TABLE 1.
Study design and findings for studies on neural substrates of PSD.
| Study | Imaging biomarker | Timing of behavioral assessment since lesion onset | Behavioral assessment method | Behavioral outcome | Regions or networks implicated | Results involving PFC |
| Traditional ROI analysis | ||||||
| Nickel and Thomalla, 2017 * | Lesion location | Varied* | Varied* | Varied* | Varied* | Yes, frontal lobe reported in 7/17 studies |
| Koenigs et al., 2008 | Lesion location | More than 3 months | BDI-II, DSM-4, and NRS for one dataset; BDI-IA or BDI-II for another dataset | Ordinal (low, intermediate, or high severity) | Bilateral DLPFC | Yes |
| Lesion subtraction analysis | ||||||
| Kim et al., 2017 | Lesion location | Within 3 months | DSM-4 and GDS | Binary PSD diagnosis (DSM-4 met and GDS > 16) | Inferior posterior lobe of the left cerebellar hemisphere | PFC not covered in study design |
| VLSM | ||||||
| Gozzi et al., 2014 | Lesion location | Within 12 days and at 1 month poststroke | DSM-4 and HADS | Binary PSD diagnosis (DSM-4 met and HADS > 11) | Negative | No |
| Kim et al., 2017 | Lesion location | Within 3 months | DSM-4 and GDS | Binary PSD diagnosis (DSM-4 met and GDS > 16) | Posterior lobe of the left cerebellar hemisphere | PFC not covered in study design |
| Padmanabhan et al., 2019 | Lesion location | Varied by five datasets with lesions of different etiologies including stroke; ranges from 28 days to 39 years | Varied by datasets: Neuro-QOL, GDSS, PHQ-9, HADS plus MINI, BDI-II | Binary PSD diagnosis (threshold varied by datasets: Neuro-QOL ≥ 59.9, GDSS ≥ 11, PHQ-9 ≥ 10, HADS ≥ 11 with DSM-4 net, BDI-II ≥ 20) | Negative | No |
| Multivariate LSM | ||||||
| Grajny et al., 2016 | Lesion location | At least 6 months | SADQ | Continuous sum score | Left DLPFC | Yes |
| Weaver et al., 2021b | Lesion location | Within 1 year, ranges from 1 to 361 days | GDS | Continuous sum score | Right amygdala and pallidum | No |
| VBM | ||||||
| Shi et al., 2017 | GMV | Ranges from 3 months to 1 year | DSM-4 and HDRS | Binary diagnosis (DSM-4 met and HDRS > 17) | Bilateral PFC, limbic system and motor cortex | Yes |
| Hong et al., 2020 | GMV | At least 6 months | DSM-4 and HDRS | Binary diagnosis (DSM-4 met and HDRS > 7) | Left middle frontal gyrus | Yes |
| Regional functional activity | ||||||
| Egorova et al., 2017 | fALFF | 3 months | PHQ-9 | Both binary diagnosis (PHQ-9 ≥ 5) and continuous sum score | Left DLPFC and right precentral gyrus; left insula | Yes |
| Goodin et al., 2019 | fALFF | 3 months | MÅDRS | Binary (MÅDRS > 8) | Frontostriatal, temporal, thalamic, and cerebellar regions | Yes |
| Direct connectome analysis | ||||||
| Lassalle-Lagadec et al., 2012 | rsFC | 3 months | HDRS | Continuous sum score | Left middle temporal cortex and precuneus | No |
| Zhang P. et al., 2014 | rsFC | Less than 2 weeks | DSM-4 and HDRS | Both binary diagnosis (HDRS > 7) and continuous sum score | Increased rsFC between the left orbital part of the inferior frontal gyrus and ACC | Yes |
| Shi et al., 2017 | rsFC | Ranges from 3 months to 1 year | DSM-4 and HDRS | Binary PSD diagnosis (DSM-4 met and HDRS > 17) | Decreased rsFC of ACC with PFC, cingulate cortex, and motor cortex, but increased rsFC with the hippocampus, parahippocampal gyrus, insula, and amygdala | Yes |
| Vicentini et al., 2017 | rsFC | Mean: 25 days | DSM-4 and BDI | Continuous BDI score | Left inferior parietal gyrus | No |
| Balaev et al., 2018 | rsFC | 7 ± 4 months | ADRS | Continuous sum score | Anterior DMN, salience network, left frontoparietal network | Yes |
| Egorova et al., 2018 | rsFC | 3 months | PHQ-9 | Both binary diagnosis (PHQ-9 ≥ 5) and continuous sum score | Decreased rsFC between left DLPFC and right supramarginal gyrus | Yes |
