GABAergic inhibition in human hMT+ predicts visuo-spatial intelligence mediated through the frontal cortex
- Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, China
- Department of Psychology and Behavioral Sciences, Zhejiang University, China
- Key Laboratory of Biomedical Engineering of Ministry of Education, Qiushi Academy for Advanced Studies, College of Biomedical Engineering and Instrument Science, Zhejiang University, China
- College of Intelligence Science and Technology, National University of Defense Technology, China
- University of Ottawa Institute of Mental Health Research, University of Ottawa, Canada
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), China
- MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, China
Figures
Figure 1
Hypothesis and experimental design.
(a) Schematic of hypothesis. The inhibition mechanism centered on MT+ GABA, including the molecular level: the GABAergic inhibition in MT+ (cyan circle), brain connectivity level: hMT+-frontal …
Figure 2 with 1 supplement
hMT+ localizer scans and hMT+ magnetic resonance spectroscopy (MRS) volume-of-interest (VOI) placement.
(a) Single task block designs. First: a cross fixation on the center of the screen (10 s). Second: a moving grating (2°) toward left last 10 s. Third: the grating keeps static for 10 s. Fourth: the …
Figure 2—figure supplement 1
The left hemisphere early visual cortex (EVC) (primarily in V1) magnetic resonance spectroscopy (MRS) scanning ROI.
The color bar indicates the overlap of the MRS volume-of-interests (VOIs) across all subjects.
Figure 3 with 4 supplements
Magnetic resonance spectroscopy (MRS) spectra and the relationships between GABA levels and suppression index (SI)/block design test (BDT).
(a) Example spectrum from the hMT+ voxel of one participant. The first line is the LCModel fitting result of all metabolites, and the following lines show the Glu and GABA spectra fitting with …
Figure 3—figure supplement 1
Relationships between GABA concentration in early visual cortex (EVC)1 (primarily in V1) and block design test (BDT)/suppression index (SI).
(a) There is no significant relationship between BDT and GABA concentrations in EVC (primarily in V1) region. (b) There is also no obvious correlation between SI and GABA concentrations in EVC …
Figure 3—figure supplement 2
Individual Glu magnetic resonance spectroscopy (MRS) spectra from hMT+/early visual cortex (EVC) (primarily in V1) regions and relationships between block design task (BDT) and Glu concentrations in hMT+/EVC (primarily in V1) regions.
(a) Individual participant fitted Glu MRS spectra from the hMT+ (top, n = 31) and EVC (primarily in V1) (bottom, n = 28) voxels from baseline measurement. The colors of the Glu spectra represent the …
Figure 3—figure supplement 3
Correlations between GABA and Glu concentrations in hMT+ and early visual cortex (EVC) (primarily in V1) regions.
(a) There is significant correlation between GABA and Glu concentrations in hMT+ region. (b) The levels of GABA also significantly correlate with Glu in EVC (primarily in V1) region. GABA and Glu …
Figure 3—figure supplement 4
Two linear correlations show without outlines results.
(a) Significant positive correlation between suppression index and block design test (BDT) scores (took out two outlines). (b) Suppression index also significantly correlates with GABA concentration …
Figure 4 with 2 supplements
Significant functional connectivities (FCs) from connectivity-behavior analyses in a priori search space.
The seed region is the left hMT+. The significant FCs are obtained from a priori space (frontal cortex). (a) The significant FCs obtained from connectivity-BDT analysis. Single voxel threshold p<0.00…
Figure 4—figure supplement 1
Significant functional connectivities (FCs) searched from connectivity-behavior (block design test [BDT]/surround suppression [SI]) analyses in the whole brain.
The seed region is the left hMT+. The significant FCs are obtained from the entire brain search, single voxel threshold p<0.01, adjacent size ≥37 voxels (AlphaSim correcting, Materials and methods). …
Figure 4—figure supplement 2
Significant functional connectivities (FCs) searched from connectivity-behavior (block design test [BDT]) analyses in the frontal and whole brain.
The seed region is the left V1. (a) The significant FCs are obtained from the frontal search, single voxel threshold p<0.005, adjacent size ≥23 (AlphaSim correcting, same methods for hMT+). (b) The …
Figure 5 with 1 supplement
Local hMT+ GABA acts on suppression index (SI) and block design test (BDT) via global hMT-frontal connectivity.
