Summary: New research suggests that people with obsessive-compulsive disorder (OCD) have trouble learning that previously threatening cues are safe. This difficulty in safety learning may help explain why compulsive behaviours often return despite treatment.
Source: University of Cambridge
People with obsessive-compulsive disorder (OCD) struggle to learn when a stimulus becomes safe, a deficit that may help explain persistent compulsive behaviours, according to new research from the University of Cambridge.
OCD is marked by intrusive thoughts and repetitive, often irrational behaviours. Examples include excessive hand washing driven by fears of contamination or repeated checking of doors to prevent imagined disasters. These compulsions can severely disrupt daily life.
One common treatment, exposure therapy, involves deliberately confronting feared situations or objects while refraining from the compulsive response — for instance, touching a contaminated surface and not washing. Although exposure can reduce anxiety and compulsive actions for many patients, its benefits are not always lasting and compulsions can reappear under stress. The new findings, published in the Proceedings of the National Academy of Sciences, shed light on why safety memories formed during exposure may not persist.
Researchers at Cambridge’s Behavioural and Clinical Neuroscience Institute tested 43 people with OCD alongside 35 matched healthy volunteers to compare how each group learned about threat and safety cues and how flexibly they updated those associations. The study combined behavioural measures with functional magnetic resonance imaging (fMRI) and autonomic responses to track learning and brain activity.
Participants lay in an fMRI scanner and viewed two face images. One face was occasionally paired with a mild electric shock (the threatening cue), while the other face was not (the safe cue). Skin conductance responses—small changes in sweat gland activity that index emotional arousal—were recorded to determine whether participants learned which face predicted a shock.
After an initial learning phase, the contingencies were reversed so that the previously threatening face became safe and the previously safe face became the threat. This reversal test assesses cognitive flexibility and the ability to update safety and threat associations.
The results showed that people with OCD could initially learn which stimulus signalled threat, but they failed to form a clear representation of the safe stimulus. During reversal, OCD participants did not distinguish between the old and new threat cues. The fMRI data mirrored these behavioural effects: when viewing the safe stimulus, people with OCD showed reduced activity in the ventromedial prefrontal cortex (vmPFC), a frontal brain region known to signal safety and support flexible updating of emotional responses.
“Our findings indicate that safety signaling in the brain is disrupted in people with OCD,” said Dr Annemieke Apergis-Schoute, the study’s lead author. “Even when patients can learn that something is threatening, they appear less able to learn and retain that a stimulus is safe. That may help explain why exposure therapy often fails to produce durable changes: patients may gain transient control over compulsions but not internalize the safety signal, leaving them vulnerable to relapse under stress.”
A related study from the same group, published in Biological Psychiatry, explored why this cognitive inflexibility might occur. Led by PhD student Matilde Vaghi, the research used resting-state fMRI to measure intrinsic functional connectivity between brain regions. The team found disrupted communication within frontostriatal networks—pathways that link frontal cortical areas with the basal ganglia, a collection of structures involved in movement, habit formation and executive control.
Poor connectivity within these networks was associated with less flexible behaviour and weaker goal-directed control, both of which are commonly impaired in OCD. When goal-directed systems are compromised, behaviour becomes more habitual and harder to adjust when circumstances change — a characteristic that can underlie repetitive compulsions.
Professor Trevor Robbins, Head of Psychology at Cambridge and senior author on both studies, commented: “Taken together, these studies point to an imbalance in frontal brain systems in people with OCD. Disrupted safety signaling and weakened frontostriatal communication likely contribute to the inflexible behaviour and relapse risk observed clinically.”
Funding: The research was funded by the Wellcome Trust.
Additional related findings are reported in Biological Psychiatry.
Source: Craig Brierley, University of Cambridge
Original research: “Neural basis of impaired safety signaling in Obsessive Compulsive Disorder” by Annemieke M. Apergis-Schoute, Claire M. Gillan, Naomi A. Fineberg, Emilio Fernandez-Egea, Barbara J. Sahakian, and Trevor W. Robbins. Published in Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1609194114
Neural basis of impaired safety signaling in Obsessive Compulsive Disorder
Assigning safety to cues in the environment is essential for adaptive behavior. The ventromedial prefrontal cortex (vmPFC) plays a central role in this evaluation. Using neuroimaging during a Pavlovian fear reversal paradigm, the study examined flexible updating of threat and safety signals in OCD, a disorder characterized by inflexible, anxiety-driven behavior. Skin conductance responses in OCD patients (n = 43) failed to differentiate threat and safety during reversal compared with healthy controls (n = 35), despite intact early conditioning and normal amygdala activation. In OCD, vmPFC safety signals were absent across learning, and elevated vmPFC responses during early conditioning predicted the degree of later generalization. Additional findings showed hyperconnectivity between the vmPFC and salience network regions (dorsal anterior cingulate, insula, thalamus) during early learning, suggesting biased processing toward threat cues. The absence of vmPFC-mediated safety signaling undermines flexible updating of threat contingencies and may reduce the effectiveness of exposure-based interventions that rely on durable safety learning.