Proposed as a third fundamental approach to religion along with Gordon Allport’s intrinsic and extrinsic religiosity, quest orientation refers to a form of religiosity that embraces honesty, doubt, and openness in the face of existential questions and complex life circumstances (Batson and Schoenrade, 1991). A multidimensional construct, religious quest as captured by the quest scale includes the following domains: (1) a search for answers to complex existential questions, (2) a perception of religious doubt as positive, and (3) an openness to change one’s religious views as one grows and changes. Despite the centrality of this orientation to religion and its association with a number of positive psychological traits, which include prosociality, openness to experience, and post-traumatic growth (Calhoun et al., 2000; Batson et al., 2001; Simpson et al., 2010), little is known about the neural structures that support this type of religiosity. Here, using diffusion tensor imaging (DTI) measures, we studied how white-matter structures related to aspects of religious quest.

Religious quest is inversely related to aspects of close-mindedness that include fundamentalism and authoritarianism (Altemeyer and Hunsberger, 1992; Hunsberger, 1995; Duck and Hunsberger, 1999), which, in turn, may predict prejudice toward those outside one’s own identity group (Altemeyer and Hunsberger, 1992; Brandt and Van Tongeren, 2015). In contrast, studies suggest that quest orientation is related to less prejudice and greater post-conventional reasoning (Batson et al., 1993; Cottone et al., 2007). Moreover, individuals high in religious quest tend to display empathetic and prosocial behavior (Batson et al., 1993, 2001). Quest religious orientation is also associated with the personality trait of openness to experience (Simpson et al., 2010). Those with this orientation tend to have both greater cognitive complexity and preference for cognitive consistency (Batson and Raynor-Prince, 1983; Barrett et al., 2005). Additionally, in the aftermath of traumatic life events, the degree of post-traumatic growth has been found to directly correlate with the quest domain of openness to change religious views (Calhoun et al., 2000).

Though the neural correlates of quest religious tendencies have not been directly investigated, brain imaging studies on potentially similar features, particularly the construct of openness to experience, serve to provide some relevant context. As measured by the Revised NEO Personality Inventory (NEO PI-R; Costa and McCrae, 1992a,b), openness has been observed to positively correlate with activity in the dorsolateral prefrontal cortex (dlPFC) during cognitive tasks and in the orbitofrontal cortex (OFC) during the resting state (DeYoung et al., 2005; Sutin et al., 2009). Openness is also associated with measures suggestive of better white-matter integrity in both hemispheres of the dlPFC, as well as the superior longitudinal fasciculus (SLF), corona radiata (CR), anterior cingulum, forceps minor, corpus callosum body, and regions adjacent to the middle frontal gyrus (MFG) and inferior frontal gyrus (IFG) (Xu and Potenza, 2012). These white-matter regions interconnect many cortical and subcortical regions in the brain. Additionally, the capacity for cognitive flexibility is associated with dlPFC activity and prefrontal measures related to white-matter integrity (Badre and Wagner, 2006; Nyhus and Barceló, 2009). Taken together, these findings suggest that connections bilaterally in the prefrontal cortex (PFC), the corpus callosum, and other cortical and subcortical brain regions may serve as a neural feature underlying religious quest.

Diffusion tensor imaging (DTI) measures water diffusion in multiple directions (Assaf and Pasternak, 2008). It can be used to generate fractional anisotropy (FA) values by calculating the normalized standard deviation of axial (λ₁) and radial diffusivities (λ_T) to index the degree to which the water diffusion deviates from isotropic diffusion in white matter, and mean diffusivity (MD) by averaging λ₁ and λ_T to index the overall diffusivity (Assaf and Pasternak, 2008; Neil, 2008). FA correlates positively with the ratio of λ₁ and λ_T, while MD correlates positively with the sum of λ₁ and λ_T. Therefore, FA and MD are sensitive to different patterns of changes in λ₁ and λ_T. For example, an increase in both λ₁ and λ_T may significantly increase MD without significantly changing FA, and a decrease in λ₁ along with an increase in λ_T may significantly decrease FA without significantly changing MD. Therefore, both FA and MD are often used as indexes of white-matter integrity, and a decreased FA and/or an increased MD value in the white matter is usually interpreted as reflecting poorer white-matter integrity (Alexander et al., 2007).

