Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania

Abstract

Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related.

Keywords: bipolar disorder; connectivity; resting state; striatum.

FIG. 1.

Key differences found in both BPD (bipolar depressed) and BPM (hypo)manic) groups compared with the HC group. (a) Post hoc results of left DC connectivity to left IFC extending to inferior OFC (p = 0.05 Bonferroni corrected for number of pairwise comparisons). (b) Post hoc results of left VSI connectivity to ACC (p = 0.05 Bonferroni corrected). ACC, anterior cingulate cortex; DC, dorsal caudate; HC, healthy control; IFC, inferior frontal cortex; OFC, orbital frontal cortex; VSI, ventral striatum inferior. Color images available online at www.liebertpub.com/brain

FIG. 2.

Differences in either BPD (bipolar depressed) and BPM ((hypo)manic) groups compared with the HC group. (a) Post hoc results of right DC connectivity to midbrain-sub nigra (p = 0.05 Bonferroni corrected for number of pairwise comparisons). (b) Post hoc results of right VSI connectivity to left and right thalamus (p = 0.05 Bonferroni corrected for number of pairwise comparisons). (c) Post hoc results of left DCP connectivity to right superior temporal gyrus–insula (p = 0.05 Bonferroni corrected for number of pairwise comparisons). DCP, dorsal caudal putamen. Color images available online at www.liebertpub.com/brain

FIG. 3.

Correlation analysis between the increase in connectivity and change in Symptom Severity Scales (Bonferroni corrected for number of main effect target regions for each reference ROI). (a) Correlation between right DC with substantia nigra connectivity and HAMD Scores (r: −0.386, p = 0.002 [corrected]). (b) Correlation between right DC with substantia nigra connectivity and YMRS scores (r: 0.297, p = 0.02 [corrected]). (c) Correlation between left DCP with right superior temporal gyrus–insula connectivity and HAMD Scores (r: 0.347, p = 0.007 [corrected]). HAMD, Hamilton Depression Rating Scale; ROI, region of interest; YMRS, Young Mania Rating Scale. Color images available online at www.liebertpub.com/brain