This study examined whether adolescents with pediatric bipolar disorder (PBD) have abnormal regional functional connectivity in distributed brain networks during an affective working memory task. Adolescents with PBD (n=41) and healthy controls (HC; n=16) performed a two-back functional magnetic resonance imaging working memory task with blocks of either angry or neutral faces. Independent component analysis methodology identified two temporally independent and functionally connected brain networks that showed differential functional connectivity in PBD and HC. Within a network for “affect evaluation and regulation,” PBD showed decreased functional connectivity relative to HC in regions involved in emotion processing such as the right amygdala, and in emotion regulation regions such as the right ventrolateral prefrontal cortex (VLPFC), while functional connectivity was increased in emotion evaluation regions such as the bilateral medial PFC. Furthermore, in an “Affective Working Memory Network,” PBD exhibited greater connectivity relative to HC in left dorsolateral PFC (DLPFC), caudate, and right VLPFC; and simultaneously reduced connectivity in emotion processing regions, such as the right amygdala, bilateral temporal regions, and the junction of DLPFC/VLPFC, which interfaces affective and cognitive processes. Dysfunction in network engagement in PBD patients illustrates that they are expending greater effort in face emotion evaluation, while being less able to engage affect regulation regions.
Get full access to this article
View all access options for this article.
References
1.
AaronAR, FletcherPC, BullmoreET, SahakianBJ, RobbinsTW. 2003. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci, 6:115–116.
2.
AlmeidaJR, MechelliA, HasselS, VersaceA, KupferDJ, PhillipsML. 2009. Abnormally increased effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during emotion labeling in bipolar disorder. Psychiatry Res, 174:195–201.
3.
American Psychiatric Association. 2000. Diagnostic and Statistical Manual of Mental Disorders IV-TR. 4th. Washington, DC: American Psychiatric Press.
4.
AnandA, LiY, WangY, LoweMJ, DzemidzicM. 2009. Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression. Psychiatry Res, 171:189–198.
5.
AnnettM. 1970. A classification of hand preference by association analysis. Br J Psychol, 61:303–321.
6.
BellAJ, SejnowskiTJ. 1995. An information-maximization approach to blind separation and blind deconvolution. Neural Comput, 7:1129–1159.
7.
BoraE, FornitoA, YücelM, PantelisC. 2010. Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry, 67:1097–1105.
8.
BraverTS, BarchDM, KelleyWM, BucknerRL, CohenNJ, MiezinFM, SnyderAZet al.2001. Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks. NeuroImage, 14:48–59.
9.
BrotmanMA, RichBA, GuyerAE, LunsfoirdJR, HorseySE, ReisingMM, ThomasLA, FrommSJ, TowbinK, PineD, LeibenluftE. 2010. Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. Am J Psychiatry, 167:61–69.
10.
CalhounVD, AdaliT, PearlsonGD, PekarJJ. 2001. A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp, 14:140–151.
11.
ChangK, AdlemanNE, DienesK, SimeonovaDI. 2004. Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder. Arch Gen Psychiatry, 61:781–792.
12.
ChepenikLG, RaffoM, HampsonM, LacadieC, WangF, JonesMM, PittmanB, SkudlarskiP, BlumbergHP. 2010. Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder. Psychiatry Res, 182:207–210.
13.
CooneyRE, JoormannJ, EugèneF, DennisEL, GotlibIH. 2010. Neural correlates of rumination in depression. Cogn Affect Behav Neurosci, 10:470–478.
14.
D'EspositoM. 2007. From cognitive to neural models of working memory. Philos Trans R Soc Lond B Biol Sci, 362:761–772.
ErhardtEB, RachakondaS, BedrickEJ, AllenEA, AdaliT, CalhounVD. 2010. Comparison of multi-subject ICA methods for analysis of fMRI data. Hum Brain Mapp, 32:2075–2095.
22.
FolandLC, AltshulerLL, BookheimerSY, EisenbergerN, TownsendJ, ThompsonPM. 2008. Evidence for deficitent modulation of amygdale response by prefrontal cortex in bipolar mania. Psychiatry Res Neuroimaging, 162:27–37.
23.
FrazierJA, AhnMS, DeJongS, BentEK, BreezeJL, GiulianoAJ. 2005. Magnetic resonance imaging studies in early-onset bipolar disorder: a critical review. Harv Rev Psychiatry, 13:125–140.
24.
FristonKJ. 2002. Bayesian estimation of dynamical systems: an application to fMRI. NeuroImage, 16:513–530.
25.
GellerB, WarnerK, WilliamsM, ZimermanB. 1998. Prepubertal and young adolescent bipolarity versus ADHD: assessment and validity using the WASH-U-KSADS, CBCL, and TRF. J Affect Disorder, 51:93–100.
26.
GurRC, SaraR, HagendoornMet al.2002. A method for obtaining 3-dimensional facial expressions and its standardization for use in neurocognitive studies. J Neurosci Methods, 115:137–143.
27.
HaxbyJV, HoffmanEA, GobbiniMI. 2002. Human neural systems for face recognition and social communication. Biol Psychiatry, 51:59–67.
28.
JohnsonSL, McMurrichS, McKenzieG. 2008. Ruminative responses to positive and negative affect among students diagnosed with bipolar disorder and major depressive disorder. Cogn Ther Res, 32:702–713.
29.
KaufmanJ, BirmaherB, BrentDA, RyanND, RauU. 2000. K-SADS-PL. Journal of the American Academy of Child and Adolescent. Psychiatry, 39,10:1208.
