Levels of Cognitive Control: A Functional Magnetic Resonance Imaging-Based Test of an RDoC Domain Across Bipolar Disorder and Schizophrenia

Abstract

In recent years, the boundaries of psychopathology as defined by diagnostic categories have been criticized as inadequately 'carving nature at its joints' with respect to the neurobiology of major mental disorders. In 2010 the NIMH launched the Research Domain Criteria (RDoC) framework for understanding mental illnesses as brain circuit disorders that extend beyond DSM-defined diagnoses. In the present study we focus on cognitive dysfunction, a core feature of schizophrenia (SZ) and bipolar disorder (BPD), and use functional magnetic resonance imaging (fMRI) during a cognitive control (CC) task in recent onset patients to test the hypothesis that at a behavioral and underlying neural circuitry level these deficits exist on a continuum (as opposed to showing categorical differences) across the two disorders. In total, 53 healthy controls, 24 recent (o1 y) onset patients with BPD Type I with psychotic features, and 70 recent onset patients with SZ performed the AX-Continuous Performance Task while undergoing event-related fMRI at 1.5 T. In addition to behavior task-associated response was examined in frontoparietal regions-of-interest. In an a priori contrast-based analysis, significant deficits across patient groups (vs controls) were observed on CC-associated performance as well as frontoparietal response. These analyses further revealed a continuum of deficits in which BPD showed intermediate levels of CC relative to controls and SZ. Poor CC was associated with poverty and disorganization symptoms across patient groups. These results support the hypothesis that CC dysfunction in BPD and SZ reflects a continuum of deficits that cuts across traditional, DSM-based classification. Implications for the neurobiology of these diseases are discussed.

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

“…These findings show that, despite the different categorical diagnoses, individuals with schizophrenia and BDs may share some neurobiological characteristics. 250 Functional neuroimaging studies with BD patients have found connectivity dysfunctions in neural circuits associated with emotion processing, emotion regulation and reward processing. 251 Patterns of amygdala activation and connectivity during emotion processing tasks were compared between individuals with BD and unipolar depression by Korgaonkar et al, with both groups in remission.…”

Neuronal underpinnings of cognitive impairment and - improvement in mood disorders

“…Six studies examined the neural basis of attention: 3 in BD 49,95,98 and 3 in UD. 43,44,68 Attention in bipolar disorder.…”

Transdiagnostic multimodal neuroimaging in psychosis: structural, resting-state, and task MRI correlates of cognitive control

“…Importantly, alterations in cognition (2)(3)(4), including cognitive control (5,6), are a key feature of psychosis. Furthermore, cognitive control alterations are observed transdiagnostically (7), including in individuals with SZ and BP (8), and other disorders (9)(10)(11). In the present work, we expand beyond prior work by using multimodal image analysis to examine transdiagnostic patterns of neural variation in structural, resting-state, and task functional imaging related to cognitive control.…”

“…Cognitive control refers to the set of cognitive functions that enable and support goal-directed behavior and regulation of one's thoughts and actions (12), including the ability to maintain information over time (e.g., working memory), protect against distraction, and combine novel inputs (12,13). Within the psychosis spectrum, SZ have poorer cognitive control performance than healthy controls (HC), and BP often have intermediary performance between SZ and HC (7,14,15). This graded performance further supports conceptualizations of psychosis as a dimensional transdiagnostic construct.…”

“…Of those, three components with spatial distribution in frontal and parietal regions corresponding to working-memory networks showed significant graded hyperactivation pattern (SZ>BP>HC). In addition, Smucny et al (7) used an a priori contrast approach to examine activation in the dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex (SPC) during AX-CPT task in a transdiagnostic population. They identified significant graded task performance (HC>BP>SZ) as well as BOLD responses in DLPFC and partially significant responses in SPC.…”