Table 1 Summary of Studies Investigating the Effective Connectivity of Emotional Face Processing in Major Depression Disorder.
Author and year | Number of Participants (% female) | Age (SD) | Treatment Type | Assessment of Depression Severity | Imaging Modality and Emotion Processing Task Type | Effective Connectivity Method | Regions Investigated (MNI coordinates or atlas used); task-based or predefined | Main Findings |
|---|---|---|---|---|---|---|---|---|
de Almeida et al. [38] | HC: 16 (75) MDD: 16 (81.2) | HC: 28.3 (8.4) MDD: 32.3 (9.7) | NA | HDRS-25 HC: NS MDD: 24.6 (6) | fMRI, event-related explicit emotional face labelling (emotional or neural) with sad and happy expressions | DCM | Bilateral vmPFC and amygdala (Wake Forest University Pick Atlas); predefined | Left hemisphere from vmPFC to amygdala was more negative in those with depression. No task associated differences in reaction time or accuracy between groups. |
Carballedo et al. [46] | HC: 15 (50) MDD: 15 (50) | HC: 35.5 (10.9) MDD: 39.9 (8.6) | NA | HDRS-21 HC: NS MDD: 22.87 (4.4) | fMRI, block design explicit emotional face matching with sad and angry expressions | SEM | Bilateral amygdala (L: 28, −6, −18; R: 28, −2, −20), vlPFC (L: −34, 26, −6; R: 34, 26, −8), dorsal ACC (L: −10, 26, 30; R: 14, 26, 28), dlPFC (L: −52, 26, 32; R: 48, 22, 34); task-based | Depression-associated reduction in bilateral amygdala to vlPFC and right-side reductions from amygdala to dorsal ACC and dorsal ACC to dlPFC. No task associated differences in reaction time or accuracy between groups. |
de Almeida et al. [37] | HC: 19 (63) MDD: 12 (63) | HC: 31.8 (6.8) MDD: 30.3 (7) | NA | HDRS-25 HC: 1.4 (2.2) MDD: 28.1 (6.3) | fMRI, implicit emotional face processing (coloring matching) of dynamic expressions between neural and either happy, sad, angry, or fearful | DCM | Amygdala, vmPFC, subgenual ACC (Wake Forest University Pick Atlas); predefined | Left hemisphere from vmPFC to amygdala was more negative during happy face processing in those with depression (only in females). Increased subgenual ACC to amygdala connectivity to fearful faces was also shown in depressed individuals. No task-associated differences in reaction time or accuracy between groups. |
Tang et al. [51] | HC: 13 (46.2) MDD: 12 (66.7) | HC: 39.5 (9.7) MDD: 31.7 (13.6) | NA | HDRS HC: 1.85 (1.9) MDD: 27.00 (8.2) | EEG, face-in-the-crowd task using schematic faces representing displaying neural expressions with targets being either positive or negative expressions | Partial directed coherence (Granger causality) | 12 electrodes: Fp1, Fp2, Fz, F5 and F6 in the prefrontal and frontal cortex, C5, C6 and Cz in the central cortex, and Pz, PO7, PO8 and Oz in the occipito-parietal cortex; predefined | Hemispheric asymmetry driven by left-frontal hypoactivity and the right-frontal hyperactivity in depressed participants. Depression was associated with slower reaction time for detecting negative faces. |
Goulden et al., [40] | HC: 21 (66.7) Remitted MDD: 22 (72.7) | HC: 31.1 (10.0) Remitted MDD: 33.7 (10.7) | NA | MADRS HC: .92 (1.4) Remitted MDD: 2.31 (3.6) | fMRI, event-related implicit emotional face processing (gender matching) with happy and sad expressions | DCM | Bilateral V1 (L: -14, -98, 0; R: 18, -96, 0), FG (L: -35, -77, -20; R: 42, -60, -15), amygdala (L: -18, -7, -15: R: 25, -4, -15), and vlPFC (L: -42, 21, -15; R: 28, 32 -15); task-based | In remitted MDD happy faces modulated bidirectional FG to vlPFC connections and sad faces modulated from FG to vlPFC. Between group comparisons of parameters were not performed. No behavioral results reported. |
Lu et al. [48] | HC: 20 (45) MDD: 20 (55) | HC: 31.3 (7.4) MDD: 30.7 (8.9) | NA | HDRS HC: < 8 MDD: >24 | MEG, explicit recognition of sad or not from series of emotional videos displaying either eating, neutral, sad, happy and rest | DCM | Left V1 ( − 20, −84, 10), precuneus (−34, −64, 54), amygdala (−28, 0, −16), rostral ACC ( − 10, 50, −2) and dlPFC (42, 32, 18); task-based | Sad face associated modulation significantly increased connectivity from rostral ACC to dlPFC in those with depression. Intrinsic connectivity from the dlPFC to amygdala was significantly reduced, whereas amygdala to rACC was increased in those with depression. No behavioral results reported. |
