Is formal thought disorder in schizophrenia related to structural and functional aberrations in the language network? A systematic review of neuroimaging findings

Abstract

Formal thought disorder (FTD) is a core feature of schizophrenia, a marker of illness severity and a predictor of outcome. The underlying neural mechanisms are still a matter of debate. This study aimed at 1) reviewing the literature on the neural correlates of FTD in schizophrenia, and 2) testing the hypothesis that FTD correlates with structural and functional aberrations in the language network. Medline, PsychInfo, and Embase were searched for neuroimaging studies, which applied a clinical measure to assess FTD in adults with schizophrenia and were published in English or German in peer-reviewed journals until December 2016. Of 412 articles identified, 61 studies were included in the review. Volumetric studies reported bilateral grey matter deficits (L > R) to be associated with FTD in the inferior frontal gyrus, the superior temporal gyrus and the inferior parietal lobe. The same regions showed hyperactivity in resting state functional magnetic resonance imaging (fMRI) studies and both hyper- and hypoactivity in fMRI studies that employed semantic processing or free speech production tasks. Diffusion tensor imaging studies demonstrated white matter aberrations in fibre tracts that connect the frontal and temporo-parietal regions. FTD in schizophrenia was found to be associated with structural and functional aberrations in the language network. However, there are studies that did not find an association between FTD and neural aberrations of the language network and regions not included in the language network have been associated with FTD. Thus, future research is needed to clarify the specificity of the language network for FTD in schizophrenia.

Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts

“…However, a definite pathway for abnormal white matter connectivity in schizophrenia remains elusive. Previous studies have proposed that FTD severity is related to integrity of white matter language tracts 10,19 . This hypothesis is not supported by our data, as we found language disturbances to be present in the absence of large scale white matter aberrations that were confirmed by previous research 18,44,45 .…”

“…Until recently, studies have used subjective observation-based instruments to investigate language disturbances in schizophrenia 10 . Although these rating scales have clinical utility, they do not support the assessment of subtle phenomena/deviations with respect to language form (i.e., grammar as well as sound structure).…”

Speech structure links the neural and socio-behavioural correlates of psychotic disorders

“…Understanding the relationship between these two levels of dysconnectivity is likely to provide an important lead in the pathophysiology of psychosis (Goghari et al, 2010). Although several attempts have been made to ascertain this connection (Sumner et al, 2017;Cavelti et al, 2018;Kircher et al, 2018), consistent neurobiological features underpinning thought disorder in psychosis are yet to be identified.…”

A systematic review of task-based functional neuroimaging studies investigating language, semantic and executive processes in thought disorder

“…One avenue to help elucidate the contributions of these cognitive processes to the manifestation of TD is through the use of neuroimaging. The most replicated structural correlates of TD (for reviews, see Cavelti et al, 2018;Sumner et al, 2018) encompass reduced volumes within the left posterior superior temporal gyrus, including the planum temporale (Anderson et al, 2002;Barta et al, 1997;Horn et al, 2009;Rajarethinam et al, 2000;Sans-Sansa et al, 2013;Shenton et al, 1992;Weinstein et al, 2007). However, other replicated findings implicate the left and/or right orbitofrontal cortex (Gur et al, 2004;Horn et al, 2010;Nakamura et al, 2008;Sans-Sansa et al, 2013), the left amygdala-hippocampus complex (Bogerts et al, 1993;Rajarethinam et al, 2001;Sallet et al, 2003;Spalletta et al, 2010), the bilateral nucleus accumbens (Ballmaier et al, 2004;Spalletta et al, 2010), the cerebellar vermis (Sandyk et al, 1991), and the corpus callosum (Arnedo et al, 2015;Kubicki et al, 2008).…”

“…The functional neuroimaging findings in relation to TD will be informative in further testing these interpretations. A quantitative meta-analysis (Wensing et al, 2017) and systematic review (Cavelti et al, 2018) of the functional neuroimaging correlates of TD have been conducted recently. However, several pertinent studies were omitted from these analyses due to the broader focus on structural and functional neuroimaging (Cavelti et al, 2018) and more constrained inclusion criteria required for quantitative comparisons (Wensing et al, 2017).…”