Dopaminergic Neurotransmission and Creativity

PETAR DIMKOV, M. Sc. In Cognitive Science Doiran 3, 2700 Blagoevgrad, Bulgaria

[email protected] +359(0)89 4 42 0 9 95

Dopaminergic Neurotransmission and Creativity Creativity is considered as one of the most important and valuable human traits. Although creativity is rather a difficult to define concept, originality and effectiveness (Abraham, 2013), novelty and appropriateness

(Dietrich, 2004), quality as well as high general intelligence

(Cropley, 1999; Batey & Furnham, 2006; Kühn et al., 2013, p. 153) are considered essential features of creativity. There is exists a vast literature on the subject (e.g. Runco & Pritzker, 1999). There is some research in (cognitive) neuroscience on creativity as well (Dietrich, 2004; Srinivasan, 2007; Dietrich & Kanso, 2010; Sawyer, 2011; Abraham, 2013; Jung et al., 2013). However, it should be emphasized that ―the findings of modern brain research have not been incorporated into research on creativity‖ (Dietrich, 2004, p. 1011), or have been , but to a minor extent. Therefore, the shedding of additional light, in accordance with the newest findings in neuroscience, in particular the relationship between the dopaminergic neurotransmission in the brain and creativity (as hypothesized and subsequently established by Takeuchi et al. (2010)), would provide an up-to-date bottom-up neurobiological account of how creativity is mediated by the brain. This would also assist in the debates on the conceptual definition of creativity. Indeed, in terms of methodological issues, there are a number of challenges that neuroscience faces when confronted

with creativity research and a number of methodological difficulties

research of creativity itself (Abraham, 2013).

To this end, a synergetic

within the

multidisciplinary

interaction between philosophy of mind and cognition, neuroscience and psychology is required. My project provides some potential solutions and approaches to these challenges. Moreover it inspires practical methods to enhance productivity and the trait of creativity. For example, Rhodes (1961/1987, quoted in: Batey & Furnham, 2006, p. 357) classifies creativity in terms of the creative

person, cognitive

processes

involved in creativity,

environment

and resultant

product. Carson (2014, p. 2) speaks of a collection of strategies rather than of a single creative process which opens the door for further studies. Various different conceptualizations in terms of types of creativity can be found in the literature (e.g. Piryov, 1987; Dietrich, 2004; Sawyer,

2011; Abraham, 2013). All this is indicating that there are multiple aspects of creativity (conceptual, causal and correlative) and emphasizes the need for additional future research as creativity is vital to all human endeavors, especially nowadays in the era of information and technology.

Creativity Features and Neurobiological Dopaminergic Mechanisms The creative process involves several essential stages. Here I will focus on two stages which are at the core of the relation between creativity and dopaminergic neurotransmission.

Indeed,

previously it has been argued that creativity is related to dopamine (Takeuchi et al., 2010) and that creativity is enhanced via behavioral and cognitive disinhibition (Carson, 2014), a state inducible by dopaminergic

agonists (Flaherty, 2011). Focus points of the current study are: 1/

creative drive and motivation and 2/ elaboration of creative ideas. Creative insight (the emergence of a creative idea), the initial stage of creativity, will not be studied here. Here it is hypothesized that:  The mesolimbic

dopaminergic

pathway (nucleus accumbens)

has a relation to

creative drive/motivation as it is known to be related to motivation (Salamone & Correa, 2012). This

hypothesis

has been

previously

postulated

by Flaherty

(2005) and confirmed by Takeuchi et al. (2010).

 Additionally,

the

mesocortical

dopaminergic

pathway (dorsolateral

prefrontal

cortex (dlPFC), central executive network (CEN) (Bressler & Menon, 2010)) seems be related to the elaboration of already formed creative ideas. Indeed, dlPFC (Dietrich, 2004; Flaherty, 2005) and the frontal lobe (Carlsson et al., 2000) in particular and CEN in general (Jung et al., 2013) have been proposed as potential neural candidate regions serving creativity. Takeuchi et al. (2010) confirmed this hypothesis (for dlPFC).  The dorsal striatum may be related to these stages and it is also implicated in various cognitive

functions

(e.g. set shifting

(Alexander

1990; MacDonald & Monchi, 2011). Takeuchi et al.

