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Brain scans reveal why it is so difficult to recover from OCD and hint at ways forward
by Annemieke Apergis-Schoute
The Conversation

March 7, 2017

We often refer to people who are extremely neat or organised as “a bit OCD”. But the reality of living with obsessive compulsive disorder is a very different and serious matter.

People with the brain disorder struggle greatly with recurrent, intrusive thoughts (obsessions) and unwanted urges to repeat safety-seeking behaviours over and over again (compulsions). Common examples are exaggerated fears of contamination or causing injury – leading to excessive washing or checking. It is easy to see why that causes extreme distress and interferes with everyday life.

In some cases, people with OCD are tormented with agonising taboo thoughts, for example the fear that they will sexually abuse a child even though they have no desire whatsoever to do so. This is coupled with the compulsion to seek reassurance, for example by avoiding children or checking newspapers in case they have been accused. Such people are often too ashamed to disclose their symptoms, worrying about being punished or judged to be “insane”. When listening to such patients it is clear their torment is real, with day after day spent enduring irrational fears and repeating seemingly purposeless behaviours.

A standard treatment for OCD involves exposure and response prevention (ERP). This involves the patient confronting their worst fears while learning to not perform their compulsions. For example, it may include touching a toilet seat and not being allowed to wash your hands. This treatment is often combined with comparatively high doses of selective serotonin re-uptake inhibitor (SSRI) drugs – typically three times higher than that needed to treat depression. Together this can help many patients with OCD, but far from all. So why is OCD such a debilitating disorder and why can it be so hard to treat? Our new research offers a clue – and some hope for those struggling.

Naomi Fineberg, who leads a specialist clinic for patients with OCD, sees many for whom daily life is difficult and who continue to struggle with their disorder despite treatment. According to her, about 40% of patients fail to respond to individually-tailored treatments. What’s more, many are left with residual troublesome symptoms such as continuing obsessive thoughts or relapse.

Such patients may still fall into depression and suicidal behaviour after treatment, becoming so overwhelmed by their obsessive compulsive behaviours that they end up neglecting their family, work, friends and health. OCD in its most severe form disrupts even the most basic self-care activities, such as eating or drinking – sometimes resulting in the need for long-term hospitalisation or residential care.

OCD on the brain
The new study from our team here at the University of Cambridge, published in the Proceedings of the National Academy of Sciences, is now beginning to show why this is. We compared 43 OCD patients with 35 healthy control participants in an experiment designed to investigate why patients with OCD struggle to learn that not performing their safety behaviours is in fact “safe”. We did this by examining their ability to flexibly adjust their reactions to changes in threat while inside an fMRI scanner, which measures brain activity by tracking changes in blood flow, at the Wolfson Brain Imaging Centre.

We showed the participants two angry faces, of which one was sometimes paired with a mild electric shock to the wrist, making it threatening. Recordings of tiny changes in sweat indicated when participants were expecting a shock. To test flexible updating of threat we also reversed the stimuli so that the “safe” face became the threatening one and vice versa. The experiment tests the individual’s ability to learn when a stimulus is safe and so not to expect a shock. By reversing the stimuli, we introduced ambiguity as both faces had by then been associated with the possibility of a shock.

Ventromedial prefrontal cortex: signals safety.
Patrick J. Lynch, medical illustrator, CC BY-SA

Patients with OCD could initially learn which face predicted threat. But once this had been reversed they were unable to differentiate between the new and the old threatening stimulus – they treated both as threatening. We think this is because they never really learned that one of the faces was truly safe – something which was reflected in their brain activity. Unlike in the healthy participants, there was no signal from the OCD patients’ ventromedial prefrontal cortex, a brain area that normally signals safety.

The results suggest that OCD patients are likely to have difficulty learning when situations are safe in everyday life – and that this has to do with differences in the brain. This has great relevance for the current psychological treatment of OCD, in which patients are expected to learn that not performing excessive and compulsive safety behaviours is in fact “safe” and therefore unnecessary. Current exposure therapies may only teach patients how to deal with their compulsions rather than truly learning that the situations they are so scared of are not actually dangerous. This means that obsessive thoughts can persist, and that it is possible for compulsive behaviour to return in future stressful situations.

