Article Figures & Data
Figures
- Figure 1.
Image processing steps. A, All participants underwent a structural brain MRI scan at baseline. B, Stroke lesions were manually drawn on each participant's T2-weighted image. C, Lesion maps were coregistered to the participant's diffusion-weighted image. D, Each participant's T1-weighted image was segmented into 104 gray matter ROIs with the JHU anatomic atlas; the segmentation maps were registered into diffusion space. E, Probabilistic tractography was computed between every possible gray matter region pair resulting in a 104 × 104 weighted, undirected adjacency matrix where structural connectivity was represented by the (corrected) number of probabilistic streamlines between regions (color bar represent log values for better visualization). F, Visualization of streamlines in brain space (for visualization purposes, this figure is based on deterministic instead of probabilistic tractography).
- Figure 2.
Lesion and regional characteristics. A, Lesion overlay of all participants included in the final analyses (n = 68). Different numbers of participants with a lesion in an area are represented by different colors. The more participants shared a lesion in an area, the warmer the color. As expected, most participants had lesions around the sylvian fissure. B, Zero-degree nodes (brain areas disconnected from the remaining network) across all participants. The more participants shared a zero-degree node in that area, the warmer the color. C, D, Regional controllability of the 20 left hemisphere language-related ROIs included in this study. The controllability values were ranked across all 104 gray matter regions. The visualizations in this figure show the average (median) ranks across all participants. The warmer the color, the higher the value of average (C) or modal (D) controllability. Note that average and modal controllability are in general inversely related: nodes with higher average controllability tend to have lower modal controllability, and vice versa.
- Figure 3.
Scatter plots of regional controllability measures versus local graph theory measures and regional lesion volume for all 20 language-related regions. The median was obtained for all variables (for each region across all 68 participants). Regional controllability measures (average and modal controllability) and local graph theory measures (node degree, node betweenness centrality) were ranked across all 104 gray matter regions, but only the 20 language-related regions are displayed here. Note that average and modal controllability did not correlate with node degree or betweenness centrality (|Spearman's ρ|< 0.20, p > 0.05), but did correlate weakly with regional lesion volume (|Spearman's ρ|> 0.4, p < 0.05). corr = Spearman's ρ.
- Figure 4.
Explanatory multivariable regression modeling. Scatter plots for the partial regression of (A) average controllability of the IFG pars opercularis, (B) modal controllability of the IFG pars orbitalis, and (C) modal controllability of the anterior insula in explaining PMG naming scores from baseline (BL) to six-month follow-up (FU) after therapy. D, Anatomical locations of the IFG pars opercularis (blue), IFG pars orbitalis (green), and anterior insula (red).
- Figure 5.
Scatter plot of total brain lesion volume versus number of zero-degree nodes. Zero-degree nodes were calculated across all 104 gray matter anatomic regions. The number of zero-degree nodes was overall related to the total brain lesion volume (Pearson correlation coefficient = 0.59; p < 0.001). corr = Pearson correlation coefficient.
- Figure 6.
The impact of the stroke lesion on global and regional connectome measures. This composite figure provides a comprehensive visual summary of how a stroke lesion affects the structural connectome and its properties. For comparison, the average connectome data from 60 healthy individuals with the same demographic and risk factor profile (described previously; Marebwa et al., 2018) is shown in the upper panel (above the horizontal gray lone). Data from one participant with aphasia (lesion volume: 266 ml) in the lower panel. A, E, Reconstructed white matter fibers, here for visualization purposes based on deterministic tractography. B, F, Edges between gray matter regions from the JHU anatomic atlas. C, G, Adjacency matrices representing probabilistic streamlines between each region pair (color bar represent log values for better visualization). D, H, All structural connectome measures used in the analyses of this study: average controllability, modal controllability, regional lesion volume, node strength, and betweenness centrality, each one within a “track” of the figure, as indicated by the inset. Each box represents one gray matter region (for full region names, see Table 1). For visualization purposes, 98 of the included 104 gray matter regions are displayed here.
Tables
- Table 1.