(2010) confirmed this as well.

areas

via

and is

functionally

Crutcher,

cortical

switching)

reciprocally connected with &

distinct

and task

loops

 From the previous three points it could be hypothesized that:

An administration of a selective dopaminergic drug could increase creativity in both creative and less creative individuals functional

and structural

properties

(controls)

and be correlated to

of the abovementioned brain regions

(dlPFC, nucleus accumbens, dorsal striatum), areas high in dopamine, and to neurobiopsychological mechanisms. This would provide direct evidence that not only those regions but also the dopaminergic neurotransmission in particular is related to stages of creativity, an aspect with translational perspectives. Additionally,

more

neurobiological

mechanisms

mediated

by

the

dopaminergic

neurotransmission seem to be involved in the creative process, namely latent inhibition (Previc, 2009, p. 64; Carson, 2003) and salience attribution as novelty salience (Kasof, 1999, p. 150151). Loosening of associations, i.e. remote associations (Sawyer, 2011), a phenomenon inherent to schizophrenia

(Chapman and Chapman, 1973), is also implicated in creativity (Mednick,

1962) and in addition is related to dopamine (Previc, 2009, p. 64). Attribution of salience mediated by the salience network (Menon, 2015), related to reward prediction error (Heinz & Schlagenhauf, 2010) and psychosis (Kapur, 2003), is involved by definition in creativity. Latent inhibition, the reduced filtering of irrelevant information,

provides additional material for

creative ideas. There is a connection between creativity, latent inhibition and psychopathology (Chirila & Feldman, 2012), although methodological problems still exist (Carson, 2014). From a pharmacological perspective it is known that an increase in noradrenaline levels results in an increase of the signal-to-noise

ratio of neurons, the result being reduction of available

associations (Heilman et al., 2003). Activation of prefrontal dopaminergic D1 -receptors also leads to an increase of the signal-to-noise ratio, whereas dopaminergic D2 -receptor activation leads to an unselective arousal (Winterer & Weinberger, 2004, p. 687; Previc, 2009, p. 64). In particular, activation of the D2 -receptor, giving rise to net decrease of inhibition, allows for keeping of multiple representations in the prefrontal cortex (PFC) network, whereas D1-receptor activation, leading to net increase of inhibition, allows for keeping of one or a limited number of representations in the network (Seamansa & Yang, 2004, pp. 40 -42). Thus, the unselective arousal caused by dopaminergic

D2 -receptors activations allows multiple representations to be

held in memory in labile form (a prerequisite for divergent thinking, thus for creativity). In addition, dopaminergic D1 - and D2 -receptors seem to be functionally antagonistic (Hass & Durstewitz, 2011). To be noted, dopaminergic D2 -receptors are abundant in many regions of the

limbic system (the ―emotional brain‖) – especially nucleus accumbens, but almost absent in the prefrontal cortex (Kessler et al., 1993). D1 -receptors are found in large quantities in PFC (the ―cognitive brain‖), in the limbic system and basal ganglia (Hall et al., 1994). This

hypothesis

schizophrenia

is

where

partially there

defended

are,

by

secondary

the to

finding

of

glutamate

dopaminergic

functioning

NMDA-receptor

in

disturbance, a

mesocortical hypo-activation of the D1 -receptors in the PFC as well as a mesolimbic hyperactivation of D2 -receptors in the limbic regions (Laruelle et al., 2003, pp. 143-146). Davis et al. (1991) hypothesize that the mesocortical hypo-activation leads to the negative symptoms, and the

mesolimbic

psychopathologies,

hyper-activation

to

the

positive

symptoms.

