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Distinct Roles for the Anterior Cingulate and Dorsolateral Prefrontal Cortices During Conflict Between Abstract Rules.

ABSTRACT: Distinct patterns of activity within the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC) reported in neuroimaging studies during tasks involving conflict between competing responses have often been cited as evidence for their key contributions to conflict-monitoring and behavioral adaptation, respectively. However, supporting evidence from neuropsychological patients has been scarce and contradictory. We administered a well-studied analog of the Wisconsin Card Sorting Test, designed to elicit conflict between 2 abstract rules, to a cohort of 6 patients with damage to ACC or dlPFC. Patients who had sustained more significant damage to the ACC were not impaired either on a measure of "conflict cost" nor on measures of "conflict-induced behavioral adaptation." In contrast, damage to dlPFC did not affect the conflict cost measure but abolished the patients' ability to adapt their behavior following exposure to conflict, compared with controls. This pattern of results complements the findings from nonhuman primates with more circumscribed lesions to ACC or dlPFC on the same task and provides converging evidence that ACC is not necessary for performance when conflict is elicited between 2 abstract rules, whereas dlPFC plays a fundamental role in behavioral adaptation.

SUBMITTER: Boschin EA

PROVIDER: S-EPMC5939207 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Distinct Roles for the Anterior Cingulate and Dorsolateral Prefrontal Cortices During Conflict Between Abstract Rules.

Boschin Erica A EA Brkic Merima M MM Simons Jon S JS Buckley Mark J MJ

Cerebral cortex (New York, N.Y. : 1991) 20170101 1

Distinct patterns of activity within the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC) reported in neuroimaging studies during tasks involving conflict between competing responses have often been cited as evidence for their key contributions to conflict-monitoring and behavioral adaptation, respectively. However, supporting evidence from neuropsychological patients has been scarce and contradictory. We administered a well-studied analog of the Wisconsin Card Sorting ...[more]

PMID: 28365775

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Project description:Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus RNA-sequencing to examine cell-specific transcriptional features in the dorsolateral PFC (DLPFC) and the subgenual anterior cingulate cortex (sgACC), regions implicated in major psychiatric disorders. Droplet-based nuclei-capture and library preparation were performed on replicate samples from 8 male donors without history of psychiatric or neurologic disorder. Unsupervised clustering identified major neural cell classes. Subsequent iterative clustering of neurons further revealed 20 excitatory and 22 inhibitory subclasses. Inhibitory cells were consistently more abundant in the sgACC and excitatory neuron subclusters exhibited considerable variability across brain regions. Excitatory cell subclasses also exhibited greater within-class transcriptional differences between the two regions. We used these molecular definitions to determine which cell classes might be enriched in loci carrying a genetic signal in genome-wide association studies or for differentially expressed genes in mental illness. We found that the heritable signals of psychiatric disorders were enriched in neurons and that, while the gene expression changes detected in bulk-RNA-sequencing studies were dominated by glial cells, some alterations could be identified in specific classes of excitatory and inhibitory neurons. Intriguingly, only two excitatory cell classes exhibited concomitant region-specific enrichment for both genome-wide association study loci and transcriptional dysregulation. In sum, by detailing the molecular and cellular diversity of the DLPFC and sgACC, we were able to generate hypotheses on regional and cell-specific dysfunctions that may contribute to the development of mental illness.SIGNIFICANCE STATEMENT Dysfunction of the subgenual anterior cingulate cortex has been implicated in mood disorders, particularly major depressive disorder, and the dorsolateral PFC, a subsection of the PFC involved in executive functioning, has been implicated in schizophrenia. Understanding the cellular composition of these regions is critical to elucidating the neurobiology underlying psychiatric and neurologic disorders. We studied cell type diversity of the subgenual anterior cingulate cortex and dorsolateral PFC of humans with no neuropsychiatric illness using a clustering analysis of single-nuclei RNA-sequencing data. Defining the transcriptomic profile of cellular subpopulations in these cortical regions is a first step to demystifying the cellular and molecular pathways involved in psychiatric disorders.

Dataset Information

Distinct Roles for the Anterior Cingulate and Dorsolateral Prefrontal Cortices During Conflict Between Abstract Rules.

Publications

Distinct Roles for the Anterior Cingulate and Dorsolateral Prefrontal Cortices During Conflict Between Abstract Rules.

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