Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study
Open accessAbstract
Objective: To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Methods: Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second‐level random effects analysis. Results: Random effects between‐group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within‐group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between‐group difference, however, was not significant. Conclusions: Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood‐dependent and disease‐dependent functional brain abnormalities in bipolar disorder.
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Because bipolar disorder pathophysiology is strongly associated with prefrontal cortex neurocircuitry, it is important to determine whether stimulating over this area has advantages compared with the vertex.
“Because the pathophysiology of bipolar disorder is strongly associated with prefrontal cortex neurocircuitry, 28 it is important to determine if there are advantages to stimulating over this area compared with the vertex.”
From Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: An open-label clinical trial (2020) · cites this paper as [28]
Patients with mood disorders have substantial disruptions in interpersonal functioning.
“On balance, patients with mood disorders experience substantial disruptions in interpersonal function, [30][31][32][33][34]”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [30]
Depressed patients with bipolar disorder have shown elevated amygdala activity and attenuated responses in the OFC and DLPFC to neutral and negative faces.
“Depressed patients with bipolar disorder have also shown elevated activity in the amygdala 102 and attenuated responses in the OFC and DLPFC to neutral and negative (e.g., angry, fearful, sad) faces.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [30]
On average, neural activity is most commonly decreased in the DLPFC and increased in the left amygdala, the fusiform gyrus and the inferior frontal gyrus in patients with mood disorders.
“On average, neural activityis most commonly decreased in the DLPFC 30,59,68,76 and increased in the left amygdala, 55,74,76,79,98,99 the fusiform gyrus 82,93,98 and the inferior frontal gyrus 82,90,98 in patients with mood disorders.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [30]
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Phillips, M. L., & Swartz, H. A. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13081008 · Cited by 636 · see citing works
“The finding of decreased ventrolateral prefrontal cortex activity parallels that shown during similar tasks by euthymic and depressed adults with bipolar disorder type I(13-16,19), and suggests that reduced ventrolateral prefrontal cortex activity during emotion processing and emotion regulation may be a trait marker…”
The functional neuroanatomy of bipolar disorder: a consensus model
Strakowski, S. M., Adler, C. M., Almeida, J., Altshuler, L. L., Blumberg, H. P., Chang, K., DelBello, M. P., Frangou, S., McIntosh, A. M., Phillips, M. L., et al. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01022.x · Cited by 540 · see citing works
“Indeed, other investigators have not observed increased amygdala activation during depression (26, 27) and have suggested that amygdala over-activation may be state dependent, as reviewed in this issue (1).”
BackgroundSelf-citationTreatment of depression with transcranial direct current stimulation (tDCS): A Review
Nitsche, M. A., Boggio, P. S., Fregni, F., & Pascual-Leone, A. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.03.038 · Cited by 498 · see citing works
“This imbalance of activation is not restricted to the dorsolateral prefrontal cortex, but might affect also orbitofrontal areas (Altshuler et al., 2008).”
Rive, M. M., van Rooijen, G., Veltman, D. J., .Phillips, M. L., Schene, A. H., & Ruhé, H. G. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.07.018 · Cited by 481 · see citing works
A quantitative meta-analysis of fMRI studies in bipolar disorder
Chen, C., John Suckling, A., Lennox, B., Ooi, C., & Bullmore, E. T. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00893.x · Cited by 457 · see citing works
“Decreased activation in BD patients was shown in the IFG [reported by six studies (29, 34, 52, 60, 62, 67)], lingual gyrus [reported by six studies (33, 43, 50, 53, 66, 73], and putamen [reported by five studies (5, 36, 41, 58, 72)] (Table 3).”
BackgroundResultInfluentialEmotion processing and regulation in bipolar disorder: a review
Townsend, J. D., & Altshuler, L. L. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01021.x · Cited by 361 · see citing works
“This decreased frontal lobe activation in bipolar depressed subjects was found in other studies using a variety of emotion paradigms (69, 73, 82) and represents a more consistent finding in bipolar depression.”
BackgroundResultInfluentialSelf-citationBrotman, M. A., Rich, B. A., Guyer, A. E., Lunsford, J. R., Horsey, S. E., Reising, M. M., Thomas, L. A., Fromm, S. J., Towbin, K., Pine, D. S., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09010043 · Cited by 322 · see citing works
Neuroimaging-based markers of bipolar disorder: Evidence from two meta-analyses
Houenou, J., Frommberger, J., Carde, S., Glasbrenner, M., Diener, C., Leboyer, M., & Wessa, M. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.03.016 · Cited by 291 · see citing works
“, 2007a) and an emotional face-matching paradigm (Altshuler et al., 2008; Foland et al., 2008).”
