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. 2017 Apr;15(3):339–352. doi: 10.2174/1570159X14666160708231216

Table 1. Included studies of fMRI in patients with bipolar disorder.

Study Sample FC Relevant Results Relevance with PoM Hypothesis
Anand et al. (2009) [13]* 11 BD (6 manic and 5 depressive) vs. 15 MDD, all unmedicated, vs. 15 HC Yes ↓FC between striatum and subgenual anterior cingulate and between
subgenual anterior cingulate and dorsomedial
thalamus in both BD and MDD, compared to HC
Against
Chepenik et al. (2010) [14] 15 BD (8 euthymic, 5 mixed/hypomanic/
manic, 2 depressive) vs. 10 HC
Yes left vPFC- left amygdala: greater neg. corr. in HC than in BD; left mvPFC- right hemisphere: greater pos. corr. in BD than in HC; left vPFC- dorsofrontal and parietal regions: greater neg. corr. in BD than in HC Uncertain
Dickstein et al. (2010) [15] 15 pædiatric BD vs. 15 HC Yes left DLPFC-right STG: greater neg. corr. in BD than in HC; right STG-left MFG, right SFG, left thalamus/caudate: greater neg. corr. in BD than in HC; right STG-right parahippocampal gyrus: greater pos. corr in BD than in HC Uncertain
Chai et al. (2011) [16] 14 BD with mania vs.
15 HC
Yes mPFC- bilateral dlPFC: neg. corr. in HC, NS corr. in BD; mPFC-right vlPFC: pos. corr. in BD, neg. corr. in HC; mPFC-left insula: pos. corr. in BD, neg. corr. in HC Uncertain
C.-H. Liu et al. (2012) [17] 21 BD-I vs. 21 matched MDD No ↓ ALFF in left superior parietal lobule and left posterior insula; ↓ ALFF in right dorsal anterior insula in BD vs. MDD Uncertain
C.-H. Liu et al. (2012) [18] 26 BD vs. 26 matched HC Yes ↑ ReHo in left medial frontal gyrus and left inferior parietal lobe in MDD vs. HC; no differences between BD and HC Uncertain
C.-H. Liu et al. (2012) [19] 26 BD with depression vs. 26 matched HC No ↑ ALFF in left insula, right caudate, temporal gyrus, bilateral IFG, and posterior cerebellar lobe and ↓ ALFF in left postcentral gyrus, left parahippocampal gyrus, and cerebellum in BD with depression vs. HC; implies dysfunction in prefrontal-limbic networks and associated striatal systems Favours
C.-H. Liu et al. (2013) [20] 21 BD with depression vs. 21 MDD vs. 26 matched HC No ↓ ReHo in right posterior cingulate cortex, right ventral anterior insular, and right parahippocampal gyrus, and ↑ ReHo in right MFG, right dorsal anterior insular, right posterior cerebellar gyrus, and left anterior cerebellar gyrus in BD with depression vs. MDD; ↓ ReHo in right parahippocampal gyrus in BD with depression vs. HC; ↓ ReHo in right MFG, right dorsal anterior insula, and right posterior cerebellar gyrus, and ↑ ReHo in right posterior cingulate in MDD vs. HC Uncertain
Liang et al. (2013) [21] 17 BD vs. 16 MDD vs.
16 HC
No ↑ ReHo in right insular cortex, left middle frontal gyrus, left precuneus, left occipital lobe, left parietal, left superior frontal gyrus and left thalamus in BD; ↓ ReHo in right anterior cerebellar lobe, pons, right precentral gyrus, left postcentral gyrus, left IFG, and right cingulate. ↑ ReHo in left middle occipital lobe, right inferior parietal lobule, right precuneus and left convolution; ↓ ReHo in left parahippocampal gyrus, right precentral gyrus, left postcentral gyrus, left precentral gyrus, and left cingulate Uncertain
Xiao et al. (2013) [22] 15 medicated pædiatric
BD with mania vs.