| Sun et al., 2018 | rsFC | Mean: 3.6 months | HDRS | Ordinal (3 levels of severity: ≤5, 6–20, and >20) | Decreased rsFC between the parietal-occipital and the frontal areas | Yes |
| Zhang et al., 2018 | rsFC | Mean: 10 days | DSM-4 and HDRS | Both binary diagnosis (HDRS > 7 with DSM-4 met) and continuous sum score | DMN, CCN, AN; left inferior parietal gyrus, the left orbital part of inferior frontal gyrus, and left angular gyrus | Yes |
| Zhang et al., 2019 | rsFC | Less than 6 months | DSM-4 and HDRS | Both binary diagnosis (HDRS ≥ 17 with DSM-4 met) and continuous sum score | Altered rsFC of amygdala with the fronto-limbic-striatal circuit | Yes |
| Shi et al., 2019 | Functional circuit | Ranges from 3 months to 1 year | DSM-4 and HDRS | Binary diagnosis (HDRS ≥ 17 with DSM-4 met) | Ventromedial PFC-ACC-amygdala-thalamus circuit | Yes |
| Liang et al., 2020 | rsFC | 3 months | GDS | Binary diagnosis (GDS ≥ 7) | DMN (inferior parietal lobule and dorsal prefrontal cortex) | Yes |
| Yang et al., 2015 | FA; Structural network topology | Within 1 month | DSM-4 and HDRS | Ordinal: major, mild and non-PSD (HDRS ≥ 20, 10–19, <10, respectively) | Wide (including frontal) areas of white matter; a depression-related subnetwork composed of 17 brain regions (including frontal cortex) | Yes |
| Shen et al., 2019 | FA, mean kurtosis | 2 weeks | DSM-5 and HDRS | Binary PSD diagnosis based on DSM-5 | Bilateral frontal and temporal lobes, genu of corpus callosum | Yes |
| Xu et al., 2019 | Structural network topology | Within 2 weeks | DSM-4 and HDRS | Binary PSD diagnosis based on DSM-4 and HDRS ≥ 7 | Disrupted global and local network topologies (involving ipsilesional superior frontal gyrus and middle frontal gyrus, etc.) | Yes |
| Oestreich et al., 2020 | FA, structural network topology | 27–82 days | GDS | Binary diagnosis (GDS ≥ 10) | Reward system (including PFC) | Yes |
| Indirect connectome analysis | ||||||
| Padmanabhan et al., 2019 | FDC | Varied by five datasets with lesions of different etiologies including stroke; ranges from 28 days to 39 years | Varied by datasets: Neuro-QOL, GDSS, PHQ-9, HADS plus MINI, BDI-II | Binary PSD diagnosis (threshold varied by datasets: Neuro-QOL ≥ 59.9, GDSS ≥ 11, PHQ-9 ≥ 10, HADS ≥ 11 with DSM-4 met, BDI-II ≥ 20) | A depression circuit centered on left DLPFC and spanning multiple regions (bilateral prefrontal, temporal and parietal) | Yes |
| Weaver et al., 2021b | SDC | Within 1 year, ranges from 1 to 361 days | GDS | Continuous sum score | Right parahippocampal white matter, right thalamus and pallidum, and right anterior thalamic radiation | Yes (anterior thalamic radiation originates from PFC) |
ACC, anterior cingulate cortex; ADRS, aphasic depression rating scale; AN, affective network; BDI, Beck Depression Inventory; CCN, cognitive control network; DLPFC, dorsolateral prefrontal cortex; DMN, default mode network; DSM, Diagnostic Statistical Manual of Mental Disorders; fALFF, fractional amplitude of low frequency fluctuations; FA, fractional anisotropy; FDC, functional disconnection; GDS, Geriatric Depression Scale; GDSS, Geriatric Depression Score Short Form; GMV, gray matter volume; HADS, Hospital Anxiety and Depression Scale; HDRS, Hamilton Depression Rating Scale; LSM, lesion-symptom mapping; MÅDRS, Montgomery-Åsberg Depression Rating Scale; MINI, Mini-International Neuropsychiatric Interview; Neuro-QOL, Neuro-QOL Depression Scale; NRS, Neurobehavioral Rating Scale; PFC, prefrontal cortex; PHQ-9, Patient Health Questionnaire; PSD, poststroke depression; ROI, region of interest; rsFC, resting-state functional connectivity; SADQ; Stroke Aphasic Depression Questionnaire; SDC, structural disconnection; VBM, voxel-based morphometry; VLSM, voxel-based lesion-symptom mapping. *The 17 traditional ROI studies reviewed by Nickel and Thomalla (2017) are not expanded in our table.