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.

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.

Early life stress can leave lasting impacts on the brain

For children, stress can go a long way. A little bit provides a platform for learning, adapting and coping. But a lot of it — chronic, toxic stress like poverty, neglect and physical abuse — can have lasting negative impacts.

A team of University of Wisconsin-Madison researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children’s brains responsible for learning, memory and the processing of stress and emotion. These changes may be tied to negative impacts on behavior, health, employment and even the choice of romantic partners later in life.

The study, published in the journal Biological Psychiatry, could be important for public policy leaders, economists and epidemiologists, among others, says study lead author and recent UW Ph.D. graduate Jamie Hanson.

"We haven’t really understood why things that happen when you’re 2, 3, 4 years old stay with you and have a lasting impact," says Seth Pollak, co-leader of the study and UW-Madison professor of psychology.

Yet, early life stress has been tied before to depression, anxiety, heart disease, cancer, and a lack of educational and employment success, says Pollak, who is also director of the UW Waisman Center’s Child Emotion Research Laboratory.

"Given how costly these early stressful experiences are for society … unless we understand what part of the brain is affected, we won’t be able to tailor something to do about it," he says.

For the study, the team recruited 128 children around age 12 who had experienced either physical abuse, neglect early in life or came from low socioeconomic status households.

Researchers conducted extensive interviews with the children and their caregivers, documenting behavioral problems and their cumulative life stress. They also took images of the children’s brains, focusing on the hippocampus and amygdala, which are involved in emotion and stress processing. They were compared to similar children from middle-class households who had not been maltreated.

Hanson and the team outlined by hand each child’s hippocampus and amygdala and calculated their volumes. Both structures are very small, especially in children (the word amygdala is Greek for almond, reflecting its size and shape in adults), and Hanson and Pollak say the automated software measurements from other studies may be prone to error.

Indeed, their hand measurements found that children who experienced any of the three types of early life stress had smaller amygdalas than children who had not. Children from low socioeconomic status households and children who had been physically abused also had smaller hippocampal volumes. Putting the same images through automated software showed no effects.

Behavioral problems and increased cumulative life stress were also linked to smaller hippocampus and amygdala volumes.

Why early life stress may lead to smaller brain structures is unknown, says Hanson, now a postdoctoral researcher at Duke University’s Laboratory for NeuroGenetics, but a smaller hippocampus is a demonstrated risk factor for negative outcomes. The amygdala is much less understood and future work will focus on the significance of these volume changes.

"For me, it’s an important reminder that as a society we need to attend to the types of experiences children are having," Pollak says. "We are shaping the people these individuals will become."

But the findings, Hanson and Pollak say, are just markers for neurobiological change; a display of the robustness of the human brain, the flexibility of human biology. They aren’t a crystal ball to be used to see the future.

"Just because it’s in the brain doesn’t mean it’s destiny," says Hanson.

People with tinnitus process emotions differently from their peers

Patients with persistent ringing in the ears – a condition known as tinnitus – process emotions differently in the brain from those with normal hearing, researchers report in the journal Brain Research.

Tinnitus afflicts 50 million people in the United States, according to the American Tinnitus Association, and causes those with the condition to hear noises that aren’t really there. These phantom sounds are not speech, but rather whooshing noises, train whistles, cricket noises or whines. Their severity often varies day to day.

University of Illinois speech and hearing science professor Fatima Husain, who led the study, said previous studies showed that tinnitus is associated with increased stress, anxiety, irritability and depression, all of which are affiliated with the brain’s emotional processing systems.

“Obviously, when you hear annoying noises constantly that you can’t control, it may affect your emotional processing systems,” Husain said. “But when I looked at experimental work done on tinnitus and emotional processing, especially brain imaging work, there hadn’t been much research published.”

She decided to use functional magnetic resonance imaging (fMRI) brain scans to better understand how tinnitus affects the brain’s ability to process emotions. These scans show the areas of the brain that are active in response to stimulation, based upon blood flow to those areas.