This study aimed to investigate in a preliminary fashion the relationships between measures related to white-matter integrity and aspects of quest orientation to religion. Based on findings of openness on the NEO being related to measures associated with better white-matter integrity and the possibility that openness on the NEO and related to the construct of openness to change on the quest scale, we hypothesized that scores on the openness-to-change subscale specifically would be positively correlated with measures related to better white-matter integrity in prefrontal areas, corpus callosum, and other regions that interconnect widespread cortical and subcortical regions across both hemispheres. We explored correlations with the two other subscales of the quest scale as we believe that this would represent a negative control condition that would provide discriminant validity for potential findings related to openness to change religious views.

Figure 1 shows the mean scores for the three subscales of the quest scale, with the openness-to-change scores being particularly relevant to the study hypothesis and subsequent figures. When applying a Bonferroni correction for 12 comparisons (3 subscales by 4 DTI parameters; P < 0.0042), a genual region of the corpus callosum was identified in the correlation between openness-to-change scores and λ_T values (Figure 2). When not applying a Bonferroni correction, scores on openness to change negatively correlated with λ_T and MD values in extensive white-matter regions in both hemispheres (Figures 3, 4). Regions showing significant negative correlations between scores on openness to change and λ_T values included the corpus callosum body, genu, and splenium, cingulum, SLF, anterior and superior CR, inferior fronto-occipital fasciculus, forceps minor, forceps major, external capsule, anterior limb of internal capsule, uncinate fasciculus, and sagittal stratum. Some, but not all, of these regions also showed significant negative correlations between scores on the openness-to-change subscale and MD. The implicated regions included the corpus callosum body, genu, and splenium, SLF, forceps minor, external capsule, and inferior fronto-occipital fasciculus. These significant correlations appeared driven by the λ_T values, because MD values represent the mean λ_T and λ₁ values, and λ₁ values did not show significant correlations with scores on the openness-to-change subscale. Scores on the openness-to-change subscale did not show significant correlations with FA values. Scores on the readiness-to-face-existential-questions and perception-of-religious-doubt-as-positive subscales did not show significant correlations with any DTI parameters.

To our knowledge, this study represents the first to investigate relationships between measures related to white-matter integrity and quest religious orientation. Our a priori hypothesis was partially supported as λ_T values correlated with openness-to-change scores and not with readiness-to-face-existential-questions or perception-of-religious-doubt-as-positive subscale scores. This finding was observed when correcting for whole-brain voxel-based tract-based spatial statistical analyses and when further applying a Bonferroni correction for 12 analyses involving 4 DTI and 3 quest subscale measures. When not applying a Bonferroni correction, λ_T and MD values in extensive regions of white matter were related to openness-to-change scores and not with readiness-to-face-existential-questions or perception-of-religious-doubt-as-positive subscale scores. Specifically, greater openness-to-change scores were related inversely to λ_T bilaterally in the corpus callosum body, genu, and splenium, cingulum, SLF, anterior and superior CR, inferior fronto-occipital fasciculus, forceps minor, forceps major, external capsule, anterior limb of internal capsule, uncinate fasciculus, and sagittal stratum. MD values in some but not all of these regions were also inversely to openness-to-change scores. Given that our a priori hypotheses were based on prior findings in a similar yet different area and concerns that stringent Bonferroni corrections may be ‘deleterious to sound statistical inference’ (Perneger, 1998, p. 1236), we will focus the discussion on non-Bonferroni-corrected findings while noting that the findings implicating the genu of the corpus callosum are the most statistically robust.

