̽��ֱ�� of Cambridge - Valerie Voon

Cambridge and London hospitals to pioneer brain implants to combat alcohol and opioid addiction

cjb250 — Mon, 17 Mar 2025 08:00:50 +0000

̽��ֱ��technique – known as deep brain stimulation – is to be trialled at Addenbrooke’s Hospital, Cambridge, and King’s College Hospital, London. ̽��ֱ��team behind the Brain-PACER: Brain Pacemaker Addiction Control to End Relapse study will soon be recruiting individuals with severe alcohol or opioid addiction who are interested in taking part.

Deep brain stimulation (DBS) is a neurosurgical procedure that delivers ongoing stimulation to the brain. DBS acts as a brain pacemaker to normalise abnormal brain activity. It is well-tolerated, effective and widely used for neurological disorders and obsessive compulsive disorder.

Although there have been several proof-of-concept studies that suggest DBS is effective in addictions, Brain-PACER – a collaboration between the ̽��ֱ�� of Cambridge, Kings College London and the ̽��ֱ�� of Oxford – is the first major, multicentre study to use DBS to treat craving and relapse in severe addiction.

Chief Investigator Professor Valerie Voon, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, said: “While many people who experience alcohol or drug addiction can, with the right support, control their impulses, for some people, their addiction is so severe that no treatments are effective. Their addiction is hugely harmful to their health and wellbeing, to their relationships and their everyday lives.

“Initial evidence suggests that deep brain stimulation may be able to help these individuals manage their conditions. We’ve seen how effective it can be for other neurological disorders from Parkinson’s to OCD to depression. We want to see if it can also transform the lives of people with intractable alcohol and opioid addiction.”

̽��ֱ��primary aim of the Brain-PACER study is to assess the effects of DBS to treat alcohol and opioid addiction in a randomised controlled trial study. Its mission is twofold: to develop effective treatments for addiction and to understand the brain mechanisms that drive addiction disorders.

DBS is a neurosurgical treatment that involves implanting a slender electrode in the brain and a pacemaker under general anaesthesia. These electrodes deliver electrical impulses to modulate neural activity, which can help alleviate symptoms of various neurological and psychiatric disorders.

Keyoumars Ashkan, Professor of Neurosurgery at King’s College Hospital and the lead surgeon for the study, said: “Deep brain stimulation is a powerful surgical technique that can transform lives. It will be a major leap forward if we can show efficacy in this very difficult disease with huge burden to the patients and society.”

During surgery, thin electrodes are carefully placed in precise locations of the brain. These locations are chosen based on the condition being treated. For addiction, the electrodes are placed in areas involved in reward, motivation, and decision-making.

Harry Bulstrode, Honorary Consultant Neurosurgeon at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and Clinical Lecturer at the ̽��ֱ�� of Cambridge, said: "We see first-hand how deep brain stimulation surgery can be life-changing for patients with movement disorders such as Parkinson’s disease and essential tremor. Thanks to this trial, I am now hopeful that we can help patients and their families – who have often struggled for years – by targeting the parts of the brain linked to addiction."

Dr David Okai, Visiting Senior Lecturer from the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, added: “DBS is safe, reversible and adjustable, so it offers a flexible option for managing chronic conditions. We hope it will offer a lifeline to help improve the quality of life for patients whose treatment until now has been unsuccessful.”

Details on the trial, including criteria for participation, can be found on the Brain-PACER website.

̽��ֱ��research is supported by the Medical Research Council, UK Research & Innovation.

People suffering from severe alcohol and opioid addiction are to be offered a revolutionary new technique involving planting electrodes in the brain to modulate brain activity and cravings and improve self-control.

We’ve seen how effective deep brain stimulation can be for neurological disorders from Parkinson’s to OCD to depression. We want to see if it can also transform the lives of people with intractable alcohol and opioid addiction

Valerie Voon

Shamir R, Noecker A and McIntyre C

Graphic demonstrating deep brain stimulation

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Magnetic field applied to both sides of brain shows rapid improvement for depression

cjb250 — Mon, 28 Oct 2024 15:23:23 +0000

̽��ֱ��treatment – known as repetitive transcranial magnetic stimulation (TMS) – involves placing an electromagnetic coil against the scalp to relay a high-frequency magnetic field to the brain.

Around one in 20 adults is estimated to suffer from depression. Although treatments exist, such as anti-depressant medication and cognitive behavioural therapy (‘talking therapy’), they are ineffective for just under one in three patients.

One of the key characteristics of depression is under-activity of some regions (such as the dorsolateral prefrontal cortex) and over-activity of others (such as the orbitofrontal cortex (OFC)).

Repetitive transcranial magnetic stimulation applied to the left side of the dorsolateral prefrontal cortex (an area at the upper front area of the brain) is approved for treatment of depression in the UK by NICE and in the US by the FDA. It has previously been shown to lead to considerable improvements among patients after a course of 20 sessions, but because the sessions usually take place over 20-30 days, the treatment is not ideal for everyone, particularly in acute cases or where a person is suicidal.

