Functional magnetic resonance imaging reveals neuroanatomical dissociations during semantic integration in schizophrenia

Abstract

Background: 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.

Figure 1. Depiction of a single trial

Each trial began with a centered yellow fixation followed by each word (450msec, ISI: 100msec). The sentence-final word was followed by a response cue (“?”), giving subjects 1850msec (ISI: 100msec) to respond before the next trial began. The sentence shown is a concrete incongruous sentence. See Table 1 for examples of sentences presented in the other three conditions.

Figure 2. Cortical statistical maps comparing the hemodynamic response to concrete and abstract sentence-final words, across patients and controls (main effects of Concreteness in the absence of any interactions involving Group)

Yellow-red: more activity to concrete than to abstract words. Blue: more activity to abstract than concrete words (shown again in Figure 3). These maps were generated by contrasting the second component of the HDR to each sentence type (lasting 550msec, from the onset of the critical sentence-final word until the onset of the “?”). They are therefore likely to reflect differences in neurocognitive activity at the point of sentence-final word, as well as during decision making (see (11) and (13) for Discussion). Hemodynamic time courses show activity in patient and control groups within each of these clusters at each TR. On the time axes, zero refers to the onset of the trial as a whole. The critical events – the sentence-final words – began 4950msec into the trial. All clusters circled are significant at a cluster-level p < 0.05. Cluster numbers correspond directly to the regions reported in Table 5A.

Figure 3. Cortical statistical maps comparing the hemodynamic response to concrete and abstract sentence-final words, across patients and controls (main effects of Concreteness in the absence of any interactions involving Group)

Blue: more activity to abstract than to concrete words. Hemodynamic time courses show activity in patient and control groups within each of these clusters at each TR (on the time axes, zero refers to the onset of the whole trial). All clusters circled are significant at a cluster-level p < 0.05. Cluster numbers correspond directly to the regions reported in Table 5B.

Figure 4. Group by Concreteness interactions: areas showing different patterns of modulation between patients and controls in comparing concrete and abstract sentence-final words

Hemodynamic time courses show activity in patient and control groups within each of these clusters at each TR (on the time axes, zero refers to the onset of the whole trial). All clusters circled are significant at a cluster-level p < 0.05. Cluster numbers correspond directly to the regions reported in Table 6.

Figure 5. Cortical statistical maps comparing the hemodynamic response to incongruous and congruous sentence-final words, across patients and controls (main effects of Congruity in the absence of any interactions involving Group)

Hemodynamic time courses show activity in patient and control groups within each of these clusters at each TR (on the time axes, zero refers to the onset of the whole trial). All clusters circled are significant at a cluster-level p < 0.05. Cluster numbers correspond directly to the regions reported in Table 7.

Figure 6. Group by Congruity interactions: areas showing different patterns of modulation between patients and controls in comparing incongruous and congruous sentence-final words

Hemodynamic time courses show activity in patient and control groups within each of these clusters at each TR (on the time axes, zero refers to the onset of the whole trial). All clusters circled are significant at a cluster-level p < 0.05. Cluster numbers correspond directly to the regions reported in Table 8.