obsessive-compulsive disorder extinction failure

Posted comment on ´Enhanced Avoidance Habits in Obsessive-Compulsive Disorder` by C.M.Gillan, S. Morein-Zamir, G.P. Urcelay, A. Sule, V. Voon, A.M. Apergis-Schoute, N.A. Fineberg, B.J. Sahakian, T.W. Robbins published in Biological Psychiatry vol 75, issue 8, Pages 631–638, April 15, 2014 doi: dx.doi.org/10.1016/j.biopsych.2013.02.002

SUMMARY

The authors took a group of 25 patients suffering from obsessive compulsive disorder (OCD) and an equal number of control subjects in order to investigate whether there is a link between habits, erroneous thinking (shown by behaviour, questionnaires and subjective reports) and physiological arousal ( shown by skin conductance). In a shock avoidance test, each subject was randomly presented with one of 3 coloured rectangles (the conditioned stimulus, CS) with 2 being warning stimuli for a shock to the left or right wrist and the third a safe stimuli that never led to the shock. Subjects learnt to avoid the shock by pressing the corresponding foot pedals while the conditioning stimulus was on the screen. Response to the third CS was always safe with no shock.

The experiment consisted of a brief training session where the subjects were informed before the experiment that the task was to avoid receiving shocks followed by a devaluation test in extinction (devaluation sensitivity test) to see if a habit had formed. Shock outcomes were devalued by disconnecting in front of the subject the shock generator from one of the subjects’ wrists (devalued) whereas the other wrist remained connected (valued). Subjects were informed that they could no longer be shocked to the wrist that was disconnected and that their only task was to avoid receiving the remaining shock. This was followed by an extended training session and then a final devaluation test in extinction (habit test) where the the alternative wrist was devalued. The experiment ended with subjects being questioned on their explicit knowledge of the stimulus-action-outcome associations experienced during training, their level of expectancy of a shock on presentation of the devalued stimulus and justification of their continued response in the habit test.
Gillan and colleagues reported that before overtraining in the devaluation sensitivity test both groups responded more to the valued than the devalued stimulus and that there was no difference between the groups by stimulus interaction indicating that OCD patients were equally capable of understanding the safety of the devalued stimulus and that responses were unnecessary. Following overtraining in the habit test responses to the valued stimulus did not differ between the groups, but was greater than the devalued stimulus. The majority of subjects did not continue to respond in the habit test, with just nine OCD patients and two control subjects making any responses and mathematical evaluation of responses altered accordingly. Both groups showed a strong devaluation effect, but OCD patients demonstrated greater avoidance of the devalued stimulus, hence showed greater stimulus-response habit learning than control subjects. The OCD patients reported a stronger urge to perform the pedal press even when unnecessary and some of this group and two control subjects said that they tried to suppress the unwanted action. Those that did respond though justified their actions by voicing irrational beliefs which may have gone against their explicit knowledge and expectations.
The authors concluded that this was the first experimental demonstration of habits in humans in avoidance using a goal devaluation procedure with OCD patients showing bias towards avoidance habits. Both groups were capable of evaluating the stimulus for risk of shock and could adapt their response accordingly, but the experiment showed that OCD patients were less able to forego responding and justified their unnecessary actions with irrational beliefs.

COMMENT

This article shows that OCD patients failed to ´re-programme` responses in a fear conditioning situation in comparison to control subjects. Extinction did not occur and therefore the pattern of behaviour was continued even though not necessary. The OCD patients justified this failure to adapt with irrational beliefs which by repetition may have reinforced the fear itself. It is this that makes this experiment interesting since the shock was initiated at a time interval when conscious awareness and corresponding cognitive processing would have occurred so that in normal circumstances there would be realisation that the pedal press to stop the shock was unnecessary. Therefore, in OCD patients the deep-rooted conditioning memory in response to the stimuli overrode the reality and illogical excuses were given why behaviour was not as expected. In behavioural terms the urge to pedal press was maintained even though the subject knew that no shock would result. These results supports other recognised research and indicates the role cognitive dissonance may have in OCD behaviour.
It can be assumed that in the initial habit formation in a fear learning situation that the brain area linked with fear, the amygdala, shows long-term potentiation associated with an increase in AMPA receptors, and that in basal ganglia areas related to emotions eg the caudate and striatum that dopamine signalling is required. The increase in dopamine release as reward for the correct behaviour leads to reinforcement of the memory synaptic connections. However, repetition leads to dopamine receptor 1 independent responses. This supports the observation that repeated retrieval targeted memories leads to decreased function of the prefrontal cortex and anterior cingulated cortex, both associated with error monitoring, decision-making and conscious awareness.
Changed experimental demands leads to adaptation of the memory traces linked to the stimulus-action habit. Learning to inhibit fear responses in extinction requires dopamine activity eg in nucleus accumbens and extinction is linked to increased levels of synaptic inhibition in fear output neurons of the amygdala caused by increased GABA interrelated neurons requiring prefrontal cortical activity. Activity in the hippocampus and perirhinal cortex is also required for the adapted memory traces.
In the case of OCD sufferers extinction appeared not to occur. In control subjects this could have several biochemical explanations. For example that the decision-making made demonstrates a preference for the older memory and the calculation of the value of the outcome by the prefrontal cortex and orbitofrontal cortex is ignored. This would signify deficient dopamine and corticostriatal pathways. Or, stronger activation of older memories leads to less accurate retrieval of newer memories simultaneously reactivated in the ventral temporal cortex and increased anterior cingulated cortex activity. It could be also that the down-regulation of Rac1 and CDK5 up-regulation of p21 activated kinase or CB1 signalling required for extinction are not occurring in the case of the OCD sufferers. These types of investigations should be carried out in order to clarify the situation further in the case of OCD patients.
Since we´re chatting about the topic………

…if the administration of glucocorticoid agonists can lead to extinction of conditioned fear can it be assumed that in the case of the OCD patient there would be no effect?

…if we could observe the right amygdala of the OCD sufferer we would see activation in the devaluation test because of the fear that forgetting would bring about the shock.

…would it be right to assume that if the delay between cue and shock was extended and that a prompt was given to re-think that the unnecessary automatic responses of the OCD patient could be reduced?

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