Lu et al. [49] | HC: 12 (100) MDD: 12 (100) | HC: 31.1 (8.6) MDD: 31.2 (7.8) | NA | HDRS HC: NS MDD: >24 | MEG, explicit recognition of sad or not from series of emotional videos displaying either eating, neutral, sad, happy and rest | Granger Causality | V1, amygdala, dorsal ACC, and dlPFC (Anatomical Automated Labeling library in the Marsbar toolbox); predefined | Depressed individuals demonstrated more positive modulation from the amygdala to dorsal ACC and dlPFC around 25 and 100 ms after stimulus onset and more negative modulation from the dlPFC to amygdala about 825 ms after stimulus onset. No behavioral results reported. |
Grant et al. [45] | HC: 19 (52.6) MDD: 20 (55) | HC: 31.2 (9.2) MDD: 34.5 (10.7) | NA | BDI HC: 0.79 (1.1) MDD: 31.6 (9.5) | fMRI, block design implicit emotional face processing (gender matching) with positive, sad and neutral and expressions | Granger Causality | Bilateral amygdala (L: -22, -2, -16; R: 20, 2, -16), subgenual ACC (L: -2, 2, -6; R: 2, 4, -10), midcingulate (L: -6, -8, 38), dorsal ACC (L:-14, 24, 34; R:14, 8, 38), dlPFC (L: -32, 20, 34; R: 32, 24, 40), hippocampus (Wake Forest University Pick Atlas); predefined | During the processing of negative expressions, MDD participants had reduced connectivity from the dlPFC to amygdala, midcingulate and subgenual ACC in comparison to healthy controls. MDD participants had greater connectivity from the midcingulate to amygdala, dlPFC, and subgenual ACC. No difference in the reaction time between groups. |
Musgrove et al. [42] | HC: 32 (76) MDD: 27 (74) | HC: 16.1 (2.1) MDD: 15.7 (1.9) | NA | BDI HC: 2.3 (3.0) MDD: 26.4 (13.5) | fMRI, block design explicit matching of emotional faces with fearful and angry expressions | DCM | OFA (L: -41, -81, -8; R: 41, -82, -4), FG (L: -42, -58, -18; R: 40, -57, -17), amygdala (L: -26, 0, -20; R: 26, 0, -20), subgenual ACC (0, 15 -14), dorsal ACC (0, 34, 30); task-based | MDD participants had lower right hemisphere amygdala to subgenual ACC intrinsic connectivity. No difference was found in modulation (combination of fearful and angry expressions). No behavioral results reported. |
Vai et al. [44] | HC: 31 (58.1) MDD: 33 (57.6) [Treatment Remitter: 21 (52.4) Treatment Non-remitter: 12 (66.7)] | HC: 30.3 (10.0) MDD: 30.3 (11.2) [Treatment Remitter: 30.1 (11.8) Treatment Non-remitter: 30.9 (10.1)] | Escitalopram 10 mg for 5/6 weeks | HDRS HC: 0.4 (.8) MDD: 23.0 (4.5) [Treatment Remitter: 22.8 (4.9) Treatment Non-remitter: 23.3 (4.0)] | fMRI, block design implicit emotional face processing (gender matching) with fearful and happy expressions | DCM | FG, amygdala, dorsal ACC, vlPFC (Wake Forest PickAtlas software); predefined | Connectivity from the dorsal ACC to amygdala was greater in treatment non-remitters compared with healthy controls during fearful face processing. Intrinsic connectivity from the dorsal ACC to amygdala and amygdala to vlPFC was greater in non-remitters compared to controls. Treatment responders and HC did not significantly differ in any connectivity parameters. No behavioral results reported. |
Kibleur et al. [52] | MDD: 5 (80) | MDD: 52 (4.1) | Deep brain stimulation to the subgenual ACC (within participant repeated measures on or off for different conditions in the task) | HDRS-17 MDD: 23.8 (4.1) | EEG, event related emotional Stroop task with neutral, fearful, and happy expressions | DCM | V1 (0, −93, 0), bilateral LOC ( ± 53, −77, 0), FG ( ± 37, −48, −15) PCC (0, −46, 27), temporal poles (±25, 0, −36), dorsal ACC (0, 25, 31) and vlPFC (±50, 24, 0); task-based | Subgenual ACC stimulation reduced connectivity to and from the temporal poles and was associated with a reduction in depressive symptoms. Brain stimulation was associated with a reduction in RT. |
Frässle et al. [39] | Treatment Remitter: 39 (72) Treatment Responder: 31 (65) Treatment Non-responder: 15 (60) | Treatment Remitter: 35.9 (11.5) Treatment Responder: 35.0 (10.0) Treatment Non-responder: 44.0 (10.0) | Non-standardized treatment (naturalistic setting) | Inventory of depressive symptomatology Treatment remitter: 31.44 (10.8) Treatment responder: 32.8 (8.4) Treatment Non-remitter: 33.72 (7.9) | fMRI, event-related emotional implicit emotional face processing (gender matching) with happy, sad, fearful, and angry faces | DCM | Bilateral OFA, FG, amygdala (Neurosyth “face”); predefined | Right amygdala to FG connectivity during happy face processing influences remission the most. This amygdala to FG connectivity was more inhibitory in remitters compared with non-remitters, however, none of the highlighted differences survived the multiple comparisons correction. No behavioral results reported. |