15 matched HC
No ↑ ReHo in bilateral hippocampus, right anterior cingulate, right parahippocampal gyrus, and left caudate; ↓ ReHo in bilateral precuneus, bilateral precentral gyrus, bilateral SFG, bilateral superior parietal lobe, right OFC, and right STG Favours
Teng et al. (2013) [23] 15 BD-I vs. 16 HC Yes ↑ FC from basal ganglia to left thalamus (visual network), to right parahippocampal gyrus (ventral default-mode network), to left parietal gyrus, precuneus, and angular gyrus (executive control network), and to the left anterior insula in BD vs. HC; ↓FC from basal ganglia to precuneus, to right retrosplenial cortex and posterior cingulate cortex (ventral default mode network), and to right caudate (right executive control) Favours
Reinke et al. (2013) [24] 21 euthymic BD vs.
20 matched HC
Yes ↓FC between Heschl's gyrus/planum temporale and left STG/MTG in euthymic BD vs. HC; ↑ FC between frontal and temporal cortices and right IFG/precentral gyrus and insula in euthymic BD vs. HC Uncertain
Torrisi et al. (2013) [25] 20 euthymic BD-I vs.
20 matched HC
Yes ↑ FC between right amygdala and right vlPFC in BD vs. HC; activity in BD partially mediated through the anterior cingulate Favours
Study Sample FC Relevant Results Relevance with PoM Hypothesis
Mamah et al. (2013) [26] 35 BD vs. 25 schizophrenia vs.
33 HC
Yes ↓FC in cingulo-opercular and cerebellar-salience networks in BD; ↓FC in schizophrenia more than in BD and in the salience and frontoparietal-cerebellar networks Uncertain; more favours than not
Meda et al. (2012) [27]# 70 schizophrenia vs. 70 unaffected first-degree relatives vs. 64 BD with psychosis vs. 52 unaffected first-degree relatives vs. 118 matched HC Yes ↓FC in schizophrenia and BD with psychosis between fronto-occipital and default mode-prefrontal networks; ↓FC in schizophrenia between mesoparalimbic and sensorimotor networks; ↑ FC between frontotemporal-paralimbic and mesoparalimbic networks Uncertain
Meda et al. (2014) [28]# 296 schizophrenia vs. 179 unaffected first-degree relatives vs. 300 BD with psychosis vs. 206 unaffected first-degree relatives vs.
324 matched HC
Yes ↓FC in schizophrenia and BD with psychosis within default mode networks with foci mPFC and anterior cingulate; abnormal connectivity between striatum and anterior cingulate in schizophrenia and BD with psychosis; abnormalities were similar between schizophrenia and their first-degree relatives,
although less in the latter; no abnormalities in
first-degree relatives of BD with psychosis
Uncertain; slightly favours
Anticevic et al. (2013) [29] 68 euthymic BD with history of psychosis vs.
51 matched HC
Yes ↓intra-mPFC connectivity, ↑ connectivity between mPFC and amygdala, and ↓ connectivity between dlPFC and amygdala in BD, compatible with striatal suppression of cortical inhibition Favours
Anticevic et al. (2014) [30] 47 euthymic BD (16.5% unmedicated) vs. matched HC Yes ↑ fronto-thalamic connectivity in BD Uncertain
Anticevic et al. (2014) [31] 90 schizophrenia vs. 73 (33 with history of psychosis) euthymic BD vs. 146 HC Yes Mediodorsal thalamic-prefrontal and lateral geniculate-occipital dysconnectivity in schizophrenia, less consistently in BD, more severe in BD with history of psychosis; dysconnectivity with cerebellum present in schizophrenia and absent in BD Uncertain
Anticevic et al. (2015) [32] 73 schizophrenia vs. 73
(33 with history of psychosis)
euthymic BD vs. 56 HC
Yes ↓ FC in anterior cingulate-PFC in schizophrenia and BD with history of psychosis; ↓ FC in anterior cingulate-PFC and ↑ anterior cingulate-amygdalar FC in BD with or without history of psychosis Favours
Argyelan et al. (2014) [33] 18 schizophrenia vs. 19 BD vs.