30.
LeibenluftE, CharneyDS, TowbinKE, BhangooRK, PineDS. 2003. Defining clinical phenotypes of juvenile mania. Am J Psychiatry, 160:430–437.
31.
LeibenluftE, RichBA, VintonDT, NelsonEE, FrommSJ, BerghorstLH, JoshiP, RobbA, SchacharRJ, DicksteinDP, McClureEB, PineDS. 2007. Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder. Am J Psychiatry, 164:52–60.
32.
LiYo, AdaliT, CalhounVD. 2007. Estimating the number of independent components for functional magnetic resonance imaging data. Hum Brain Mapp, 28:1251–1266.
33.
McDonaldC, BullmoreET, ShamPC, ChitnisX, WickhamH, BramonE, MurrayRM. 2004. Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiatry, 61,10:974–984.
34.
McIntoshAR, GradyCL, UngerleiderLG, HaxbyJV, RapoportSI, HorwitzB. 1993. Network analysis of cortical visual pathways mapped with PET. J Neuroscience, 14:655–666.
35.
OchsnerKN, RayRD, HughesB, McRaeK, CooperJC, WeberJ, GabrieliJDE, GrossJJ. 2009. Bottom-up and top-down processes in emotion generation. Psychol Sci, 20:1322–1321.
36.
OngürD, LundyM, GreenhouseI, ShinnAK, MenonV, CohenBM, RenshawPF. 2010. Default mode network abnormalities in bipolar disorder and schizophrenia. Psychiatry Res, 183:59–68.
37.
OwenAM, McMillanKM, LairdAR, BullmoreE. 2005. N-back working memory paradigm: a meta-analysis of normative functional Neuroimaging studies. Hum Brain Mapp, 25:46–59.
38.
PassarottiAM, PavuluriMN. 2011. Brain functional domains inform therapeutic interventions in attention-deficit/hyperactivity disorder and pediatric bipolar disorder. Expert Rev Neurother, 11:897–914.
39.
PassarottiAM, SmithJ, DeLanoM, HuangJ. 2007. Developmental differences in the neural bases of the face inversion effect show progressive tuning of face-selective regions to the upright orientation. NeuroImage, 34:1708–1722.
40.
PassarottiAM, SweeneyJA, PavuluriMN. 2010a. Differential engagement of cognitive and affective neural systems in pediatric bipolar disorder and attention deficit hyperactivity disorder. J Int Neuropsychol Soc, 16:106–117.
41.
PassarottiAM, SweeneyJA, PavuluriMN. 2010b. Neural correlates of response inhibition deficits in pediatric bipolar disorder and attention deficit hyperactivity disorder. Psychiatry Res Neuroimaging, 181:36–43.
42.
PassarottiAM, SweeneyJA, PavuluriMN. 2010c. Emotion processing influences working memory circuits in pediatric bipolar disorder and attention deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry, 9:1064–1080.
43.
PassarottiAM, SweeneyJA, PavuluriMN. 2011. Fronto-limbic dysfunction in mania pre-treatment and persistent amygdala over-activity post-treatment in pediatric bipolar disorder. Psychopharmacology, 216:485–499.
44.
PavuluriMN, O'ConnorMM, HarralEM, SweeneyJA. 2008. An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder. Psychiatry Res, 162:244–245.
45.
PavuluriMN, PassarottiAM, HarralE, SweeneyJA. 2009a. An fMRI study of the neural correlates of incidental versus directed emotion processing in pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry, 48:308–319.
46.
PavuluriMN, PassarottiAM, MohammedT, CarbrayJ, SweeneyJA. 2010. Enhanced working and verbal memory after lamotrigine treatment in Pediatric Bipolar Disorder. Bipolar Disorders, 12:213–220.
47.
PavuluriMN, ShenkelLS, AryalS, HarralE, HillK, HerbenerES, SweeneyJA. 2006. Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients. Am J Psychiatry, 163:286–293.
48.
PavuluriMN, WestA, HillS, JindalK, SweeneyJA. 2009b. Neurocognitive function in pediatric bipolar disorder: 3-year follow-ups show cognitive development lagging behind health youth. J Am Acad Child Adolesc Psychiatry, 48:235–236.
49.
PetridesM, PandyaD. 2002. Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. Eur J Neurosci, 16:291–310.
50.
PoznanskiE, GrossmanJ, BuchsbaumY, BanegasM, FreemanL, GibbonsR. 1984. Preliminary studies of the reliability and validity of the children's depression rating scale. J Am Acad Child Adolesc Psychiatry, 23:191–197.
RichBA, FrommSJ, BerghorstLH, DicksteinDP, BrotmanMA, PineDS, LeibenluftE. 2008. Neural connectivity in children with bipolar disorder: impairment in the face emotion processing circuit. J Child Psychol Psychiatry, 49:88–96.
53.
RichBA, VintonDT, Roberson-NayRet al.2006. Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder. Proc Natl Acad Sci U S A, 103:8900–8905.
54.
ShelineYI, PriceJL, YanZ, MintunMA. 2010. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A, 107:11020–11025.
55.
StevensMC, KiehlKA, PearlsonGD, CalhounVD. 2007. Functional neural networks underlying response inhibition in adolescents and adults. Behav Brain Res, 181:12–22.
WilliamsJMG, MatthewsA, McLeadC. 1996. The emotional stroop task and psychopathology. Psychol Bull, 120:3–24.
62.
YoungRC, BiggsJT, ZieglerVE, MeyerDA. 1978. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry, 133:429–435.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
