Diffusion tensor imaging tractography of the fornix and belief confidence in first-episode psychosis

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Abstract

Previous studies have demonstrated that patients with psychosis are more confident in beliefs and judgments compared to healthy participants and psychiatric controls with major depression. A recent study conducted by our research group has provided evidence for hippocampal pathology in association with overconfidence in a first-episode psychosis sample. The fornix is the primary efferent neural pathway of the hippocampus and may also play a role in self-certainty pathophysiology. The current investigation applied diffusion tensor imaging tractography to a first-episode psychosis sample to explore whether integrity of the fornix is associated with self-certainty. High resolution structural magnetic resonance and diffusion tensor images were obtained in 44 people with a first-episode psychosis. Diffusion tensor imaging tractography was used to estimate fractional anisotrophy (FA), a measure of white matter integrity, in the fornix. Confidence in beliefs and judgments was measured with the self-certainty subscale of the Beck Cognitive Insight Scale (BCIS). The analysis showed that self-certainty significantly correlated to FA values in the right fornix but was nonsignificant for the left fornix. The findings indicate anatomical dysconnectivity of the right fornix in correlation with BCIS-rated self-certainty in our first-episode psychosis sample. When considered with our previously published self-certainty—hippocampus result in a first-episode psychosis sample, overlapping with that of this study, the results indicate a concurrence of volumetric reductions in hippocampus and fornix pathology in correlation with self-certainty.

Introduction

A plethora of studies has demonstrated biases in reasoning and cognitive distortions in people with schizophrenia (Garety et al., 2005). For example, it has repeatedly been shown that schizophrenia patients show an enhanced need for closure (Colbert et al., 2006), jump to conclusions (Garety et al., 1991) and attribute failure to others (Fornells-Ambrojo and Garety, 2009). Recently, the Beck Cognitive Insight Scale (BCIS) has proven to be helpful in our understanding of reasoning processes and cognitive distortions in psychosis (Beck et al., 2004, Riggs et al., 2012). In the BCIS, participants rate how much they agree with statements tapping two dimensions of cognitive insight: self-reflectiveness and self-certainty. Self-reflectiveness captures the willingness to acknowledge fallibility, corrigibility and recognition of dysfunctional reasoning, and self-certainty refers to overconfidence in beliefs and judgments. Relative to healthy people and patients with major depression, individuals with psychotic disorders endorse significantly lower self-reflectiveness and higher self-certainty (Beck et al., 2004, Martin et al., 2010), suggesting that these reasoning styles may play an important role in psychosis.

There is now evidence to suggest a relationship between cognitive insight in psychosis and neurocognitive deficits of hippocampal and frontally mediated functions. Several investigators have found self-certainty to be negatively correlated with performance on verbal memory, (Lepage et al., 2008, Orfei et al., 2012), a fronto-hippocampal task, and executive cognitive functions including cognitive set switching (Orfei et al., 2010) and strategy formation (Cooke et al., 2010), associated with frontal-lobe functioning. In an earlier study we have also reported a positive association between self-reflectiveness and verbal memory performance (Buchy et al., 2010). In order to address the question whether cognitive insight and memory and/or executive functions share qualitatively similar neural networks, we examined inter-relationships between self-certainty, verbal memory and hippocampal morphology in a first-episode psychosis sample (Buchy et al., 2010). Our results showed that participants who endorsed higher self-certainty had smaller bilateral hippocampal volumes than individuals who scored lower on self-certainty, independent of the effect of verbal memory, suggesting a selective contribution of hippocampal structure to self-certainty. In contrast, the data suggested no association of hippocampal structure with self-reflectivity. Taken together, the current literature suggests an involvement of the hippocampus and frontal cortex in the basic neuropathology of self-certainty in psychosis. Therefore, abnormal connectivity between these regions can be expected in patients with psychotic disorders.