In research published in Psychological Medicine, scientists from Cambridge, UK, and Guiyang, China, tested how effective an accelerated form of TMS is. In this approach, the treatment is given over 20 sessions, but with four sessions per day over a period of five consecutive days.

̽��ֱ��researchers also tested a ‘dual’ approach, whereby a magnetic field was additionally applied to the right-hand side of the OFC (which sits below the dorsolateral prefrontal cortex).

Seventy-five patients were recruited to the trial from the Second People’s Hospital of Guizhou Province in China. ̽��ֱ��severity of their depression was measured on a scale known as the Hamilton Rating Scale of Depression.

Participants were split randomly into three groups: a ‘dual’ group receiving TMS applied first to the right- and then to the left-hand sides of the brain; a ‘single’ group receiving sham TMS to the right-side followed by active TMS applied to the left-side; and a control group receiving a sham treatment to both sides. Each session lasted in total 22 minutes.

There was a significant improvement in scores assessed immediately after the final treatment in the dual treatment group compared to the other two groups. When the researchers looked for clinically-relevant responses – that is, where an individual’s score fell by at least 50% – they found that almost half (48%) of the patients in the dual treatment group saw such a reduction, compared to just under one in five (18%) in the single treatment group and fewer than one in 20 (4%) in the control group.

Four weeks later, around six in 10 participants in both the dual and single treatment groups (61% and 59% respectively) showed clinically relevant responses, compared to just over one in five (22%) in the control group.

Professor Valerie Voon from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, who led the UK side of the study, said: “Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression. This means it could be particularly useful in severe cases of depression, including when someone is experiencing suicidal thoughts. It may also help people be discharged from hospital more rapidly or even avoid admission in the first place.

“ ̽��ֱ��treatment works faster because, by targeting two areas of the brain implicated in depression, we’re effectively correcting imbalances in two import processes, getting brain regions ‘talking’ to each other correctly.”

̽��ֱ��treatment was most effective in those patients who at the start of the trial showed greater connectivity between the OFC and the thalamus (an area in the middle of the brain responsible for, among other things, regulation of consciousness, sleep, and alertness). ̽��ֱ��OFC is important for helping us make decisions, particularly in choosing rewards and avoiding punishment. Its over-activity in depression, particularly in relation to its role in anti-reward or punishment, might help explain why people with depression show a bias towards negative expectations and ruminations.

Dr Yanping Shu from the Guizhou Mental Health Centre, Guiyang, China, said: “This new treatment has demonstrated a more pronounced – and faster – improvement in response rates for patients with major depressive disorder. It represents a significant step forward in improving outcomes, enabling rapid discharge from hospitals for individuals with treatment-resistant depression, and we are hopeful it will lead to new possibilities in mental health care.”

Dr Hailun Cui from Fudan ̽��ֱ��, a PhD student in Professor Voon’s lab at the time of the study, added: “ ̽��ֱ��management of treatment-resistant depression remains one of the most challenging areas in mental health care. These patients often fail to respond to standard treatments, including medication and psychotherapy, leaving them in a prolonged state of severe distress, functional impairment, and increased risk of suicide.

“This new TMS approach offers a beacon of hope in this difficult landscape. Patients frequently reported experiencing ‘lighter and brighter’ feelings as early as the second day of treatment. ̽��ֱ��rapid improvements, coupled with a higher response rate that could benefit a broader depressed population, mark a significant breakthrough in the field.”

Just under a half (48%) of participants in the dual treatment group reported local pain where the dual treatment was applied, compared to just under one in 10 (9%) of participants in the single treatment group. However, despite this, there were no dropouts.

For some individuals, this treatment may be sufficient, but for others ‘maintenance therapy’ may be necessary, with an additional day session if their symptoms appear to be worsening over time. It may also be possible to re-administer standard therapy as patients can then become more able to engage in psychotherapy. Other options include using transcranial direct current stimulation, a non-invasive form of stimulation using weak electrical impulses that can be delivered at home.

̽��ֱ��researchers are now exploring exactly which part of the orbitofrontal cortex is most effective to target and for which types of depression.

̽��ֱ��research was supported by in the UK by the Medical Research Council and by the National Institute for Health and Care Research Cambridge Biomedical Research Centre.*

Reference
Cui, H, Ding, H & Hu, L et al. A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study. Psychological Medicine; 23 Oct 2024; DOI: 10.1017/S0033291724002289

*A full list of funders is available in the journal paper.

A type of therapy that involves applying a magnetic field to both sides of the brain has been shown to be effective at rapidly treating depression in patients for whom standard treatments have been ineffective.

Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression

Valerie Voon

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One in three adults drank more alcohol during first lockdown

cjb250 — Mon, 21 Dec 2020 11:44:53 +0000

In early March, the World Health Organization declared COVID-19 a pandemic and many countries put in place drastic safety measures to control the spread of the virus, including an extended lockdown period.

In the UK, the first nationwide lockdown started on 23 March 2020 and lasted until 1 June, when restrictions began to be eased. Since then more localised lockdowns have been implemented where necessary.

A team of researchers at the ̽��ֱ�� of Cambridge has explored whether the stress of the pandemic and lockdown measures affected people’s alcohol consumption. Between 14 and 28 May 2020, 1,346 people around the world completed an online survey about their drinking habits before and during lockdown. ̽��ֱ��researchers used their responses to compare the amount of alcohol consumed during lockdown against that in November 2019, as well as their drinking severity (occurrences of problem drinking such as drinking to the point of memory loss or neglecting personal responsibilities due to drinking). They also assessed mental health factors such as depression and anxiety.

̽��ֱ��survey revealed that while the units of alcohol consumed per week decreased during lockdown – down from a mean average of 8.32 units in November to 8.03 during lockdown – a substantial percentage of individuals (36%) increased their drinking during lockdown. In the UK, the units of alcohol consumed per week increased from 10.94 to 11.25 units.

Samantha N Sallie, the study’s first author and a PhD student at the Department of Psychiatry, said: “While in countries such as Canada and the USA people drank less during lockdown, in the UK there was a small increase in alcohol consumption.”

Older individuals tended to increase their alcohol consumption more than younger people during lockdown, from 10 to 11 units weekly. Age may play a particularly unique role in the context of COVID-19 due to the greater need for older people to have more stringent isolation, with potentially fewer support mechanisms, and hence a risk of greater isolation and loneliness, as well as concern about the impact of COVID-19 on their personal health.

Respondents with children reported a greater increase in alcohol consumption during lockdown, of between 0.54 and 2.02 units, though their depression and anxiety scores were lower than for those without children. ̽��ֱ��researchers say this suggests the additional burden of childcare and home schooling contributed to the tendency towards drinking, possibly in the context of stress relief, but the presence of children may also be protective against depression and anxiety.

“For parents having to take on extra childcare responsibilities during lockdown, possibly at the same time as having to manage changes to their work routine, it’s possible that the extra stress increased their tendency to drink,” said Sallie. “On the other hand, having children may mitigate against loneliness that has been highlighted as a major issue during the isolation of lockdown.”

̽��ֱ��team found that essential workers – specifically healthcare workers responsible for taking care of individuals with COVID-19 – showed an increase in drinking amount of between 0.45 and 1.26 units, while those whose loved ones became severely ill or died from COVID-19 showed an increase in problem drinking during the lockdown.

“This demonstrates how the virus itself has affected alcohol consumption in those who have had close contact with the very real and devastating effects of COVID-19,” added Sallie.

Although men consumed more alcohol than women, they showed a decrease in both drinking amount and severity during lockdown, while women demonstrated the opposite trend, with women consuming an extra unit of alcohol a week during lockdown. This finding corroborates evidence that indicates women are more likely than men to consume alcohol in order to cope with stress.

Individuals who reported a change in their employment status or were isolating alone were more likely to have higher depression scores, but showed no change in their drinking behaviour. Those individuals isolating with others but reporting a poor relationship were more likely to have higher depression and anxiety scores.

Dr Valerie Voon, senior author of the study from the ̽��ֱ�� of Cambridge, said: “As COVID-19 remains part of daily life, many of us are turning to alcohol to cope with stress. For many people, drinking in moderation can be help with stress relief, but for others it can be more problematic.

“Alcohol misuse is a major public health issue in the United Kingdom, costing £21-52 billion with NHS costs of £3.5 billion per year. Our findings highlight a need to identify those individuals who are at risk for problem drinking so we can offer them greater support during the ongoing pandemic.”

̽��ֱ��researchers say there may be a number of reasons for the overall decrease in alcohol use and problematic use, including stringent lockdown measures leading to a decrease in the availability of alcoholic drinks within the immediate household and because people tend to consume alcohol in social situations, such as at the pub or when eating out.

Reference
Sallie, S N et al Assessing International Alcohol Consumption Patterns During Isolation from the COVID-19 Pandemic Using an Online Survey: Highlighting Negative Emotionality Mechanisms. BMJ Open; 26 Nov 2020; DOI: 10.1136/bmjopen-2020-044276

COVID-19 and lockdown measures drove some individuals more than others to use alcohol to cope with stress, a new study has revealed. While overall alcohol consumption appeared to fall, a study published in BMJ Open found that more than one in three adults (36%) increased their consumption during the first lockdown.