Three groups of participants were used in the study: people with mild-to-moderate hearing loss and mild tinnitus; people with mild-to-moderate hearing loss without tinnitus; and a control group of age-matched people without hearing loss or tinnitus. Each person was put in an fMRI machine and listened to a standardized set of 30 pleasant, 30 unpleasant and 30 emotionally neutral sounds (for example, a baby laughing, a woman screaming and a water bottle opening). The participants pressed a button to categorize each sound as pleasant, unpleasant or neutral.

The tinnitus and normal-hearing groups responded more quickly to emotion-inducing sounds than to neutral sounds, while patients with hearing loss had a similar response time to each category of sound. Over all, the tinnitus group’s reaction times were slower than the reaction times of those with normal hearing.

Activity in the amygdala, a brain region associated with emotional processing, was lower in the tinnitus and hearing-loss patients than in people with normal hearing. Tinnitus patients also showed more activity than normal-hearing people in two other brain regions associated with emotion, the parahippocampus and the insula. The findings surprised Husain.

“We thought that because people with tinnitus constantly hear a bothersome, unpleasant stimulus, they would have an even higher amount of activity in the amygdala when hearing these sounds, but it was lesser,” she said. “Because they’ve had to adjust to the sound, some plasticity in the brain has occurred. They have had to reduce this amygdala activity and reroute it to other parts of the brain because the amygdala cannot be active all the time due to this annoying sound.”

Because of the sheer number of people who suffer from tinnitus in the United States, a group that includes many combat veterans, Husain hopes her group’s future research will be able to increase tinnitus patients’ quality of life.

“It’s a communication issue and a quality-of-life issue,” she said. “We want to know how we can get better in the clinical realm. Audiologists and clinicians are aware that tinnitus affects emotional aspects, too, and we want to make them aware that these effects are occurring so they can better help their patients.”

(Image caption:This is an overall fMRI composite comparison of the brains of highly sensitive people (HSP) compared to non-HSPs. The areas in color represent some of the regions of the brain where greater activation occurs in HSPs compared to non-HSPs. The brain region highly associated with empathy and noticing emotion (Anterior Insula) shows significantly greater activation in HSPs than non-HSPs when viewing a photo of their partner smiling. Credit: Art Aron)

Sensitive? Emotional? Empathetic? It Could Be in Your Genes

Do you jump to help the less fortunate, cry during sad movie scenes, or tweet and post the latest topics and photos that excite or move you? If yes, you may be among the 20 percent of our population that is genetically pre-disposed to empathy, according to Stony Brook University psychologists Arthur and Elaine Aron. In a new study published in Brain and Behavior, Drs. Aron and colleagues at the University of California, Albert Einstein College of Medicine, and Monmouth University found that Functional Magnetic Resonance Imaging (fMRI) of brains provide physical evidence that the “highly sensitive” brain responds powerfully to emotional images.

Previous research suggests that sensory processing sensitivity (SPS) is an innate trait associated with greater sensitivity, or responsiveness, to environmental and social stimuli. According to Dr. Arthur Aron, the trait is becoming increasingly associated with identifiable behaviors, genes, physiological reactions, and patterns of brain activation. Highly sensitive people (HSP), those high in SPS, encompass roughly 20 percent of the population. Elaine Aron, PhD, originated the HSP concept. Humans characterized as HSPs tend to show heightened awareness to subtle stimuli, process information more thoroughly, and be more reactive to both positive and negative stimuli. In contrast, the majority of people have comparatively low SPS and pay less attention to subtle stimuli, approach situations more quickly and are not as emotionally reactive.

In “The Highly Sensitive Brain: An fMRI study of Sensory Processing Sensitivity and Response to Others’ Emotions,” Drs. Aron and colleagues used fMRI brain scans to compare HSPs with low SPS individuals. The analysis is the first with fMRI to demonstrate how HSPs’ brain activity processes others’ emotions.

The brains of 18 married individuals (some with high and some with low SPS) were scanned as they viewed photos of either smiling faces, or sad faces. One set of photos included the faces of strangers, and the other set included photos of their husbands or wives.

“We found that areas of the brain involved with awareness and emotion, particularly those areas connected with empathetic feelings, in the highly sensitive people showed substantially greater blood flow to relevant brain areas than was seen in individuals with low sensitivity during the twelve second period when they viewed the photos,” said Dr. Aron, a Research Professor in Psychology at Stony Brook. “This is physical evidence within the brain that highly sensitive individuals respond especially strongly to social situations that trigger emotions, in this case of faces being happy or sad.”