It is unknown whether functional and/or structural disruptions of the hippocampus and frontal cortex observed in patients with high self-certainty may indicate underlying structural dysconnectivities. The fornix is the main white matter pathway connecting the hippocampus with other brain regions. It projects to medial prefrontal cortex and septal areas, as well as to the mamillary bodies and nucleus accumbens. Fornix integrity is known to be correlated with hippocampal volumes (Zahajszky et al., 2001, Kuroki et al., 2006) and is believed to play a role in verbal memory in both healthy individuals and those with schizophrenia (McMackin et al., 1995, Gaffan, 2005, Fitzsimmons et al., 2009). Of further note, white matter tracts interconnecting frontal and temporal cortices have long been implicated in the pathogenesis of schizophrenia (Ellison-Wright and Bullmore, 2009). A fiber abnormality could potentially increase the vulnerability of aberrant reasoning styles, or could be marking a concomitant secondary effect from psychosis. In either case, such finding would suggest a circuit-based biomarker for self-certainty in psychosis.

In the present study, we explore the relation between fornix connectional architecture and self-certainty in a first-episode psychosis sample. In particular, diffusion tensor imaging (DTI) followed by fornix tractography was performed on high-resolution structural magnetic resonance imaging (MRI) scans. DTI enables the examination of white matter fiber tracts interconnecting gray matter regions of the brain, while DTI tractography assembles local diffusion tensor data to infer the paths of fiber tracts. White matter integrity was quantified using fractional anisotropy (FA) values, which provide information about microstructural organization of white matter, incorporating information on fiber structure and fiber orientation. With DTI technique we tested the hypothesis that disturbed fornix connectivity would be correlated with high self-certainty in our FEP sample.

Section snippets

Participants

Participants were part of a longitudinal naturalistic outcome study of first-episode psychosis treated in a specialized early intervention service, the Prevention and Early Intervention Program for Psychoses (PEPP-Montreal), Douglas Institute in Montreal, Canada. The program involves a comprehensive approach with intensive medical and psychosocial interventions provided within the context of a modified assertive case management program. Individuals aged 14–35 years from the local catchment area

Results

Table 1 displays clinical and demographic characteristics of the sample as well as FA values of left and right fornices.

Fig. 2 displays correlations between self-certainty scores and FA values of the left and right fornices. The analysis showed that self-certainty was positively correlated to FA values in right fornix, r(43) = 0.32, p = 0.04. The correlation between self-certainty and left fornix FA values was nonsignificant, r(43) = 0.01, p = 0.96. No significant effects emerged between

Discussion

The present study used DTI tractography to explore whether disruptions in fornix integrity, as inferred by fractional anisotropy (FA), may relate to high self-certainty in a first-episode psychosis sample. Our finding of a significant positive correlation between right fornix FA values and self-certainty scores indicates that, in addition to previously demonstrated gray matter deficits in hippocampal volume in a sample overlapping with this study, anatomical dysconnectivity among the

Role of the funding source

Funding for this study was provided by the Canadian Institute of Health Research (CIHR) (operating grant 68961; studentship to L.B.), Sackler Foundation (to M.L., A.M.), Fonds de la Recherche en Sante du Que'bec (FRSQ) (salary award to M.L.), and Canada Research Chairs Program (to A.M.).

Contributors

The first author assisted in conceptualizing the study, analyzed the data, interpreted results and wrote the manuscript. The second author designed the tractography protocol and assisted in analyzing the data and interpreting results. The third author contributed to the assessment of inter-rater reliability. The fourth and fifth authors provided laboratory space and resources for data collection, and collaborated in the writing of the final version of the manuscript. The sixth author assisted

Conflict of interest

All authors declare no conflict of interest.

Acknowledgments

We would like to express our thankfulness to Ilana Leppert for her assistance with the DTI protocol. For conducting the MRI scans, we are thankful to Douglas Brain Imaging Group members Amélie Achim, Audrey Benoit, Mathieu Brodeur, Jennifer Dell'Elce, David Luck, Mathieu Menear, Philippe-Olivier Harvery, Karine Sergerie and Hazel Sutton. Many thanks to PEPP-Montreal research staff for their help with recruitment and for conducting the symptom assessments. We are very appreciative to all the

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