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Essay: To what extent can the placebo effect be regarded as a cognitive bias regarding Parkinson’s Disease?

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EPQ: To what extent can the placebo effect be regarded as a cognitive bias regarding Parkinson’s Disease? (draft)
Abstract
The aim of this report is to explore and compare the placebo effect and cognitive biases, in particular the confirmation bias. I intend to review the mechanisms of both and the similarities and differences between them so that I can differentiate the two and come to a sound conclusion. I will also delve into how they are relevant in the medical world, specifically relating to Parkinson’s Disease. Overall, my purpose in this is to determine whether or not the placebo effect can be regarded as a form of cognitive bias.
Introduction
The word ‘placebo’ is Latin, meaning ‘I shall please,’ so the placebo effect can be seen as a sort of pleasing effect. Essentially that is all the placebo effect is; an inert substance that is given as a sham treatment to a patient in order to trigger a natural response, in the hopes of pleasing or alleviating the worries and ailments of the patient. In more scientific terms, “the true psychobiological placebo effect,” can be defined as a change in the patient’s “emotional state” (Benedetti, F. 2009). This means the mechanism of the placebo effect lies in the mind, showing how much power the mind has over our bodies and our wellbeing. I should clarify that the placebo effect does not heal illnesses, however it can cause an increased rate of improvement or acceptance of treatment. For example, cancer patients undergoing chemotherapy are often treated with a form of the placebo effect, in order to relieve them of side effects, such as nausea and general pain. This does not cure the patient, but rather eases their ailments. As a result of the accelerated rate, there is often an overall improvement to health and general wellbeing. There is much to be said about the expectation and the consequential intensity of the placebo effect, which will be explored later, but a fundamental concept of the placebo effect is that “trust, beliefs and expectations are crucial in placebo and placebo-related effects” (Benedetti, F. 2009).
Parkinson’s disease is a motor neuron disease that affects approximately 1 in 500 people. It is degenerative and, as of now, has no cure. It is caused by the accumulation of toxic proteins, called alpha synuclein, in the part of the brain called the substantia nigra, that kill nerve cells and lead to the depletion of dopamine . Dopamine is a neurotransmitter; “a chemical that ferries information between neurons.” Electrical impulses are sent from our brains to our bodies via neurons found in the central nervous system, comprising of the brain and the spinal cord. These neurons can only pass on signals to other neurons using the chemical dopamine. It is an essential substance in all humans, and it regulates many of our bodily functions, such as movement, hence it plays such a key role in Parkinson’s disease. The most common symptoms and struggles of Parkinson’s disease include, but are not restricted to, tremors, bradykinesia (slowness of movement), rigidity, issues with gait (movement of limbs) and balance and cognitive impairments, such as depression and anxiety and memory loss .
The brain is an incredible and complex organ. It processes information, controls our movements and regulates our internal functions, as well as much more. However, it is susceptible to lapses and mistakes. “A cognitive bias is a systematic error in thinking that affects the decisions and judgments that people make” (Cherry, K. 2018). There are many types of cognitive bias, but one of particular interest that relates quite well to the placebo effect is the confirmation bias. The confirmation bias can be viewed rather pessimistically as a form of deception within one’s self. It occurs “when an individual looks for and uses the information to support their own ideas or beliefs” (Spencer and Heneghan, 2018). This links to the pivotal idea of expectation vs. intensity in the placebo effect by saying that if one anticipates a certain outcome, it is more likely to happen, and with more power and strength over the mind. The concept of scotomization (a psychological ‘blind spot’ where the mind blocks undesirable ideas) and ‘you see what you want to see’ stems from here. The 17th century English scientist, Francis Bacon described the confirmation bias as:

“Once a man’s understanding has settled on something (either because it is an accepted belief or because it pleases him), it draws everything else also to support and agree with it. And if it encounters a larger number of more powerful countervailing examples, it either fails to notice them, or disregards them, or makes fine distinctions to dismiss and reject them, and all this with much dangerous prejudice, to preserve the authority of its first Conceptions.”