32 HC
Yes ↓ FC in paracingulate gyrus and right thalamus in schizophrenia and BD; schizophrenia showed additional ↓ FC in other areas Uncertain
Favre et al. (2014) [34] 20 euthymic BD vs. 20 HC Yes mPFC-dlPFC: neg. corr. in HC, NS corr. in BD; mPFC-amygdala: pos. corr. in BD, NS corr. in HC Uncertain
Gao et al. (2014) [35] 17 pædiatric BD with
depression vs. 18 HC
(age 10-18 years)
No ↓ ReHo in medial frontal gyrus, bilateral middle frontal gyrus, middle temporal gyrus, right putamen in BD vs. HC Favours
Rashid et al. (2014) [36] 60 schizophrenia or schizoaffective disorder vs. 38 euthymic BD vs.
61 matched HC differing for
gender composition
Yes Aberrant FC patterns in various default-mode components including dmPFC, bilateral angular gyrus, and bilateral precuneus in schizophrenia/schizoaffective disorder and BD Uncertain
Rashid et al. (2016) [37] 60 schizophrenia or schizoaffective disorder vs. 38 euthymic BD vs.
61 matched HC differing for
gender composition
Yes Functional network connectivity analysis of the previous results; the analysis allowed to classify subjects as BD,
HC, and schizophrenia/schizoaffective
disorder similarly to previous study
Uncertain
Singh et al. (2014) [38] 24 healthy offspring of BD parents (8-17-year-old) vs. matched HC
with no affected family members
Yes ↑ FC in vlPFC and other frontoparietal regions of the left executive control network in BD-risk vs. HC; ↓FC between left amygdala and pregenual cingulate, between subgenual
cingulate and supplementary motor cortex,
and between left vlPFC and left caudate
Favours
Study Sample FC Relevant Results Relevance with PoM Hypothesis
H. Liu et al. (2014) [39] 18 schizophrenia vs.
18 BD vs. 18 HC
Yes ↓ FC between laterobasal/centromedial amygdala and left dlPFC/left middle cingulate and ↑ FC between laterobasal amygdala and left rostral PFC in schizophrenia vs. HC; ↓ FC between laterobasal amygdala and right ventral and middle cingulate in BD vs. HC; ↓ FC between laterobasal/centromedial amygdala and right dlPFC in schizophrenia vs. BD; ↓ FC between laterobasal amygdala and pregenual anterior cingulate/rostral PFC in BD vs. schizophrenia; ↓ FC between centromedial amygdala and right ventral anterior cingulate/left pregenual cingulate/bilateral rostral PFC in BD vs. HC; ↓ FC between superficial amygdala and bilateral dlPFC/left middle cingulate and ↑ FC between superficial amygdala and left rostral/dlPFC in schizophrenia vs. HC; ↓ FC between superficial amygdala and left ventral anterior cingulate/right rostral PFC in BD vs. HC; ↓ FC between superficial amygdala and bilateral dlPFC in schizophrenia vs. BD; ↓ FC between superficial amygdala and pregenual/ventral cingulate/rostral PFC/bilateral OFC extending to the temporal pole in BD vs. schizophrenia Uncertain
Lu et al. (2014) [40] 18 BD-I with mania vs.
18 matched HC
No ↑ ALFF in bilateral caudate and left pallidum, ↓ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus in BD-I vs. HC Favours
Xu et al. (2014) [41] 29 BD vs. 29 matched HC No ↑ ALFF in vm/vlPFC, dlPFC, frontal visual field, insula, and putamen extending to ventral striatum in BD vs. HC ↓ ALFF in lingual gyrus in BD vs. HC Favours
Yang et al. (2014) [42] Independent samples with chronic schizophrenia
(90 and 71 patients) vs.
