The correlation between regional brain volumetrics and openness in healthy individuals has been examined in several studies with varying results. While some structural neuroimaging studies have found no relationship between openness and cortical brain volume (31), others have implicated a diverse set of structures. DeYoung and colleagues found that individuals who score high in openness tend to have a larger prefrontal cortex, which is the part of the brain responsible for higher-order thinking, decision-making, and planning (2). They also found an association with the volume of the inferior parietal lobule, which is linked with working memory, attention control, and general intelligence, suggesting that these cognitive processes might be associated with openness (2).

Openness has also been associated with increased gray matter volume in the anterior cingulate cortex (ACC), which is involved in emotion regulation and conflict monitoring (32).

Another neuroimaging study of healthy older adults from the Baltimore longitudinal study of aging found that higher openness was associated with increased gray matter volume in the frontopolar cortex. These regions are involved in cognitive control and executive function (33, 34), and enable individuals with higher openness to hold alternative actions in working memory in order to evaluate new options and ideas (33). The same study showed negative correlations between openness and volume in the right ventromedial prefrontal (vmPFC) and left fronto-insular cortex, regions that are involved in evaluation of negative outcomes and are linked to inhibitory or cautionary reactions to unpleasant or threatening stimuli. These data suggest that people with higher trait openness might be less vulnerable to such inhibitory reactions, while individuals with higher levels of anxiety are less likely to engage in cognitive or behavioral openness due to perceived risk (33, 35).

Two networks, in particular, appear in the majority of functional connectivity studies of creativity. The first, typically called the default mode network (DMN), includes the posterior cingulate cortex (PCC), dorsomedial prefrontal cortex (dmPFC), lateral parietal cortex, and hippocampal memory regions (33, 36). This network is involved in self-referential processing and social perspective-taking and is thought to be involved in a range of cognitive processes, including interpersonal perspective taking, introspection, and autobiographical memory (37). The second network relevant to trait openness is the executive control network (ECN), which comprises the dorsolateral prefrontal cortex (dlPFC) and the lateral posterior parietal cortex (PPC). It is an externally-oriented network involved in attentional selection, active task control, and executive functions, and is responsible for higher-order reasoning and decision-making. The dlPFC has also been implicated in the regulation of affect via reallocation of attention (36, 38).

Task-free functional imaging studies suggest that openness may be associated with increased functional connectivity between brain networks involved in cognitive control (i.e., the ECN) and self-referential processing (the DMN) (27). While higher levels of activity within the DMN have been found to predict lower trait openness, higher levels of connectivity between the DMN and ECN appear to allow individuals with higher levels of openness to better process information, generate new ideas, and approach challenges in creative and innovative ways. This DMN-ECN connectivity pattern in individuals with higher levels of trait openness is also correlated with cognitive flexibility, allowing these individuals to switch between different mental sets and think outside the box (38). Furthermore, evidence from these studies suggests that connectivity of the DMN and ECN networks with the brain’s reward regions (including the vmPFC, nucleus accumbens, and head of the caudate) allows individuals with higher trait openness to be better able to integrate diverse sources of emotional and cognitive information, and to have a greater propensity to turn self-reflection and introspection about emotionally salient ideas and experiences into creative action (35).

In otherwise neurologically healthy individuals, certain cognitive and behavioral approaches and personality traits can be maladaptive, even falling on the spectrum of psychopathology. Dogmatism, or fundamentalism, can be understood to represent the opposite of trait openness because it is characterized by rigid adherence to a set of ideas and the intentional exclusion of competing beliefs. Thus, studies of dogmaticism are relevant to the neurobiology of openness, and have important implications for the mechanisms of decision-making, problem-solving, and learning (28). Task-based fMRI studies have shown that individuals with high levels of mental rigidity exhibit lower activation in the vmPFC during tasks that require flexible thinking, such as set-shifting or task-switching, compared to individuals with high levels of mental flexibility (28, 39). Dogmatism has been found to be associated with decreased functional connectivity between the vmPFC and the temporoparietal junction (TPJ) (28), while ideologic openness is associated with increased functional connectivity between the vmPFC and the ACC, regions involved in error monitoring and motivation (28, 40, 41).

One of the key neural systems that has been implicated in trait openness is the dopaminergic mesolimbic pathway, which is involved in reward processing, motivation, and novelty-seeking behavior. Several lines of research have demonstrated that individuals high in openness exhibit greater activation in the ventral striatum, a key component of the mesolimbic reward pathway, during tasks that involve processing novel or unexpected information. Other studies showed that individuals who have a particular variant of the dopamine receptor gene (DRD4) tend to score higher in openness (42). The DRD4 gene has also been linked to sensation-seeking behavior and risk-taking (43, 44).

