Creativity and its link to epilepsy

Abstract

Creative thinking represents one of our highest‐order cognitive processes, involving multiple cortical structures and an intricate interplay between several cortical and subcortical networks. It results in novel ideas that translate to useful products or concepts. The evolutionary purpose of creativity is therefore apparent, as it advances our adaptation and survival. Elucidating the neurobiology and neuroanatomy of creative cognition is challenging because the construct of creativity is not clearly defined, and the many neuropsychological measures attempting to assess it are often biased, leading to imprecise findings. Using examples from the medical and music fields, creativity is demonstrably linked to the default mode network (DMN), which has the unique property of becoming activated at times of “quiet wakefulness,” facilitating “defaulted” internally focused cognitive operations. Creative thoughts result from a process involving the activation and deactivation of the DMN as part of a dynamic interplay shared with the central executive network and affective salience network. The question is posed whether seizures originating from DMN‐related cortical areas should be considered as having overlap with eloquent cortex, potentially exempting them from removal in epilepsy surgery.

Plain Language Summary

Creative thinking is a higher‐order cognitive process involving multiple brain structures and networks. It results in insightful and original thoughts that translate to useful products or concepts, which allow us to adapt to our surroundings. This Narrative Review presents conceptual, investigational, and neurobiological aspects of creativity, including information about a unique brain network termed “default mode network (DMN),” which activates at times of “quiet wakefulness,” facilitating internally focused cognitive operations. The review ends with a discussion on whether regions of the DMN from which seizures originate should be regarded as “eloquent” and their removal should be deferred by epilepsy surgery.

Key Points.

• Creative cognitive processes produce novel thoughts that translate to useful products or concepts, expressed in better adaptation.

• Defining what or who is “creative” is challenging, as it is to elucidate the underlying neurobiological operation of creativity.

• Creative thinking reflects a higher‐order cognitive process, entailing multiple cortical structures and an interplay between cortical and subcortical networks.

• One neural network involved in creativity is the default mode network (DMN). It is activated during “quiet wakefulness” and facilitates internally directed processes.

• Seizures may originate from cortical areas associated with the DMN. This Review raises the discussion on whether the DMN areas should be regarded as “eloquent” when facing their potential removal by epilepsy surgery.

1. INTRODUCTION

We are honored to contribute to this special issue celebrating the legacy of Solomon Nico Moshé, MD, himself a master of creativity in developmental neuroscience and great fan of the arts. Dr. Moshe's clinical insights contributed to significant improvement in the management of children with epilepsy, and his expansive research, focused on elucidating the mechanisms of epileptogenesis, provided momentous advancement to the field of epilepsy. Moreover, one could always find him at the piano bench during musical performances at conferences, imbibing the music with a keen interest in the arts and humanities. His range of interests is amazingly broad and has always impressed us, from an ardent love of soccer to an appreciation for the creation of outstanding films by his son, Jared!

