Hyperactive Error Responses and Altered Connectivity in Ventromedial and Frontoinsular Cortices in Obsessive-Compulsive Disorder

In the paper

“While there was no effect of medication (p = .25), VMPFC deactivation was smallest in mOCD and greatest in mPC subjects (trend medication-by-diagnosis interaction, p = .067, Figure 2C).”

In the paper

“Parameter estimates from VMPFC revealed negative signals relative to implicit baseline for null errors in all four groups and for loss errors in both control groups.”

In the paper

“Groups did not differ in number of errors or perception of error frequency (p > .1 for all effects)”

In the paper

“OCD patients were more flustered by mistakes (F (1,73) = 5.8, p = .02) and marginally more frustrated with their performance (F (1,73) = 3.3, p = .075).”

In the paper

“While both groups showed VMPFC deactivation in response to errors, the extent of this deactivation was larger for controls”

In the paper

“with a post-hoc ANOVA on contrast estimates (errors > corrects) revealing no effect of incentive (p = .54) and no interaction between incentive and diagnosis (p = .11).”

In the paper

“Post-hoc ANOVAs on contrast estimates (errors > corrects) revealed no effect of incentive (p = .11) or incentive-by-diagnosis interaction (p = .35), suggesting a relative failure of VMPFC deactivation in OCD for all three errors types (null, fail-to-gain, and loss).”

In the paper

“Group comparisons yielded significant differences in VMPFC (Figure 3B), with no other regions surviving correction; however, OCD patients also showed greater activity than controls in right aI/fO when correcting within aI/fO ROIs.”

In the paper

“Across all errors, OCD patients showed reduced deactivation of VMPFC and greater activation in left aI/fO as compared to controls.”

• Also stated in: § Event-related activity · plain

  “While both groups showed VMPFC deactivation in response to errors, the extent of this deactivation was larger for controls (Figure 2A and Table 1), leading to a significant OCD > control difference for errors > corrects (Figure 2B).”

• Also stated in: § Event-related activity · plain

  “results from a targeted analysis of aI/fO showed significantly greater activation in left aI/fO in OCD patients than controls (Figure 2B).”

In the paper

“Post-hoc ANOVAs performed on parameter estimates extracted from these regions revealed a medication-by-diagnosis interaction in right aI/fO (p = .04, see Figure 4B), indicating that mOCD patients showed the most positive connectivity with VMPFC while mPCs showed the least.”

In the paper

“Post-hoc ANOVAs on contrast estimates (loss > null errors) revealed no effects of medication and no medication-by-diagnosis interactions in either region (Figure 3C).”

In the paper

“Whereas controls exhibited negative connectivity between VMPFC and pMFC as well as a region of left aI/fO located superior and posterior to aI/fO areas showing positive connectivity with VMPFC, no negative coupling was found in OCD patients.”

In the paper

“Extent of positive coupling between VMPFC and aI/fO was greater in OCD patients than controls, and overlapped with aI/fO regions that were activated in the errors > corrects and loss > null errors contrasts in patients”

In the paper

“OCD patients also exhibited more positive connectivity between VMPFC and left aI/fO as well as VMPFC and right thalamus, although this may be due to differences in generalized depression and anxiety”

In the paper

“OCD patients showed significantly more activity for errors when they failed to gain money as compared to null errors in right aI/fO (x = 51, y = 27, z = -12, k = 43, z = 4.02), with no deactivations.”

In the paper

“No interactions were found for left aI/fO and thalamus, and no main effects of medication were found in any regions.”

In the paper

“OCD patients show greater activation in neural regions associated with emotion and valuation when making errors, which could be related to altered intrinsic functional connectivity between brain networks.”

In the paper

“Increased error-related VMPFC activity has been reported in OCD (12), perhaps reflecting an inability of patients to disengage from automatic evaluative processes when errors occur.”