As COVID-19 remains part of daily life, many of us are turning to alcohol to cope with stress. For many people, drinking in moderation can be help with stress relief, but for others it can be more problematic

Valerie Voon

congerdesign

Wine glass and bottle

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Researchers to track impact of lockdown on alcohol, gambling and pornography use

cjb250 — Mon, 11 May 2020 23:16:03 +0000

̽��ֱ��UK was first placed on lockdown in response to the coronavirus pandemic on 23 March. Only essential businesses were allowed to remain open and everyone was told to stay at home, only to venture out for exercise and shopping.

Almost overnight, people’s lives were up-ended, with some people working from home while others have lost their jobs or been furloughed. People who live by themselves have suddenly found themselves with no social contact other than virtual.

To find out what impact this has had on people’s behaviour, Dr Valerie Voon from the ̽��ֱ�� of Cambridge and Prof Henrietta Bowden-Jones, Director of the National Problem Gambling Clinic, London, have launched an online survey, HabiT – Habit Tracker – asking about changes in habits during lockdown, specifically quantifying alcohol, smoking, and online use of gambling, gaming and pornography. ̽��ֱ��habit tracker survey is available online. All responses will be anonymous.

̽��ֱ��survey is short, only taking 10 minutes to complete. ̽��ֱ��researchers are keen to hear from both those people who do not consider themselves to be vulnerable or exhibit problem behaviours and those who have struggled in the past or are struggling now.

“We expect to see an increase in these behaviours across the UK in response to the unprecedented circumstances we find ourselves in,” says Dr Voon. “In many cases, these changes will be people’s strategies for coping with the anxiety and stress caused by the pandemic and lockdown and, we hope, won’t have a long term impact if the behaviour can be controlled.

“For some people who might already have been struggling with or have a history of addiction these increased habits could prove problematic. ̽��ֱ��same goes for those people who find themselves in difficult circumstances, for example having lost their job or facing financial difficulties, or are struggling to cope with the lockdown. These more vulnerable individuals may find their behaviour has a more marked longer lasting effect, triggering an alcohol relapse, for instance, or reigniting a gambling addiction.”

Survey respondents may also take part in CrusH, an alcohol avoidance online training game for smartphones being developed which can be accessed as part of the survey.

Five tips for coping during the lockdown

Keep active: exercise outdoors and take part in online exercise workouts
Keep in touch with people socially online – try FaceTime, Skype or Zoom so that you see people
Maintain some regular structure: sleep, wake, work
Don't spend too much time looking at news
Use this as an opportunity to try something new – try baking, learning a new language, writing that novel you always dreamed of writing

Is the lockdown leading us to drink more alcohol or spend more time gambling online or watching pornography? Researchers today launch a survey aimed at tracking how our habits have changed in response to our forced isolation.

We expect to see an increase in these behaviours across the UK in response to the unprecedented circumstances we find ourselves in... For some people who might already have been struggling with or have a history of addiction these increased habits could prove problematic

Valerie Voon

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Opinion: Why danger is exciting – but only to some people

Anonymous — Tue, 06 Sep 2016 13:17:41 +0000

It has been the most deadly summer for wingsuit flying to date. But what makes some people want to base jump off a cliff, binge drink to oblivion or hitchhike with strangers while others don’t even enjoy a rollercoaster ride? Is there such a thing as scaredy-cat gene or a daredevil brain structure? Or is our level of attraction to danger down to how protective our parents were?

Whether our weakness is extreme sports, speeding, drugs or other dangerous behaviours, it is typically a mix of risk and novelty that draw us in. What psychologists call “novelty seeking” is the preference for the unexpected or new. People with this trait are often impulsive and easily bored – but new experiences release a surge of pleasure chemicals in their brains. A rat or human with preferences for novelty will be more likely to do drugs and binge drink.

̽��ֱ��concepts of risk and novelty are to some extent linked: a new stimulus is inherently more risky in that any associated consequence is unknown. However, we can dissociate these two in the laboratory.

It’s (always) about dopamine

Dopamine, used by neurons to transmit messages to other neurons, is often described as the brain’s “pleasure chemical”. Dopamine cells lie in the mid-brain, deep in the base of the brain, and send “projections” to brain regions where the dopamine molecule is released – such as those involved in the control of action, cognition and reward. Studies have shown that the dopamine system can be activated by rewarding experiences, such as eating, having sex or taking drugs.

In a study of patients with Parkinson’s disease, who were on drugs that stimulated dopamine receptors used to treat their movement symptoms, 17% developed highly unexpected behavioural addictions to gambling or compulsive sexual, shopping or eating behaviours. These patients also sought out risks more, and showed a preference for novelty on lab tests. So it seems that an active dopamine system can make us take more risks.