2. THE CONCEPT AND MEASURES OF CREATIVITY

There is an overall consensus that the process of creativity reflects a series of cognitive occurrences involving several cortical structures and networks, resulting in novel thoughts. ¹ Unlike convergent thoughts, which generate a single correct answer, divergent thoughts created by creative thinking produce many potential answers. An individualist definition of creativity would characterize it as a new mental combination expressed in the world. Another approach to creativity suggests that as novel as a thought may be, it should be regarded as creative (versus frivolous) if it leads to pragmatic benefits within a sociocultural context. ² , ³ , ⁴ Accordingly, a sociocultural view of creativity asserts that it is the generation of a product judged to be novel and also to be appropriate, useful, or valuable by a suitably knowledgeable social group. To some degree, the neurobiological mechanisms eliciting creative thoughts exist in every living organism, including non‐human animals, which rely on cognitive flexibility and innovative behavior for survival. This has been demonstrated in apes, ⁵ pigeons, ⁶ and other non‐human animals. ⁷ Moreover, having the right ratio of creative vs. less creative subjects in a population is presumed to be important for a group's durability. ⁸ Elucidating the neurobiology of creativity is challenging because the construct of creativity, or what is considered “creative,” is not clearly defined and does not have strict operational and quantifiable measures. Many psychometric methods aimed at assessing creativity were developed. Notable examples include the: (1) Consensual Assessment Technique (CAT), ⁹ in which participants are asked to create a poem or caption for a single‐frame image, and then their creation is rated by two or more experts in the field; (2) Remote Associations Test ¹⁰ , ¹¹ which evaluates the ability to develop remote associations. It argues that individuals with a “steep associative hierarchy” or “narrow horizon” form common associations, while those with a “flat associative hierarchy” or “widened horizon” can produce many remote associations between unrelated concepts. For example, when hearing the word “umbrella,” an individual considered “less creative” would associate it with “rain.” In turn, the “more creative” individual would associate it with something such as a “parachute”; (3) Creative Achievement Questionnaire (CAQ) ¹² in which individuals are asked to check off their life accomplishments across 10 domains belonging to three main subgroups of creativity: expressive, performance, and scientific; (4) Runco Ideational Behavior Scales ¹³ which examine individuals' agreement level with 23 statements relating to creativity such as, “I come up with a lot of ideas or solutions to problems”; (5) Creative Functioning Test (CFT) ¹⁴ which measures ideational flexibility and creative strength by examining participants' responses to various association tasks based on still‐life images of two primary objects; and (6) Torrance Test of Creative Thinking (TTCT) ¹⁵ which belongs to the group of the most widely used creative tests, the Divergent Thinking Tests. In the Figural section of this test, participants are asked to construct, complete (Figure 1), or sketch different objects. In the Verbal section, they are presented with a picture, and their ability to ask questions, create a narrative, or imagine improbable consequences relating to that picture is assessed. There are many serious issues concerning the reliability and validity of creativity tests, ¹⁶ , ¹⁷ as high or low scores do not equate to being more or less creative in real life. Several important biases lead to their imprecision. Intelligence, and specifically verbal intelligence, has been shown to correlate with the capacity for spontaneous associative processes, ¹⁸ and so has a person's sociocultural environment, mother tongue, education, and motivation. ¹⁹ With respect to the impact of education and motivation in this context, an analogy can be made to a quote from Hemingway's “The Old Man and the Sea” ²⁰ : “It is better to be lucky. But I would rather be exact. Then when luck comes you are ready.” Creative thoughts do not emerge from a vacuum but are built on layers of prior education and knowledge, allowing one to ask the right questions. It has been argued that a minimum of 10 years of experience is required to contribute creatively in a certain field. ²¹ Moreover, concocting divergent solutions to complex problems often requires an incessant intention to do so. An archetype of this notion is the story leading to the Nobel Prize Award of Ada Yonath. Nearing the end of her career, and while recovering from a bicycle accident, she stumbled upon a magazine article about polar bears. Being constantly immersed in her open scientific questions, she made a remote association between the hibernation of polar bears and her research, learning that the bears' ribosomes are packed in an orderly fashion in their inner cell membranes. This led her to discover the stable but remaining active ribosomes that can crystallize, further revealing the principles by which novel compounds can serve as antibiotics. ²²

FIGURE 1.

A picture completion task taken from the Figural Form of the Torrance Tests of Creative Thinking (TTCT). ¹⁵ The examinee is asked to draw objects from these incomplete sketches.

2.1. The evolutionary importance of creativity

The evolutionary purpose of creativity is based on creative thoughts being translated into useful, adaptive actions. Considered, thus, potentially essential for survival, creativity could be perceived as the highest level of cognitive ability, driving humanity forward in science and technology, improving and extending life. One issue arising from mandating “usefulness” from creative processes is that the term “useful” is prone to subjective interpretation. ²³ For example, a trailblazing idea may initially seem insignificant; however, over time, it may meet the definition of being useful. One (of many) example from the medical world is that of Dr. Ignac Semmelweis, an obstetrician working in Vienna in the 1850s. His astute clinical insights and divergent reasoning led to an investigation showing that the “unholy” hands of “holy” physicians who performed autopsies, did not wash their hands, and proceeded to the delivery room, are directly linked to a higher occurrence rate of puerperal fever and maternal mortality. He proposed that “death particles” were transmitted from the physicians' hands to laboring women and imposed a mandatory hand‐washing policy before entering the delivery room. This resulted in a dramatic decrease in maternal mortality. ²⁴ His beliefs and actions received crushing rejections from senior colleagues in his field. It was only after his lifetime that they were found to be significantly contributory to the discovery of microbiological systems and the prevention of mortality. Music offers another excellent means by which the usefulness of creativity can be demonstrated. The argument of whether musical creations are “useful” has been studied over the past 200 years. ²⁵ Some researchers debate that it is merely an incidental peculiarity of our nervous system, ²⁶ eliciting pleasure and entertainment (an “auditory cheesecake”). ²⁷ However, most investigators are convinced that music has a significant evolutionary purpose, considering it central to every culture. Some theories focus on its essence for courtship practices, as bearing musical talent indicates inherent well‐developed cognitive abilities. ²⁸ , ²⁹ , ³⁰ Other and more substantial arguments are based on music's power to establish cultural communication systems between individuals and create group coherence. Mirroring the sounds and movements of other group members reflects an emotional exchange termed “emotional contagion,” ³¹ which increases the personal sense of belonging, cooperation, and attachment between the group's members. ³⁰ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ As opposed to being alone, belonging to a group raises chances of survival, and there lies the “usefulness” of music. This concept was beautifully summarized by the renowned musicologist H.C Robbins Landon, who described Mozart's music as “an excuse for mankind's existence and a small hope for our ultimate survival.” ³⁷

