Hippocampi, Thalami, and Accumbens Microstructural Damage in Schizophrenia: A Volumetry, Diffusivity, and Neuropsychological Study

Abstract

Volumetric abnormalities in the subcortical structures have been described in schizophrenia. However, it still has to be clarified if subtle microstructural damage is also present. Thus, we aimed to detect subcortical volume and mean diffusivity (MD) alterations in 45 patients with diagnosis of schizophrenia compared with 45 age-, gender-, and educational attainment-matched healthy comparison (HC) participants, by using a combined volumetry and diffusion tensor imaging (DTI) method. A secondary aim was to identify the neuropsychological correlates of subcortical abnormalities in the schizophrenic group. We found thalami and hippocampi bilaterally and left accumbens to show MD increase in the schizophrenic group. No volumetric decrease was found. Moreover, significant correlations between the MD values in subcortical structures (right thalamus and hippocampus and left accumbens) and working memory performance were found. Thus, subcortical microstructural alterations are present in schizophrenia even in absence of volumetric abnormalities. Furthermore, microstructural damage in subcortical areas is linked to working memory, suggesting the presence of a subtle microstructural subcortical dysfunction in the pathoetiological mechanism underlying high cognitive load performances in schizophrenia. Finally, our findings indicate that MD is a more sensitive marker of brain tissue deficits than signal intensity variations measured in T1-weighted imaging data, consistently with previous reports. Thus, DTI appears to be an invaluable tool to investigate subcortical pathology in schizophrenia, greatly enhancing the ability to detect subtle brain changes in this complex disorder.

Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults

“…The negative relationship between right hippocampus and working memory in the combined group is substantiated by previously reported findings in bipolar disorder (Ali et al, 2000) as well as in schizophrenia (Spoletini et al, 2011). Furthermore, functional MRI studies have shown hippocampal activity during working memory tasks in healthy individuals , suggesting hippocampal involvement in short-term memory networks as well as in long-term memory networks.…”

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

“…This is not the first study pointing to altered diffusion parameters in the thalamus or thalamocortical pathways. DTI findings supporting altered integrity of thalamocortical connectivity in schizophrenia include controversial alterations of fractional anisotropy in the anterior limb of the internal capsule (ALIC) Kubicki et al, 2005;Mamah et al, 2010;Sprooten et al, 2009;Sussmann et al, 2009;Zhang et al, 2010;Zhou et al, 2008, but see Ashtari et al, 2007;Kito et al, 2009;Kyriakopoulos et al, 2008;Szeszko et al, 2005;White et al, 2007 for negative findings in younger individuals and Beasley et al, 2009 for lack of evidence of myelin abnormalities post-mortem), of the tracts connecting to the LPFC (Kim et al, 2008;Oh et al, 2009) and altered FA (Hashimoto et al, 2009) or mean diffusivity in the thalamus itself (Agarwal et al, 2008;Rose et al, 2006;Spoletini et al, 2011). Kim et al (2007) have performed a similar DTI study, with an identical a-priori hypothesis, but found only differences in the thalamic CDR defined by connectivity to the orbitofrontal, parietal, and medial prefrontal cortices.…”

Cortico-subcortical underpinnings of narrative processing impairment in schizophrenia

“…Our group recently demonstrated that patients with schizophrenia have relatively disturbed lexico-semantic processing and are less informative and more tangential than healthy controls (Marini et al, 2008). There is evidence that patients with schizophrenia are characterized by structural abnormalities in subcortical brain areas, such as the hippocampus (Kalus et al, 2004), amygdala (Meisenzahl et al, 2008), thalamus (Rose et al, 2006), caudate, putamen, and accumbens (Spoletini et al, 2009), as well as in cortical areas such as fronto-temporal regions (Honea et al, 2005). These structures have also been reported as playing a crucial role in language processing (e.g.…”