A study on anticipating risk showed that expecting a win is associated with an increase in brain activity in dopamine regions, whereas expecting a loss is associated with a decrease in such activity. Both drive us to take risk. Wingsuit flying or roller coaster riding are motivated by our expectation of reward – a thrill – but wingsuit flying may also driven by an urge to avoid loss (in this case death). ̽��ֱ��likelihood of a thrill from base jumping or a roller coaster is close to 100%. But while the likelihood of death from a rollercoaster ride is close to 0%, the chances of dying from basejumping are considerably higher. ̽��ֱ��closer to the extremes, 0% or 100%, the more certain, whereas the closer to 50%, the more uncertain.

Dopamine reward pathways in the human brain. Oscar Arias-Carrión1, Maria Stamelou, Eric Murillo-Rodríguez, Manuel Menéndez-González and Ernst Pöppel. - Oscar Arias-Carrión1, Maria Stamelou, Eric Murillo-Rodríguez, Manuel Menéndez-González and Ernst Pöppel., CC BY-SA

Many, but not all, studies have found that people with a certain dopamine receptor are more likely to be thrill seeking. This gene variant is also associated with greater responses to unexpected rewards in the brain, making the unexpected thrill more thrilling. Genetic hardwiring might therefore explain the tendency towards base jumping, linking the preference for novelty and also possibly for risk and reward. But how we are brought up also has an impact. And adolescents are known to be more risk taking, partly because their brains are still developing and they are more susceptible to peer pressure.

And, of course, there may be other reasons why we enjoy bungee jumping or binge drinking than an attraction to risk and novelty. For example, this can happen in social situations where there’s peer pressure for us to conform, or if we are feeling down or stressed.

Why are we inconsistent?

But if our genes can influence whether we’re brave or fearful, how come we are so inconsistent in our behaviour? For example, we may sky dive on holiday yet buy travel insurance.

Have we all got an inner piglet? wikimedia

We act differently based on whether the risk is perceived to gain reward or avoid loss – an effect known as framing. Most of us tend to avoid risky rewards – we’d rather not go sky diving – but in the case of an unlikely event with a high payout such as a lottery ticket, we’re happy to take a risk. We also normally seek risk in order to avoid huge losses. This is affected by how likely it is that the outcome might occur. In the case of an unlikely but possibly very bad outcome, such as the risk of incurring massive debt while hospitalised in a foreign country, we become risk averse and buy travel insurance.

People who enjoy danger or suffer from disorders of addiction have different risk tendencies. Pathological users of illegal drugs, alcohol or food all seek risk in the face of rewards – by going after the high. But those who use illegal drugs are driven by more risky high rewards whereas those that pathologically use alcohol or food are driven by less risky lower rewards.

How likely we are to take risks can also be manipulated. A study in rats showed that risk taking can be reduced by mimicking the dopamine signal providing information about the negative outcomes from previous risky choices – such as a shock to the foot or not receiving food. Risk taking in binge drinkers can also be reduced when they are explicitly exposed to a loss outcome – such as experiencing a loss of money rather than just expecting it. A night in an emergency room may therefore be enough to change their behaviour.

Also, a new and unexpected context can increase risk-taking behaviours, which could explain why we are more likely to take risks on holiday. In a recent study, my colleagues and I showed participants a series of faces – familiar or unknown ones – and asked them to choose between a risky gamble or a safe choice. When shown a new face, subjects were more likely to take the risky gamble. ̽��ֱ��study showed that those with greater brain activity in the striatum, a region involved in dopamine release, to the new face made greater risky choices. These findings suggest that novelty increases dopamine release in this area of the brain, which then possibly enhances the expectation of reward.

But being drawn to danger isn’t necessarily a bad thing. Our society needs both risk takers and risk avoiders to function. We need those that push boundaries – to set up camp on Mars or rescue people from fires – and we need those that write the rules and enforce regulations to keep society functioning.

Valerie Voon, Honorary Consultant Neuropsychiatrist and Senior Clinical Research Associate, Department of Psychiatry, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Valerie Voon (Department of Psychiatry) discusses what makes some people want to base jump off a cliff, while others don’t even enjoy a rollercoaster ride.

Kontizas Dimitrios

BASE Jumping from Sapphire Tower, Istanbul

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Highway to addiction: how drugs and alcohol can hijack your brain

cjb250 — Thu, 25 Feb 2016 15:14:44 +0000

There is a road down which those with substance addiction travel. Its beginnings are influenced by circumstances and genetics; it becomes well trodden, habitual, initially reinforced by pleasurable effects and then by cues; and, for some, it will become a road they can never leave.

Addiction is a chronic, relapsing psychiatric disease, with complex behavioural processes and equally complex changes to brain circuits. ̽��ֱ��brain of a person who has drunk alcohol or taken drugs is different to the brain of one who has not, as pharmacologist Dr David Belin describes: “I like whisky. I started drinking whisky when I was 20 and I have only a small amount now and then. But if I were to scan my brain, it changed that very first time, and it continues to be changed.”

And because drugs change the brain in ways that foster compulsive drug and alcohol abuse, quitting is difficult, even for those who want to. Belin and Professor Barry Everitt, from the Department of Pharmacology, have shown that some are more vulnerable than others to developing addiction – and to relapsing.