The research follows another recent study published in Biological Psychiatry, which discovered a lack of communication between specific brain areas in patients with OCD. In particular, it found disrupted connectivity between neural pathways that connect the front of the brain with the basal ganglia, which are critical for flexible thinking and goal-directed behaviours that we know are impaired in OCD patients and are likely to contribute to the difficulty of overcoming the drive to perform needless compulsions.

An avenue for improving future treatment for OCD would be to explore better learning in patients that not performing compulsive safety behaviours is truly safe. This could be achieved by boosting rewards in therapy for not performing safety behaviour or possibly with the help of certain drugs that can enhance the positive experience of not having to perform the compulsions.


What Causes OCD?​

OCD is a brain disorder caused by multiple factors that are not completely known nor understood. In some cases, OCD is genetic (inherited through the mother’s or father’s genes), but in other cases it is related to certain infections (in rare situations, some children develop obsessive symptoms after a severe throat infection, for example), traumatic events (such as threatening situations, abuse, or bullying), and/or chronic stress [2]. We already know that OCD is not caused by anything that the patient or his/her parents did “wrong.”

The brain works like a computer, with multiple networks connecting brain regions that are responsible for different functions. We have complex systems for every function. For example, one brain network is responsible for acquiring and managing the data that comes in from our senses, another is responsible for creating and managing our emotions, another is responsible for movements, and another is responsible for creating, managing and prioritizing our thoughts.

In OCD, the communication system between parts of the brain, namely the orbitofrontal cortex and the basal ganglia, is disrupted and the brain makes mistakes when processing and prioritizing information.

The orbitofrontal cortex is responsible for using information from the senses to make decisions, and anticipating the result of our life choices. In OCD, this region is hyperactivated and detects errors and dangers where there is not anything wrong.

The basal ganglia controls movements and thinking, and acts as a control system that filters and stops anxious thoughts. In OCD, the basal ganglia fail to control the errors and dangers wrongly identified by the orbitofrontal cortex, which makes the patient overwhelmed by his or her thoughts and actions (Figure 1).



Though motor disorders are the most common associated with the basal ganglia, recent research shows that basal ganglia disorders can lead to other dysfunctions such as obsessive–compulsive disorder (OCD) and Tourette syndrome.

Since the realization that syndromes such as Tourette syndrome and OCD are caused by dysfunction of the non-motor loops of basal ganglia circuits, new treatments for these disorders, based on treatments originally designed to treat movement disorders are being developed.


The cortico-basal ganglia-thalamo-cortical loop (CBGTC loop) is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease,[1] as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD),[2] obsessive–compulsive disorder (OCD),[3] and Tourette syndrome.[4]


The role of inflammation in OCD has been strengthened by the higher rate of anti-basal ganglia antibodies (ABGA) in patients with primary OCD versus control subjects. Moreover, significantly increased levels of cytokines and inflammatory agents have been observed in OCD patients, such as IL-2/4/6/10 and TNF-α, compared to controls. In a recent study using positron emission tomography (PET) imagery, the presence of inflammation in the cortico-striatal-thalamo-cortical circuit was shown to induce microglial cell activation in OCD patients...

In low doses, lithium may appear to be interesting against OCD because of its potential inhibitory effect on oxidative stress, inflammation, and the glutamatergic pathway.
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May 2019

A striking change OCD patients repeatedly describe following treatment with deep brain stimulation (DBS) of the ventral anterior limb of internal capsule (vALIC) is an immediate increase in self-confidence. We show how the DBS-induced changes in self-confidence reported by our patients can be understood neurocognitively in terms of active inference...

Furthermore, we have observed that when DBS stimulation parameters are set too high, the patient behaves more impulsively, a sign of excessive self-confidence...

Self-confidence is reduced in OCD. The person’s power to act in the world is severely diminished by their illness. OCD patients anticipate dangers such as contamination, and threats such as causing harm to others, or performing actions they find morally repugnant [6]. The reduced self-confidence our patients report is the result of their actions being driven by their anticipation of threat and danger. We suggest that DBS increases self-confidence by allowing the patient to again be open to other possibilities for action and not only those that relate to their fear and anxiety...

We hypothesise that people with OCD weigh the precision of their action policies, in part, based on their fearful and anxious mode of relating to the world. This has the consequence that their anxious anticipations are in the driving seat when it comes to selecting the action possibilities that drive their behaviour (Box 1). The effect of DBS is to restore the context-sensitive weighing of precision expectations. This allows the person to better anticipate what is relevant to them, and thus to once again be open to the many action possibilities of significance to them. It is the recovery of their readiness for and grip on the world that accounts for their increased self-confidence...

