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Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.

Higher cognitive functioning is supported by adaptive reconfiguration of large-scale functional brain networks. Cognitive control (CC), which plays a vital role in flexibly guiding cognition and behavior in accordance with our goals, supports a range of executive functions via distributed brain networks. These networks process information dynamically and can be represented as functional connectivity changes between network elements. Using graph theory, we explored context-dependent network reorganization in 56 healthy adults performing fMRI tasks from two cognitive domains that varied in CC and episodic-memory demands. We examined whole-brain modular structure during the DPX task, which engages proactive CC in the frontal-parietal cognitive-control network (FPN), and the RiSE task, which manipulates CC demands at encoding and retrieval during episodic-memory processing, and engages FPN, the medial-temporal lobe and other memory-related networks in a context dependent manner. Analyses revealed different levels of network integration and segregation. Modularity analyses revealed greater brain-wide integration across tasks in high CC conditions compared to low CC conditions. Greater network reorganization occurred in the RiSE memory task, which is thought to require coordination across multiple brain networks, than in the DPX cognitive-control task. Finally, FPN, ventral attention, and visual systems showed within network connectivity effects of cognitive control; however, these cognitive systems displayed varying levels of network reorganization. These findings provide insight into how brain networks reorganize to support differing task contexts, suggesting that the FPN flexibly segregates during focused proactive control and integrates to support control in other domains such as episodic memory.

Goal maintenance is an aspect of cognitive control that has been identified as critical for understanding psychopathology according to criteria of the NIMH-sponsored CNTRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) and Research Domain Criteria (RDoC) initiatives. CNTRICS proposed the expectancy AX-CPT, and its visual-spatial parallel the dot probe expectancy (DPX), as valid measures of the cognitive and neural processes thought to be relevant for goal maintenance. The goal of this study was to specifically examine the functional neural correlates and connectivity patterns of both goal maintenance tasks in the same subset of subjects to further validate their neural construct validity and clarify our understanding of the nature and function of the neural circuitry engaged by the tasks. Twenty-six healthy control subjects performed both the letter (AX) and dot pattern (DPX) variants of the CPT during fMRI. Behavioral performance was similar between tasks. The 2 tasks engaged the same brain networks including dorsolateral prefrontal cortex (DLPFC) and dorsal parietal regions, supporting their validity as complementary measures of the goal maintenance construct. Interestingly there was greater engagement of the frontal opercular insula region during the expectancy AX-CPT (letter) and greater functional connectivity between the PFC and medial temporal lobe in the DPX (dot pattern). These differences are consistent with differential recruitment of phonological and visual-spatial processes by the two tasks and suggest that additional long-term memory systems may be engaged by the dot probe version.

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.