Gilbert et al. [50] | HC: 15 (73.3) MDD: 19 (57.9) | HC: 34.7 (11.8) MDD: 36.7 (10.9) | Ketamine hydrochloride 0.5 mg/kg, single dose and saline placebo | MADRS HC: 1.5 (1.6) MDD: 33.4 (4.7) (from full sample) | MEG, dot-probe task with an emotional (happy or angry) and neutral expression (required to indicate which side dot was presented following the display of the faces) | DCM | Left VI ( − 8, −94, −8), FG (−52, −52, −22), amygdala (−25, −3, −16), vlPFC (−48, 28, −2); task-defined | Treatment with ketamine was associated with increased NMDA transmission in the FG, and slower NMDA transmission in the amygdala. Reduction of depressive symptoms following treatment was associated with AMPA transmission in the early visual cortex. No reaction time differences, however, the MDD group was more accurate than controls. |
Jamieson et al. [41] | HC: 89 (56.5) MDD: 77 (61.4) [Treatment Responders: 37 (62.2) Treatment Non-responders: 40 (67.5)] | HC: 20.1 (2.9) MDD: 19.8 (2.7) [Treatment Responders: 19.6 (2.8) Treatment Non-responders: 20.0 (2.6)] | 12 weeks of CBT and either a placebo or a daily 20-mg capsule of fluoxetine | MADRS HC: 2.1 (2.8) MDD: 32.4 (7.1) [Treatment Responders: 31.95 (5.1) Treatment Non-responders: 33.28 (5.9)] | fMRI, block design implicit emotional face processing (gender matching) with sad and fearful expressions | DCM | HC: Right OFA (28, -92, -8), FG (40, -60, -18), amygdala (20, -6, -16), dlPFC (50, 26, 20), and vmPFC (0, 46, -2); task-defined MDD: Right OFA (24, -94, -4), FG (38, -58, -16), amygdala (22, -6, -12), dlPFC (46, 26, 22), and vmPFC (2, 48, 0); task-defined | Depression-associated with reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. Treatment response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing. No behavioral difference in reaction time or accuracy. |
Sacu et al. [43] | HC: 48 (70.8) MDD-First Degree Relative: 49 (67.3) MDD: 103 (61.1) | HC: 31.3 (9.3) MDD- First Degree Relative: 28.5 (8.1) MDD: 31.9 (9.0) | NA | BDI HC: 1 (3.5) MDD- First Degree Relative: 3 (4.5) MDD: 21 (16.5) | fMRI, block design implicit emotional face processing (identity matching) with angry and fearful expressions | DCM | Bilateral FG (L: -36, -73, -13; R: 39, -55, -16), amygdala (L: -24, -4, -19; R: 27, -4, -19), dorsal ACC (9, 26, 20), dlPFC (L: -51, 29, 23; R: 54, 32 20), vlPFC (L: -36, 32, -16; R: 33, 32, -16) and insular (L: -36, 23 -1; R: 36, 29, -1); task-defined | Depression was associated with greater negative effective connectivity from the left amygdala and left dlPFC to the right FG as well as from the left vlPFC to left FG. No behavioral differences in reaction time or accuracy. |
Willinger et al. [47] | HC: 33 (70) MDD: 30 (67) | HC: 16.2 (1.9) MDD: 16.1 (1.4) | NA | CDI HC: 8.4 (6.6) MDD: 29.6 (9.3) | fMRI, block design implicit emotional face processing (gender matching) with dynamic positive, negative and neutral valenced expressions | DCM | Right FG (41, -52, -24), amygdala (19, -8, -18), vlPFC (53, 32, 0) and subgenual ACC (1, 24, -4); task-defined | Depressed participants illustrated decreased connectivity from the subgenual ACC to vlPFC, subgenual ACC to amygdala as well as increased connectivity from the vlPFC to subgenual ACC. No behavioral differences in reaction time or accuracy. |
Li et al. [53] | HC: 20 (55) MDD: 20 (45) | HC: 37.3 (11.3) MDD: 31.9 (9.4) | NA | PHQ-9 HC: 0.7 (1.2) MDD 17.8 (5.3) | EEG, event related emotional Stroop task with sad and happy expressions (only examined happy expressions for DCM analysis) | DCM | Left V1 (-36, 93, -8), inferior temporal gyrus (-14, -16, -48), FG (-46, -24, -24), hippocampus (-28, -78, 16), amygdala (-24, 0, -22), and dlPFC (-46, 16, 28); predefined and task-defined | In MDD participants, incongruent happy faces modulated connectivity from the FG to amygdala and inferior temporal gyrus as well as from the amygdala to inferior temporal gyrus. Between group comparisons of paramters were not performed. Reaction time was slower for MDD participants for happy incongruent, sad congruent and sad incongruent trials. |