Their recent research, published in Nature Communications, uncovers a new neural ‘short cut’, or ‘back door’, in rat brains that could explain why some cocaine addicts relapse without intending to. ̽��ֱ��results, they believe, could suggest new forms of behavioural and pharmacological therapies.

A decade ago, both Belin and Everitt, independently, were the first to show that addiction manifests itself differently in different individuals and that, for some, compulsive cocaine-seeking behaviour would continue despite adverse circumstances. In a rat model, around 20% of animals addicted to cocaine still sought the drug despite the risk of receiving mild electric shocks on doing so.

“This was the first time in the field of addiction that the idea of inter-individual differences in vulnerability to compulsive drug seeking was raised,” explains Belin, who is funded by the Wellcome Trust. “With regard to psychiatric disorders, we are not equally vulnerable.”

Drug addiction had largely been regarded as the end point of a progressive loss of control over drug seeking resulting from a failure of part of the brain – the prefrontal cortex – that deals with decision making.

“Certainly, chronic exposure to drugs alters the prefrontal cortex, which governs motivation, inhibitory control and choice. But it also alters an area of the brain called the basolateral amygdala, which is associated with the link between a stimulus and an emotion,” explains Belin.

To explain further he gives the example of choosing to eat a cake or an apple. “ ̽��ֱ��basolateral amygdala stores the pleasurable memories associated with eating the cake, but the prefrontal cortex manipulates this information, helping you to weigh up whether or not you should eat another slice or choose the apple instead. If you eat the slice, regions of the ventral striatum, the structure that processes reward and links emotions to actions, are activated.”

However, Belin and Everitt’s latest research has shown that this is not the only neuronal circuit that underlies cocaine-seeking behaviour.

Using their rat model, they identified a completely new highway that links impulses with habits. This brain circuit links the basolateral amygdala indirectly with the dorsolateral striatum, which is the neural locus of habits.

“Because it doesn’t recruit the prefrontal cortex it doesn’t involve choice,” explains Belin. “It’s a short cut or back door directly to habit. It means that addicts can have internal urges they are not aware of that drive drug seeking. It’s a newly recognised function of this brain circuitry.

“It would explain situations in which individuals who have been abstinent for five years suddenly relapse, telling their counsellor ‘I was walking in the street and I found myself with a glass of wine – and I promise you I didn’t want it.’ This has often been dismissed as ‘weakness of the will’ and then denial. This may also happen, but what our results in rats suggest is that there are occasions in which the stimuli go via motivation straight to the habit part of the brain without an individual even being aware of it.”

̽��ֱ��researchers believe that this is a breakthrough in understanding how drugs like cocaine can hijack the brain with such devastating consequences. “We can speculate that the subset of individuals currently using drugs who are especially vulnerable to addiction might have a stronger pathway – a ‘superhighway’ to habit formation.”

̽��ֱ��finding could explain the puzzling feature of why substance abusers repeatedly do something they know is bad for them. This is an area that interests Dr Valerie Voon in the Department of Psychiatry. “There appears to be a form of impulsivity called ‘waiting impulsivity’ that doesn’t involve choice and that predisposes to drug addiction.”

Waiting impulsivity is seen when a runner takes off before the starter pistol, or when someone interrupts inappropriately. Voon has devised a way of measuring it in humans based on tasks studied in rats. She also uses another task that teases apart decisions that are made through choices that are goal directed (i.e. taking into account the goal or outcome) from those that are habitual (i.e. relying rather automatically on past rewarding choices).

“We find that alcohol addiction correlates with waiting impulsivity. Once you’re abstinent, the compulsivity or habits also improve. Now that we have this test we can start to cut across other addictions – is there an underlying neural process shared by all? Can we ascribe causality? Can we suggest new treatments?”

Belin suggests that a combination of behavioural and pharmacological treatments might be the answer to helping addicts quit.

Treatments such as cognitive behavioural therapy aim to restore the function of the prefrontal cortex so that emotions don’t automatically elicit habits. “But if people are not aware of their impulses then they can’t subjectively or cognitively apprehend the motivation and the impulse to take drugs or drink,” says Belin. “It’s possible that mindfulness might be beneficial in helping them identify the impulses.”

Although there is currently no effective pharmacological treatment for cocaine addiction, his team has recently shown that N-acetylcysteine might be a possibility, but only if used early enough on the road to addiction when the individual still has the motivation to stop.

̽��ֱ��researchers now plan to extend their study of cocaine addiction to compulsive alcohol- and heroin-seeking behaviour. They and Voon would like to understand to what degree behavioural traits such as impulsivity, novelty preference and anxiety – using brain imaging to identify neural correlates – can be used as a predictor of compulsive drug seeking.