The brain activity was even higher when HSPs viewed the expressions of their spouses. The highest activation occurred when viewing images of their partner as happy. Most of the participants were scanned again one year later, and the same results occurred.

Areas of the brain indicating the greatest activity – as shown by blood flow – include sections known as the “mirror neuron system,” an area strongly associated with empathetic response and brain areas associated with awareness, processing sensory information and action planning.

Dr. Aron believes the results provide further evidence that HSPs are generally highly tuned into their environment. He said the new findings via the fMRI provide evidence that especially high levels of awareness and emotional responsiveness are fundamental features of humans characterized as HSPs.

Hippocampal activity during music listening exposes the memory-boosting power of music

For the first time the hippocampus—a brain structure crucial for creating long-lasting memories—has been observed to be active in response to recurring musical phrases while listening to music. Thus, the hippocampal involvement in long-term memory may be less specific than previously thought, indicating that short and long-term memory processes may depend on each other after all.

The study was conducted at the University of Jyväskylä and the AMI Center of Aalto University, by a group of researchers led by Academy Professor Petri Toiviainen, the Finnish Centre for Interdisciplinary Music Research (CIMR) at the University of Jyväskylä, and Dr. Elvira Brattico, Aalto University and the University of Helsinki. Results of the study were published in Cortex, a journal devoted to the study of the nervous system and behaviour.

“Our study basically shows an increase of activity in the medial temporal lobe areas—best known for being essential for long term memory—when musical motifs in the piece were repeated. This means that the lobe areas are engaged in the short-term recognition of musical phrases,” explains Iballa Burunat, the leading author of the study. Dr. Brattico adds: “Importantly, this hadn’t been observed before in music neuroscience.”

A fundamental highlight of the study is the use of a setting that is more natural than those traditionally employed in neuroscience: the participants’ only task was to attentively listen to an Argentinian tango from beginning to end. This kind of music provides well-defined, salient musical motifs that are easy to follow. They can be used to study recognition processes in the brain without having to resort to sound created in a lab. By using this more realistic approach, the researchers were able to identify brain areas involved in motif tracking without having to rely on the participants’ ability to self-report, which would have constrained the study of brain processes.

“We think that our novel method allowed us to uncover this phenomenon. In other words, the identified areas may also be related to the formation of a more permanent memory trace of a musical piece, enabled precisely by the very use of a real-life stimulus (the recording of a live performance) in a realistic situation where participants just listen to the music as their brain responses are recorded,” Iballa Burunat goes on to explain. Listening to the music from beginning to end may have imprinted the participants with a long lasting memory of the tune. This might not be expected were the participants exposed to a simpler stimulus in controlled conditions, as is the case in most studies in music and memory.

Although a real-life setting may be sufficient to trigger the involvement of the hippocampus, another explanation could lie in music’s capacity to elicit emotions. “We cannot ignore music’s emotional power which is thought to be crucial for the mnemonic power of music as to how and what we remember. There is evidence on the robust integration of music, memory and emotion—take for instance autobiographical memories. So it wouldn’t be surprising that the emotional content of the music may well have been a factor in triggering these limbic responses,” she continues. This makes sense, since the chosen musical piece by Astor Piazzolla was a tribute to his father after his sudden death, and so the main purpose of the piece was to be of a deeply emotional nature”. Certainly, the hippocampus—as part of the limbic system—is connected to neural circuitry involved in emotional behavior, and ongoing research suggests that emotional events seem to be more memorable than neutral ones. The authors emphasize that these results should motivate similar approaches to study verbal or visual short term memory by tracking the themes or repetitive structures of a given stimulus. Moreover, the study has implications for neurodegenerative diseases associated with hippocampal atrophy, like Alzheimer’s. “Music may positively affect patients if used wisely to stimulate their hippocampi, and thus their memory system,” Academy Professor Petri Toiviainen indicates. A better understanding of the link between music and memory could have widespread repercussions, leading to novel interventions to rehabilitate or improve the life quality of patients with neurodegenerative conditions.