Similarly, the neurotransmitter serotonin is associated with emotion regulation, and individuals who have the long allele variant of the serotonin transporter gene (5-HTTLPR) tend to score higher in openness (45). The short allele variant of the 5-HTTLPR gene has also been linked to anxiety and depression (46), which are negatively correlated with trait openness. Studies have examined the relationship between openness and the serotonergic system using positron emission tomography (PET) with different serotonergic receptor-binding radioligands, but with varied results. Kalbitzer and colleagues showed that participants’ scores on the NEO-PI-R openness scale, and particularly the two subscales openness to actions and openness to values, were negatively correlated with the [11C] DASB binding radioligand for 5-HTT in limbic areas including the caudate (47). The authors suggested that because there was less serotonin available in these areas, the action of the remaining serotonin was potentiated, similar to the facilitation caused by antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs). However, other PET studies using different serotonin ligands [5-HT2AR (48) and 5-HT4R (49)] to investigate trait openness found no significant neural associations.

Certain drugs, such as psychedelics (i.e., LSD and psilocybin, which are agonists for the 5-HT2AR serotonin receptor), have been shown to increase openness in some individuals (50, 51). fMRI studies have also shown altered DMN activity and connectivity (52) in individuals during psychedelic use. As described earlier, the DMN is involved in self-referential thinking and introspection, leading to better self-awareness and self-regulation, though heightened DMN activity alone corresponds with decreased openness (36). However, the pattern of brain activity induced by psychedelics is characterized by increased variability and decreased stability, which may in turn result in greater connectivity between the DMN and other networks. The authors posit that this leads to a “liberation” of cognitive and affective processes, allowing for increased creativity and divergent thinking as part of the trait openness (52).

Research using magnetic resonance spectroscopy (MRS) has also revealed that individuals with high levels of openness have higher levels of the neurotransmitter glutamate in anterior cingulate cortex (ACC) regions related to error monitoring and motivation, as well as in vmPFC reward areas (53). Glutamate is a key neurotransmitter involved in synaptic plasticity and learning, and these results suggest that increased glutamatergic activity in these reward and motivation areas in more open individuals may lead to a greater capacity for cognitive flexibility and learning (53).

While the studies described thus far have included predominantly healthy individuals, additional insights about the neuroanatomical and neurochemical basis of openness can be derived from research models of neurological diseases as well. Lesion studies can shed light on which brain areas are both necessary and sufficient for particular behaviors and thought processes. Studying altered neural activity and connectivity in individuals with brain aging, injury, and disease who also show atypical levels of trait openness can facilitate our understanding of the underlying neural mechanisms.

Studies have investigated how trait openness relates to aging as and age-related cognitive decline. Several investigations have found a negative correlation between openness and age (11, 15, 65); however, others showed that openness can have a protective effect against cognitive decline in middle-aged and older adults (66, 67) and correlates with better cognitive performance, social abilities, and well-being in older age (66, 68). Other research has suggested that openness may represent a behavioral channel to cognitive and social engagement, which are linked to a lower risk of dementia and cognitive decline (13, 69, 70).

Studies of individuals with severe structural brain lesions (28, 71), such as penetrating traumatic brain injury (pTBI) (28), show that they often exhibit an extreme lack of openness in the form of mental rigidity, dogmatism, and ideological or religious fundamentalism. Brain-behavior studies of these individuals’ patterns of mental rigidity highlight the role of the vmPFC and its connectivity with other brain regions (28). In a study that included a large sample of patients with pTBI, Zhong and colleagues found that patients with injuries to the vmPFC scored higher than patients with dlPFC lesions on a standardized scale of religious fundamentalism, and that on average both groups showed abnormally high scores compared to neurologically healthy individuals. Analyses adjusting for the size of the lesions in the vmPFC suggested the interaction between vmPFC and dlPFC drove patients to have less cognitive flexibility and openness, again supporting the idea that the connection between reward- and executive-processing areas supports trait openness. This study gives insight into the role of both vmPFC and dlPFC in the revision of religious beliefs, suggesting that loss of cognitive flexibility is linked to an increase in fundamentalist belief adherence and resistance to novel information (28).

The neurobiological mechanisms underlying changes in openness in individuals with neurodegenerative brain disease are complex and are still being elucidated. Similar to what has been observed in neurologically healthy individuals, studies in individuals with neurodegenerative disease have suggested that changes in the levels of dopamine, serotonin, and other neurotransmitters may play a role (54, 72). Additionally, the changes in frontal and temporal brain structure and connectivity often observed in patients with neurodegenerative disorders have been repeatedly linked to dysregulation and alteration of previously stable personality traits (73).

