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BMe Research Grant |
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The boundary between schizophrenia and normality is blurred; people from the general population display schizotypal traits, that is, personality traits resembling schizophrenia symptoms. In Parkinson’s disease, dopaminergic therapy can cause elevated schizotypy, and might facilitate the unfolding of hidden creative potentials. The motivation behind our studies is to understand the neurocognitive underpinnings of these curious side effects.
The studies are conducted within the Laboratory for Perception & Cognition and Clinical Neuroscience (LPCCN), in cooperation with Semmelweis University, Department of Neurology. LPCCN is integrated into Budapest University of Technology and Economics, Department of Cognitive Science and the Nyírő Gyula Hospital - National Institute of Psychiatry and Addictions. LPCCN applies a multidisciplinary approach to study neurocognitive and molecular mechanisms of psychiatric disorders, Parkinson’s disease, memory disorders, and other clinical conditions.
There is evidence that schizotypal traits overlap with symptoms of schizophrenia at the phenomenological, the genetic, the cognitive, and the neural level [1]. Curiously, they are also related to creative thinking skills and real life creative achievement [2]. Dopaminergic abnormalities have been central to the pathophysiology of schizophrenia since decades [3], and recent research has linked alterations in the dopaminergic systems to schizotypy [4] and creativity [5] as well.
Dopamine plays a key role in how we attribute salience to events. Midbrain dopamine neurons’ activity increases if something important happens: when reward, novelty or a physically intense stimulus is encountered, dopaminergic signalling energises behaviour, and improves learning [6].
Parkinson’s disease is a multistage progressive neurodegenerative disorder [7]. Motor symptoms (e.g. tremor, gait abnormalities) emerge when neurodegenerative processes reach the nigrostriatal dopamine pathway, which is critical in motor control. Importantly, the mesolimbic dopamine pathway is not affected initially in the disease course (Fig. 1). Therefore, dopaminergic therapy, while alleviating motor symptoms by optimising dopamine levels in the nigrostriatal pathway, might overdose the mesolimbic dopamine system [8]. Depending on pre-treatment and disease-related factors, side effects of dopaminergic therapy might include hallucinations and delusions [9] or development of creativity [10].
Figure 1. In Parkinson’s disease (PD), the reward prediction error was diminished in the dorsal striatum (part of the nigrostriatal pathway) as revealed by functional magnetic resonance imaging (fMRI). Activity was intact in the ventral striatum (part of the mesolimbic pathway). Image source: [11]
Connections between altered dopamine function, schizotypy, and creativity have long been implicated. However, little is known about the lower level processes involved. In addition, it has not been investigated so far whether pre-treatment factors can predict the “creativity side effect” of dopaminergic therapy in Parkinson’s disease. Moreover, data is lacking about the relationship between schizotypy and problem solving with remote associations, which is essential to creativity.
In the first study, we examined changes in divergent thinking (an indicator of creative potential) after dopaminergic therapy in Parkinson’s disease. We attempted to predict change from pre-treatment factors.
In the second study, we tested reactions to expectancy violations in Parkinson’s disease patients treated with dopaminergic therapy. Importantly, quick adaptation to unexpected events is not only associated with creativity, but it is also characteristic of schizophrenia and schizotypy. In the Parkinson’s disease group, we correlated individual differences in cognition and personality with medication dosage and disease-specific factors.
In the third, still ongoing study, we measure problem solving and schizotypy in young healthy adults. Although problem solving with remote associations has long been associated with creativity, its relationship with schizotypy remains to be explored.
Schizotypy was measured with the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) questionnaire [12]. Its subscales measure four dimensions of schizotypy:
positive: hallucination- and delusion-like experiences
negative: avoidance of intimacy and reduced pleasure
disorganised: loosened associations and disturbed attention
impulsive: quick-tempered, asocial and aggressive behaviour
We investigated three aspects of creativity. Divergent thinking was measured with the “Just Suppose” subtest of the Torrance Test of Creative Thinking (TTCT) [13]. Participants were asked to imagine fantastic scenarios (e.g.“clouds had strings attached to them which hang down to earth”) and were requested to come up with as many creative ideas about the consequences as possible. The originality scores reflects infrequency of the ideas, the flexibility score reflects the number of shifts between categories, and finally, the fluency score mirrors the quantity of the ideas.
Lifetime creative achievements were explored with the Creative Achievement Questionnaire (CAQ) [14]. The questionnaire covers 10 domains of creative accomplishment: visual arts, music, dance, architectural design, creative writing, humour, inventions, scientific discovery, theatre and film, and culinary arts.
Problem solving was examined with the Remote Associates Task [15]. In this task, participants are shown 50 word triads on a computer screen (e.g. night, wrist, stop) and they should try to find a fourth word, which forms compound words with all three words (you can find the solution of the example at the end of the methods*).