(a) Significant negative correlation between the functional connectivity (FC) of left hMT+-right DLPFC (BA46) and hMT+ GABA (false discovery rate [FDR] correction). (b) Significant positive …
Figure 5—figure supplement 1
The alternative serial mediation models from local hMT+ GABA to global performance of block design test (BDT).
The pathway that hMT+ GABA was predicted to be associated with suppression index (SI), followed by the functional connectivity (FC) of hMT+-BA46, and then BDT, did not yield the chained mediation …
Figure 6 with 1 supplement
Sketch depicting the multi-level inhibitory mechanisms centered on hMT+ GABA contributing to visuo-spatial intelligence.
Inhibitory GABA in hMT+ (a sensory cortex, shown in green circle), coupling with the functional connectivity between hMT+ and BA46 (cognitive control core, shown in purple circle), and mediated by …
Figure 6—figure supplement 1
Correlation matrix shows correlations between all measured in our biochemistry and behavior level.
*: p<0.05, **: p<0.01, ***: p<0.001.
Tables
Table 1
Functional connectivity (FC) of voxels showing significant correlation with block design test (BDT) scores across subjects in frontal cortex.
| FC number | Connected regions | BA | Size | Peak coordinate | r | p |
|---|---|---|---|---|---|---|
| MNI (x, y, z) | ||||||
| 1 | Frontal_Sup_Orb_R | 11 | 33 | (12,63,–19.5) | –0.57 | 0.0011 |
| 2 | Frontal_Inf_Orb_L | 47 | 24 | (−34.5,28.5,–13.5) | –0.63 | 0.0003 |
| 3 | Frontal_Med_Orb_R | 11 | 41 | (3,43.5,–12) | –0.58 | 0.0009 |
| 4 | Frontal_Inf_Orb_R | 47 | 48 | (−31.5,24,–12) | 0.59 | 0.0008 |
| 5 | Frontal_Inf_Orb_R | 47 | 29 | (25.5,30,–13.5) | 0.67 | 0.0001 |
| 6 | Insula_L | \ | 26 | (–28.5,27,0) | 0.67 | 0.0001 |
| 7 | Frontal_Inf_Oper_R | 45 | 41 | (43.5,16.5,6) | 0.64 | 0.0002 |
| 8 | Frontal_Sup_R | 10 | 25 | (31.5,57,9) | 0.59 | 0.0008 |
| 9 | Frontal_Mid_L | 10 | 82 | (–33,48,12) | 0.62 | 0.0003 |
| 10 | Frontal_Inf_Oper_R | 44 | 49 | (51,7.5,21) | 0.59 | 0.0007 |
| 11 | Frontal_Inf_Oper_R | 46 | 96 | (49.5,16.5,28.5) | –0.62 | 0.0003 |
| 12 | Frontal_Mid_L | 10 | 32 | (–31.5,49.5,24) | 0.57 | 0.0012 |
| 13 | Frontal_Mid_R | 10 | 102 | (31.5,36,30) | 0.59 | 0.0009 |
| 14 | Precentral_L | 6 | 46 | (−49.5,–1.5,34.5) | 0.59 | 0.0007 |
| 15 | Frontal_Mid_R | 9 | 107 | (51,19.5,40.5) | –0.67 | 0.0001 |
| 16 | Frontal_Sup_L | 9 | 35 | (–9,60,37.5) | –0.69 | 0.0001 |
| 17 | Frontal_Sup_Medial_R | 9 | 74 | (4.5,52.5,43.5) | –0.57 | 0.0011 |
| 18 | Frontal_Sup_R | 6 | 136 | (28.5,–7.5,63) | –0.64 | 0.0002 |
| 19 | Supp_Motor_Area_L | 6 | 48 | (–10.5,6,54) | 0.63 | 0.0003 |
| 20 | Frontal_Mid_L | 6 | 119 | (–24,4.5,55.5) | 0.63 | 0.0003 |
| 21 | Precentral_L | 6 | 229 | (−24,–18,66) | 0.60 | 0.0005 |
| 22 | Frontal_Sup_R | 6 | 32 | (16.5,–18,67.5) | 0.68 | 0.0001 |
| 23 | Precentral_R | 6 | 80 | (30,–24,70.5) | 0.70 | 0.0001 |
| 24 | Precentral_R | 6 | 23 | (16.5,–25.5,76.5) | 0.70 | 0.0001 |
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Single voxel threshold p<0.005 (t>3.057 or t<–3.057), adjacent size ≥23 voxels (AlphaSim corrected).