This hints that the confirmation bias can be hazardous and lead to ignorance and egotism, however, it is a powerful tool that can be utilised in medicine, as it has similar foundations and mechanisms to the placebo effect.
The Mechanism of the Placebo Effect
As aforementioned, the vital concept and origin of the placebo effect lies in belief and persuasive mental activities, resulting in substantially powerful mind-body interactions . There are two main sets of mechanisms which maintain and sustain the placebo effect; appraisals and precognitive associations.
Precognitive associations are innate responses to external and internal stimuli that can occur without cognitive engagement. These responses are specific to certain stimuli and they are learned and based on experience, as only from experience can the correct neural pathways be formed in the nervous system. The placebo effect mimics pavlovian conditioning in some ways. In humans, the placebo effect is commonly delivered through pharmacological conditioning, in which over several, usually consecutive, days, both drugs and drug cues are given to the subject, and then eventually, only the drug cues are given. This often results in changes to hormonal and immune functions in the body, which are then unresponsive to verbal cues negating the use of the drugs. At this stage, it is assumed that the subject’s belief and power of mind supports the effect of the drug cues, resulting in a stable outcome . Research conducted on the role of explicit verbal information in conditioned analgesia concludes that the meaning allocated to the drug cue engages the cerebrum and produces a learning process, from which the neural pathways are formed . Without this meaning and association, the stimuli is insufficient independently and a response will not be induced.
Appraisals are, as the name suggests, appraisals of situations and events. These situations and events can be things such as memories, understanding of emotions, goals, conceptions, precognitive associations and interoception (a sense and awareness of the internal bodily state). Appraisals are constructed and conceptual, whereas precognitive associations are reactive and stimulated . They aim to twist and manipulate stimuli, cognitively reconstructing it so that the desired response is produced. A real-life example of this has been conducted in an experiment. Researchers explored the amount of empathy and consideration conveyed in a general practitioner’s check-up for the common cold in a patient and found that “the interaction between patient and health care practitioner can have significant healing influences” (Rakel, D., et al. 2011). From the 200 patients who partook in this experiment, 64% of those who had positive interaction reported recovery or an accelerated recovery rate, whereas only 39% of those who had a negative interaction or a normal interaction experienced faster recovery . From this, it can be deduced that patient appraisal, particularly the aspect that understands emotions, has a monumental impact on health and immune function.
It is the relationship between precognitive associations and appraisals that produces the placebo effect. Appraisals rely on the stimuli of the external environment to trigger the formation of neural pathways in precognitive association and morph what is learned into what ‘should’ be learnt, so that the required response can be developed and expressed. The biggest and most effective placebo effects are induced when there is repeated, successful cognitive experience and reinforcement of pathways. Essentially, the more the pathway is recalled and used, the stronger it is, so the induced effect is more powerful and easier to summon.
The Mechanism of the Confirmation Bias
The confirmation bias is one of the oldest and most ordinary psychological phenomena. I say ordinary because, as Nickerson (1998) put it:

“If one were to attempt to identify a single problematic aspect of human reasoning that deserves attention above all others, the confirmation bias would have to be among the candidates for consideration.”

