Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder

Jonathan Posner, Inkyung Song, Seonjoo Lee, Carolyn I Rodriguez, Holly Moore, Rachel Marsh, H Blair Simpson, Jonathan Posner, Inkyung Song, Seonjoo Lee, Carolyn I Rodriguez, Holly Moore, Rachel Marsh, H Blair Simpson

Abstract

Deficits in attention have been implicated in Obsessive-Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs-fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN-SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN-SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN-SN networks that subserve attentional processes and this effect of OCD on DMN-SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN-SN connectivity may represent a trans-diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN-SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp 38:678-687, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: attention; connectivity; default mode network; insula; obsessive-compulsive disorder; salience network.

© 2016 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Resting‐state functional connectivity maps with the seed in the medial prefrontal cortex (amPFC). In participants with obsessive‐compulsive disorder (OCD) and in healthy controls (HC), the amPFC seed was positively correlated with posterior cingulate cortex (PCC), a region within the default mode network, and inversely correlated with regions within the salience network including the anterior insular (aIN) and dorsal anterior cingulate cortex (dCg) (corrected P's 

Figure 2

(A) The cluster in red…

Figure 2

(A) The cluster in red depicts the region within the right anterior insular…
Figure 2
(A) The cluster in red depicts the region within the right anterior insular cortex (aIN) in which connectivity with the medial prefrontal cortex (amPFC) differs significantly between individuals with OCD relative to healthy controls (HC, corrected P < 0.05). (B) Bar graphs indicate the mean connection strength between the amPFC and aIN in OCD and HC participants. (C) In the OCD participants, connection strength between the amPFC and right aIN correlated with OCD symptom severity (red squares, r = 0.56; P = 0.005) as determined by the Yale‐Brown Obsessive Compulsive Scale (YBOC) total score, and (D) with decreased sustained attention (blue diamonds, r = 0.50; P = 0.015), as determined by reaction time (RT) variability on the continuous performance task (CPT).

Figure 3

Path analysis indicated that OCD…

Figure 3

Path analysis indicated that OCD is associated with altered connectivity between the default…

Figure 3
Path analysis indicated that OCD is associated with altered connectivity between the default mode network and salience network (DMN‐SN connectivity), which, in turn, correlates with decreased sustained attention. In the first linear regression of this path analysis, we found that OCD symptom severity was a significant predictor of DMN‐SN connectivity (path a, beta = 0.02, t = 3.10, P = 0.005). In the second linear regression model, we found that while controlling for OCD symptom severity, DMN‐SN connectivity was a significant predictor of sustained attention (path b, beta = 68.93, t = 2.76, P = 0.012). Bias corrected bootstrapping found that the indirect effect of OCD symptoms on reaction time variability was mediated by DMN‐SN connectivity (path c', coefficient = 1.54; 95% CI = 0.04–3.23).
Figure 2
Figure 2
(A) The cluster in red depicts the region within the right anterior insular cortex (aIN) in which connectivity with the medial prefrontal cortex (amPFC) differs significantly between individuals with OCD relative to healthy controls (HC, corrected P < 0.05). (B) Bar graphs indicate the mean connection strength between the amPFC and aIN in OCD and HC participants. (C) In the OCD participants, connection strength between the amPFC and right aIN correlated with OCD symptom severity (red squares, r = 0.56; P = 0.005) as determined by the Yale‐Brown Obsessive Compulsive Scale (YBOC) total score, and (D) with decreased sustained attention (blue diamonds, r = 0.50; P = 0.015), as determined by reaction time (RT) variability on the continuous performance task (CPT).
Figure 3
Figure 3
Path analysis indicated that OCD is associated with altered connectivity between the default mode network and salience network (DMN‐SN connectivity), which, in turn, correlates with decreased sustained attention. In the first linear regression of this path analysis, we found that OCD symptom severity was a significant predictor of DMN‐SN connectivity (path a, beta = 0.02, t = 3.10, P = 0.005). In the second linear regression model, we found that while controlling for OCD symptom severity, DMN‐SN connectivity was a significant predictor of sustained attention (path b, beta = 68.93, t = 2.76, P = 0.012). Bias corrected bootstrapping found that the indirect effect of OCD symptoms on reaction time variability was mediated by DMN‐SN connectivity (path c', coefficient = 1.54; 95% CI = 0.04–3.23).