What the sources say

• Not checked yetcites [12] Fitzgerald, 2005, Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder, Biol Psychiatry source

In the paper

“Multiple regression analyses probed for effects of generalized depression and anxiety, OC symptom severity, and SRI dosage on neural activity in regions exhibiting group differences”

In the paper

“These data suggest that the enhanced error response in OCD may be due to an overvaluation of error significance potentially related to altered intrinsic connectivity between regions involved in valuation and emotion.”

In the paper

“Intriguingly, VMPFC deactivation in healthy adults may be modulated by saliency signals coming from aI/fO (18), suggesting that interactions between these regions may impact how errors are processed.”

What the sources say

• Not checked yetcites [18] Sridharan, 2008, A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks, Proc Natl Acad Sci U S A source

In the paper

“was found to differ between OCD patients and controls based on whether errors were associated with a monetary loss versus no loss (41).”

What the sources say

• Not checked yetcites [41] Luck, 2005

In the paper

“There is evidence that OCD involves an overactive error signal indicating that “something is wrong” (2), leading to ritualistic behaviors aimed at preventing harmful consequences of perceived “mistakes.””

What the sources say

• Not checked yetcites [2] Pitman, 1987, A cybernetic model of obsessive-compulsive psychopathology, Compr Psychiatry source

In the paper

“While error-related activation in pMFC may signal the presence of cognitive events that require behavioral control, such as detecting mismatch between actual and intended responses (i.e., response conflict) (24, 25), aI/fO and adjacent lateral OFC may be preferentially linked to the emotional/motivational salience of errors, consistent with their role in somatic-autonomic and evaluative processes”

What the sources say

• Not checked yetcites [24] Carter, 1998, Anterior cingulate cortex, error detection, and the online monitoring of performance, Science source
• Not checked yetcites [25] Botvinick, 2001, Conflict monitoring and cognitive control, Psychol Review source
• Not checked yetcites [23] Craig, 2009, How do you feel—now?, Nat Rev Neurosci source
• Not checked yetcites [26] Simmons, 2004, Anticipation of emotionally aversive visual stimuli activates right insula, Neuroreport source
• Not checked yetcites [27] Paulus, 2006, An insular view of anxiety, Biol Psychiatry source
• Not checked yetcites [28] Critchley, 2005, Neural mechanisms of autonomic, affective, and cognitive integration, J Comp Neurol source
• Not checked yetcites [29] Cechetto, 2009, Functional neuroanatomy of autonomic regulation, Neuroimage source
• Not checked yetcites [30] Kringelbach, 2004, The functional neuroanatomy of the human orbitofrontal cortex: Evidence from neuroimaging and neuropsychology, Prog Neurobiol source

In the paper

“VMPFC plays a role in internal mentation and automatic value judgments (36-38), in contrast to lateral OFC, which may be associated with externally-triggered valuation (39).”

What the sources say

• Not checked yetcites [36] Hare, 2009, Self-control in decision-making involves modulation of the vmPFC valuation system, Science source
• Not checked yetcites [37] Buckner, 2008, The brain's default network: Anatomy, function, and relevance to disease, Ann N Y Acad Sci source
• Not checked yetcites [38] Bouret, 2010, Ventromedial and orbital prefrontal neurons differentially encode internally and externally driven motivational values in monkeys, J Neurosci source

In the paper

“aI/fO may respond to the perceived value of external events, in contrast to pMFC, which may be more engaged in processing cognitive information (21) or the initiation of volitional behaviors when responding to salient events (23).”

What the sources say

• Not checked yetcites [21] Mohr, 2010, Neural processing of risk, J Neurosci source
• Not checked yetcites [23] Craig, 2009, How do you feel—now?, Nat Rev Neurosci source

In the paper

“Subjects provided written informed consent and were evaluated by a trained clinician using the Structured Clinical Interview for Diagnosis (43).”

What the sources say

• Not checked yetcites [43] Goodman, 1989, The Yale-Brown Obsessive Compulsive Scale, Arch Gen Psychiatry source

In the paper

“Previous research suggests that aI/fO, along with pMFC/dACC, is part of a network responding to salient external events (18, 19).”