Systematic review of the neural basis of social cognition in patients with mood disorders
Cusi, A. M., Nazarov, A., Holshausen, K., MacQueen, G. M., & McKinnon, M. C. (2012) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.100179 · Cited by 278 · see citing works
“Several studies excluded patients with comorbid conditions.(30,80,82,84,85,87,187)”
BackgroundAlmeida, J. R. C., Versace, A., Hassel, S., Kupfer, D. J., & Phillips, M. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.027 · Cited by 226 · see citing works
“Similarly, recent studies reported no abnormality in amygdala activity to fearful, angry, or sad facial expressions in depressed BD adults (BDd) (14,15).”
Delvecchio, G., Fossati, P., Boyer, P., Brambilla, P., Falkai, P., Gruber, O., Hietala, J. A., Lawrie, S. M., Martinot, J., McIntosh, A. M., et al. (2011) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.07.003 · Cited by 230 · see citing works
“illness in the last 4 years Altshuler et al. (2008) YMRS score BD:2.”
BackgroundDepression and the hyperactive right-hemisphere
Hecht, D. (2010) · Neuroscience Research · doi:10.1016/j.neures.2010.06.013 · Cited by 221 · see citing works
Frontal-Amygdala Connectivity Alterations During Emotion Downregulation in Bipolar I Disorder
Townsend, J. D., Torrisi, S. J., Lieberman, M. D., Sugar, C. A., Bookheimer, S. Y., & Altshuler, L. L. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.030 · Cited by 210 · see citing works
“While amygdala function may vary as a function of mood state (27,58), vlPFC hypoactivation has been reported in euthymia (29,61,62), mania, and depression (63,64).”
BackgroundSelf-citationVersace, A., Thompson, W. K., Zhou, D., Almeida, J. R. C., Hassel, S., Klein, C. R., Kupfer, D. J., & Phillips, M. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.11.025 · Cited by 194 · see citing works
Developmental Meta-analyses of the Functional Neural Correlates of Bipolar Disorder
Wegbreit, E., Cushman, G. K., Puzia, M., Weissman, A. B., Kim, K. L., Laird, A. R., & Dickstein, D. P. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.660 · Cited by 160 · see citing works
Delvecchio, G., Sugranyes, G., & Frangou, S. (2012) · Psychological Medicine · doi:10.1017/s0033291712001432 · Cited by 156 · see citing works
“…BD remitted (5/10) 15 BD depressed (1/14) Explicit facial affect labeling task Event related Whole-brain and ROI analyses Sad>Neutral 15 HS (3/12) Altshuler et al. (2008) 11 BD (5/6) Explicit facial affect matching task Block Fearful and angry>Shapes17 HS (9/8) Whole-brain analysis Blumberg et…”
BackgroundInfluentialGigante, A. D., Young, L. T., Yatham, L. N., Andreazza, A. C., Nery, F. G., Grinberg, L. T., Heinsen, H., & Lafer, B. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114571000146x · Cited by 143 · see citing works
“Other studies on functional neuroimaging have shown decreased cortical activity in the DLPFC of BD subjects (Altshuler et al. 2008; Brooks et al. 2009).”
BackgroundPerry, A., Roberts, G. M. P., Mitchell, P. B., & Breakspear, M. J. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0267-2 · Cited by 146 · see citing works
Townsend, J. D., Bookheimer, S. Y., Foland‐Ross, L. C., Sugar, C. A., & Altshuler, L. L. (2010) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2009.11.010 · Cited by 145 · see citing works
“However, this brain region has previously been reported as active in bipolar subjects across a variety of tasks in ours (Altshuler et al., 2008) and others′ (Roth et al.”
BackgroundSelf-citationMahon, K., Burdick, K. E., Wu, J., Ardekani, B. A., & Szeszko, P. R. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.00984.x · Cited by 131 · see citing works
Liu, C., Li, F., Li, S., Wang, Y., Tie, C.-L., Wu, H., Zhou, Z., Zhang, D., Dong, J., Yang, Z., et al. (2012) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2012.02.007 · Cited by 131 · see citing works
“Our results demonstrated increased ALFF in the BD depressive subjects in a series of anatomically connected structures (Fuster, 2001; Altshuler et al., 2008), including the left insula, the right caudate, the bilateral temporal gyrus, and the bilateral IFG.”
