Skip to main content Accessibility help
×
Home

Brain mechanisms of anxiety's effects on cognitive control in major depressive disorder

  • N. P. Jones (a1), H. W. Chase (a1) and J. C. Fournier (a1)

Abstract

Background

Adults with major depressive disorder (MDD) demonstrate increased susceptibility to interfering effects of anxiety on cognitive control; although under certain conditions adults with MDD are able to compensate for these effects. The brain mechanisms that may facilitate the ability to compensate for anxiety either via the recruitment of additional cognitive resources or via the regulation of interference from anxiety remain largely unknown. To clarify these mechanisms, we examined the effects of anxiety on brain activity and amygdala–prefrontal functional connectivity in adults diagnosed with MDD.

Method

A total of 22 unmedicated adults with MDD and 18 healthy controls (HCs) performed the Tower of London task under conditions designed to induce anxiety, while undergoing a functional magnetic resonance imaging assessment.

Results

During the easy condition, the MDD group demonstrated equivalent planning accuracy, longer planning times, elevated amygdala activity and left rostrolateral prefrontal cortex (RLPFC) hyperactivity relative to HCs. Anxiety mediated observed group differences in planning times, as well as differences in amygdala activation, which subsequently mediated observed differences in RLPFC activation. During the easy condition, the MDD group also demonstrated increased negative amygdala–dorsolateral prefrontal cortex (DLPFC) connectivity which correlated with improved planning accuracy. During the hard condition, HCs demonstrated greater DLPFC activation and stronger negative amygdala–DLPFC connectivity, which was unrelated to planning accuracy.

Conclusions

Our results suggest that persons with MDD compensate for anxiety-related limbic activation during low-load cognitive tasks by recruiting additional RLPFC activation and through increased inhibitory amygdala–DLPFC communication. Targeting these neural mechanisms directly may improve cognitive functioning in MDD.

Copyright

Corresponding author

*Address for correspondence: N. P. Jones, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15216, USA. (Email: jonesnp@upmc.edu)

