surprised to discover that active interpretation occurs early on in signal processing. In other words, we see not only with our eyes, but with our brain, too. Current Biology is publishing these results in the July issue.

The results obtained by the Radboud University researchers are illustrated, for example, by the visual illusion on the left: we see a triangle that in fact is not there. The triangle is only suggested because of the way the ‘Pac-Man’ shapes are positioned; there appears to be a light-grey triangle on top of three black circles.

Seen in the fMRI
How does the brain do that? That was the question Peter Kok and Floris de Lange, from the Donders Institute at Radboud University in Nijmegen, asked themselves. Using fMRI, they discovered that the triangle – although non-existent – activates the primary visual brain cortex. This is the first area in the cortex to deal with a signal from the eyes.

The primary visual brain cortex is normally regarded as the area where eye signals are merely processed, but that has now been refuted by the results Kok and De Lange obtained.

Active interpretation
Recent theories assume that the brain does not simply process or filter external information, but actively interprets it. In the example described above, the brain decides it is more likely that a triangle would be on top of black circles than that three such circles, each with a bite taken out, would by coincidence point in a particular direction. After all, when we look around, we see triangles and circles more often than Pac-Man shapes.

Furthermore, objects very often lie on top of other things; just think of the books and piles of paper on your desk. The imaginary triangle is a feasible explanation for the bites taken out of the circles; the brain ‘understands’ they are ‘merely’ partly covered black circles.

The unexpected requires more processing
Kok and De Lange also noticed that whenever the Pac-Man shapes do not form a triangle, more brain activity is required. In the above image on the right, we see that the three Pac-Man shapes ‘underneath’ the triangle cause little brain activity (coloured blue), but the separate Pac-Man on the right causes more activity. This also fits in with the theory that perception is a question of interpretation: if something is easy to explain, less brain activity is needed to process that information, compared to when something is unexpected or difficult to account for – as in the adjacent diagram.

Running, Combined with Visual Experience, Restores Brain Function

In a new study by UC San Francisco scientists, running, when accompanied by visual stimuli, restored brain function to normal levels in mice that had been deprived of visual experience in early life.

In addition to suggesting a novel therapeutic strategy for humans with blindness in one eye caused by a congenital cataract, droopy eyelid, or misaligned eye, the new research—the latest in a series of UCSF studies exploring effects of locomotion on brain function—suggests that the adult brain may be far more capable of rewiring and repairing itself than previously thought.

In 2010, Michael P. Stryker, PhD, the W.F. Ganong Professor of Physiology, and postdoctoral fellow Cris Niell, PhD, now at the University of Oregon, made the surprising discovery that neurons in the visual area of the mouse brain fired much more robustly whenever the mice walked or ran.

Earlier this year, postdoctoral fellow Yu Fu, PhD, Stryker and a number of colleagues built on these findings, identifying and describing the neural circuit responsible for this locomotion-induced “high-gain state” in the visual cortex of the mouse brain.

Neither of these studies made clear, however, whether this circuit might have broader functional or clinical significance.

It has been known since the 1960s that visual areas of the brain do not develop normally if deprived of visual input during a “critical period” of brain development early in life. For example, in humans, if amblyopia (“lazy eye”) or other major eye problems are not surgically corrected in infancy, vision will never be normal in the affected eye—if such individuals lose sight in their “good” eye in later life, they are blind.

In the new research, published June 26, 2014 in the online journal eLife, Stryker and UCSF postdoctoral fellow Megumi Kaneko, MD, PhD, closed one eyelid of mouse pups at about 20 days after birth, and that eye was kept closed until the mice reached about five months of age.

As expected, the mice in which one eye had been closed during the critical developmental period showed sharply reduced neural activity in the part of the brain responsible for vision in that eye.

As in the previous UCSF experiments in this area, some mice were allowed to run freely on Styrofoam balls suspended on a cushion of air while recordings were made from their brains.

Little improvement was seen in the mice that had been deprived of visual input either when they were simply allowed to run or when they received visual training with the deprived eye not accompanied by walking or running.

But when the mice were exposed to the visual stimuli while they were running or walking, the results were dramatic: within a week the brain responses to those stimuli from the deprived eye were nearly identical to those from the normal eye, indicating that the circuits in the visual area of the brain representing the deprived eye had undergone a rapid reorganization, known in neuroscience as “plasticity.”

Interestingly, this recovery was stimulus-specific: if the brain activity of the mice was tested using a stimulus other than that they had seen while running, little or no recovery of function was apparent.

“We have no idea yet whether running puts the human cortex into a high-gain state that enhances plasticity, as it does the visual cortex of the mouse,” Stryker said, “but we are designing experiments to find out.”