The functional neuroanatomy of bipolar disorder
Cerullo, M. A., Adler, C. M., Delbello, M. P., & Strakowski, S. M. (2009) · International Review of Psychiatry · doi:10.1080/09540260902962107 · Cited by 113 · see citing works
Kanske, P., Schönfelder, S., Forneck, J., & Wessa, M. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.137 · Cited by 106 · see citing works
Vizueta, N., Rudie, J. D., Townsend, J. D., Torrisi, S., Moody, T. D., Bookheimer, S. Y., & Altshuler, L. L. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11030349 · Cited by 102 · see citing works
“However, research conducted by our group has revealed that bipolar I patients with depression also exhibit hypoactivation in BA 47 (6), suggesting that the modulatory role of the ventrolateral prefrontal cortex may be more complex and not necessarily associated only with the manic mood state.”
BackgroundResultInfluentialSelf-citationGrotegerd, D., Suslow, T., Bauer, J., Ohrmann, P., Arolt, V., Stuhrmann, A., Heindel, W. L., Kugel, H., & Dannlowski, U. (2012) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-012-0329-4 · Cited by 100 · see citing works
Yildirim, B. O., & Derksen, J. J. L. (2015) · Aggression and Violent Behavior · doi:10.1016/j.avb.2015.05.001 · Cited by 100 · see citing works
Hulvershorn, L. A., Karne, H. S., Gunn, A. D., Hartwick, S. L., Wang, Y., Hummer, T. A., & Anand, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.10.038 · Cited by 100 · see citing works
“All subjects underwent a detailed structured diagnostic interview: the Diagnostic Interview for Genetic Studies (5) and/or the Mini-International Neuropsychiatric Interview, as well as a clinical interview by a psychiatrist (A.”
Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing
Liu, J., Blond, B. N., van Dyck, L. I., Spencer, L., Wang, F., & Blumberg, H. P. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01018.x · Cited by 95 · see citing works
Marchand, W. R., Lee, J. N., Johnson, S., Thatcher, J. W., Gale, P. D., Wood, N., & Jeong, E. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.10.016 · Cited by 92 · see citing works
“…that these structures play a role in mediating the relationship between aberrant selfreferential thinking and negative affect in mood disorders (Altshuler et al., 2005, 2008; Chen et al., 2006; Cooney et al., 2010; Elliott et al., 2004; Grimm et al., 2009a, 2009b; Lagopoulos and Malhi, 2011;…”
BackgroundFernández‐Corcuera, P., Salvador, R. M., Monté, G. C., Sarró, S., Goikolea, J. M., Amann, B. L., Moro, N., Sans-Sansa, B., Ortiz‐Gil, J., Vieta, E., et al. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.04.009 · Cited by 87 · see citing works
“, 2007) or other parts of the medial frontal cortex (Altshuler et al., 2008; Chen et al., 2006; Lawrence et al., 2004; Malhi et al., 2004), a finding which could conceivably reflect failure of de-activation.”
BackgroundInfluentialAll the world’s a (clinical) stage: rethinking bipolar disorder from a longitudinal perspective
Frank, E., Nimgaonkar, V. L., Phillips, M. L., & Kupfer, D. J. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.71 · Cited by 87 · see citing works
Jackowski, A. P., Filho, G. M. D. A., Almeida, A. G.-D., de Araújo, C. M., dos Reis, M. A., Nery, F., Batista, I. R., Silva, I., & Lacerda, A. L. T. (2012) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462012000200014 · Cited by 82 · see citing works
Foland‐Ross, L. C., Bookheimer, S. Y., Lieberman, M. D., Sugar, C. A., Townsend, J. D., Fischer, J., Torrisi, S., Penfold, C., Madsen, S. K., Thompson, P. M., et al. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.07.054 · Cited by 86 · see citing works
“The affective task paradigm used during fMRI scanning has been detailed previously (Hariri et al., 2000; Lieberman et al., 2007) and used in prior studies by our group examining bipolar subjects scanned during the manic mood state (Altshuler et al., 2005a, 2008; Foland et al., 2008).”
Self-citationHájek, T., Alda, M., Hajek, E., & Ivanoff, J. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.08.015 · Cited by 78 · see citing works
Brain functional changes across the different phases of bipolar disorder
Pomarol‐Clotet, E., Alonso-Lana, S., Moro, N., Sarró, S., Bonnin, M. C., Goikolea, J. M., Fernández‐Corcuera, P., Amann, B. L., Romaguera, A., Vieta, E., et al. (2014) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.152033 · Cited by 79 · see citing works
Kupferschmidt, D. A., & Zakzanis, K. K. (2011) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2011.02.011 · Cited by 80 · see citing works
Townsend, J. D., Bookheimer, S. Y., Foland‐Ross, L. C., Moody, T. D., Eisenberger, N. I., Fischer, J., Cohen, M. S., Sugar, C. A., & Altshuler, L. L. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01020.x · Cited by 79 · see citing works
“Prior studies by our group using different cognitive tasks performed in patients with bipolar disorder taking similar medications have demonstrated hyperactivation in certain brain regions despite being medicated (10, 38).”