2.2. Neuroanatomical and neurophysiological aspects of creativity

In addition to being a construct eliciting great interest from psychologists and philosophers, creativity has ignited the curiosity of neuroscientists in the last decades. Initial theories asserted that the origin of creative thoughts is predominantly lateralized to the right hemisphere. ³⁸ The hemispheric asymmetry hypothesis continued to prevail for decades, catching much attention from neuroscientists and the public. ³⁹ , ⁴⁰ Concepts such as the “right hemisphere syndrome” described individuals with impairments of graphomotor and visuospatial skills, speed of task performance, emotional regulation, and attention. ⁴¹ Individuals were described in the psychological and educational spheres as either “left‐brained,” implying analytical, mathematical, dogmatic, and emotionally closed, while the “right‐brained” meant holistic, meditative, loving, and free‐spirited. Moreover, ample data based on various neurophysiologic and neuroimaging modalities indicated that right‐hemispheric neurobiological processes are primarily amenable to generating novel thoughts. ⁴² Nowadays, in line with the notion that creativity must be based on a rich background of knowledge and experience, it is understood that the analytical and memory acquisition properties associated with the left hemisphere must be engaged with those of the right hemisphere. ⁴² In recent years, emerging evidence has also shown that the left hemisphere may be predominantly involved in various creative tasks ⁴³ and that original artistic expression can be linked with either left frontotemporal ⁴⁴ or right temporal lobe epilepsies. ⁴⁵ Hence, creativity is a phenomenon brought about by the continuous interaction of both hemispheres, and uniquely associating it with the right hemisphere is oversimplified. The” disinhibition hypothesis,” another leading theory aiming to explain the neurobiology of creativity, suggests cortical activation may suppress access to divergent associations (or novel synaptic merging). The disinhibited creative processes can unfold and materialize when cortical activation is relatively reduced. Other investigations in the field proposed that the posterior cortical areas ⁴⁶ or subcortical structures ⁴⁷ are more involved in creative cognition.

Considering the above, it is discernable that creativity does not originate from a single brain region; rather, it entails mutual executive and associative processes located in multiple cortical regions and likely involves broad synaptic networks. The discovery of the default mode network (DMN) disentangled some of the ambiguity underlying the roots of creativity. The DMN represents a network interconnecting a collection of dispersed cortical areas in the medial prefrontal cortex, posterior cingulate cortex, precuneus and inferior parietal lobes, and medial temporal lobes. ⁴⁸ , ⁴⁹ The precise cognitive duties of the DMN are yet to be fully determined. However, mounting empirical evidence shows it possesses a unique property of being suppressed in periods of attention to external stimuli and activated at times of “quiet wakefulness.”