What the sources say

• Not checked yetcites [18] Sridharan, 2008, A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks, Proc Natl Acad Sci U S A source
• Not checked yetcites [19] Seeley, 2007, Dissociable intrinsic connectivity networks for salience processing and executive control, J Neurosci source

In the paper

“One- and two-sample t-tests were thresholded with an alpha of .05, cluster-level corrected for multiple comparisons within the FST search area using Monte-Carlo simulations as implemented by AlphaSim in AFNI (49, 50).”

What the sources say

• Not checked yetcites [49] Ward
• Not checked yetcites [50] Preuschoff, 2008, Human insula activation reflects risk prediction errors as well as risk, J Neurosci source

In the paper

“Although OCD patients exhibit an increased ERN, which has a source in pMFC (67)”

What the sources say

• Not checked yetcites [67]

In the paper

“Recent data suggests that aI/fO may be a central “hub” that initiates switching between central executive and default modes of processing (18).”

What the sources say

• Not checked yetcites [18] Sridharan, 2008, A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks, Proc Natl Acad Sci U S A source

In the paper

“Performance feedback provided on each trial was used to increase motivation, but made it impossible to disentangle neural activity to responses versus feedback.”

In the paper

“VMPFC, a region of DMN that has been associated with a variety of motivational behaviors, including the experience of positive and negative emotions (45, 53-55), self-referential processing (56), and risky decision-making (57, 58).”

What the sources say

• Not checked yetcites [45] Yang, 2002, Simultaneous perfusion and BOLD imaging using reverse spiral scanning at 3T: Characterization of functional contrast and susceptibility artifacts, Magn Reson Med source
• Not checked yetcites [53] Phan, 2002, Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI, Neuroimage source
• Not checked yetcites [54] O'Doherty, 2003, Dissociating valence of outcome from behavioral control in human orbital and ventral prefrontal cortices, J Neurosci source
• Not checked yetcites [55] Phan, 2004, Neural correlates of individual ratings of emotional salience: A trial-related fMRI study, Neuroimage source
• Not checked yetcites [56] Clark, 2008, Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making, Brain source

In the paper

“our results highlight the role of motivational brain systems in OCD, pointing to an overvaluation of errors related to alteration in functional relationships between networks processing external salience and emotional-evaluative internal thought”

In the paper

“Right aI/fO in particular has been associated with sympathetic arousal (29) and anticipation of aversive stimuli (26).”

What the sources say

• Not checked yetcites [29] Cechetto, 2009, Functional neuroanatomy of autonomic regulation, Neuroimage source
• Not checked yetcites [26] Simmons, 2004, Anticipation of emotionally aversive visual stimuli activates right insula, Neuroreport source

In the paper

“there have been inconsistent results regarding the location of medial frontal increases in OCD, with one fMRI study finding differences only in VMPFC (12), another only in pMFC (7), and others in both regions (9, 35).”

What the sources say

• Not checked yetcites [12] Fitzgerald, 2005, Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder, Biol Psychiatry source
• Not checked yetcites [7] Ursu, 2003, Overactive action monitoring in obsessive-compulsive disorder: Evidence from functional magnetic resonance imaging, Psychol Sci source
• Not checked yetcites [9] Maltby, 2005, Dysfunctional action monitoring hyperactivates frontal-striatal circuits in obsessive-compulsive disorder: An event-related fMRI study, Neuroimage source

In the paper

“areas within VMPFC are densely interconnected and strongly positively correlated (38, 59)”

What the sources say

• Not checked yetcites [38] Bouret, 2010, Ventromedial and orbital prefrontal neurons differentially encode internally and externally driven motivational values in monkeys, J Neurosci source
• Not checked yetcites [59] Andrews-Hanna, 2010, Functional-anatomic fractionation of the brain's default network, Neuron source