References

Hide All
Abend, R, Dan, O, Maoz, K, Raz, S, Bar-Haim, Y (2014). Reliability, validity and sensitivity of a computerized visual analog scale measuring state anxiety. Journal of Behavior Therapy and Experimental Psychiatry 45, 447453.
Adhikari, A, Lerner, TN, Finkelstein, J, Pak, S, Jennings, JH, Davidson, TJ, Ferenczi, E, Gunaydin, LA, Mirzabekov, JJ, Ye, L, Kim, S-Y, Lei, A, Deisseroth, K (2015). Basomedial amygdala mediates top-down control of anxiety and fear. Nature 527, 179185.
Anticevic, A, Barch, DM, Repovs, G (2010). Resisting emotional interference: brain regions facilitating working memory performance during negative distraction. Cognitive, Affective, and Behavioral Neuroscience 10, 159173.
Baron, RM, Kenny, DA (1986). The moderator–mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology 51, 11731182.
Bishop, SJ (2009). Trait anxiety and impoverished prefrontal control of attention. Nature Neuroscience 12, 9298.
Clarke, R, Johnstone, T (2013). Prefrontal inhibition of threat processing reduces working memory interference. Frontiers in Human Neuroscience 7, 228.
Cox, R (1996). AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Computational Biomedical Research 29, 162173.
Davey, HM, Barratt, AL, Butow, PN, Deeks, JJ (2007). A one-item question with a Likert or visual analog scale adequately measured current anxiety. Journal of Clinical Epidemiology 60, 356360.
Degras, D, Lindquist, MA (2014). A hierarchical model for simultaneous detection and estimation in multi-subject fMRI studies. NeuroImage 98, 6172.
Desrochers, TM, Chatham, CH, Badre, D (2015). The necessity of rostrolateral prefrontal cortex for higher-level sequential behavior. Neuron 87, 13571368.
Dolcos, F, Kragel, P, Wang, L, McCarthy, G (2006). Role of the inferior frontal cortex in coping with distracting emotions. Neuroreport 17, 15911594.
Dolcos, F, McCarthy, G (2006). Brain systems mediating cognitive interference by emotional distraction. Journal of Neuroscience 26, 20722079.
Erk, S, Mikschl, A, Stier, S, Ciaramidaro, A, Gapp, V, Weber, B, Walter, H (2010). Acute and sustained effects of cognitive emotion regulation in major depression. Journal of Neuroscience 30, 1572615734.
Etkin, A, Schatzberg, AF (2011). Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders. American Journal of Psychiatry 168, 968978.
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 14761488.
Fales, C, Barch, D, Burgess, G, Schaefer, A, Mennin, D, Gray, J, Braver, T (2008). Anxiety and cognitive efficiency: differential modulation of transient and sustained neural activity during a working memory task. Cognitive, Affective, and Behavioral Neuroscience 8, 239253.
First, MB, Spitzer, RL, Gibbon, M, Williams, JB (1996). Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition. Biometrics Research Department, New York State Psychiatric Institute: New York.
Fissell, K, Tseytlin, E, Cunningham, D, Carter, CS, Schneider, W, Cohen, JD (2003). Fiswidgets: a graphical computing environment for neuroimaging analysis. Neuroinformatics 1, 111125.
Forster, S, Nunez Elizalde, AO, Castle, E, Bishop, SJ (2015). Unraveling the anxious mind: anxiety, worry, and frontal engagement in sustained attention versus off-task processing. Cerebral Cortex 25, 609618.
Godard, J, Grondin, S, Baruch, P, Lafleur, MF (2011). Psychosocial and neurocognitive profiles in depressed patients with major depressive disorder and bipolar disorder. Psychiatry Research 190, 244252.
Gold, AL, Morey, RA, McCarthy, G (2015). Amygdala–prefrontal cortex functional connectivity during threat-induced anxiety and goal distraction. Biological Psychiatry 77, 394403.
Guthrie, D, Buchwald, JS (1991). Significance testing of difference potentials. Psychophysiology 28, 240244.
Harvey, P-O, Fossati, P, Pochon, J-B, Levy, R, LeBastard, G, Lehéricy, S, Allilaire, J-F, Dubois, B (2005). Cognitive control and brain resources in major depression: an fMRI study using the n-back task. NeuroImage 26, 860869.
Hayes, AF, Preacher, KJ (2010). Quantifying and testing indirect effects in simple mediation models when the constituent paths are nonlinear. Multivariate Behavioral Research 45, 627660.
Jones, NP, Siegle, G, Mandell, D (2015). Motivational and emotional influences on cognitive control in depression: a pupillometry study. Cognitive, Affective, and Behavioral Neuroscience 15, 263275.
Kalu, U, Sexton, C, Loo, C, Ebmeier, K (2012). Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychological Medicine 42, 17911800.
Kim, C, Kroger, JK, Calhoun, VD, Clark, VP (2015). The role of the frontopolar cortex in manipulation of integrated information in working memory. Neuroscience Letters 595, 2529.