When activated, it facilitates “defaulted” internally focused cognitive operations such as self‐reflection, social cognition, daydreaming, recollection of episodic, language, and semantic memories, future envisioning, and mind wandering. ⁴⁸ At these momentary lapses in attention, the DMN constructs our personal “internal narrative”. ⁵⁰ A number of studies have also demonstrated that the DMN plays an integral role in spontaneous associative thinking, ⁵¹ , ⁵² , ⁵³ creative ideation, ⁵⁴ and the capacity to form a “chain” of single‐word sequential associations. ⁵⁵ The field of music can also be “exploited” to better understand the neurobiology of creativity. Many features of music creation and even listening require creative cognitive processes. ⁵⁶ However, music improvisation, or “instant composition,” reflects a prototypical creative process. Neuroimaging and neurophysiologic‐based studies consistently demonstrate the DMN is activated during improvisation. ⁵⁷ , ⁵⁸ Interestingly, improvisation also involves the simultaneous activation of the central executive network (including dorsolateral prefrontal and posterior parietal areas) associated with executive planning and stepwise implementation of tasks, ⁵⁹ and the affective salience network (connecting areas in the anterior cingulate gyrus, fronto‐insular cortex, amygdala, and temporal poles) linking the DMN and executive networks (Figure 2). ⁶⁰ , ⁶¹ The described network interplay evinces the notion that creative processes rely on extensive experience and knowledge and that they stem from a process of cooperative defocusing and refocusing of attention. ⁶² , ⁶³ Studies have complemented this assumption by demonstrating that music education improves our cognitive pattern‐decoding and problem‐solving abilities. ⁶⁴ , ⁶⁵

FIGURE 2.

A schematic depiction of the anatomical areas associated with the three networks whose interplay is crucial for creative thinking: The default mode network (DMN) associated with social recognition, self‐reflection, recollection of episodic memories, and mind wandering, the central executive network (CEN) associated with executive functions and stepwise task implementation, and the affective salience network (ASN) that mediates the integration between the DMN and CEN by dynamically activating and deactivating them. ACC‐ anterior cingulate cortex; aINS‐ anterior insula; AMG‐ amygdala; dlPFC‐ dorsolateral prefrontal cortex; iPL‐ inferior parietal lobe; mPFC‐ medial prefrontal cortex; PCC‐ posterior cingulate cortex; pPL‐ posterior parietal lobe; TMp‐ temporal pole.

2.3. Seizures originating from and propagating to DMN‐related area

Several case reports and series described the characteristics of seizures originating from DMN‐related cortical areas. A seizure onset zone located in the posteromedial cortex, a core DMN region, elicited a seizure semiology reported as an “altered sense of self, depersonalization, and self‐dissociation.” ⁶⁶ Out‐of‐body experiences were also described to emerge from stimulation of the right temporoparietal junction. ⁶⁷ , ⁶⁸ The seizure semiologies of patients with a stereotactic encephalography (sEEG)‐captured posterior cingulate ictal onset zone consisted of either bilateral asymmetric tonic seizures and hypermotor seizures (that propagated to the lateral premotor and orbitofrontal areas, supplementary motor area, anterior cingulate gyrus, precuneus, and inferior parietal lobes), or loss‐of‐consciousness and automotor seizures (that propagated to mesial temporal structures and inferior parietal lobes). ⁶⁹ Seizures originating from the precuneus (also captured via sEEG) presented with various auras including body image disturbances as well as vestibular, somatosensory, visual, and other non‐specific auras. Motor semiologies consisted of bilateral asymmetric tonic seizures and hypermotor seizures. ⁷⁰ Seizures emanating from the inferior parietal regions have been associated with hyperkinetic behavior ⁷¹ and ictal grimacing. ⁷²

Propagation of focal onset seizures (primarily from the temporal lobes) to areas of the DMN has been implicated in loss of consciousness. Correspondingly, when the propagation of focal onset seizures is limited and spares the DMN (and other subcortical networks), awareness is maintained. ⁷³ Accounting for the brief or prolonged lapses in consciousness, the DMN‐cortical areas have been shown to have cerebral blood flow hypoperfusion in spontaneous and induced generalized tonic–clonic seizures, ⁷⁴ , ⁷⁵ and decreased fMRI‐blood oxygenation level‐dependent (BOLD) signals during the generalized spike–wave discharges of absence seizures. ⁷⁶ , ⁷⁷ Interestingly, in generalized tonic–clonic and absence seizures, DMN‐related activity initially increases (preceding the electrographic seizure onset) and then profoundly decreases. ⁷⁸