Table 2
Correlations between functional connectivity (FC) in Table 1 and GABA/Glu concentrations in hMT+.
| FC number | hMT+ GABA concentrations | hMT+ Glu concentrations | ||||
|---|---|---|---|---|---|---|
| r | p | FDR | r | p | FDR | |
| 1 | –0.07 | 0.72 | 0.75 | –0.11 | 0.58 | 0.85 |
| 2 | –0.28 | 0.14 | 0.36 | –0.27 | 0.15 | 0.81 |
| 3 | –0.13 | 0.52 | 0.59 | –0.07 | 0.71 | 0.85 |
| 4 | 0.10 | 0.59 | 0.64 | 0.12 | 0.54 | 0.85 |
| 5 | 0.14 | 0.48 | 0.58 | 0.24 | 0.21 | 0.81 |
| 6 | 0.31 | 0.11 | 0.33 | 0.15 | 0.43 | 0.85 |
| 7 | 0.20 | 0.30 | 0.48 | 0.07 | 0.74 | 0.85 |
| 8 | 0.14 | 0.45 | 0.58 | 0.05 | 0.79 | 0.85 |
| 9 | 0.20 | 0.30 | 0.48 | 0.10 | 0.60 | 0.85 |
| 10 | –0.13 | 0.49 | 0.58 | –0.16 | 0.41 | 0.85 |
| 11 | –0.56 | 0.0018 | 0.02* | –0.22 | 0.25 | 0.81 |
| 12 | 0.18 | 0.34 | 0.51 | 0.15 | 0.43 | 0.85 |
| 13 | 0.20 | 0.30 | 0.48 | 0.05 | 0.81 | 0.85 |
| 14 | 0.39 | 0.04 | 0.14 | 0.22 | 0.24 | 0.81 |
| 15 | –0.40 | 0.03 | 0.12 | –0.21 | 0.27 | 0.81 |
| 16 | –0.27 | 0.15 | 0.36 | –0.12 | 0.53 | 0.85 |
| 17 | 0.17 | 0.37 | 0.52 | 0.06 | 0.74 | 0.85 |
| 18 | 0.26 | 0.18 | 0.39 | 0.16 | 0.40 | 0.85 |
| 19 | 0.39 | 0.03 | 0.12 | 0.31 | 0.10 | 0.81 |
| 20 | 0.01 | 0.98 | 0.98 | 0.14 | 0.46 | 0.85 |
| 21 | 0.40 | 0.03 | 0.12 | 0.24 | 0.21 | 0.81 |
| 22 | 0.22 | 0.25 | 0.48 | 0.06 | 0.76 | 0.85 |
| 23 | 0.69 | 0.0001 | 0.002** | 0.47 | 0.01 | 0.24 |
| 24 | 0.41 | 0.03 | 0.12 | 0.001 | 0.97 | 0.97 |
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*: pFDR < 0.05; **: pFDR < 0.01; ***: pFDR < 0.001; Bold font indicates the significant correlations survived from multi-correlation correction.
Additional files
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Supplementary file 1
Functional connectivity (FC) of voxels showing significant correlation with block design test (BDT) scores across subjects in whole brain.
- https://cdn.elifesciences.org/articles/97545/elife-97545-supp1-v1.docx
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Supplementary file 2
Functional connectivities (FCs) of voxels showing significant correlation with suppression index (SI) across subjects in frontal cortex.
- https://cdn.elifesciences.org/articles/97545/elife-97545-supp2-v1.docx
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Supplementary file 3
Functional connectivities (FCs) of voxels showing significant correlation with suppression index (SI) across subjects in whole brain.
- https://cdn.elifesciences.org/articles/97545/elife-97545-supp3-v1.docx
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Supplementary file 4
Correlations between functional connectivity (FC) in Supplementary file 1 and GABA/Glu concentrations in hMT+.
- https://cdn.elifesciences.org/articles/97545/elife-97545-supp4-v1.docx
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Supplementary file 5
Correlations between functional connectivities (FCs) in Supplementary file 2 and GABA/Glu concentrations in hMT+.
- https://cdn.elifesciences.org/articles/97545/elife-97545-supp5-v1.docx
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Supplementary file 6
Correlations between functional connectivities (FCs) in Supplementary file 3 and GABA/Glu concentrations in hMT+.
- https://cdn.elifesciences.org/articles/97545/elife-97545-supp6-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/97545/elife-97545-mdarchecklist1-v1.docx