Self-citationLiu, Y., Wu, X., Zhang, J., Guo, X., Long, Z., & Li, Y. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.04.009 · Cited by 78 · see citing works
Cortical thickness differences between bipolar depression and major depressive disorder
Lan, M. J., Thapa-Chhetry, B., Oquendo, M. A., Sublette, M. E., Sullivan, G. M., Mann, J. J., & Parsey, R. V. (2014) · Bipolar Disorders · doi:10.1111/bdi.12175 · Cited by 76 · see citing works
“Several functional MRI studies have shown alterations during behavioral tasks in the right dorsolateral prefrontal cortex of patients with BD, such as processing affect in images of faces (37, 38) and performing tasks of executive function (39, 40).”
BackgroundYildirim, B. O., & Derksen, J. J. L. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.009 · Cited by 75 · see citing works
“disorder (Altshuler et al., 2008), substance abuse (Alia-Klein et al.”
Differences in functional connectivity in major depression versus bipolar II depression
Marchand, W. R., Lee, J. N., Johnson, S., Gale, P. D., & Thatcher, J. W. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.01.028 · Cited by 71 · see citing works
“…CMS structures play a direct role in mediating the relationship between aberrant self-referential thinking and negative affect in mood disorders (Altshuler et al., 2005, 2008; Chen et al., 2006; Cooney et al., 2010; Elliott et al., 2004; Grimm et al., 2009a, 2009b; Lagopoulos and Malhi, 2011;…”
BackgroundHummer, T. A., Hulvershorn, L. A., Karne, H. S., Gunn, A. D., Wang, Y., & Anand, A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.036 · Cited by 71 · see citing works
Regional homogeneity of resting-state brain abnormalities in bipolar and unipolar depression
Liu, C., Ma, X., Wu, X., Zhang, Y., Zhou, F., Li, F., Tie, C.-L., Dong, J., Wang, Y., Yang, Z., et al. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.11.010 · Cited by 72 · see citing works
Perlman, S. B., Almeida, J., Kronhaus, D. M., Versace, A., LaBarbara, E. J., Klein, C. R., & Phillips, M. L. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.00999.x · Cited by 68 · see citing works
Brotman, M. A., Tseng, W.-L., Olsavsky, A. K., Fromm, S. J., Muhrer, E. J., Rutenberg, J. G., Deveney, C. M., Adleman, N. E., Zarate, C. A., Pine, D. S., et al. (2013) · Psychological Medicine · doi:10.1017/s003329171300202x · Cited by 69 · see citing works
“2012), neutral (Rich et al. 2006; Altshuler et al. 2008; Hassel et al. 2009; Garrett et al. 2012; Thomas et al. 2012, 2013) and fearful (Yurgelun-Todd et al.”
InfluentialShaffer, J. J., Johnson, C. P., Fiedorowicz, J. G., Christensen, G. E., Wemmie, J. A., & Magnotta, V. A. (2017) · Brain Imaging and Behavior · doi:10.1007/s11682-017-9741-8 · Cited by 61 · see citing works
“…have only examined participants during the euthymic state and only a handful of studies have looked at participants during bipolar depression (Altshuler et al. 2008; Cerullo et al. 2014; Cerullo et al. 2012; Chen et al. 2006; Diler et al. 2013; Li et al. 2015; Liu et al. 2012; Pomarol-Clotet…”
BackgroundGoswami, D. B., Jernigan, C. S., Chandran, A., Iyo, A. H., May, W. L., Austin, M. C., Stockmeier, C. A., & Karolewicz, B. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.12.010 · Cited by 57 · see citing works
“Furthermore, recent mRNA expression and imaging studies indicate altered activity and size of BA 10 in subjects diagnosedwithMDD (Altshuler et al., 2008;Monkul et al., 2012; Richieri et al., 2011; Savitz and Drevets, 2009; Shelton et al., 2011).”
Pomarol‐Clotet, E., Moro, N., Sarró, S., Goikolea, J. M., Vieta, E., Amann, B. L., Fernández‐Corcuera, P., Sans-Sansa, B., Monté, G. C., Capdevila, A., et al. (2011) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.573808 · Cited by 59 · see citing works
“On the other, however, a fi nding that manic patients fail to suppress activity in the amygdala when they have to turn their attention to outwardly-directed tasks might be relevant to the confl icting fi ndings of increased and decreased activation in this structure reported in bipolar patients (Lennox, et al. 2004; A…”
BackgroundDiler, R. S., Almeida, J., Ladouceur, C. D., Birmaher, B. B., Axelson, D., & Phillips, M. L. (2013) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2013.06.013 · Cited by 55 · see citing works
“, 2004) and in BDd adults (Altshuler et al., 2008; Chen et al., 2006) as well as a recent meta-analysis in BDd adults (Van der Schot et al.”