2.4. Deliberating the “eloquence” of the DMN

Reduced or disrupted DMN connectivity has been linked to generalized epilepsy ⁷⁹ and shown to correlate with duration of epilepsy and medication resistance. ⁸⁰ Naturally, this serves as yet additional data to favor aggressive treatment to control generalized epilepsy. Surgical treatment of focal seizures originating from DMN‐related areas is not as straightforward. The typical areas considered as eloquent cortex to be spared in epilepsy surgery are primary motor and sensory cortices, occipital visual cortex, and at times, the dominant hemisphere temporal and frontal lobes and hippocampus. ⁸¹ , ⁸² Thus, the areas comprising the DMN are currently not perceived as eloquent, as removing them is not directly linked to motor, sensory, language, or memory impairments. A number of investigations also demonstrated that mapping the “dispensable” areas of the DMN via electrical stimulation does not elicit a specific effect. ⁸³ , ⁸⁴ However, the patients included in those studies did not or could not perform creativeness‐requiring tasks, and the stimulation targets were not network‐based. In contrast, other studies tested comparable objectives through direct cortical stimulation of separate areas associated and not associated with the DMN in awake patients while they participated in divergent thinking and alternate‐uses tasks. Their findings showed that direct cortical stimulation of the DMN areas led to a decreased ability to produce alternate uses and reduced creative fluency. Stimulation of the non‐DMN areas did not affect creative thinking processes. ⁸⁵

Another example is provided by lesion‐based studies and those involving network mapping analyses, showing that individuals with lesions in the medial prefrontal cortex exhibit less mind‐wandering compared to those with lesions not located in the DMN areas. ⁸⁶ , ⁸⁷ It is evident from these and other investigations that disrupting the DMN impedes the ability to generate original thoughts from existing conceptual platforms. However, is the “risk” of hindering one's ability to mind‐wander and produce creative thoughts bigger than the benefit of seizure reduction or resolution? As is the case with any epilepsy surgery candidacy determination, it depends on the individual circumstances. Another factor should be acknowledged when addressing this issue, as demonstrated in an sEEG and laser ablation of a seven‐year‐old child with the epileptogenic zone involving components of the DMN (Figure 3). From an evolutionary perspective, it is plausible that the DMN is pivotal for managing the daily unexpected adversities appearing in our complex immediate environment. Occurrences that are not pre‐determined and for which guidelines are unavailable, require a rapid analysis, decision‐making, and reaction. ⁸⁸ , ⁸⁹ Hence, with consideration of the patient's clinical and neuropsychological context, surgical removal of an area playing a critical adaptive role and possibly affecting survival should arguably be contemplated as part of epilepsy surgery planning.

FIGURE 3.

Stereotactic encephalography (sEEG) epochs and MRI images (including the sEEG electrode placements) of a seven‐year‐old child with focal onset epilepsy originating from the (A) right posterior cingulate cortex and (B) right inferior parietal lobe and precuneus. The black arrows on the sEEG epochs point to the ictal onset patterns, and the red stars on the MRI images indicate the electrode contact from which seizure onsets were captured. The child's seizures were characterized by tonic stiffening of the left hand with or without a preceding nonspecific or emotion‐eliciting aura. The patient underwent Laser interstitial Thermal Therapy (LiTT) of the aforementioned seizure onset zones, after which the seizure burden was reduced. A post‐operative neuropsychological evaluation demonstrated greater difficulties in tasks requiring higher‐level spatial reasoning, mental rotation, understanding part‐whole relationships, and analysis of abstract visual stimuli.

3. CONCLUSION

Highest‐order cognitive processes carried out by several cortical structures and networks allow us to devise creativity‐ those insightful “eureka‐moment” thoughts that benefit our adaptive needs and, in direct correlation, survival. Several neuropsychological approaches have been developed to measure creativity; however, defining what or who is “creative” is challenging. Hence, it is also difficult to elucidate the underlying neurobiological operation of creative thinking. Novel research methods that emerged in the last two decades have enabled us to understand that there is no single brain region responsible for creativity; rather, it is the dynamic interplay between the default mode network (activated at times of “quiet wakefulness,” and responsible for self‐reflection, recollection of episodic memories, and mind wandering), central executive network (responsible for step‐wise task completion), and affective salience network (integrating between the default mode and executive networks). Focusing and defocusing allow us to diverge our reasoning and actions. Focal seizures may originate from DMN‐related areas. Considering the importance of the DMN to creative cognition, removing these areas in epilepsy surgery should be assessed within the context of the patient's specific clinical and neuropsychological profile. Additionally, future studies should explore the risks entailed in surgical removal of currently considered “dispensable” DMN‐related areas vs. the benefit of seizure reduction and resolution.

CONFLICT OF INTEREST STATEMENT

None of the authors has any conflict of interest to disclose.

ETHICS STATEMENT

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.