List of gray matter regions selected from the Johns Hopkins University (JHU) anatomic atlas
Left hemisphere Region from JHU anatomic atlas Right hemisphere Region group Region label Region label Region group Left frontal SFG_L Superior frontal gyrus (posterior segment) SFG_R Right frontal SFG_PFC_L Superior frontal gyrus (prefrontal cortex) SFG_PFC_R SFG_pole_L Superior frontal gyrus (frontal pole) SFG_pole_R MFG_L* Middle frontal gyrus (posterior segment) MFG_R MFG_DPFC_L Middle frontal gyrus (dorsal prefrontal cortex) MFG_DPFC_R IFG_opercularis_L* Inferior frontal gyrus pars opercularis IFG_opercularis_R IFG_orbitralis_L* Inferior frontal gyrus pars orbitralis IFG_orbitralis_R IFG_triangularis_L* Inferior frontal gyrus pars triangularis IFG_triangularis_R LFOG_L Lateral fronto-orbital gyrus LFOG_R MFOG_L Middle fronto-orbital gyrus MFOG_R RG_L Rectus gyrus RG_R PrCG_L* Precentral gyrus PrCG_R rostral_ACC_L Rostral anterior cingulate gyrus rostral_ACC_R subcallosal_ACC_L Subcallosal anterior cingulate gyrus subcallosal_ACC_R subgenual_ACC_L Subgenual anterior cingulate gyrus subgenual_ACC_R dorsal_ACC_L Dorsal anterior cingulate gyrus dorsal_ACC_R Left insula Ins_L* Anterior insula Ins_R Right insula PIns_L* Posterior insula PIns_R Left temporal STG_L* Superior temporal gyrus STG_R Right temporal STG_L_pole* Pole of superior temporal gyrus STG_R_pole MTG_L* Middle temporal gyrus MTG_R MTG_L_pole* Pole of middle temporal gyrus MTG_R_pole ITG_L* Inferior temporal gyrus ITG_R PHG_L Parahippocampal gyrus PHG_R ENT_L Entorhinal area ENT_R FuG_L Fusiform gyrus FuG_R Amyg_L Amygdala Amyg_R Hippo_L Hippocampus Hippo_R PSTG_L* Posterior superior temporal gyrus PSTG_R PSMG_L* Posterior middle temporal gyrus PSMG_R PSIG_L Posterior inferior temporal gyrus PSIG_R Left subcortical Caud_L Caudate nucleus Caud_R Right subcortical Put_L* Putamen Put_R GP_L* Globus pallidus GP_R Thal_L Thalamus Thal_R Hypothalamus_L Hypothalamus Hypothalamus_R Mynert_L Nucleus innominata of mynert Mynert_R NucAccumbens_L Nucleus accumbens NucAccumbens_R Left Parietal PoCG_L* Postcentral gyrus PoCG_R Right parietal SPG_L Superior parietal gyrus SPG_R SMG_L* Supramarginal gyrus SMG_R AG_L* Angular gyrus AG_R PrCu_L Precuneus PrCu_R PCC_L Posterior cingulate gyrus PCC_R Left occipital SOG_L Superior occipital gyrus SOG_R Right occipital MOG_L* Middle occipital gyrus MOG_R IOG_L Inferior occipital gyrus IOG_R Cu_L Cuneus Cu_R LG_L Lingual gyrus LG_R Regions on the left side of the circular diagrams of Figure 6 correspond in counterclockwise order to regions listed from top to bottom in this table. Likewise, regions on the right side of the circular diagrams correspond in clockwise order to regions listed from top to bottom in this table. Because of visualization purposes substantia nigra, red nucleus and mammillary body are not displayed in the circular diagrams or listed in this table. JHU = Johns Hopkins University.
↵* denote regions that were included in the set of 20 language-related left hemisphere gray matter regions.
- Table 2.