Brain imaging shows enhanced executive brain function in people with musical training

A controlled study using functional MRI brain imaging reveals a possible biological link between early musical training and improved executive functioning in both children and adults, report researchers at Boston Children’s Hospital. The study, appearing online June 17 in the journal PLOS ONE, uses functional MRI of brain areas associated with executive function, adjusting for socioeconomic factors.

Executive functions are the high-level cognitive processes that enable people to quickly process and retain information, regulate their behaviors, make good choices, solve problems, plan and adjust to changing mental demands.

"Since executive functioning is a strong predictor of academic achievement, even more than IQ, we think our findings have strong educational implications," says study senior investigator Nadine Gaab, PhD, of the Laboratories of Cognitive Neuroscience at Boston Children’s. "While many schools are cutting music programs and spending more and more time on test preparation, our findings suggest that musical training may actually help to set up children for a better academic future."

While it’s already clear that musical training relates to cognitive abilities, few previous studies have looked at its effects on executive functions specifically. Among these studies, results have been mixed and limited by a lack of objective brain measurements, examination of only a few aspects of executive function, lack of well-defined musical training and control groups, and inadequate adjustment for factors like socioeconomic status.

Gaab and colleagues compared 15 musically trained children, 9 to 12, with a control group of 12 untrained children of the same age. Musically trained children had to have played an instrument for at least two years in regular private music lessons. (On average, the children had played for 5.2 years and practiced 3.7 hours per week, starting at the age of 5.9.) The researchers similarly compared 15 adults who were active professional musicians with 15 non-musicians. Both control groups had no musical training beyond general school requirements.

Since family demographic factors can influence whether a child gets private music lessons, the researchers matched the musician/non-musician groups for parental education, job status (parental or their own) and family income. The groups, also matched for IQ, underwent a battery of cognitive tests, and the children also had functional MRI imaging (fMRI) of their brains during testing.

On cognitive testing, adult musicians and musically trained children showed enhanced performance on several aspects of executive functioning. On fMRI, the children with musical training showed enhanced activation of specific areas of the prefrontal cortex during a test that made them switch between mental tasks. These areas, the supplementary motor area, the pre-supplementary area and the right ventrolateral prefrontal cortex, are known to be linked to executive function.

"Our results may also have implications for children and adults who are struggling with executive functioning, such as children with ADHD or [the] elderly," says Gaab. "Future studies have to determine whether music may be utilized as a therapeutic intervention tools for these children and adults."

The researchers note that children who study music may already have executive functioning abilities that somehow attract them to music and predispose them to stick with their lessons. To establish that musical training influences executive function, and not the other way around, they hope to perform additional studies that follow children over time, assigning them to musical training at random.

Neural reward response may demonstrate why quitting smoking is harder for some

For some cigarette smokers, strategies to aid quitting work well, while for many others no method seems to work. Researchers have now identified an aspect of brain activity that helps to predict the effectiveness of a reward-based strategy as motivation to quit smoking.

The researchers observed the brains of nicotine-deprived smokers with functional magnetic resonance imaging (fMRI) and found that those who exhibited the weakest response to rewards were also the least willing to refrain from smoking, even when offered money to do so.

"We believe that our findings may help to explain why some smokers find it so difficult to quit smoking," said Stephen J. Wilson, assistant professor of psychology, Penn State. "Namely, potential sources of reinforcement for giving up smoking — for example, the prospect of saving money or improving health — may hold less value for some individuals and, accordingly, have less impact on their behavior."

The researchers recruited 44 smokers to examine striatal response to monetary reward in those expecting to smoke and in those who were not, and the subsequent willingness of the smokers to forego a cigarette in an effort to earn more money.

"The striatum is part of the so-called reward system in the brain," said Wilson. "It is the area of the brain that is important for motivation and goal-directed behavior — functions highly relevant to addiction."

The participants, who were between the ages of 18 and 45, all reported that they smoked at least 10 cigarettes per day for the past 12 months. They were instructed to abstain from smoking and from using any products containing nicotine for 12 hours prior to arriving for the experiment.

Each participant spent time in an fMRI scanner while playing a card-guessing game with the potential to win money. The participants were informed that they would have to wait approximately two hours, until the experiment was over, to smoke a cigarette. Partway through the card-guessing task, half of the participants were informed that there had been a mistake, and they would be allowed to smoke during a 50-minute break that would occur in another 16 minutes.