73 BD vs. 220 HC
Yes Wide resting-state fluctuations in schizophrenia samples, but not in BD or HC (analysis of global brain signal) Uncertain, not relevant
Yip et al. (2014) [43] 15 drug-naïve euthymic BD-II vs. 20 matched HC Yes ↑ FC in the temporo-insular resting-state network (↑ engagement across regions of the right caudate, left pre- and post-central gyri, left IFG, left supplementary motor area, bilateral putamen, and bilateral insula) in euthymic BD-II vs. HC Uncertain
Das et al. (2014) [44] 16 BD vs. 14 with Borderline Personality Disorder vs. 13 HC Yes ↑ FC between the social salience network (dorsal anterior cingulate, OFC-insula, IFG, posterior superior temporal sulcus, inferior parietal lobule, temporoparietal junction) and each of the right frontoparietal network, the precuneus, and the vmPFC, and between the default-mode network and the precuneus in BD vs. borderline personality disorder; ↑ FC between default-mode and precuneus, and between social salience and vmPFC in BD vs. HC (differences did not survive multiple comparisons testing) Favours
Knöchel et al. (2014) [45] 21 BD vs.
21 schizophrenia vs.
21 HC
Yes ↓ FC between hippocampus and left frontal lobe in BD vs. HC; ↓ FC between hippocampus and left frontal lobe/right lenticular nucleus/putamen, and left thalamus and ↑ FC in bilateral parahippocampal gyrus and bilateral cingulate in schizophrenia vs. HC Uncertain
Oertel-Knöchel et al. (2015) [46] 21 euthymic BD vs.
21 matched HC
Yes ↓FC within frontal areas and between frontal and temporal/hippocampal/limbic regions in BD vs. HC; ↑ frontal-limbic FC in BD vs. HC Not relevant; uncertain
Lois et al. (2015) [47] 30 euthymic BD-I vs.
35 matched HC
Yes ↑ FC between meso/paralimbic (amygdala, hippocampus, parahippocampal gyrus, and temporal lobes) and right frontoparietal networks in BD-I vs. HC Uncertain
Lui et al. (2015) [48] 37 schizophrenia vs.
38 unaffected first-degree relatives vs. 57 psychotic BD vs. 28 unaffected first-degree relatives vs. 59 HC
Yes ↓ALFF in OFC and cingulate in schizophrenia and less in BD and their unaffected relatives; ↑ ALFF in striatal-thalamo-cortical networks in BD;
↑ FC between thalamus and bilateral insula in BD
Favours
Y. Liu et al. (2015) [49] 17 BD vs. 17 MDD Yes ↑ connection strength between mPFC and posterior cingulate, and between right inferior parietal cortex and left hippocampus/right insula in BD vs. MDD; ↓/unapparent connection strength between mPFC/right
insula and bilateral hippocampus in BD
Uncertain
Study Sample FC Relevant Results Relevance with PoM Hypothesis
Du et al. (2015) [50] 20 BD vs. 20 schizophrenia vs. 20 schizoaffective with mania vs. 13 schizoaffective with depression vs. 20 HC No ↑activity in right precuneus in BD correlating negatively with BPRS scores; activity in BD more similar to HC than other groups Uncertain
Jie et al. (2015) [51] 21 BD vs. 25 MDD vs. 23 HC No ↑ activity in anterior cingulate in BD vs. MDD and vs. HC; differences were reported also in other structures Favours
Jie et al. (2015) [52] 21 BD vs. 25 MDD vs. 23 HC Yes ↑ FC in hypothesis-related structures, like default-mode in BD vs. MDD; differences were reported also in the IFG, the dlPFC and the cerebellum Slightly favours
Li C.-T. et al. (2015) [53] 20 euthymic BD vs.
20 unaffected siblings vs.
20 matched HC
Yes ↓ dlPFC-amygdalar FC in BD vs. siblings and in BD and siblings vs. HC; ↓ top down control from dlPFC to limbic structures Favours
Li M. et al. (2015) [54] 18 BD with mania vs. 10 BD with depression vs. 28 HC Yes ↓ amygdala-IFG (orbital)/striatum/right lingual gyrus/posterior cerebellar lobe FC in BD vs. HC. ↑ amygdala-hippocampal FC in BD with mania vs. BD with depression Favours
Satterthwaite et al. (2015) [55] 27 BD (21 BD-I) with depression vs. 25 MDD vs.
