Faulty Suppression of Irrelevant Material in Patients with Thought Disorder Linked to Attenuated Frontotemporal Activation

Abstract

Formal thought disorder is a feature schizophrenia that manifests as disorganized, incoherent speech, and is associated with a poor clinical outcome. The neurocognitive basis of this symptom is unclear but it is thought to involve an impairment in semantic processing classically described as a loosening of meaningful associations. Using a paradigm derived from the n400 event-related, potential, we examined the extent to which regional activation during semantic processing is altered in schizophrenic patients with formal thought disorder. Ten healthy control and 18 schizophrenic participants (9 with and 9 without formal thought disorder) performed a semantic decision sentence task during an event-related functional magnetic resonance imaging experiment. We employed analysis of variance to estimate the main effects of semantic congruency and groups on activation and specific effects of formal thought disorder were addressed using post-hoc comparisons. We found that the frontotemporal network, normally engaged by a semantic decision task, was underactivated in schizophrenia, particularly in patients with FTD. This network is implicated in the inhibition of automatically primed stimuli and impairment of its function interferes with language processing and contributes to the production of incoherent speech.

Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia

“…The interpretation of this finding may be that patients with positive FTD ineffectively struggle to suppress inappropriate mental activity along with increased speech production. In line with previous reports, increased severity of positive FTD was associated with higher perfusion of a large cluster in the frontal lobe, interpreted as a faulty suppression of irrelevant material . In addition, the association within the SMA seems to be specific for positive FTD, as it remained significant when controlling for the severity of negative and linguistic FTD.…”

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

“…Specifically, anterior cingulate hyperactivation was found for both appropriate and inappropriate semantic retrieval (Assaf et al, 2006;Jamadar et al, 2013), as well as semantic-dependent sentence comprehension (Borofsky et al, 2010). Anterior cingulate hypoactivation was associated with semantic fluency (Ragland et al, 2008) and decisions of semantic congruence for sentence completion (Arcuri et al, 2012). Language production tasks were associated with hypoactivation of left and right, anterior and posterior cingulate cortices.…”

“…Right-sided middle temporal hyperactivation was elicited using a more divergent range of tasks that included semantic-dependent sentence comprehension (Borofsky et al, 2010), monitoring of undistorted speech relative to pitch-distorted speech (Kumari et al, 2010), and rate of articulation during freely produced speech (Kircher et al, 2002). TD-related middle temporal hypoactivation in either hemisphere appeared to correspond with generative language tasks (Kircher et al, 2001a;Kircher et al, 2005;Kircher et al, 2001b;Kircher et al, 2002;Kircher et al, 2008), with an additional study reporting left middle temporal hypoactivation for decisions of semantically congruent sentence completion (Arcuri et al, 2012).…”

“…Correlates of the semantic and comprehension tasks included hypoactivation and hyperactivation, and were generally centred on the left pars triangularis, with a locus at the junction between the left pars orbitalis and pars triangularis for passive semantic tasks (Han et al, 2007;Horn et al, 2012), and within the pars triangularis for active judgements of semantic congruence (Chen et al, 2013), semantic-and syntax-dependent sentence comprehension (Borofsky et al, 2010), and decisions of appropriate sentence completion (Kircher et al, 2001b). TD-related activation for syntax-dependent comprehension (Borofsky et al, 2010), decisions of semantically congruent sentence completion (Arcuri et al, 2012), and word generation for appropriate sentence completion (Kircher et al, 2001b) approached and encroached on the border with the left pars opercularis.…”

Frequency and Neural Correlates of Pauses in Patients with Formal Thought Disorder

“…We then tested the hypothesis that between-clause pauses and filled pauses in schizophrenic patients with FTD would be associated with attenuated activation in these regions. This was based on the putative impairments in speech planning and verbal self-monitoring in patients with FTD and previous evidence linking FTD to functional and structural abnormalities in these regions in schizophrenia (23–29). …”