Thus,

persons

with

such as schizophrenics, could be creative on the level of production of

creative ideas and have high creative drive, but not on the level of their elaboration. Indeed, there are states of high mesolimbic dopaminergic levels which are also characterized by high levels of creativity: bipolar disorder (Johnson et al., 2012), psychosis proneness (Fink et al., 2014) and individuals with Parkinson’s disease treated with dopaminergic drugs (Lhommée et al., 2014). Creative drive is represented by the psychomotor excitation induced by dopaminergic agonists and

psychomotor retardation

induced

by

dopaminergic

antagonists.

On

the

one

hand,

antipsychotics (dopamine D2-receptor antagonists) cause neurolepsy: a state characterized by reduced locomotion and affective, volitional and drive activity, anhedonia, apathy, indifference towards

the external world, reduced creativity,

productivity and the quantity of available

associations (Temkov & Kirov, 1976, pp. 21, 59; Flaherty, 2005; Haralanov et al., 2012, p. 24), reduced motivation to act and received reward pleasure (Wise, 2004). On the other hand, dopaminergic

drugs

among others increase

forward or approach locomotion

and arousal,

improve attention, alertness and vigilance, elevate mood (euphoria), reduce fatigue (Temkov & Kirov, 1976, p. 22; Favrod-Coune

& Broers, 2010), i.e. they have some minor cognitive

enhancing properties. The general psychopharmacological principle states that such drugs are usable for controlling excessive or deficient neurotransmitter

levels, but in healthy individuals

they do not have any positive effects. Some authors even speak of negative effects in healthy individuals (Mohamed, 2014), e.g. impaired cognition and reduced creativity after administration of psychostimulants.

Nonetheless, tests with low doses of selective dopaminergic drugs such as

the MAO-B inhibitor and dopamine reuptake inhibitor (DRI) selegiline seem warranted as suggested by Lhommée et al. (2014, p. 7). MAO-B degrades selectively dopamine resulting in

activation of all pre- and postsynaptic dopaminergic receptors (D 1 and D2 types) by dopamine. Selegiline

has

half-life

of 1.5 hours (Mahmood,

1997) which implies

ethical and other

advantages.

Experimental Schedule /3 Years/ Subjects: Creative individuals and controls (less creative individuals), Bachelor or Master students (matched for age), non-smokers, without history of neurological or psychiatric disorders, no current or past intake of ps ychotropic drugs. Experiment 1, Hypothesis 1: Administration of the selective dopaminergic (DA) drug selegiline (an indirect DA-agonist, a selective MAO-B (monoaminooxidase B inhibitor) and a DRI) in the dose range of 5-15 mg to creative individuals (drug condition) in a be havioral experiment (without brain imaging) with within subject desig n is e xpected to increase creativity scores in comparison to scores in a non-drug condition. Famous tests such as the Torrance Tests of Creative Thinking (Chávez-Eakle et al., 2007) and the Alternate Uses Tas k Test (Wallach & Kogan, 1965 ) could be use d to determine the level of creativity of each s ubject. Experiment 2, Hypothesis 1: Resting state connectivity and activity (as sessed by functional mag netic resonance imaging (fMRI)) within and between the central executive network (CEN) (dorsolateral prefrontal cortex (dlPFC)) and the mesolimbic DA pathway (nucleus accumbens) are e xpected to be increased in more creative individuals compared less creative ones. Experiment 2, Hypothesis 2: The average levels of dopamine in dlPFC (CEN) and the mesolimbic DA pathway are expected to be higher in more creative individuals compared less creative ones as assessed by s pectroscopy in mag netic resonance imaging (MRI). Experiment 2, Hypothesis 3: The average size of CEN (dlPFC) and mesolimbic DA payhway (nucle us accumbens) are expected to be higher in more creative individuals compare d less creative ones as assessed by voxel based morphometry after collecting a structural MRI scan. Experiment 3: Testing of other dopaminergic mechanis ms involved in creativity, namely latent inhibition (auditory discrimination tas k (Lubo w et al., 1992; Weiner, 2003)), novelty salience (salience attribution test (Roiser et al., 2013)) and loosening (remoteness) of associatio ns (remote associates test (Klein & Badia, 2014)). The results from experiments 1, 2 & 3 could subsequently be tested for positive correlations forming a general creativity variable (representing the level of creativity of a given subject).

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