33 HC
Yes Nodal connectivity strength of left ventral striatum correlated inversely with depression severity (BDI scores) in both BD and MDD; diminished edge network connectivity with greater depression between ventral striatum and thalamus, and between ventral tegmental area and vmPFC Favours
Z. Wang et al. (2015) [56]# 220 schizophrenia vs. 150 first-degree relatives vs. 147 with schizoaffective disorder vs.
126 first-degree relatives vs.
180 with psychotic BD vs.
134 first-degree
relatives vs. 242 HC
No Structural MRI and resting-state fMRI scans were combined to provide “fused” data of combined structural/functional alterations. Combined structural abnormalities in default-mode network and functional prefrontal–striatal–thalamic–cerebellar network alterations in schizophrenia, schizoaffective disorder and BD vs. HC; fused alteration in temporal lobe in schizophrenia and schizoaffective disorder, but not in BD; no alterations detected in groups of relatives Uncertain
Stoddard et al. (2015) [57] 14 BD vs. 19 with severe mood dysregulation vs. 20 HC in the 9–18.5 years age range Yes ↑ FC between left basolateral amygdala-medial left frontal pole and basolateral amygdala-posterior cingulate/precuneus in BD vs. mood dysregulation vs. HC (focused only connectivity concerning basolateral, centromedial, and superficial amygdala) Unclear
Stoddard et al. (2016) [58] 39 BD (22 aged 10-22; 17 aged >22-50) (27 euthymic, 3 mixed/hypomanic, 7 depressed) vs. 78 HC (36 aged 10-22;
42 aged >22-50)
Yes ↑ FC in right inferior parietal lobule right posterior cingulate, left STG, and left precentral gyrus in BD vs. HC Unclear
Y. Wang et al. (2015) [59] 26 unmedicated BD-II with depression vs. 40 HC Yes ↓FC in mPFC (core hub of default-mode network) and ITG (interhemispheric synchronisation) in BD-II with depression vs. HC Uncertain
Y. Wang et al. (2015) [60] 36 BD-II with depression
(24 unmedicated) vs. 32 MDD with depression
(23 unmedicated) vs. 40 HC
Yes No differences in FC between BD-II with depression and MDD with depression; ↓FC in fusiform/lingual gyrus, and anterior and posterior cerebellar lobes in BD-II with depression vs. HC; ↓FC in
posterior cingulate, fusiform/lingual gyrus, and posterior
cerebellar lobe in MDD with depression vs. HC.
Both BD-II and MDD show interhemispheric abnormalities
Uncertain
Y. Wang et al. (2016) [61] 37 unmedicated BD-II with depression vs. 37 HC Yes ↓FC strength in bilateral mPFC, bilateral MTG, left precuneus, and right posterior cingulate (default-mode network), right supramarginal gyrus and angular gyrus, right SFG, and right superior parietal gyrus in BD-II with depression vs. HC; ↑ FC strength in bilateral temporal pole (including parahippocampal gyrus and amygdalæ), left anterior cingulate, left STG, right lingual gyrus, and left anterior cerebellar lobe in BD-II with depression vs. HC; results consistent with decreased default-mode and limbic function during depression in BD-II Uncertain
Study Sample FC Relevant Results Relevance with PoM Hypothesis
Altinay et al. (2016) [62] 30 BD with mania/hypomania vs.
