Kuperberg, G. R. (2008).
Building meaning in schizophrenia.
Clin EEG Neurosci ,
39 (2), 99-102.
Full TextAbstractThe schizophrenia syndrome is clinically characterized by abnormal constructions of meaning during comprehension (delusions), perception (hallucinations), action (disorganized and non-goal-directed behavior) and language production (thought disorder). This article provides an overview of recent studies from our laboratory that have used event-related potentials and functional magnetic resonance imaging to elucidate abnormalities in temporal and spatial patterns of neural activity as meaning is built from language and real-world visual events in schizophrenia. Our findings support the hypothesis that automatic activity across semantic memory spreads further within a shorter period of time in thought-disordered patients, relative to non-thought-disordered patients and healthy controls. Neuroanatomically, increased activity to semantic associates is reflected by inappropriate recruitment of temporal cortices. In building meaning within sentences, the fine balance between semantic memory-based mechanisms and semantic-syntactic integration (dictating "who does what to whom") is disrupted, such that comprehension is driven primarily by semantic memory-based processes. Neuroanatomically, this imbalance is reflected by preserved (and sometimes increased) activity within temporal and inferior prefrontal cortices, but abnormal modulation of dorsolateral prefrontal and parietal cortices. In building meaning across sentences (discourse), patients fail to immediately construct coherence links, but may show inappropriate recruitment of temporal and inferior prefrontal cortices to incoherent discourse, again reflecting inappropriate semantic memory-based processing (abnormal inferencing). Finally, these abnormalities may generalize to real-world visual event comprehension, where patients show reduced neural activity in determining relationships around goal-directed actions, and comprehension is again dominated by semantic memory-based mechanisms.
Kuperberg, G. R., West, C. W., Lakshmanan, B. M., & Goff, D. (2008).
Functional magnetic resonance imaging reveals neuroanatomical dissociations during semantic integration in schizophrenia.
Biol Psychiatry ,
64 (5), 407-18.
Full TextAbstractBACKGROUND: Schizophrenia symptoms can be conceptualized in terms of a breakdown of a balance between 1) activating, retrieving, and matching stored representations to incoming information (semantic memory-based processing) and 2) fully integrating activated semantic representations with one another and with other types of representations to form a gestalt representation of meaning (semantic integration). Semantic memory-based processes are relatively more dependent on inferior frontal and temporal cortices, whereas particularly demanding integrative processes additionally recruit the dorsolateral prefrontal cortex (DLPFC) and sometimes parietal cortices. We used functional magnetic resonance imaging (fMRI) to determine whether the modulation of temporal/inferior frontal cortices and the DLPFC can be neuroanatomically dissociated in schizophrenia, as semantic integration demands increase. Integration demands were manipulated by varying the nature (concrete vs. abstract) and the congruity (incongruous vs. congruous) of words within sentences. METHODS: Sixteen right-handed schizophrenia patients and 16 healthy volunteers, matched on age and parental socioeconomic status, underwent event-related fMRI scanning while they read sentences. Blood oxygen level dependent (BOLD) effects were contrasted to words within sentences that were 1) concrete versus abstract and 2) semantically incongruous versus congruous with their preceding contexts. RESULTS: In both contrasts, large networks mediating the activation and retrieval of verbal and imagistic representations were normally modulated in patients. However, unlike control subjects, patients failed to recruit the DLPFC, medial frontal and parietal cortices to incongruous (relative to congruous) sentences, and failed to recruit the DLPFC to concrete (relative to abstract) sentences. CONCLUSIONS: As meaning is built from language, schizophrenia patients demonstrate a neuroanatomical dissociation in the modulation of temporal/inferior frontal cortices and the DLPFC.