“Drug taking is always volitional to begin with – you take drugs because you want to experience something,” adds Belin. “Unfortunately they hijack the learning mechanisms in your brain so that you don’t really take them because you want them but because stimuli in your environment tell you to do so. We want to work out how we can help people become aware that their impulses are wrongly triggering their habits.”

̽��ֱ��discovery of a brain circuit ‘shortcut’ could explain why some addicts unintentionally relapse, and suggests that a shift in focus for therapies might help those who want to stay off drugs.

I started drinking whisky when I was 20 and I have only a small amount now and then. But if I were to scan my brain, it changed that very first time, and it continues to be changed

David Belin

̽��ֱ��District

Highway to addiction

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Online porn may feed sex addicts’ desire for new sexual images

cjb250 — Mon, 23 Nov 2015 12:12:04 +0000

In a study published in the Journal of Psychiatric Research, researchers also report that sex addicts are more susceptible to environment ‘cues’ linked to sexual images than to those linked to neutral images.

Sex addiction – when an individual has difficulty controlling their sexual thoughts, feelings or behaviour – is relatively common, affecting as many as one in 25 young adults. It is heavily stigmatised and can lead to a sense of shame, affecting an individual’s family and social life as well as their work. There is no formal definition of the condition to help with diagnosis.

In previous work led by Dr Valerie Voon from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, scientists found that three brain regions were more active in sex addicts compared with the healthy volunteers. Significantly, these regions – the ventral striatum, dorsal anterior cingulate and amygdala – were regions that are also activated in drug addicts when shown drug stimuli.

In the new study, funded by the Wellcome Trust, Dr Voon and colleagues studied the behaviour of 22 sex addicts and 40 ‘healthy’ male volunteers undergoing tasks. In the first task, individuals were shown a series of images in pairs, including naked women, clothed women and furniture. They were then shown further image pairs, including familiar and new images, and asked to choose an image to ‘win £1’ – although the participants were unaware of the odds, the probability of winning for either images was 50%.

̽��ֱ��researchers found that sex addicts were more likely to choose the novel over the familiar choice for sexual images relative to neutral object images, whereas healthy volunteers were more likely to choose the novel choice for neutral human female images relative to neutral object images.

“We can all relate in some way to searching for novel stimuli online – it could be flitting from one news website to another, or jumping from Facebook to Amazon to YouTube and on,” explains Dr Voon. “For people who show compulsive sexual behaviour, though, this becomes a pattern of behaviour beyond their control, focused on pornographic images.”

In a second task, volunteers were shown pairs of images – an undressed woman and a neutral grey box – both of which were overlaid on different abstract patterns. They learned to associate these abstract images with the images, similar to how the dogs in Pavlov’s famous experiment learnt to associate a ringing bell with food. They were then asked to select between these abstract images and a new abstract image.

This time, the researchers showed that sex addicts where more likely to choose cues (in this case the abstract patterns) associated with sexual and monetary rewards. This supports the notion that apparently innocuous cues in an addict’s environment can ‘trigger’ them to seek out sexual images.

“Cues can be as simple as just opening up their internet browser,” explains Dr Voon. “They can trigger a chain of actions and before they know it, the addict is browsing through pornographic images. Breaking the link between these cues and the behaviour can be extremely challenging.”

̽��ֱ��researchers carried out a further test where 20 sex addicts and 20 matched healthy volunteers underwent brain scans while being shown a series of repeated images – an undressed woman, a £1 coin or a neutral grey box.

They found that when the sex addicts viewed the same sexual image repeatedly, compared to the healthy volunteers they experienced a greater decrease of activity in the region of the brain known as the dorsal anterior cingulate cortex, known to be involved in anticipating rewards and responding to new events. This is consistent with ‘habituation’, where the addict finds the same stimulus less and less rewarding – for example, a coffee drinker may get a caffeine ‘buzz’ from their first cup, but over time the more they drink coffee, the smaller the buzz becomes.

This same habituation effect occurs in healthy males who are repeatedly shown the same porn video. But when they then view a new video, the level of interest and arousal goes back to the original level. This implies that, to prevent habituation, the sex addict would need to seek out a constant supply of new images. In other words, habituation could drive the search for novel images.

“Our findings are particularly relevant in the context of online pornography,” adds Dr Voon. “It’s not clear what triggers sex addiction in the first place and it is likely that some people are more pre-disposed to the addiction than others, but the seemingly endless supply of novel sexual images available online helps feed their addiction, making it more and more difficult to escape.”

Reference
Banca, P et al. Novelty, conditioning and attentional bias to sexual rewards. Journal of Psychiatric Research; published in advance 27 October 2015

People who show compulsive sexual behaviour – sex addiction – are driven to search more for new sexual images than their peers, according to new research led by the ̽��ֱ�� of Cambridge. ̽��ֱ��findings may be particularly relevant in the context of online porn, which potentially provides an almost endless source of new images.