30 BD with depression, all unmedicated, vs. 30 HC
Yes ↑ FC between left dorsal striatum and midbrain; ↑ FC between ventral striatum and thalamus in BD with mania/hypomania; ↑ FC between dorsal striatum and insula and temporal cortex in BD with depression; extensive abnormalities in BD connectivity between striatum on one hand, and cortex, midbrain, and limbic structures on the other Favours
Goya-Maldonado et al. (2016) [63] 20 BD with depression vs. 20 MDD Yes ↑ FC in the frontoparietal network in BD; ↑ FC in default network in MDD; ↓ FC in anterior, pregenual and subgenual cingulate in MDD Slightly favours
He et al. 2016 [64] 13 BD vs. 40 MDD vs. 33 HC,
all unmedicated
Yes ↑ FC in dlPFC and vlPFC with anterior cingulate in BD compared to MDD Favours
Lv et al. (2016) [65] 23 BD with depression, 19 euthymic BD (medicated with benzodiazepines) vs. 28 matched HC Yes ↓FC strength in language regions (left triangular part of IFG, left opercular part of IFG, left middle temporal gyrus, and left angular gyrus) in BD with depression vs. HC Uncertain
Magioncalda et al. (2016) [66] 40 BD (11 in manic phase, 11 in depressive, 7 in mixed state, and
11 euthymic) vs. 40 matched HC
Yes ↓FC between perigenual anterior cingulate to posterior cingulate and ITG (default mode network) and in salience network (supragenual anterior cingulate and vlPFC) in BD vs. HC. Uncoupling between perigenual anterior cingulate FC and variability within target regions in BD; ↓ FC between perigenual anterior cingulate and supragenual cingulate in BD with depression and between perigenual anterior cingulate and posterior cingulate in BD with mania Slightly favours
Martino et al. (2016) [67] 20 BD with depression vs. 20 BD with mania vs. 20 BD in euthymia vs. 40 HC Yes ↑ FC in default mode vs. sensorimotor networks in BD with depression; ↑ FC in sensorimotor vs. default mode networks in BD with mania; balanced activity in BD with euthymia; whereas the opposite topographical pattern was observed in mania Uncertain
Rey et al. (2016) [68]* 27 BD (15 euthymic vs. 12 non-euthymic: 7 with depression, 3 with hypomania, and 2 with mixed state) vs. 27 matched HC Yes ↑ FC in left amygdala-left subgenual anterior cingulate and posterior cingulate in BD vs. HC; ↓FC between right amygdala and subgenual anterior cingulate in non-euthymic BD; ↓FC between posterior cingulate and subgenual anterior in euthymic BD; ↑ FC between subgenual anterior cingulate and right vlPFC in euthymic BD Impossible to assess due to lumping depressive with hypomanic/mixed
Skåtun et al. (2016) [69] 71 schizophrenia vs. 43 BD vs.
196 HC
Yes ↓FC in high-centrality clusters, i.e., sensory regions in schizophrenia and subcortical regions in both schizophrenia and BD; ↑ FC in frontal and parietal clusters in schizophrenia, intermediate alterations in BD Uncertain
Solé-Padullés et al. (2016) [70] 27 offspring of patients with schizophrenia vs. 39 offspring of patients with BD vs. 40 offspring of HC (all three samples in the
7-19 year-old range)
Yes No difference in FC between offspring of patients with BD and offspring of HC; ↓FC in offspring of patients with schizophrenia in left basal ganglia network vs. HC. FC correlated with left caudate grey matter volume (i.e., the greater the grey matter loss, the less the connectivity). The patient-related sample drove the results Uncertain
Souza-Queiroz et al. (2016) [71] 32 BD (most were medicated) vs.
47 HC
Yes No difference in FC between vmPFC and amygdala or hippocampus and in general fractional anisotropy in the uncinate fasciculus in BD vs. HC Unclear-uncertain
Brady et al. (2016) [72] 28 manic BD vs. 24 euthymic BD (all medicated) vs. 23 matched HC Yes ↓ FC between amygdala and anterior cingulate in BD with mania vs. eythymic BD; ↑ FC between amygdala and supplementary motor area in BD with mania vs. euthymic BD; ↑ FC between amygdala and left cerebellum in BD with mania vs. HC; ↑ FC between left vlPFC and anterior cingulate in euthymic BD vs. manic BD; ↑ FC between OFC and cerebellum in manic BD vs. euthymic BD and HC Uncertain

*These studies did not distinguish between BD patients with opposite phases. Caution needed in interpreting their results. #This group found different results with the same methodology in these two studies. Two further studies by the same group reported on schizophrenia spectrum and involved large numbers of schizoaffective disorder patients. The diagnostic consistency of these studies, that reported on samples without defining whether the patients among across the three studies were different or partially overlapping, is doubtful.