As long as precision is high for anxious anticipations, this will result in the person focusing only on the dominant affordance(s) relating to their anxious state of anticipation. When anxiety reduces, the person is once again open to dealing with the many other action possibilities the environment makes available. The result of this openness and readiness for the world is increased self-confidence.
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"The main reason that compulsions seem so hard to stop is because you have rehearsed them so often that they have become very automatic habits that are easy to do without thinking. You get good at things you rehearse a lot."

David Baxter PhD

Late Founder

"The main reason that compulsions seem so hard to stop is because you have rehearsed them so often that they have become very automatic habits that are easy to do without thinking. You get good at things you rehearse a lot."

Exactly... unfortunately. :(


“We saw this wide span in how likely the mice were to naturally become compulsive. Neurobiological variability is an interesting thing to take advantage of to understand how psychiatric illnesses might result from being on the tail ends of distributions, and looking what circuits control that variability in animal models will be really important for understanding human variability.”

The dorsomedial striatum (DMS) receives excitatory inputs from prefrontal cortices and is implicated in goal-directed action control, whereas the dorsolateral striatum (DLS) primarily receives inputs from sensorimotor and premotor cortices and is implicated in habit and skill learning.


  • Random interval training causes punishment-resistant reward seeking in some mice
  • DMS dopamine signals predict which mice will develop punishment resistance
  • Enhancing DMS dopamine signals accelerates the development of punishment resistance
  • Inhibiting DMS dopamine signals slows the development of punishment resistance

Compulsive behavior is a defining feature of disorders such as substance use disorders. Current evidence suggests that corticostriatal circuits control the expression of established compulsions, but little is known about the mechanisms regulating the development of compulsions.

We hypothesized that dopamine, a critical modulator of striatal synaptic plasticity, could control alterations in corticostriatal circuits leading to the development of compulsions (defined here as continued reward seeking in the face of punishment)...

Individual variability in the speed with which compulsions emerged was predicted by DMS dopamine axon activity. Amplifying this dopamine signal accelerated animals’ transitions to compulsion, whereas inhibition delayed it.

In contrast, amplifying DLS dopamine signaling had no effect on the emergence of compulsions. These results establish DMS dopamine signaling as a key controller of the development of compulsive reward seeking...

Our findings suggest there is a predisposition to punishment resistance [PR] present in some individuals before they confront punishments (analogous to our PR mice), rather than a stochastic process occurring during the experience of punishment.

We often perform actions even when they incur heavy costs or no longer serve any clear purpose. Two recent studies have independently identified heightened phasic dopamine release in the dorsomedial striatum as a predisposing factor for such behavioral inflexibility.

On the positive side:

People with OCD tend to be very persistent in achieving their goals. The same drive that someone has toward completing a compulsion, when directed toward more meaningful goals, will allow them the ability to stick with a task, even when it feels adverse or difficult. This persistence can be what makes someone with OCD a loyal parent, colleague, or friend, and it is also what makes them highly successful in achieving their personal goals. The natural persistence someone with OCD has can be such a strength, when directed toward health and well-being, rather than completing a compulsion...

Similar to persistence, determination is another trait often found in people with OCD. Determination is different in that it is the driving force behind someone’s desire to complete a goal. The sense of “I am going to do this thing even if it is hard”, is what is needed in order for someone to be persistent. Again, the same steadfastness that is found in someone when they feel determined to complete a compulsion in order to gain certainty, can be repurposed in someone with OCD to fuel their completion of more useful tasks or goals.


The main reasons for failure of CBT include patients’ lack of motivation in reducing rituals and the presence of comorbid disorders, such as moderate-to-severe depression or avoidant personality disorder. Unfortunately, even with effective medication, responders who suffer from severe symptoms show residual impairments and there are also serious health concerns with long-term pharmacotherapy usage.

At present, no treatment has been demonstrated to be totally curative for OCD. Most interventions can be expected to reduce symptoms by 50–80%. However, the illness is cyclic, and worsens when the individual is under stress. Additional treatment strategies are thus required to more effectively tailor this complex symptomatology.