Demographic and diagnostic information of all participants included in the final analyses (n = 68)
Demographic information Age, mean (SD; range) 59.7 (10.2; 30–77) Sex, n (%) Female 20 (29.4) Male 48 (70.6) Race, n (%) White 56 (82.3) African American 10 (14.7) Asian 2 (3.0) Education (highest year of school completed); years, mean (SD; range) 14.8 (2.4; 10–20) Diagnostic information Years since stroke, mean (SD; range) 3.4 (3.3; 0.5–16.9) WAB-AQ (max. 100), mean (SD; range) 59.0 (19.5; 27.8–93.7) Average correct responses in the 2 PNTs at baseline (max. 175), mean (SD; range) 60.8 (43.4; 0.5–139) Average change in correct responses in the 2 PNTs from baseline to 6 months after therapy (max. 175), mean (SD; range) 6.6 (14.6; −32–52.5) n = number; PNT = Philadelphia Naming Test (Roach et al., 1996); WAB-AQ = Aphasia Quotient of the Western Aphasia Battery (Revised; Kertesz, 2007).
- Table 3.
Multiple linear regression model to assess the influence of average controllability on the outcome PMG naming scores from baseline to 24 weeks (six months) after therapy with an overall model fit of R2 = 0.31
Variable β SE β β p Intercept 0.053 0.310 0.864 Average controllability Pars opercularis 0.004 0.002 0.391 0.038* Precentral gyrus <−0.001 0.002 −0.002 0.992 Supramarginal gyrus −0.001 0.002 −0.131 0.609 Angular gyrus <0.001 0.002 0.060 0.817 Pole of superior temporal gyrus <0.001 0.003 −0.043 0.855 Pole of middle temporal gyrus 0.001 0.003 0.060 0.831 Middle occipital gyrus 0.002 0.002 0.175 0.445 Anterior insula −0.001 0.003 −0.055 0.779 Putamen −0.003 0.002 −0.249 0.239 Posterior insula 0.003 0.002 0.282 0.232 Posterior superior temporal gyrus −0.002 0.002 −0.280 0.251 Posterior middle temporal gyrus −0.001 0.002 −0.280 0.715 WAB-AQ baseline 0.002 0.002 0.223 0.191 Age −0.005 0.003 −0.274 0.128 Education 0.007 0.011 0.095 0.519 Therapy type (A-tDCS vs S-tDCS) 0.061 0.052 0.171 0.246 Total lesion volume <−0.001 0 −0.113 0.636 Number of edges <0.001 0 0.168 0.388 β = standardized regression coefficient;
↵*significant at the α level p < 0.05.
- Table 4.
Multiple linear regression model to assess the influence of modal controllability on the outcome PMG naming scores from baseline to 24 weeks (six months) with an overall model fit of R2 = 0.44
Variable β SE β β p Intercept 0.181 0.379 0.636 Modal controllability Middle frontal gyrus −0.001 0.001 −0.099 0.560 Pars opercularis 0.001 0.001 0.160 0.415 Pars orbitalis −0.002 0.001 −0.343 0.033* Pars triangularis −0.001 0.001 −0.194 0.296 Postcentral gyrus −0.003 0.002 −0.358 0.143 Supramarginal gyrus −0.001 0.001 −0.165 0.380 Angular gyrus 0.001 0.001 0.221 0.225 Superior temporal gyrus 0.002 0.002 0.222 0.310 Pole of superior temporal gyrus <0.001 0.001 −0.023 0.889 Middle temporal gyrus <0.001 0.001 −0.062 0.756 Pole of middle temporal gyrus <0.001 0.001 −0.061 0.706 Inferior temporal gyrus <0.001 0.001 −0.064 0.763 Middle occipital gyrus −0.002 0.002 −0.257 0.156 Anterior insula 0.002 0.002 0.359 0.036* Globus pallidus <0.001 0.002 0.013 0.934 Posterior insula <0.001 0.001 −0.034 0.832 Posterior superior temporal gyrus −0.001 0.001 −0.104 0.529 Posterior middle temporal gyrus <0.001 0.001 0.050 0.811 WAB-AQ baseline 0.003 0.002 0.377 0.047* Age −0.005 0.003 −0.276 0.116 Education 0.016 0.010 0.216 0.139 Therapy type (A-tDCS vs S-tDCS) 0.045 0.052 0.126 0.392 Total lesion volume <0.001 <0.001 0.093 0.719 Number of edges <−0.001 <0.001 −0.122 0.528 β = standardized regression coefficient;
↵*significant at the α level p < 0.05.
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