It’s not clear what triggers sex addiction, but the seemingly endless supply of novel sexual images available online helps feed their addiction, making it more and more difficult to escape

Valerie Voon

Frederico Cintra

Control is an Option to Command (cropped)

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Brain activity in sex addiction mirrors that of drug addiction

cjb250 — Fri, 11 Jul 2014 18:00:00 +0000

Although precise estimates are unknown, previous studies have suggested that as many as one in 25 adults is affected by compulsive sexual behaviour, an obsession with sexual thoughts, feelings or behaviour which they are unable to control. This can have an impact on a person’s personal life and work, leading to significant distress and feelings of shame. Excessive use of pornography is one of the main features identified in many people with compulsive sexual behaviour. However, there is currently no formally accepted definition of diagnosing the condition.

In a study funded by the Wellcome Trust, researchers from the Department of Psychiatry at the ̽��ֱ�� of Cambridge looked at brain activity in nineteen male patients affected by compulsive sexual behaviour and compared them to the same number of healthy volunteers. ̽��ֱ��patients started watching pornography at earlier ages and in higher proportions relative to the healthy volunteers.

“ ̽��ֱ��patients in our trial were all people who had substantial difficulties controlling their sexual behaviour and this was having significant consequences for them, affecting their lives and relationships,” explains Dr Valerie Voon, a Wellcome Trust Intermediate Clinical Fellow at the ̽��ֱ�� of Cambridge. “In many ways, they show similarities in their behaviour to patients with drug addictions. We wanted to see if these similarities were reflected in brain activity, too.”

̽��ֱ��study participants were shown a series of short videos featuring either sexually explicit content or sports whilst their brain activity was monitored using functional magnetic resonance imaging (fMRI), which uses a blood oxygen level dependent (BOLD) signal to measure brain activity.

̽��ֱ��researchers found that three regions in particular were more active in the brains of the people with compulsive sexual behaviour compared with the healthy volunteers. Significantly, these regions – the ventral striatum, dorsal anterior cingulate and amygdala – were regions that are also particularly activated in drug addicts when shown drug stimuli. ̽��ֱ��ventral striatum is involved in processing reward and motivation, whilst the dorsal anterior cingulate is implicated in anticipating rewards and drug craving. ̽��ֱ��amygdala is involved in processing the significance of events and emotions.

̽��ֱ��researchers also asked the participants to rate the level of sexual desire that they felt whilst watching the videos, and how much they liked the videos. Drug addicts are thought to be driven to seek their drug because they want – rather than enjoy – it. This abnormal process is known as incentive motivation, a compelling theory in addiction disorders.

As anticipated, patients with compulsive sexual behaviour showed higher levels of desire towards the sexually explicit videos, but did not necessarily rate them higher on liking scores. In the patients, desire was also correlated with higher interactions between regions within the network identified – with greater cross-talk between the dorsal cingulate, ventral striatum and amygdala – for explicit compared to sports videos.

Dr Voon and colleagues also found a correlation between brain activity and age – the younger the patient, the greater the level of activity in the ventral striatum in response to pornography. Importantly, this association was strongest in individuals with compulsive sexual behaviour. ̽��ֱ��frontal control regions of the brain – essentially, the ‘brakes’ on our compulsivity – continue to develop into the mid-twenties and this imbalance may account for greater impulsivity and risk taking behaviours in younger people. ̽��ֱ��age-related findings in individuals with compulsive sexual behaviours suggest that the ventral striatum may be important in developmental aspects of compulsive sexual behaviours in a similar fashion as it is in drug addictions, although direct testing of this possibility is needed.

“There are clear differences in brain activity between patients who have compulsive sexual behaviour and healthy volunteers. These differences mirror those of drug addicts,” adds Dr Voon. “Whilst these findings are interesting, it’s important to note, however, that they could not be used to diagnose the condition. Nor does our research necessarily provide evidence that these individuals are addicted to porn – or that porn is inherently addictive. Much more research is required to understand this relationship between compulsive sexual behaviour and drug addiction.”

Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust, says: “Compulsive behaviours, including watching porn to excess, over-eating and gambling, are increasingly common. This study takes us a step further to finding out why we carry on repeating behaviours that we know are potentially damaging to us. Whether we are tackling sex addiction, substance abuse or eating disorders, knowing how best, and when, to intervene in order to break the cycle is an important goal of this research.”

Pornography triggers brain activity in people with compulsive sexual behaviour – known commonly as sex addiction – similar to that triggered by drugs in the brains of drug addicts, according to a ̽��ֱ�� of Cambridge study published in the journal PLOS ONE. However, the researchers caution that this does not necessarily mean that pornography itself is addictive.

There are clear differences in brain activity between patients who have compulsive sexual behaviour and healthy volunteers

Valerie Voon

Nick Olejniczak

Browsing (cropped). Homepage image: Ecstacy by Terminallychll

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