ResultAkhtar, H., Bukhari, F., Nazir, M., Anwar, M. N., & Shahzad, A. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-015-0009-2 · Cited by 58 · see citing works
Trait and state dependent functional impairments in bipolar disorder
van der Schot, A. C., Kahn, R. S., Ramsey, N. F., Nolen, W. A., & Vink, M. (2010) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2010.07.009 · Cited by 50 · see citing works
“, 2008), depressed (decrease: Baxter et al., 1989; Ketter et al., 2001; Altshuler et al., 2008; increase: Chen et al., 2006) and manic patients (decrease: Blumberg et al.”
BackgroundInfluentialBenson, B. E., Willis, M. W., Ketter, T. A., Speer, A., Kimbrell, T. A., Herscovitch, P., George, M. S., & Post, R. M. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.05.045 · Cited by 46 · see citing works
“Attention and executive functioning, which depend on these memory skills, may be compromised with greater illness severity (Altshuler et al., 2008b; McClintock et al., 2010); however, deficits persist in euthymia (Bearden et al., 2010).”
BackgroundThakker‐Varia, S., Jean, Y. Y., Parikh, P., Sizer, C. F., Ayer, J., Parikh, A., Hyde, T. M., Buyske, S. G., & Alder, J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5987-09.2010 · Cited by 46 · see citing works
“…and functional deficits associated with psychiatric disorders on the basis of neuroimaging, neuropsychology, and postmortem neuropathology studies (Dickstein et al., 2005; Nakatani et al., 2006; Altshuler et al., 2008; Bonilha et al., 2008; Melcher et al., 2008; Koenigsberg et al., 2009).”
BackgroundThe Role of Amygdala in Patients With Euthymic Bipolar Disorder During Resting State
Li, G., Liu, P., Andari, E., Zhang, A., & Zhang, K. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00445 · Cited by 45 · see citing works
Diagnostic and clinical implications of functional neuroimaging in bipolar disorder
Brooks, J. O., & Vizueta, N. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.05.018 · Cited by 45 · see citing works
Shared and distinct regional homogeneity changes in bipolar and unipolar depression
Yao, X., Yin, Z., Liu, F., Wei, S., Zhou, Y., Jiang, X., Wei, Y., Xu, K., Wang, F., & Tang, Y. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.02.033 · Cited by 43 · see citing works
Neuroimaging biomarkers in bipolar disorder
Houenou, J. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/402 · Cited by 40 · see citing works
“(23, 24), emotional memory tasks (25) and emotional facematching paradigms (26, 27).”
BackgroundAltered functioning of reward circuitry in youth offspring of parents with bipolar disorder
Manelis, A., Ladouceur, C. D., Graur, S., Monk, K., Bonar, L. K., Hickey, M. B., Dwojak, A., Axelson, D., Goldstein, B., Goldstein, T. R., et al. (2015) · Psychological Medicine · doi:10.1017/s003329171500166x · Cited by 40 · see citing works
“…our findings may provide further support for dysfunctional coupling between the vlPFC and subcortical regions during emotionally-salient processing as a pathophysiological process underlying vulnerability to, or protection against, future BD (Altshuler et al. 2008; Phillips & Swartz, 2014).”
BackgroundResultAbnormal functional connectivity of the medial cortex in euthymic bipolar II disorder
Marchand, W. R., Lee, J. N., Johnson, S., Gale, P. D., & Thatcher, J. W. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.01.004 · Cited by 38 · see citing works
“…that the CMS structures play a role in mediating the relationship between aberrant self-referential thinking and negative affect in mood disorders (Altshuler et al., 2005, 2008; Chen et al., 2006; Cooney et al., 2010; Elliott et al., 2004; Grimm et al., 2009a,b; Lagopoulos and Malhi, 2011;…”
BackgroundAhmed, Y. B., Al-Bzour, A. N., Alzghoul, S. M., Ibrahim, R. B., Al-Khalili, A. A., Al-Majali, G. N., Hamza, A. I., Al-Zamer, Y. S., Al‐Hayk, K., Kofahi, R., et al. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.11.071 · Cited by 40 · see citing works
Are working memory deficits in bipolar disorder markers for psychosis?