However, when the time came for the cigarette break, the participant was told that for every 5 minutes he or she did not smoke, he or she would receive $1 — with the potential to earn up to $10.

Wilson and his colleagues reported in a recent issue of Cognitive, Affective and Behavioral Neuroscience that they found that smokers who could not resist the temptation to smoke also showed weaker responses in the ventral striatum when offered monetary rewards while in the fMRI.

"Our results suggest that it may be possible to identify individuals prospectively by measuring how their brains respond to rewards, an observation that has significant conceptual and clinical implications," said Wilson. "For example, particularly ‘at-risk’ smokers could potentially be identified prior to a quit attempt and be provided with special interventions designed to increase their chances for success."

MRI brain scans detect people with early Parkinson’s

The new MRI approach can detect people who have early-stage Parkinson’s disease with 85% accuracy, according to research published in Neurology, the medical journal of the American Academy of Neurology.

'At the moment we have no way to predict who is at risk of Parkinson's disease in the vast majority of cases,' says Dr Clare Mackay of the Department of Psychiatry at Oxford University, one of the joint lead researchers. 'We are excited that this MRI technique might prove to be a good marker for the earliest signs of Parkinson's. The results are very promising.'

Claire Bale, research communications manager at Parkinson’s UK, which funded the work, explains: ‘This new research takes us one step closer to diagnosing Parkinson’s at a much earlier stage – one of the biggest challenges facing research into the condition. By using a new, simple scanning technique the team at Oxford University have been able to study levels of activity in the brain which may suggest that Parkinson’s is present. One person every hour is diagnosed with Parkinson’s in the UK, and we hope that the researchers are able to continue to refine their test so that it can one day be part of clinical practice.’

Parkinson’s disease is characterised by tremor, slow movement, and stiff and inflexible muscles. It’s thought to affect around 1 in 500 people, meaning there are an estimated 127,000 people in the UK with the condition. There is currently no cure for the disease, although there are treatments that can reduce symptoms and maintain quality of life for as long as possible.

Parkinson’s disease is caused by the progressive loss of a particular set of nerve cells in the brain, but this damage to nerve cells will have been going on for a long time before symptoms become apparent.

If treatments are to be developed that can slow or halt the progression of the disease before it affects people significantly, the researchers say, we need methods to be able to identify people at risk before symptoms take hold.

Conventional MRI cannot detect early signs of Parkinson’s, so the Oxford researchers used an MRI technique, called resting-state fMRI, in which people are simply required to stay still in the scanner. They used the MRI data to look at the ‘connectivity’, or strength of brain networks, in the basal ganglia – part of the brain known to be involved in Parkinson’s disease.

The team compared 19 people with early-stage Parkinson’s disease while not on medication with 19 healthy people, matched for age and gender. They found that the Parkinson’s patients had much lower connectivity in the basal ganglia.

The researchers were able to define a cut-off or threshold level of connectivity. Falling below this level was able to predict who had Parkinson’s disease with 100% sensitivity (it picked up everyone with Parkinson’s) and 89.5% specificity (it picked up few people without Parkinson’s – there were few false positives).

Dr Mackay explains: ‘Our MRI approach showed a very strong difference in connectivity between those who had Parkinson’s disease and those that did not. So much so, that we wondered if it was too good to be true and carried out a validation test in a second group of patients. We got a similar result the second time.’

The scientists applied their MRI test to a second group of 13 early-stage Parkinson’s patients as a validation of the approach. They correctly identified 11 out of the 13 patients (85% accuracy).

'We think that our MRI test will be relevant for diagnosis of Parkinson's,' says joint lead researcher Dr Michele Hu of the Nuffield Department of Clinical Neurosciences at Oxford University and the Oxford University Hospitals NHS Trust. 'We tested it in people with early-stage Parkinson's. But because it is so sensitive in these patients, we hope it will be able to predict who is at risk of disease before any symptoms have developed. However, this is something that we still have to show in further research.'

To see if this is the case, the Oxford University researchers are now carrying out further studies of their MRI technique with people who are at increased risk of Parkinson’s.