Several studies have suggested that individuals with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) may experience a decline in openness, particularly with respect to creativity and decision-making (74). Parkinson’s disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra that can lead to both motor and non-motor symptoms. Individuals with PD are more likely to have reduced openness to experience, the degree of which has been associated with the severity of motor symptoms and cognitive decline (75). In PD, atrophy in the vmPFC and dlPFC have been shown to impact both social cognition and decision-making, leading to a decrease in intellectual curiosity (76).

Notably, there is a growing evidence that some personality traits increase the likelihood of developing Alzheimer’s disease and other dementias (77, 78). Several studies showed that openness, as a premorbid personality trait, was related to better cognitive outcomes in later life, suggesting that openness to experience contributes to cognitive reserve (79, 80). Openness also correlates with lower levels of aging-related hippocampal volume loss (81), and less Alzheimer’s disease-related tau accumulation in the entorhinal cortex in cognitively healthy individuals (82).Tautvydaite and colleagues found that in a mixed group of individuals with and without AD-positive biomarkers, premorbid openness predicted cognitive performance regardless of the individual’s cognitive level, demographics, APOEε4 status, or CSF biomarker levels. They found that openness was the only personality domain from the five-factor model that contributed independently to cognitive performance (83). These findings imply that openness as a lifelong personality trait may play a protective role against age-related neuropathological processes (33, 79, 82).

Another neurodegenerative disorder that has been shown to directly impact trait openness is frontotemporal dementia (FTD). FTD is characterized by the degeneration of the frontal and temporal lobes of the brain, leading to changes in behavior, personality, and language (84). Research has shown that individuals with the behavioral variant FTD syndrome (bvFTD) have significantly lower scores on measures of openness compared to healthy controls (85, 86), and that this decline has been linked to neurodegeneration in regions including the vmPFC and ACC (87).

Mental rigidity and dogmatism are common symptoms of FTD, and can manifest in various ways. For example, many individuals with FTD exhibit perseveration, which is the repetition of the same behavior or thought despite changes in the environment. Studies suggest this behavior may be due to atrophy in the dlPFC and ACC, areas involved in cognitive flexibility and inhibitory control (88). Some patients may present with intense resistance to changes in their routine or environment, such as trying new foods, moving to a new residence, or wearing different clothes day to day. Again, studies have linked this with atrophy in the dlPFC and other brain regions that support cognitive flexibility and adaptive behavior (89). Other patients with FTD, particularly those with the right temporal or semantic variant of bvFTD (90), may hold rigid or inflexible beliefs and refuse to consider alternative viewpoints (91, 92). Evidence suggests this may be due to disruptions in the vmPFC, which is involved in making evaluations of rewards during decision-making (93, 94). Furthermore, disruptions in the white matter tracts connecting the dlPFC and other brain regions such as the insula and anterior cingulate cortex, correlate with cognitive inflexibility and dogmatism in FTD (95).

On the other hand, studies of individuals with FTD have also highlighted the relationship between openness and creativity, which can be unleashed in a subset of these patients. For instance, specific patients with bvFTD have been found to display enhanced creativity and divergent thinking in specific contexts such as artistic production (96–98). A subset of individuals with FTD may exhibit dramatically increased engagement in an artistically creative behavior, such as painting, drawing, or composing music, that was not present before the onset of the disease (85, 99). This enhanced creative production is thought to be related to changes in the brain network connectivity between the DMN and the salience network (SN) (95). This phenomenon has been referred to as “unleashed creativity” and may be related to changes in neural networks involved in the processing of semantic and emotional information (96).

An alternate theory to explain this phenomenon is that the loss of inhibitory control that occurs in FTD may release previously suppressed creative tendencies (100). Certain patterns of dysfunction in the vmPFC and dlPFC may lead to a shift in cognitive processing that favors creative thinking over other, more rigorous cognitive processes (99). Persons with FTD who show this unleashed creativity show greater atrophy in the left hemisphere of the brain, particularly in the ventral and dorsolateral frontal and temporal regions associated with social cognition, executive functioning, and semantic processing. This atrophy appears to release inhibitions in the creative process, allowing for a more free-flowing expression of ideas and emotions (97, 99, 100), and thus, greater openness. Further research into this complex phenomenon in persons with FTD may provide new insights into the neural basis of openness and ultimately inform new strategies for the treatment and care of these individuals.