Despite the above-described correlations between the openness-to-change scores and λ_T and MD values, the former were not related to either λ1 or FA values. As diffusion-weighted MRI may be considered as indirect assessments of white-matter integrity, findings from these and other tensor-derived indices should be interpreted with caution. However, increases in both λ1 and FA have been linked to axonal loss, whereas increases in both MD and λ_T have been associated with demyelination (Song et al., 2002; Jones et al., 2013). The finding of significant negative correlations between λ_T and MD values and scores on openness to change suggests that better white-matter integrity in specific regions relates to a greater openness to change religious views. Different processes in the brain may influence λ₁ and λ_T differently. Axonal degeneration has been associated with changes in λ₁ value (Concha et al., 2006; Sidaros et al., 2008), while demyelination has been associated with increased λ_T values (Song et al., 2002). However, the current study investigated young adults who are unlikely to have experienced significant axonal degeneration or demyelination; thus, the findings are likely to reflect individual differences with respect to λ_T, possibly relating to degrees of myelination. This line of reasoning suggests that greater openness to change religious beliefs may be related to better myelination of multiple white-matter tracts, and this may relate to better communication among brain regions connected by these tracts (Au Duong et al., 2005; Greicius et al., 2009). Future studies using different approaches (e.g., investigating how functional connectivity at rest or during cognitive and emotional processing relates to openness to change religious beliefs) are warranted in order to examine how openness to change religious beliefs may relate to other aspects of brain structure and function.

The corpus callosum body and forceps minor interconnect middle and superior frontal regions and motor, sensory, and auditory cortices, and are critical to interhemispheric communication (de Lacoste et al., 1985; Schulte et al., 2005; Voineskos et al., 2010). The SLF interconnects the PFC and the parietal cortex, is important for communication between these brain regions and contributes importantly to executive control, cognitive process, and emotional modulation (Alexander et al., 1986; Clark et al., 2009; Sexton et al., 2009). The inferior fronto-occipital fasciculus connects inferior and lateral margins of the occipital lobe to the lateral PFC and contributes importantly to the processing of visual and spatial information (Catani et al., 2002; Schmahmann et al., 2008). The present finding of correlations between measures of openness to change religious views and measures suggestive of better white-matter integrity in the corpus callosum, SLF, forceps minor, external capsule, and inferior fronto-occipital fasciculus is consistent with the notion that a greater openness to change religious views is associated with more efficient integration of information among extensive brain regions with wide-ranging functions in both hemispheres.

Changing and adapting one’s religious views as one grows and changes may be considered a creative process, as it involves integrating multiple domains of knowledge and employing divergent forms of thinking. Thus, it is worthwhile to consider whether these findings converge with previous brain research on creativity. Takeuchi et al. (2010) found that creativity correlated with measures linked to white-matter integrity in widespread bilateral regions which overlap with the current findings in the frontal lobe and corpus callosum body, as well as white-matter regions adjacent to the striatum, temporo-parietal junction, and inferior parietal lobe. In addition, creativity has been associated with greater interhemispheric and intrahemispheric EEG (electroencephalogram) findings (Jaušovec, 2000), right prefrontal cortex activation (Howard-Jones et al., 2005), and corpus callosum volume (Moore et al., 2009).

The findings suggestive of greater interhemispheric communication observed in the current data are noteworthy, as research suggests that the left and right hemispheres each possess particular specializations and encode information differently (McGlone, 1984; Barrett et al., 1998; Kosslyn et al., 1998; Heilman et al., 2000). Thus, increased interconnection between the two hemispheres may facilitate a variety of cognitive strategies to be used when negotiating and reconciling one’s religious views with other sources of knowledge and experience. Similarly, extensive white-matter connections throughout the brain may allow for the integration of knowledge previously encoded in disparate and/or isolated neural networks (Heilman et al., 2003). The current results are consistent with the notion that creativity involves efficient integration of information in the brain and facility with diverse cognitive functions (Takeuchi et al., 2010). It should be noted, however, that a previous DTI investigation on personality and creativity found negative correlations between FA values and both creativity and openness to experience in inferior frontal white matter (Jung et al., 2010), suggesting that these two tendencies may be related to poorer white-matter integrity. Further investigation could uncover nuances in relationships between creativity and white-matter integrity.