Allen, D. N., Randall, C., Bello, D. T., Armstrong, C. M., Frantom, L., Cross, C. L., & Kinney, J. W. (2010) · Neuropsychology · doi:10.1037/a0018159 · Cited by 37 · see citing works
Deficits in tasks of executive functioning that mimic real‐life scenarios in bipolar disorder
Torralva, T., Strejilevich, S., Gleichgerrcht, E. L., Roca, M., Martino, D. J., Cetkovich, M., & Manes, F. F. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.00987.x · Cited by 36 · see citing works
Stress and reward processing in bipolar disorder: a functional magnetic resonance imaging study
Berghorst, L. H., Kumar, P., Greve, D. N., Deckersbach, T., Öngür, D., Dutra, S. J., & Pizzagalli, D. A. (2016) · Bipolar Disorders · doi:10.1111/bdi.12444 · Cited by 36 · see citing works
Penfold, C., Vizueta, N., Townsend, J. D., Bookheimer, S. Y., & Altshuler, L. L. (2014) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2014.11.005 · Cited by 33 · see citing works
“Bilateral IFC hypoactivation has previously been reported in subjects with BP I while performing emotion-processing tasks during depression (Altshuler et al., 2008) and mania (Foland et al., 2008).”
BackgroundSelf-citationPrefrontal hypoactivation during working memory in bipolar II depression
Brooks, J. O., Vizueta, N., Penfold, C., Townsend, J. D., Bookheimer, S. Y., & Altshuler, L. L. (2015) · Psychological Medicine · doi:10.1017/s0033291714002852 · Cited by 31 · see citing works
“However, unlike medicated subjects with bipolar I disorder, who exhibited hyperactivation of BA 10 (Altshuler et al. 2008), the present study of unmedicated depressed subjects with the bipolar II subtype found hypoactivation of BA 10.”
BackgroundSelf-citationAn inter-hemispheric imbalance in the psychopath’s brain
Hecht, D. (2011) · Personality and Individual Differences · doi:10.1016/j.paid.2011.02.032 · Cited by 29 · see citing works
Furlong, L. S., Rossell, S. L., Caruana, G. F., Cropley, V., Hughes, M. E., & Rheenen, T. E. V. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.10.038 · Cited by 28 · see citing works
Zhang, L., Wu, H., Zhang, A., Bai, T., Ji, G., Tian, Y., & Wang, K. (2021) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-020-01219-7 · Cited by 28 · see citing works
“1 3 in mechanisms of attention, memory, and cognitive control [42] —cognitive features altered by structural or functional alteration of brain in BP patients [2, 23, 57].”
BackgroundHoráček, J., Mikoláš, P., Tintěra, J., Novák, T., Páleníček, T., Brunovský, M., Höschl, C., & Alda, M. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.140044 · Cited by 27 · see citing works
Disrupted brain structural connectivity in Pediatric Bipolar Disorder with psychosis
Fernandes, H. M., Cabral, J., van Hartevelt, T. J., Lord, L.-D., Gleesborg, C., Møller, A., Deco, G., Whybrow, P. C., Petrović, P., James, A. C., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50093-4 · Cited by 26 · see citing works
Neural correlates of treatment response in depressed bipolar adolescents during emotion processing
Diler, R. S., Ladouceur, C. D., Segreti, A. M., Almeida, J., Birmaher, B. B., Axelson, D., Phillips, M. L., & Pan, L. A. (2013) · Brain Imaging and Behavior · doi:10.1007/s11682-012-9219-7 · Cited by 26 · see citing works
“…may be related to habituation of amygdala response after repeated affective stimuli (Breiter et al. 1996), blunted activity during depression (Altshuler et al. 2008; Chen et al. 2006; Townsend and Altshuler 2012), or difference in neurodevelopment of amygdala in adolescents with BD relative…”
BackgroundFournier, J. C. J., Bertocci, M. A., Ladouceur, C. D., Bonar, L. K., Monk, K., Abdul‐waalee, H., Versace, A., Santos, J. P. L., Iyengar, S., Birmaher, B. B., et al. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01001-w · Cited by 25 · see citing works
Marchand, W. R. (2011) · Depression Research and Treatment · doi:10.1155/2012/246725 · Cited by 25 · see citing works
“However, a number of function imaging studies using emotional activation paradigms suggest a relationship between CMS function and emotional dysregulation in depression [147, 148, 155], mania [156– 158], as well as euthymia [162].”