We examined the processing of expectancy violations with two paradigms. Latent inhibition was measured with a computerised visual search task [16]. In the first phase of the task, participants searched for a target among distractors. The following phase comprised two important conditions: the previous target became a distractor in both, and the target was either the previous distractor or a new stimulus. The previous distractor is assumed to be under latent inhibition, and the degree of latent inhibition is indicated by the difference between response speeds in these two conditions. Reduced latent inhibition reflects rapid adaptation to unexpected changes.
Recognising unlikely, anomalous stimuli can be difficult for many people. In our experiment, we presented participants normal playing cards and an anomalous card [17] (Fig. 2). Presentation times progressively increased. We recorded the number of trials required to correct categorisation.
Figure 2. Do you notice something odd? (examples of stimuli used in the cards task)
We investigated the role of dopamine via examining patients with Parkinson’s disease undergoing dopaminergic therapy. In the first study, we examined patients before and after 12 weeks of dopamine agonist therapy. It can be assumed that the difference between the two sessions reflects altered dopamine function. In the second study, we tested patients who were already receiving dopaminergic treatment. The variability in the medication dosage offered to possibility to look at neurochemical aspects of individual differences in personality and cognition.
*WATCH
Results
In the first study, 18 patients with Parkinson’s disease and 19 healthy controls took part, who were matched for demographics, intelligence, creative achievement and schizotypy. Both groups were tested twice. At follow-up, the patients showed elevated positive and impulsive schizotypy: dopaminergic therapy increased hallucination- and delusion-like experiences and made quick-tempered and asocial traits more pronounced.
The quality and variability of ideas on the divergent thinking task seemed to increase among patients with Parkinson’s disease. Curiously, there were individual differences in change of divergent thinking among the patients. Originality of ideas was more likely to increase among patients who already had high positive schizotypy at pre-treatment. Patients with high IQ appeared to produce more ideas after treatment. Finally, patients with more real life creative achievements produced more variable ideas after dopaminergic treatment.
In the second study, we examined 26 patients with Parkinson’s disease and 24 matched healthy controls. Positive, negative, and impulsive schizotypy was higher among the patients, relative to the controls. Strikingly, patients outperformed controls in terms of expectancy violation processing: latent inhibition was reduced and anomaly categorisation was enhanced.
Then, we looked at the relationship between dopamine dose [18], and schizotypy and expectancy violation processing. The analyses revealed dopamine dose dependent individual differences in positive schizotypy, latent inhibition, and anomaly categorisation. The greater the dopamine dosage of a patient, the more likely he or she will have hallucination- and delusion-like experiences, demonstrate reduced latent inhibition, and recognise the anomalous card after a few trials (Fig. 3). These results were not due to severity of Parkinson’s symptoms, laterality of symptom onset, or disease duration.
Figure 3. Linear association of dopamine dose with positive schizotypy, latent inhibition, and anomaly categorisation. The results are statistically significant. Dark grey shadings indicate 95% confidence intervals.
In the third study, 85 healthy young adults have participated so far. We plan to extend this sample with 50 participants. Scores on the Remote Associates Task were related to schizotypy: high positive schizotypy was more likely to be associated with reduced performance, while high disorganised and impulsive schizotypy predicted better problem solving. This pattern shows a previously unknown, specific relationship between the separable, but not independent schizotypal traits and problem solving.
Our studies shed light on pre-treatment factors which might influence the side effects of dopaminergic therapy in Parkinson’s disease. They also provided information about lower level cognitive mechanisms in action. We have not only replicated previous results, but we have reported several, novel findings as well. Additionally, our data contribute to the understanding of neurobiological aspects of psychotic-like experiences and creativity.
We find the preliminary results on the role of schizotypy in problem solving promising; they suggest a specific pattern which has not been described before. We are excited to analyse the data and report the results after extending the sample.
At the moment, we are investigating problem solving in patients with Parkinson’s disease taking dopaminergic medications. We plan to apply brain imaging and computational modelling in order to understand the neurocomputational background of the results.
Related papers.
Publications in peer-reviewed journals
Polner B, Nagy H, Takáts A, Kéri S (in press). Kiss of the muse for the chosen ones: de novo schizotypal traits and lifetime creative achievement are related to changes in divergent thinking during dopaminergic therapy in Parkinson’s disease. Psychol Aesthet Creat Arts. http://dx.doi.org/10.1037/a0039303
Polner B, Kéri S (in press) Egyéni különbségek az alkotó gondolkodásban: pszichózis az adaptív működésben? M Pszichol Szle.
Polner B, Nagy H, Takáts A, Kéri S (under revision) Dopamine improves learning after expectancy violations and induces psychotic-like experiences in patients with Parkinson’s disease. Neurosci Lett.
Polner B, Aichert D, Macare C, Costa A, Ettinger U (2014) Gently restless: association of ADHD-like traits with response inhibition and interference control. Eur Arch Psychiatry Clin Neurosci 1–11. http://doi.org/10.1007/s00406-014-0531-7
Presentations at international and national conferences
Polner B, Nagy H, Kéri Sz (2013) Dopaminergic therapy and creativity in Parkinson’s disease: do schizotypal traits play a mediating role? Lemanic Workshop on Schizotypy. Geneva, Switzerland, 5-7 December 2013
Polner B, Nagy H, Kéri Sz (2014) Dopaminerg terápia és kreativitás Parkinson-kórban: a szkizotípiás vonások közvetítenek? A Magyar Pszichiátriai Társaság VIII. Nemzeti Kongresszusa. Budapest, Hungary, 22-25 January 2014
Polner B (2014) A valóságtól elrugaszkodva: kreativitás vagy téboly? XVIII. Pszinapszis. Budapest, Hungary, 4-6 April 2014
Polner B, Nagy H, Takáts A, Kéri Sz (2015) Gondolkodási keretek fellazulása, pszichotikus tünetek és a dopamin szerepe Parkinson-kórban. A Magyar Pszichiátriai Társaság XIX.Vándorgyűlése. Szeged, Hungary, 28-31 January 2015
Polner B (2015) Loner, psychic or genius? XIX. Pszinapszis. Budapest, Hungary, 17-19 April 2015
Recommended links
The Mervyn Peake award celebrates the talent and creativity of people with Parkinson’s disease. The site is worth visiting, as you can enjoy the award-winning artwork and also read the stories of the people who created them.
References
1. Ettinger U, Meyhofer I, Steffens M, et al. (2014) Genetics, Cognition, and Neurobiology of Schizotypal Personality: A Review of the Overlap with Schizophrenia. Front Psychiatry. doi: 10.3389/fpsyt.2014.00018
2. Acar S, Sen S (2013) A multilevel meta-analysis of the relationship between creativity and schizotypy. Psychol Aesthet Creat Arts 7:214–228. doi: 10.1037/a0031975
3. Winton-Brown TT, Fusar-Poli P, Ungless MA, Howes OD (2014) Dopaminergic basis of salience dysregulation in psychosis. Trends Neurosci 37:85–94. doi: 10.1016/j.tins.2013.11.003
4. Mohr C, Ettinger U (2014) An Overview of the Association between Schizotypy and Dopamine. Front Psychiatry. doi: 10.3389/fpsyt.2014.00184
5. DeYoung CG (2013) The neuromodulator of exploration: A unifying theory of the role of dopamine in personality. Front Hum Neurosci. doi: 10.3389/fnhum.2013.00762
6. Shohamy D, Adcock RA (2010) Dopamine and adaptive memory. Trends Cogn Sci 14:464–472. doi: 10.1016/j.tics.2010.08.002
7. Braak H, Tredici KD, Rüb U, et al. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211. doi: 10.1016/S0197-4580(02)00065-9
8. Cools R (2006) Dopaminergic modulation of cognitive function-implications for l-DOPA treatment in Parkinson’s disease. Neurosci Biobehav Rev 30:1–23. doi: 10.1016/j.neubiorev.2005.03.024
9. Fénelon G, Alves G (2010) Epidemiology of psychosis in Parkinson’s disease. J Neurol Sci 289:12–17. doi: 10.1016/j.jns.2009.08.014
10. Canesi M, Rusconi ML, Isaias IU, Pezzoli G (2012) Artistic productivity and creative thinking in Parkinson’s disease: Creativity in Parkinson’s disease. Eur J Neurol 19:468–472. doi: 10.1111/j.1468-1331.2011.03546.x
11. Schonberg T, O’Doherty JP, Joel D, et al. (2010) Selective impairment of prediction error signalling in human dorsolateral but not ventral striatum in Parkinson’s disease patients: evidence from a model-based fMRI study. NeuroImage 49:772–781. doi: 10.1016/j.neuroimage.2009.08.011
12. Mason O, Claridge G, Jackson M (1995) New scales for the assessment of schizotypy. Personal Individ Differ 18:7–13. doi: 10.1016/0191-8869(94)00132-C
13. Torrance EP (1974) Torrance Tests of Creative Thinking, Verbal and Figural: Directions, Manual and Scoring Guide. Personal Press, New York, NY
14. Carson SH, Peterson JB, Higgins DM (2005) Reliability, validity, and factor structure of the creative achievement questionnaire. Creat Res J 17:37–50.
15. Mednick S (1962) The associative basis of the creative process. Psychol Rev 69:220–232.
16. Kéri S (2011) Solitary minds and social capital: Latent inhibition, general intellectual functions and social network size predict creative achievements. Psychol Aesthet Creat Arts 5:215–221. doi: 10.1037/a0022000
17. Bruner JS, Postman L (1949) On the Perception of Incongruity: A Paradigm. J Pers 18:206–223. doi: 10.1111/j.1467-6494.1949.tb01241.x
18. Tomlinson CL, Stowe R, Patel S, et al. (2010) Systematic review of levodopa dose equivalence reporting in Parkinson’s disease. Mov Disord 25:2649–2653. doi: 10.1002/mds.23429