Attentional engagement increases inferior frontal gyrus activity and mutes limbic activity in pediatric bipolar disorder: Meta-analyses of fMRI studies

Prog Neuropsychopharmacol Biol Psychiatry. 2019 Apr 20;91:14-19. doi: 10.1016/j.pnpbp.2018.05.011. Epub 2018 May 19.


Objectives: Attention deficit has been shown to exist in adult and pediatric bipolar disorder across the life span. Given that emotion dysregulation is central to bipolar disorder, this study hypothesizes that emotional circuitry regions are altered along with anomalies in the attentional systems during cognitive deployment in bipolar disorder.

Methods: An activation likelihood estimation meta-analysis of attentional activities using GingerALE software was completed for adult and pediatric bipolar disorder populations in all published studies till December 2017. The meta-analysis of all fMRI studies included a total of ten pediatric studies (comprised of pediatric bipolar disorder (PBD) and typically developing (TD) groups) and nine adult patient studies (comprised of adult bipolar disorder (ABD) and healthy control (HC) groups).

Results: While engaged in attentional tasks, increased activation was seen in inferior frontal gyrus with decreased activation in limbic regions in subjects with PBD, relative to TD. Differential patterns of underactivity were also noted in the dorsal attentional system i.e., frontostriatal circuit (dorsolateral prefrontal cortex, anterior cingulate cortex, right lentiform nucleus and right globus pallidus) in PBD patients relative to the TD. However, we did not see any significant differences between the adult groups i.e., ABD vs. HC.

Conclusions: In PBD, deploying attentional system potentially improves the fronto-limbic affective circuitry function, despite impaired dorsal attentional system i.e., fronto-striatal circuitry. In contrast, these neural correlates underlying attentional engagement appeared to be not significant in adult BD.

Limitations: We examined the PBD vs. TD and the ABD vs. HC separately instead of four-way contrast (dual meta-analytic study). Also, attentional tasks were not unidimensional and tend to capture selective and sustained attention along with response inhibition, thereby recruiting multiple brain circuits.

Publication types

  • Meta-Analysis

MeSH terms

  • Attention* / physiology
  • Bipolar Disorder / diagnostic imaging*
  • Bipolar Disorder / physiopathology
  • Bipolar Disorder / psychology
  • Child
  • Humans
  • Limbic System / diagnostic imaging*
  • Limbic System / physiopathology
  • Magnetic Resonance Imaging / methods*
  • Prefrontal Cortex / diagnostic imaging*
  • Prefrontal Cortex / physiopathology