BackgroundSankar, A., Shen, X., Čolić, L., Goldman, D. A., Villa, L. M., Kim, J. A., Pittman, B. P., Scheinost, D., Constable, R. T., & Blumberg, H. P. (2023) · Psychological Medicine · doi:10.1017/s003329172300003x · Cited by 22 · see citing works
“Based on previous literature exploring group-level differences in brain function, we expected that whole-brain, intra- and inter-hemispheric functional connectivity alterations in a left dlPFC system would predict individual differences in depressed mood symptom severity (Altshuler et al., 2008; Brooks et al., 2009; F…”
Townsend, J. D., Sugar, C. A., Walshaw, P. D., Vasquez, R. E., Foland‐Ross, L. C., Moody, T. D., Bookheimer, S. Y., McGough, J. J., & Altshuler, L. L. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.08.019 · Cited by 22 · see citing works
“We specifically chose this block design to match the paradigm we had previously used in manic and depressed subjects (Altshuler et al., 2005, 2008).”
Self-citationTang, V. M., Blumberger, D. M., Dimitrova, J., Throop, A., McClintock, S. M., Voineskos, D., Downar, J., Knyahnytska, Y., Mulsant, B. H., Fitzgerald, P. B., et al. (2020) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.190098 · Cited by 22 · see citing works
Hegarty, C. E., Foland‐Ross, L. C., Narr, K. L., Sugar, C. A., McGough, J. J., Thompson, P. M., & Altshuler, L. L. (2012) · Bipolar Disorders · doi:10.1111/bdi.12024 · Cited by 21 · see citing works
“Functional deficits in portions of this network are associated with the emotional dysregulation characteristic of BP (32, 61-66).”
BackgroundSelf-citationHarada, M., Hoaki, N., Terao, T., Hatano, K., Kohno, K., Araki, Y., Mizokami, Y., Kodama, K., Toyokawa, K., Izumi, T., et al. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.05.066 · Cited by 21 · see citing works
Nabulsi, L., McPhilemy, G., Kilmartin, L., Whittaker, J. R., Martyn, F. M., Hallahan, B. P., McDonald, C., Murphy, K., & Cannon, D. M. (2019) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.10.015 · Cited by 19 · see citing works
Förster, K., Maliske, L., Schurz, M., Henneberg, P. M., Dannlowski, U., & Kanske, P. (2023) · Bipolar Disorders · doi:10.1111/bdi.13341 · Cited by 19 · see citing works
“As discussed above, we identified 31 studies 16,17,26– 31, of BD-patients.”
Guo, Z., Liu, X., Jia, X., Hou, H., Cao, Y., Wei, F., Li, J., Chen, X., Zhang, Y., Shen, Y., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150460 · Cited by 18 · see citing works
Atypical right hemispheric functioning in the euthymic state of bipolar affective disorder
Najt, P., & Hausmann, M. (2014) · Psychiatry Research · doi:10.1016/j.psychres.2014.08.015 · Cited by 17 · see citing works
“However, evidence here indicates left rather than right orbitofrontal and prefrontal areas (e.g., Lawrence et al., 2004; Altshuler et al., 2008).”
BackgroundKupfer, D. J., Angst, J., Berk, M., Dickerson, F., Frangou, S., Frank, E., Goldstein, B. I., Harvey, A. G., Laghrissi‐Thode, F., Leboyer, M., et al. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06336.x · Cited by 16 · see citing works
The Highs and Lows of Amygdala Reactivity in Bipolar Disorders
Hariri, A. R. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12050639 · Cited by 16 · see citing works
Zeng, C., Ross, B., Xue, Z., Huang, X., Wu, G., Liu, Z., Tao, H., & Pu, W. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.634299 · Cited by 15 · see citing works
Neurofunctional Correlates of Response to Quetiapine in Adolescents with Bipolar Depression
Chang, K., DelBello, M. P., Garrett, A. S., Kelley, R. G., Howe, M. E., Adler, C. M., Welge, J. A., Strakowski, S. M., & Singh, M. K. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2017.0030 · Cited by 15 · see citing works
“in dorsal and ventral portions of the prefrontal cortex (Altshuler et al. 2008; Townsend et al. 2010; Liu et al. 2012), both limbic hypoactivity (Vizueta et al.”
BackgroundA treatise on secondary psychopathy: Psychobiological pathways to severe antisociality
Yildirim, B. O. (2016) · Aggression and Violent Behavior · doi:10.1016/j.avb.2016.09.004 · Cited by 14 · see citing works
Kwaśniewicz, Ł., Wójcik, G. M., Schneider, P., Kawiak, A., & Wierzbicki, A. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.659243 · Cited by 13 · see citing works
“44 (Altshuler et al., 2008; Klempan et al., 2009; Goodman et al., 2011; Alexander et al., 2019), may also be related to mental illnesses such as depression.”
