Functional neuroimaging of word priming in males with chronic schizophrenia

Abstract

Word-priming studies have suggested that the associative disturbance of schizophrenia may reflect aberrant spread of activation through the lexicon of the brain. To explore this, we examined lexical activation using a semantic word-priming paradigm coupled with functional magnetic resonance imaging (fMRI). We also wanted to determine whether brain activation to this paradigm correlated with relevant clinical symptom measures. In addition to completing clinical symptom measures, twelve chronic patients and twelve demographically-matched control subjects completed a lexicaldecision semantic-priming paradigm developed as an event-related BOLD fMRI task. This paradigm consisted of words that differed in connectivity. Words with many connections between shared semantic associates are considered high in connectivity and produce the largest behavioral semantic priming effects in control subjects, while words with few connections between shared semantic associates are considered low in connectivity and produce a relatively smaller amount of semantic priming. In fMRI, a respective step-wise increase in activation from high connectivity to low connectivity to unrelated word pairs was expected for normal subjects. Controls showed the expected pattern of activation to word connectivity; however, patients showed a less robust pattern of activation to word connectivity. Furthermore, this aberrant response correlated with measures of Auditory Hallucinations, Distractive Speech, Illogicality, and Incoherence. The patients did not display left frontal and temporal activation as a function of the degree of word connectivity as seen in healthy controls. This may reflect a disease-related disturbance in functional connectivity of lexical activation, which in turn may be associated with clinical symptomatology.

Altered language network activity in young people at familial high-risk for schizophrenia

“…While the precise functional interpretation of this observation is somewhat unclear, it may reflect a neural basis of risk for developing unusual ideas, perceptions and disorganized language (Grimshawet al, 2010). Previous studies have also reported relationships between abnormal frontal modulation during language processing and clinical symptoms in participants with FHR and SZ (Whyte et al, 2006; Han et al, 2007), (including a relationship between reduced IFG suppression during semantic priming and clinical symptoms in SZ) (Han et al, 2007). The extent of IFG non-suppression during semantic priming could potentially reflect a continuum of risk for SZ, with moderate levels of non-suppression associated with attenuated positive symptoms, and higher levels, with frank psychosis.…”

“…Consistent with altered semantic processing in SZ, fMRI studies of semantic priming in SZ have reported less association-induced suppression in left frontal and temporal regions (Han et al, 2007; Kuperberg et al, 2007), and sometimes even the opposite pattern of modulation, with more activity to semantically associated relative to unrelated pairs (‘association-induced enhancement’) (Kuperberg et al, 2007). These abnormalities were seen even when behavioral semantic priming was normal.…”

Reduced Task-Related Suppression During Semantic Repetition Priming in Schizophrenia

“…Previous studies of semantic priming have focused on the language network that includes left inferior frontal and left temporal regions (Bergerbest et al, 2009;Han et al, 2007;Tivarus et al, 2006;Wig et al, 2009). Current study, however, demonstrated an independent component showing semantic repetition priming-related activation being broader, and consisting of bilateral orbitofrontal, superior parietal and inferior temporal regions.…”

“…The late information processing responsible for N400 during semantic priming task in ERP study could be associated with the dysfunction in left inferior frontal gyrus, as suggested by a functional magnetic resonance imaging (fMRI) study (Kubicki et al, 2003). Schizophrenics also showed a differential increase in activation of both left frontal and temporal cortices from high connectivity to low connectivity to unrelated word pairs (Han et al, 2007). In addition, semantic repetition priming effect (Guillaume et al, 2009) observed with the left inferior frontal gyrus (Bergerbest et al, 2009;Wig et al, 2009) has been also reported to be decreased in schizophrenia (Matsuoka et al, 1999).…”

“…A meta-analysis using behavioral data reported that schizophrenics with thought disorder showed an increased semantic priming, when compared with healthy controls (Pomarol-Clotet et al, 2008). In terms of priming effect, words with high connectivity between shared semantic associates are considered to produce the larger semantic priming effects, faster response in lexical decision and less brain activation in region that includes the left inferior frontal gyrus (Tivarus et al, 2006;Weems and Zaidel, 2005), while words with low semantic connectivity are considered to produce a relatively smaller effect in healthy subjects (Han et al, 2007). In an event-related potential (ERP) study, the negative relationship between N400 amplitude and the degree of the association of prime-to-target stimulus, even though evident in control subjects, was not present in schizophrenia (Kiang et al, 2008).…”