References

    1. Abramovitch A, Dar R, Hermesh H, Schweiger A (2012): Comparative neuropsychology of adult obsessive‐compulsive disorder and attention deficit/hyperactivity disorder: Implications for a novel executive overload model of OCD. J Neuropsychol 6:161–191.
    1. Abramovitch A, Abramowitz JS, Mittelman A (2013): The neuropsychology of adult obsessive–compulsive disorder: A meta‐analysis. Clin Psychol Rev 33:1163–1171.
    1. Baron RM, Kenny DA (1986): The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51:1173.
    1. Behzadi Y, Restom K, Liau J, Liu TT (2007): A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37:90–101.
    1. Benjamini Y, Hochberg Y (1995): Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Ser B (Method) 57:289–300.
    1. Beucke JC, Sepulcre J, Eldaief MC, Sebold M, Kathmann N, Kaufmann C (2014): Default mode network subsystem alterations in obsessive‐compulsive disorder. Br J Psychiatry 205:376–382.
    1. Castellanos FX, Margulies DS, Kelly C, Uddin LQ, Ghaffari M, Kirsch A, Shaw D, Shehzad Z, Di Martino A, Biswal B (2008): Cingulate‐precuneus interactions: A new locus of dysfunction in adult attention‐deficit/hyperactivity disorder. Biol Psychiatry 63:332–337.
    1. Cha J, Fekete T, Siciliano F, Biezonski D, Greenhill L, Pliszka SR, Blader JC, Roy AK, Leibenluft E, Posner J (2015): Neural correlates of aggression in medication‐naive children with adhd: Multivariate analysis of morphometry and tractography. Neuropsychopharmacology 40:1717–1725.
    1. Chai XJ, Castanon AN, Ongur D, Whitfield‐Gabrieli S (2011): Anticorrelations in resting state networks without global signal regression. Neuroimage 59:1420–1428.
    1. Conners CK, Staff M (2000): Conners' Continuous Performance Test II (CPT II V. 5). North Tonawanda, NY: Multi‐Health Systems Inc.
    1. Eklund A, Nichols TE, Knutsson H (2016): Cluster failure: Why fMRI inferences for spatial extent have inflated false‐positive rates. Proc Natl Acad Sci U S A 107:4734–4739.
    1. Epstein JN, Langberg JM, Rosen PJ, Graham A, Narad ME, Antonini TN, Brinkman WB, Froehlich T, Simon JO, Altaye M (2011): Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations. Neuropsychology 25:427.
    1. Fitzgerald KD, Stern ER, Angstadt M, Nicholson‐Muth KC, Maynor MR, Welsh RC, Hanna GL, Taylor SF (2010): Altered function and connectivity of the medial frontal cortex in pediatric obsessive‐compulsive disorder. Biol Psychiatry 68:1039–1047.
    1. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005): The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102:9673–9678.
    1. Friston KJ, Ashburner CD, Frith JB, Poline JB, Heather RS, Frackowiak RS (1995): Spatial registration and normalization of images. Hum Brain Mapp 3:165–189.
    1. Gallo EF, Posner J (2016): Attention‐deficit hyperactivity disorder 1 Moving towards causality in attention‐deficit hyperactivity disorder: Overview of neural and genetic mechanisms. Lancet 3:555–567.
    1. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS (1989a): The yale‐brown obsessive compulsive scale: II. Validity. Arch Gen Psychiatry 46:1012.
    1. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS (1989b): The Yale‐Brown obsessive compulsive scale: I. Development, use, and reliability. Arch Gen Psychiatry 46:1006.
    1. Hamilton JP, Furman DJ, Chang C, Thomason ME, Dennis E, Gotlib IH (2011): Default‐mode and task‐positive network activity in major depressive disorder: Implications for adaptive and maladaptive rumination. Biol Psychiatry 70:310–311.
    1. Hayes AF (2009): Beyond Baron and Kenny: Statistical mediation analysis in the new millennium. Commun Monogr 76:408–420.
    1. Jang JH, Kim JH, Jung WH, Choi JS, Jung MH, Lee JM, Choi CH, Kang DH, Kwon JS (2010): Functional connectivity in fronto‐subcortical circuitry during the resting state in obsessive‐compulsive disorder. Neurosci Lett 474:158–162.
    1. Koran LM, Thienemann ML, Davenport R (1996): Quality of life for patients with obsessive‐compulsive disorder. Am J Psychiatry 153:783–788.
    1. Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC (2014): Psychiatric aspects of impulsivity. Am J Psychiatry 158:1783–1793.
