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Neural correlates of predictable and unpredictable threat in internalizing psychopathology.

ABSTRACT: Converging lines of evidence suggest that heightened responding to unpredictable threat may be an important neurobiological marker of internalizing psychopathology (IP). Prior data also indicate that aversive responding to uncertainty may be mediated by hyperactivation of several brain regions within the frontolimbic circuit, namely the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). To date, however, the majority of this research has been focused on individual diagnoses and it is unclear whether abnormal neural reactivity to unpredictable threat is observed within heterogeneous, transdiagnostic IP patient populations, as theory would suggest. The aim of the current study was to therefore examine the neural correlates of temporally unpredictable (U) and predictable (P) threat in a sample of healthy controls (n?=?24) and patients with a broad range of IP diagnoses (n?=?51). We also examined whether symptom severity measures of fear and distress/misery dimensions correlated with neural reactivity to U- and P-threat. All participants completed a modified version of a well-validated threat-of-shock task during functional magnetic resonance imaging (fMRI). Across all participants, U- and P-threat elicited heightened activation in the aINS and brainstem, while P-threat alone also activated the dACC. Relative to healthy controls, patients displayed greater activation in the right aINS during U-threat, and greater right brainstem activation during P-threat. In addition, we found that brainstem activity during U-threat correlated with fear, but not distress/misery, psychopathology. Taken together, these preliminary results suggest that exaggerated aINS reactivity during U-threat and brainstem reactivity during P-threat may have the potential to become important transdiagnostic biomarkers of IP; however, future research efforts are needed to corroborate and expand the present findings.

SUBMITTER: Radoman M

PROVIDER: S-EPMC6476657 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Neural correlates of predictable and unpredictable threat in internalizing psychopathology.

Radoman Milena M Phan K Luan KL Gorka Stephanie M SM

Neuroscience letters 20190227

Converging lines of evidence suggest that heightened responding to unpredictable threat may be an important neurobiological marker of internalizing psychopathology (IP). Prior data also indicate that aversive responding to uncertainty may be mediated by hyperactivation of several brain regions within the frontolimbic circuit, namely the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). To date, however, the majority of this research has been focused on individual diagnoses ...[more]

PMID: 30825592

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Project description:One prevalent theory of learning states that dopamine neurons signal mismatches between expected and actual outcomes, called temporal difference errors (TDEs). Evidence indicates that dopamine system dysfunction is involved in negative symptoms of schizophrenia (SZ), including avolition and anhedonia. As such, we predicted that brain responses to TDEs in dopamine midbrain nuclei and target areas would be abnormal in SZ. A total of 18 clinically stable patients with chronic SZ and 18 controls participated in an fMRI study, which used a passive conditioning task. In the task, the delivery of a small amount of juice followed a light stimulus by exactly 6 s on approximately 75% of 78 total trials, and was further delayed by 4-7 s on the remaining trials. The delayed juice delivery was designed to elicit the two types of TDE signals, associated with the recognition that a reward was omitted at the expected time, and delivered at an unexpected time. Main effects of TDE valence and group differences in the positive-negative TDE contrast (unexpected juice deliveries-juice omissions) were assessed through whole-brain and regions of interest (ROI) analyses. Main effects of TDE valence were observed for the entire sample in the midbrain, left putamen, left cerebellum, and primary gustatory cortex, bilaterally. Whole-brain analyses revealed group differences in the positive-negative TDE contrast in the right putamen and left precentral gyrus, whereas ROI analyses revealed additional group differences in the midbrain, insula, and parietal operculum, on the right, the putamen and cerebellum, on the left, and the frontal operculum, bilaterally. Further, these group differences were generally driven by attenuated responses in patients to positive TDEs (unexpected juice deliveries), whereas responses to negative TDEs (unexpected juice omissions) were largely intact. Patients also showed reductions in responses to juice deliveries on standard trials, and more blunted reinforcer responses in the left putamen corresponded to higher ratings of avolition. These results provide evidence that SZ patients show abnormal brain responses associated with the processing of a primary reinforcer, which may be a source of motivational deficits.

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Neural correlates of predictable and unpredictable threat in internalizing psychopathology.

Publications

Neural correlates of predictable and unpredictable threat in internalizing psychopathology.

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