Kraemer, HC, Wilson, GT, Fairburn, CG, Agras, WS (2002). Mediators and moderators of treatment effects in randomized clinical trials. Archives of General Psychiatry 59, 877883.
MacKinnon, DP, Lockwood, CM, Hoffman, JM, West, SG, Sheets, V (2002). A comparison of methods to test mediation and other intervening variable effects. Psychological Methods 7, 83104.
McCall, JG, Al-Hasani, R, Siuda, ER, Hong, DY, Norris, AJ, Ford, CP, Bruchas, MR (2015). CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety. Neuron 87, 605620.
Minzenberg, MJ, Watrous, AJ, Yoon, JH, Ursu, S, Carter, CS (2008). Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI. Science 322, 17001702.
Muthén, LK, Muthén, BO (1998–2006). Mplus User's Guide, 4th edn. Muthén & Muthén: Los Angeles, CA.
Nelson, HE, Willison, JR (1991). National Adult Reading Test (NART): Test Manual. nfer-Nelson Publishing Co.: Slough, UK.
Preacher, KJ, Hayes, AF (2008). Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behavior Research Methods 40, 879891.
Ramasubbu, R, Konduru, N, Cortese, F, Bray, S, Gaxiola-Valdez, I, Goodyear, B (2014). Reduced intrinsic connectivity of amygdala in adults with major depressive disorder. Frontiers in Psychiatry 5, 17.
Ray, RD, Zald, DH (2012). Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex. Neuroscience and Biobehavioral Reviews 36, 479501.
Shallice, T (1982). Specific impairments of planning. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 298, 199209.
Siegle, GJ, Steinhauer, SR, Stenger, VA, Konecky, R, Carter, CS (2003). Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data. NeuroImage 20, 114124.
Siegle, GJ, Steinhauer, SR, Thase, ME, Stenger, VA, Carter, CS (2002). Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry 51, 693707.
Siegle, GJ, Thompson, WS, Carter, CS, Steinhauer, SR, Thase, ME (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198209.
Stewart, WF, Ricci, JA, Chee, E, Hahn, SR, Morganstein, D (2003). Cost of lost productive work time among US workers with depression. JAMA Psychiatry 289, 31353144.
Tang, Y, Kong, L, Wu, F, Womer, F, Jiang, W, Cao, Y, Ren, L, Wang, J, Fan, G, Blumberg, H (2013). Decreased functional connectivity between the amygdala and the left ventral prefrontal cortex in treatment-naive patients with major depressive disorder: a resting-state functional magnetic resonance imaging study. Psychological Medicine 43, 19211927.
Thibodeau, R, Jorgensen, RS, Kim, S (2006). Depression, anxiety, and resting frontal EEG asymmetry: a meta-analytic review. Journal of Abnormal Psychology 115, 715729.
Tovote, P, Fadok, JP, Luthi, A (2015). Neuronal circuits for fear and anxiety. Nature Reviews. Neuroscience 16, 317331.
Trivedi, MH, Greer, TL (2014). Cognitive dysfunction in unipolar depression: implications for treatment. Journal of Affective Disorders 152–154, 1927.
Trujillo, JP, Gerrits, NJ, Vriend, C, Berendse, HW, van den Heuvel, OA, van der Werf, YD (2015). Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity. Human Brain Mapping 36, 37033715.
Unterrainer, JM, Rahm, B, Kaller, CP, Ruff, CC, Spreer, J, Krause, BJ, Schwarzwald, R, Hautzel, H, Halsband, U (2004). When planning fails: individual differences and error-related brain activity in problem solving. Cerebral Cortex 14, 13901397.
Vytal, K, Cornwell, B, Arkin, N, Grillon, C (2012). Describing the interplay between anxiety and cognition: from impaired performance under low cognitive load to reduced anxiety under high load. Psychophysiology 49, 842852.
Wagner, G, Koch, K, Reichenbach, JR, Sauer, H, Schlösser, RGM (2006). The special involvement of the rostrolateral prefrontal cortex in planning abilities: an event-related fMRI study with the Tower of London paradigm. Neuropsychologia 44, 23372347.
Woods, RP, Cherry, SR, Mazzoitta, JC (1992). Rapid automated algorithm for aligning and reslicing PET images. Journal of Computer Assisted Tomography 16, 620633.
Yerkes, RM, Dodson, JD (1908). The relation of strength of stimulus to rapidity of habit-formation. Journal of Comparative Neurology and Psychology 18, 459482.
Yohai, VJ (1987). High breakdown-point and high efficiency robust estimates for regression. Annals of Statistics 15, 642656.
Yun, R, Krystal, J, Mathalon, D (2010). Working memory overload: fronto-limbic interactions and effects on subsequent working memory function. Brain Imaging and Behavior 4, 96108.

Keywords

Type Description Title
WORD
Supplementary materials

Jones supplementary material
Jones supplementary material 1

 Word (1.4 MB)
1.4 MB

Brain mechanisms of anxiety's effects on cognitive control in major depressive disorder

  • N. P. Jones (a1), H. W. Chase (a1) and J. C. Fournier (a1)

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed