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

Abstract

The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age-and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.

Subanesthetic Ketamine Treatment Promotes Abnormal Interactions between Neural Subsystems and Alters the Properties of Functional Brain Networks

“…This is consistent with our previous observation that acute ketamine treatment enhances connectivity between the thalamic nuclei (Dawson et al, 2013). This contrasts with the thalamocortical dysconnectivity widely reported in schizophrenia, which is particularly evident in terms of PFC-thalamic dysconnectivity (Marenco et al, 2012;Welsh et al, 2010;Zhou et al, 2007;Woodward et al, 2012), although this is not always found (Klingner et al, 2013;Schlösser et al, 2003). In addition, there are examples of enhanced thalamic connectivity to other cortical subfields in schizophrenia, such as to motor and somatosensory areas (Woodward et al, 2012) and to the insular cortex (CorradiDell'Acqua et al, 2012).…”

Disrupted Working Memory Circuitry in Schizophrenia: Disentangling fMRI Markers of Core Pathology vs Other Aspects of Impaired Performance

“…A meta-analysis of human imaging studies reported the left thalamus, dlPFC, and dACC to be activated significantly less in schizophrenia patients during cognitive tasks (Minzenberg et al, 2009). In addition, structural thalamocortical connectivity to the lateral prefrontal cortex was previously associated with WM performance (Marenco et al, 2012). In addition to the decreased thalamus-FPCN coupling, we also observed abnormally increased connectivity between the thalamus and parahippocampal gyrus in patients during task performance.…”

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

“…The thalamus is connected to all cortical areas and conveys information to the neocortex, including information from the basal ganglia. Though a number of other studies have identified thalamic connectivity changes in the chronic stage of schizophrenia, 17,19,[22][23][24] such studies provide little information about early illness pathophysiology. In contrast, studies of FE schizophrenia have the advantage to specify brain changes at illness onset, thus providing crucial information about the pathogenesis of schizophrenia.…”

“…[17][18][19][20][21][22][23][24] Despite numerous leads, the reported findings are somewhat inconsistent and the core regions associated with the pathogenesis of schizophrenia still remain controversial.…”