Altered Function and Connectivity of the Medial Frontal Cortex in Pediatric Obsessive-Compulsive Disorder

Fitzgerald, Kate D.; Stern, Emily; Angstadt, Mike; Nicholson-Muth, Karen C.; Maynor, McKenzie R.; Welsh, Robert C.; Hanna, Gregory L.; Taylor, Stephan F.

doi:10.1016/j.biopsych.2010.08.018

Cited by 130 publications

(142 citation statements)

References 66 publications

(89 reference statements)

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“…The urge to perform an experimentally trained habit has been shown to be associated with hyperactivity in the caudate in OCD patients (33), whereas the vmPFC is thought to influence the caudate for goal selection (35,36). Therefore, an aberrant vmPFC valuation system as demonstrated across several tasks in OCD (5,17,37) is of critical relevance to the maintenance of the disorder.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the significance of the role of the vmPFC to estimate values to guide goal-directed behavior (12) and the interference of maladaptive vmPFC functioning in a variety of tasks in OCD (5,8,(13)(14)(15)(16)(17), we postulated that impaired vmPFC valuation would be central to the disorder. We sought to determine how patients with OCD perform on a task that is dependent on accurate and flexible value signaling by this prefrontal region.…”

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confidence: 99%

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Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Apergis-Schoute

Gillan

Fineberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

138

152

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The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD). Skin conductance responses in OCD patients (n = 43) failed to differentiate during reversal compared with healthy controls (n = 35), although significant differentiation did occur during early conditioning and amygdala BOLD signaling was unaffected in these patients. Increased vmPFC activation (for CS+ > CS-) during early conditioning predicted the degree of generalization in OCD patients during reversal, whereas vmPFC safety signals were absent throughout learning in these patients. Regions of the salience network (dorsal anterior cingulate, insula, and thalamus) showed early learning task-related hyperconnectivity with the vmPFC in OCD, consistent with biased processing of the CS+. Our findings reveal an absence of vmPFC safety signaling in OCD, undermining flexible threat updating and explicit contingency knowledge. Although differential threat learning can occur to some extent in the absence of vmPFC safety signals, effective CS-signaling becomes crucial during conflicting threat and safety cues. These results promote further investigation of vmPFC safety signaling in other anxiety disorders, with potential implications for the development of exposure-based therapies, in which safety signaling is likely to play a key role.Obsessive Compulsive Disorder | vmPFC | Pavlovian | fMRI | safety signals C urrent behavioral therapies in anxiety-related disorders are based on Pavlovian fear extinction models. As fear extinction relies on revaluation of threatening stimuli as safe, it is critical to address how the brain processes the safety of stimuli in the environment. The ventromedial prefrontal cortex (vmPFC) is known to play a multifaceted role in integrating affective evaluative processes while mediating flexible behavior and is implicated in fear learning and anxiety-related disorders (1-7). Prefrontal inflexibility in Obsessive Compulsive Disorder (OCD) suggests rigidity in threat estimation alongside a persistent urge to perform compulsive behaviors, yet only one study has examined the neural correlates of fear learning and extinction in this disorder, implicating a maladaptive vmPFC (8).Human fear learning studies usually involve contrasting a threatening (CS+) stimulus that is occasionally paired with a shock with a stimulus that is never paired with a shock and thus safe (CS-). When using the CS+ > CS-contrast, the vmPFC consistently exhibits negative activation values in healthy controls, indicating stronger activation to the CS-than to the CS+ in this region (1-3, 7, 9). Fear reversal (Fig. 1A)...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Apergis-Schoute

Gillan

Fineberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

138

152

View full text Add to dashboard Cite

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“…Existing resting-state studies in patients with OCD demonstrated altered resting-state functional connectivity in the default mode network (involving structures such as the anterior cingulate cortex and medial frontal gyrus) (Fitzgerald et al, 2010;Koç ak et al, 2012), and within the CSTC circuitry that included the fronto-striatal regions (Harrison et al, 2009;Jang et al, 2010;Stern et al, 2012). Abnormal restingstate functional connectivity between the middle cingulate cortex and parahippocampal region have also been reported in OCD, and connectivity strength between these regions was positively correlated with response inhibition deficits (Kang et al, 2013).…”

Section: Evidence Of Anomalies Using Resting-state Functional Connectmentioning

confidence: 98%

“…Of the 35 articles, 19 articles employed executive function tasks and contributed studies for inclusion in the three themes: 6 studies in Theme 1 (Response Inhibition), 11 studies in Theme 2 (Interference) and 6 studies in Theme 3 (Set-shifting/switching) (Britton et al, 2010;de Wit et al, 2012b;Fitzgerald et al, 2005Fitzgerald et al, , 2010Gu et al, 2008;Han et al, 2011;Huyser et al, 2011;Kang et al, 2013;Maltby et al, 2005;Marsh et al, 2013;Nabeyama et al, 2008;Nakao et al, 2005Nakao et al, , 2009Page et al, 2009;Remijnse et al, 2013;Roth et al, 2007;Schlosser et al, 2010;Woolley et al, 2008;Yucel et al, 2007). Notably, 2 articles employed multiple tasks and contributed studies in all three themes (Page et al, 2009;Woolley et al, 2008).…”

Section: Study 2: Executive-task Related Fmri Studiesmentioning

confidence: 99%

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: An integrative review

Eng

Sim

Chen

2015

Neuroscience & Biobehavioral Reviews

125

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“…The rationale for the use of NIBS has been that if behavioral changes arising from a clinical condition occur due to altered activity within a given brain network, normalizing this activity with NIBS should lead to improved behavior. Such a rationale has motivated studies utilizing NIBS across a range of clinical conditions, including, but not limited to, stroke (Grefkes and Fink, 2014), schizophrenia (Frantseva et al, 2014), depression (Fitzgerald et al, 2009;Fox et al, 2013), and obsessive-compulsive disorder (Fitzgerald et al, 2010). Despite some encouraging results, symptomatic improvement following NIBS in such conditions has generally been modest, and often clinically insignificant (Kalu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%