We see, and indeed succumb, to this phenomenon every day. For example, if person X is a supporter of LGBTQ rights, they will hear stories and read articles and interpret them in such a way that agree or comply with their perception. Alternatively, person Y, who is very against LGBTQ rights, may specifically search for sources and information that is in favour of their view. These persons have vastly contrasting views, so even if they hear or read the same story, their confirmation bias will influence the way they perceive the information and lead to a further encouragement of their opinion .
As with the placebo effect, there are two main mechanisms that cause and conserve the confirmation bias; the desire to believe and selective attention .
Selective attention is when the individual is particular about the information they find regarding subjects, ensuring, unconsciously, that it agrees with their beliefs. It is “the process of directing our awareness to relevant stimuli while ignoring irrelevant stimuli in the environment.” (McLeod, 2018) This is both a good thing and a bad thing. On one hand, it is an automatic filtering system, allowing us to focus on what we need and discard that which is irrelevant., hence it is linked with high academic achievement in children , as the better selective attention skills one has, the less they are distracted by the external environment. However, it may also result in a very close-minded, narrow view. Treisman’s Attenuation Model is often used as a theory to explain selective attention. The model shows that the attenuator, essentially, mutes and filters input that is unnecessary and gives full attention to that which is necessary to the individual. However, research conducted by Treisman herself has shown that, while the attenuated information does not remain in short term memory, individuals are aware of the information for a period of time. This shows that all entries are processed, but only some are retained in the memory.
Desire to believe is the key to unlocking the mechanism of confirmation bias. It is exactly what it sounds like; you believe what you want to believe and actively, yet often unconsciously, seek out information that supports and strengthens your beliefs. Without the desire to believe, one would not be able to divide their attention selectively, leading to the downfall of the confirmation bias.
How This Relates to Parkinson’s Disease
Parkinson’s Disease is an excellent model for mind-body interactions and “studying the neurobiological mechanisms of the placebo effect.” (Benedetti, F. 2009) The placebo effect is also commonly used to treat parkinsonian patients, as there is a relatively high success rate. As can be seen in Figure 2, in the first approximately 8 months, the rate of clinical improvement in Parkinson’s Disease symptoms is the same in real surgery and sham surgery. Even almost two years after the procedure, the projected rate of improvement is not vastly different. This shows how effective sham or placebo surgery treatments are, and more importantly, how potent the mind is. Furthermore, in a double-blind placebo surgery trial for parkinsonism, psychiatrists concluded “In all cases, those who thought they received the transplant reported better scores… demonstrating the value of placebo-controlled surgical trials.” (McRae, et al. 2004) This concurs with the findings of Benedetti (2009) who discovered that, after 18 months, there was substantial improvement in both real and sham surgery groups for both motor performance and quality of life. Therefore, the placebo effect and related treatments can be widely utilised for parkinsonian patients, as it delivers the desired outcome without the possible side effects.
As I previously mentioned, the symptoms of Parkinson’s Disease include tremors, bradykinesia, rigidity and issues with gait and balance. Studies have shown that bradykinesia is more prone to improvement via verbal placebo treatment, and while all aspects of Parkinson’s Disease are liable to improvement by placebo treatment, symptoms of rigidity and bradykinesia are more sensitive than the others. “Bradykinesia results from a failure of basal ganglia output to reinforce the cortical mechanisms that prepare and execute the commands to move.” (Berardelli, A., et al. 2001) In basic terms this means the neurons which control body movements are not functioning correctly, resulting in a reduced and slower velocity of movement. This symptom may be more inclined to the placebo effect than others because it is dependent on the formation of neural pathways. As I explained in the mechanisms of the placebo effect, the more these pathways are recalled and travelled, the stronger they become. This also links as to why verbal cues are most effective with regards to this aspect of parkinsonism; the learning process and the experience associated causes the formation of neurons and pathways. Eventually, this leads to an overall improvement in Parkinson patients, showing the full potential and effectiveness of the placebo effect in medicine.
Expectation vs. Intensity
This is perhaps the most predominant similarity between the confirmation bias and the placebo effect. Expectations cause changes and adjustments in cognitive and neuroscientific behavior, which may lead to, in the case of the placebo effect, more neural pathways being formed, or certain ones being travelled more frequently. This results in a stronger and more effective outcome, which may be more intense and powerful to some patients. When it comes to the confirmation bias, the more one seeks out and believes a particular opinion or thought, the more they will find things agreeing with their perception, so their bias increases in intensity, as does their strength in opinion.
Studies and experiments have shown that for parkinsonian patients who have been, unknowingly, treated by placebo treatments, there is significant dopamine release when the declared probability of improvement is 75% or above. However, for those in the trial who were told they only received 25% to 50% of the medication, or were not verbally encouraged, the rate of improvement and dopamine release plateaued or decreased slightly. Verbal manipulation was used as the bulk of the treatment, with inert drugs and cues also being administered. Reflecting on her findings, specialist psychiatrist Lidstone (2010) said “placebos have been shown to activate reward circuitry, including stimulation of dopamine release in the ventral striatum… These results indicate that the expectation of therapeutic benefit in [Parkinson’s Disease] patients can directly modulate dopamine release.” This agrees with Benedetti (2009) who found that “dopamine activation was better related to the expectations of reward.” From these collective results, we can see that the more positive undertones and anticipations are conveyed to the patient, the more powerful the outcome is, and so more dopamine is released, hence the intensity and velocity of the formation of neural pathways is high as a result.
Nickerson (1998) said, when writing of the effects of expectation on confirmation bias “expectations become self-fulfilling prophecies.” By this, he meant that what you expect will become or willingly present itself to you, whether it’s meant to or not. Therefore, one can deduce that the more you anticipate something, the more intensely the emotions associated will overcome you, so the expectation will present itself more forcefully and easily. Research conducted by Nickerson et al, has shown that in schools, teachers’ expectations of students’ performance model the hypothesis well.
In both cases, it can be seen that there is a strong link between expectation and intensity, which correlate with each other.
Optimism
Certain personality traits and mindsets are also related to placebo responsiveness and the confirmation bias.
Desire vs. Deception
Does the Confirmation Bias Strengthen the Placebo Effect?
Conclusion

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