Abstract
BACKGROUND: Cognitive impairments are core symptoms in schizophrenia. Among them, memory deficits seem to be strongly related to several outcomes, such as psychosocial functioning and accelerated aging. However, the neurobiological mechanisms associated with this dysfunction are still unclear. One hypothesis would be related to white matter microstructural abnormalities, considering that neuronal connectivity underlies cognitive processing. Therefore, we aimed to study the relationship between white matter integrity in major tracts using diffusion tensor imaging (DTI) and episodic memory and working memory in individuals with schizophrenia (SZ) compared to healthy controls (HC). METHODS: This was a cross-sectional study. We included 100 participants, 43 individuals with SZ that were medicated according to guidelines and stable for at least 6 months, and 52 unaffected individuals. All participants were informed about study procedures and signed consent before assessment. Research protocol was conducted in accordance with the Helsinki Declaration. The Institutional Review Board approved the study protocol. Participants underwent cognitive assessment with Hopkins Verbal Learning Test for episodic memory and Letter-Number Sequencing subtest from WAIS-III for working memory. Diffusion tensor imaging was performed on a Philips Achieva 1.5T scanner and was processed in FreeSurfer 5.3 TRACULA. We performed exploratory linear regression models separately for patients and controls with the sum of left and right fractional anisotropy (FA) predicting memory performance, controlling for age, sex, and years of education. The pathways analyzed were: corticospinal tract (CST), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UNC), anterior thalamic radiation (ATR), cingulum – cingulate gyrus (supracallosal) bundle (CCG), cingulum – angular (infracallosal) bundle (CAB), superior longitudinal fasciculus – parietal bundle (SLFP), superior longitudinal fasciculus – temporal bundle (SLFT), corpus callosum – forceps minor (FMIN) and forceps major (FMAJ). RESULTS: Individuals with SZ did not show differences among FA of white matter tracts (p > .05), although they had worse episodic and working memory performances compared to HC (p < .001). Episodic memory was not predicted by any of the white matter pathways analyzed (p > .05). Conversely, findings regarding verbal working memory were different between groups, showing that it was predicted only by CAB in SZ (t = 2.303, p = .027, Beta = .307; model: F = 5.209, p = 0.002, R2Adj = .286), whereas in HC it was predicted only by CST (t = -2.203, p = .032, Beta = -.266; model: F = 9.262, p < 0.001, R2Adj = .389). DISCUSSION: Decreased white matter integrity in cingulum-angular bundle, which are posterior fibers of the cingulum with parahippocampal connections, was related to worse working memory performance in schizophrenia. This finding implicates cingulate bundle neuronal connectivity abnormalities to higher-order cognitive processes, what may underlie the mechanisms of memory impairment in schizophrenia.