BackgroundČolić, L., Clark, A., Sankar, A., Rathi, D. J., Goldman, D. A., Kim, J. A., Villa, L. M., Edmiston, E. K., Lippard, E., Pittman, B. P., et al. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2022.07.186 · Cited by 12 · see citing works
“Based on these findings and the literature, we speculate that emotional subtypes of CM may contribute to changes in frontal pole structure that may impair mood and emotion regulation in BD (Altshuler et al., 2008; Bludau et al., 2014) Effects of mood state on brain structure were reported previously for frontal region…”
Dellink, A., Hebbrecht, K., Zeeuws, D., Baeken, C., Fré, G. D., Bervoets, C., Witte, S. D., Sabbe, B., Morrens, M., & Coppens, V. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.06.078 · Cited by 11 · see citing works
Harada, M., Terao, T., Hatano, K., Kohno, K., Araki, Y., Mizokami, Y., Kodama, K., Hoaki, N., Arasaki, M., Shimomura, T., et al. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.06.017 · Cited by 12 · see citing works
“Depressive patients with bipolar I disorder have been reported to show attenuation in bilateral orbitofrontal cortex (BA 47) and increased activation in left lateral orbitofrontal cortex (BA 10) during face matching paradigm (Altshuler et al., 2008).”
BackgroundFunctional Brain Imaging in Bipolar Disorder
Altshuler, L. L., & Townsend, J. D. (2012) · Oxford University Press eBooks · doi:10.1093/med/9780199797608.003.0032 · Cited by 11 · see citing works
Self-citationStrakowski, S. M. (2012) · Oxford University Press eBooks · doi:10.1093/med/9780199797608.003.0109 · Cited by 11 · see citing works
Shao, J., Zhang, Y., Li, X., Wang, X., Wang, H., Zhu, R., Yao, Z., & Lü, Q. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01290-9 · Cited by 9 · see citing works
“The manic episodes in BD patients may cause a decrease in OFC activity, resulting in lower or higher than HC, which may be the reason for the inconsistency of previous studies [60, 61].”
ResultAntipsychotic effects of sex hormones and atypical hemispheric asymmetries
Hodgetts, S., & Hausmann, M. (2020) · Cortex · doi:10.1016/j.cortex.2020.02.016 · Cited by 8 · see citing works
Mao, M., Chen, G., Feng, K., Xu, D., Hua, X., Shan, C., & Liu, P. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.946543 · Cited by 7 · see citing works
“In congruent with most neuroimaging studies investigating emotion processing in patients with BD, the present study revealed that negativity bias was more prominent in patients with BD (Altshuler et al., 2008; Frey et al., 2013; Matsubara et al., 2014, 2015; Segar et al., 2021).”
ResultThe Brain in Overdrive: A New Look at Borderline and Related Disorders
Stone, M. H. (2013) · Current Psychiatry Reports · doi:10.1007/s11920-013-0399-7 · Cited by 7 · see citing works
“In bipolar-I patients experiencing a depressive phase, lowered activity was observed in the orbitofrontal cortex bilaterally and in the right dorsolateral prefrontal cortex [41].”
BackgroundNeuroimaging and Neuropathological Findings in Bipolar Disorder
Savitz, J. B., & Drevets, W. C. (2010) · Current topics in behavioral neurosciences · doi:10.1007/7854_2010_68 · Cited by 7 · see citing works
Lyoo, I. K., & Renshaw, P. F. (2010) · doi:10.1002/9780470661277.ch14 · Cited by 7 · see citing works
To BD or not to BD: functional neuroimaging and the boundaries of bipolarity
Kuiper, S., McLean, L., & Malhi, G. S. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.126 · Cited by 6 · see citing works
- Authors
- Altshuler, L., Bookheimer, S., Townsend, J., Proenza, M. A., Sabb, F., Mintz, J., & Cohen, M. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Altshuler, Lori
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2008-08-18
- Volume
- 10
- Issue
- 6
- Pages
- 708-717
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- PMC
- PMC3260079
- OpenAlex
- W1964476186
- Cited by
- 135
- References
- 83
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 11 · 2013: 14 · 2012: 27
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Simons Foundation
- Stanley Medical Research Institute
- National Alliance for Research on Schizophrenia and Depression
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health
- National Institute of Mental Health (K24MH001848)
- National Institute on Drug Abuse (R01DA013054, DA13054)
- National Center for Research Resources (RR08655, P41RR013642, RR 13642, C06RR012169)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar I depression, bipolar disorder, prefrontal cortex, amygdala, orbitofrontal cortex, dorsolateral prefrontal cortex, brain activation, facial emotion recognition, negative affect
- MeSH terms
- Adult, Bipolar Disorder, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Pattern Recognition, Visual, Photic Stimulation, Reaction Time, Young Adult
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