Abstract
Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control—reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX-CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization.
Highlights
While decades of research illustrate that schizophrenia is associated with deficits across a wide variety of cognitive domains, including attention, memory, and language, recent theories propose that impaired cognitive control-related dysfunction of the prefrontal cortex may account for many of these findings (Barch and Ceaser, 2012; Lesh et al, 2011)
To accurately interpret activity in regions surviving FWE correction in the whole-brain task by group interaction, we evaluated beta weights extracted from the local maximum coordinates in each significant region
The interaction analysis of group and task showed that controls increased activity in dorsolateral prefrontal cortex (DLPFC) as well as inferior parietal cortex during proactive compared to reactive control, while patients did not show this increase
Summary
While decades of research illustrate that schizophrenia is associated with deficits across a wide variety of cognitive domains, including attention, memory, and language, recent theories propose that impaired cognitive control-related dysfunction of the prefrontal cortex may account for many of these findings (Barch and Ceaser, 2012; Lesh et al, 2011). Recent work highlights a distinction between proactive and reactive modes of cognitive control, which Braver and colleagues have termed the dual mechanisms of control (DMC) theory (Braver et al, 2007, 2009). Due to its connectivity with sensorimotor regions, DLPFC plays a central role in the maintenance of goals and rules for action (Asaad et al, 2000; Watanabe, 1990, 1992), which should be reflected in increased DLPFC activity during proactive control. Proactive control may depend more on the ability to mount a sustained pattern of neural activity, a well-characterized aspect of prefrontal cortex that is observed during both physiological recording in non-human primates (Goldman-Rakic, 1995) and fMRI in
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