Research has furthermore suggested that post-traumatic growth directly correlates with both creative cognitive capacities and openness to change religious views (Calhoun et al., 2000; Peterson et al., 2008). Traumatic life events often upend people’s sense of self and view of the world (Calhoun et al., 2000). In addition, greater levels of religiosity have been reported following traumatic and stressful life events (Park et al., 1996). Thus, the capacity to embrace new religious perspectives may contribute to the capacity for resilience and for experiencing positive change in the aftermath of difficult life circumstances. Consistent with this notion, previous studies have linked reduced white-matter integrity with post-traumatic stress symptoms and greater white-matter integrity with increased resilience (Frodl et al., 2012; Daniels et al., 2013; Sanjuan et al., 2013; van der Werff et al., 2017).

The current study has several limitations. It identified correlations between measures related to white-matter integrity and aspects of religious quest, but the cross-sectional nature limits insight into causality. The study also relied on a relatively small sample of young adults. Thus, future studies should examine larger samples to investigate the extent to which the findings replicate and more diverse groups, including but not limited to older individuals. Additionally, possible gender-related differences should be examined. Ideally, future studies should also acquire a larger number of diffusion directions. While the different scalar indices used in this study each summarize different properties of the diffusion tensor and it has been recommended to use multiple indices in studies (Jones et al., 2013; Soares et al., 2013), they are not wholly independent. However, a Bonferroni correction for multiple corrections identified a region of the genu of the corpus callosum as most robustly related to λ_T values. In non-Bonferroni-corrected findings thresholded at p_TFCE < 0.05, the specificity of the findings to the subscale assessing openness to change religious views is in line with our a priori hypotheses based on our prior study of openness more broadly defined (Xu and Potenza, 2012). Additionally, the specificity of the relationship between openness to change religious views and both MD and λ_T and not λ₁ or FA suggests a role for myelination in these relationships (Song et al., 2002; Jones et al., 2013), and this possibility should be examined in future studies. Furthermore, values of λ₁ and λ_T are affected by crossing fibers, changes in fiber directions induced by local pathology (Wheeler-Kingshott and Cercignani, 2009; Jbabdi et al., 2010), and local neuropil packing density (Beaulieu, 2002). For these reasons, findings from the current study should be considered preliminary and reflective of measures that have been associated with white-matter integrity but may arise from multiple etiologies. Thus, interpretation is limited, and questions should be examined by other approaches.

The current findings suggest that greater openness to changing religious views is related to better white-matter integrity in multiple tracts, including those connecting extensive brain regions between the two hemispheres. The widespread structural connections suggest neural pathways by which the capacity to embrace new religious perspectives as one grows and changes may occur. Furthermore, the results suggest brain structural features that may link openness to changing religious views to other potentially associated positive psychological tendencies, including those related to creative cognition and post-traumatic growth. Future studies should investigate these currently speculative possibilities, especially in larger and more diverse samples.

This study was carried out in accordance with the recommendations of Yale Human Investigations Committee with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Yale Human Investigations Committee.

LM and MP designed the study. IB acquired the data, and JX analyzed the data. CM and JX wrote the manuscript, while LM and MP revised the manuscript. All authors reviewed and approved the final manuscript.

No funding agencies had input into the content of this manuscript, and none of the authors have any relevant conflicts of interests. MP has: consulted for Ironwood, Lundbeck, Shire, INSYS, RiverMend Health, Opiant/Lightlake Therapeutics, and Jazz Pharmaceuticals; received research support (to Yale) from Pfizer, Mohegan Sun Casino, and the National Center for Responsible Gaming; participated in surveys, mailings or telephone consultations related to addictions, impulse-control disorders or other health topics; consulted for and/or advised to gambling and legal entities on issues related to impulse-control/addictive disorders; provided clinical care in a problem gambling services program; performed grant reviews for the National Institutes of Health and other agencies; edited journals and journal sections; given academic lectures in grand rounds, CME events, and other clinical or scientific venues; and generated books or book chapters for publishers of mental health texts. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.