    1. Posner J, Maia TV, Fair D, Peterson BS, Sonuga‐Barke EJ, Nagel BJ (2011): The attenuation of dysfunctional emotional processing with stimulant medication: An fMRI study of adolescents with ADHD. Psychiatry Res: Neuroimaging 193:151–160.
    1. Posner J, Hellerstein DJ, Gat I, Mechling A, Klahr K, Wang Z, McGrath PJ, Stewart JW, Peterson BS (2013): Antidepressants normalize the default mode network in patients with dysthymia. JAMA Psychiatry 70:373–382.
    1. Posner J, Marsh R, Maia TV, Peterson BS, Gruber A, Simpson HB (2014a): Reduced functional connectivity within the limbic cortico‐striato‐thalamo‐cortical loop in unmedicated adults with obsessive‐compulsive disorder. Hum Brain Mapp 35:2852–2860.
    1. Posner J, Park C, Wang Z (2014b): Connecting the dots: A review of resting connectivity mri studies in attention‐deficit/hyperactivity disorder. Neuropsychol Rev 24:3–15.
    1. Posner J, Siciliano F, Wang Z, Liu J, Sonuga‐Barke E, Greenhill L (2014c): A multimodal MRI study of the hippocampus in medication‐naive children with ADHD: What connects ADHD and depression? Psychiatry Res: Neuroimaging 224:112–118.
    1. Posner J, Amira L, Algaze A, Canino G, Duarte CS (2016a): Reduced functional connectivity within the mesocorticolimbic system in substance use disorders: An fMRI study of Puerto Rican young adults. Front Behav Neurosci 10:102.
    1. Posner J, Cha J, Wang Z, Talati A, Warner V, Gerber AJ, Peterson BS, Weissman MM (2016b) Increased default mode network connectivity in individuals at high familial risk for depression. Neuropsychopharmacology 41:1759–1767.
    1. Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2011): Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59:2142–2154.
    1. Raichle M, Snyder A (2007): A default mode of brain function: A brief history of an evolving idea. Neuroimage 37:1083–1090.
    1. Rucker DD, Preacher KJ, Tormala ZL, Petty RE (2011): Mediation analysis in social psychology: Current practices and new recommendations. Soc Pers Psychol Compass 5:359–371.
    1. Schaefer A, Burmann I, Regenthal R, Ar√©lin K, Barth C, Pampel A, Villringer A, Margulies DS, Sacher J (2014): Serotonergic modulation of intrinsic functional connectivity. Curr Biol 24:2314–2318.
    1. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD (2007): Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27:2349–2356.
    1. Sonuga‐Barke EJ, Castellanos FX (2007): Spontaneous attentional fluctuations in impaired states and pathological conditions: A neurobiological hypothesis. Neurosci Biobehav Rev 31:977–986.
    1. Spitzer R, Williams J, Gibbon M (1995): Structured Clinical Interview for DSM‐IV (SCID). New York: Biometrics Research.
    1. Stern ER, Welsh RC, Fitzgerald KD, Gehring WJ, Lister JJ, Himle JA, Abelson JL, Taylor SF (2011): Hyperactive error responses and altered connectivity in ventromedial and frontoinsular cortices in obsessive‐compulsive disorder. Biol Psychiatry 69:583–591.
    1. Stern ER, Fitzgerald KD, Welsh RC, Abelson JL, Taylor SF (2012): Resting‐state functional connectivity between fronto‐parietal and default mode networks in obsessive‐compulsive disorder. PloS One 7:e36356.
    1. Stuss D, Stethem L, Hugenholtz H, Picton T, Pivik J, Richard M (1989): Reaction time after head injury: Fatigue, divided and focused attention, and consistency of performance. J Neurol Neurosurg Psychiatry 52:742–748.
    1. Wechsler D (1999): Wechsler abbreviated scale of intelligence. Psychol Corp.
    1. Weissman D, Roberts K, Visscher K, Woldorff M (2006): The neural bases of momentary lapses in attention. Nat Neurosci 9:971–978.
    1. Whitfield‐Gabrieli S, Ford JM (2012): Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol 8:49–76.
    1. Whitfield‐Gabrieli S, Nieto‐Castanon A (2012): Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2:125–141.
    1. Whitfield‐Gabrieli S, Thermenos HW, Milanovic S, Tsuang MT, Faraone SV, McCarley RW, Shenton ME, Green AI, Nieto‐Castanon A, LaViolette P (2009): Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first‐degree relatives of persons with schizophrenia. Proc Natl Acad Sci 106:1279.
    1. Zhao X, Lynch JG, Chen Q (2010): Reconsidering Baron and Kenny: Myths and truths about mediation analysis. J Consum Res 37:197–206.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться