Anterior temporal lobe connectivity correlates with functional outcome after aphasic stroke

Abstract

Focal brain lesions are assumed to produce language deficits by two basic mechanisms: local cortical dysfunction at the lesion site, and remote cortical dysfunction due to disruption of the transfer and integration of information between connected brain regions. However, functional imaging studies investigating language outcome after aphasic stroke have tended to focus only on the role of local cortical function. In this positron emission tomography functional imaging study, we explored relationships between language comprehension performance after aphasic stroke and the functional connectivity of a key speech-processing region in left anterolateral superior temporal cortex. We compared the organization of left anterolateral superior temporal cortex functional connections during narrative speech comprehension in normal subjects with left anterolateral superior temporal cortex connectivity in a group of chronic aphasic stroke patients. We then evaluated the language deficits associated with altered left anterolateral superior temporal cortex connectivity in aphasic stroke. During normal narrative speech comprehension, left anterolateral superior temporal cortex displayed positive functional connections with left anterior basal temporal cortex, left inferior frontal gyrus and homotopic cortex in right anterolateral superior temporal cortex. As a group, aphasic patients demonstrated a selective disruption of the normal functional connection between left and right anterolateral superior temporal cortices. We observed that deficits in auditory single word and sentence comprehension correlated both with the degree of disruption of left-right anterolateral superior temporal cortical connectivity and with local activation in the anterolateral superior temporal cortex. Subgroup analysis revealed that aphasic patients with preserved positive intertemporal connectivity displayed better receptive language function; these patients also showed greater than normal left inferior frontal gyrus activity, suggesting a possible 'top-down' compensatory mechanism. These results demonstrate that functional connectivity between anterolateral superior temporal cortex and right anterior superior temporal cortex is a marker of receptive language outcome after aphasic stroke, and illustrate that language system organization after focal brain lesions may be marked by complex signatures of altered local and pathway-level function.

Figure 1

Functional imaging data in the normal and aphasic groups. (A) Activation related to speech comprehension in the normal (green) and aphasic (red) groups, determined by the contrast of narrative and control conditions. Statistical parametric maps are displayed using a voxel-level statistical threshold of P < 0.05, corrected for false discovery rate (FDR), with a cluster extent threshold equivalent to 5% of the total number of suprathreshold voxels (see Experimental Methods). SPMs have been rendered onto a template brain in standard MNI stereotactic space, with intensity scales representing T values. Ant = anterior. (B) Left anterolateral superior temporal functional connectivity in the normal (green-blue) and aphasic (red-yellow) groups. Statistical thresholding and display procedures are the same as in panel A. (C) Location of anatomical regions used in the region of interest analyses (upper row), displayed for comparison with the distribution and overlap of stroke lesions in the aphasic group (lower row). To assess lesion overlap, hand-drawn images of stroke lesions were normalized into standard MNI stereotactic space; regions of interest and lesion images are displayed on coronal slices of a canonical averaged T₁-weighted MNI-space brain image available in SPM99. The intensity scale refers to the number of patients with lesions at a particular voxel.

Figure 2

Region of interest analyses in the normal and aphasic groups. (A) Mean connection strength (normalized correlation coefficient, r′) (left) and mean speech-related activity (effect size) (right) in the normal and aphasic groups. Units of measurement for effect size are arbitrary. Error bars represent standard error of the mean. In the aphasic group, data relating to the LIFG region of interest are based on the 12 subjects with lesions sparing this region; data relating to all other regions are based on the entire group of 16 subjects. Significant between-group differences and non-significant trends are indicated: *P < 0.005; ^#P < 0.1 (see text for exact P-values). (B) Statistically significant correlations between physiological markers and behavioural measures of speech comprehension in the aphasic group. Dashed lines represent lines of best fit.

Figure 3

Cluster analysis in the aphasic group. The cluster dendrogram demonstrates separation of the aphasic group into two subgroups on the basis of LalSTC–RalSTC functional connection strength.

Figure 4

Region of interest-based functional connectivity and speech-related activity in the aphasic subgroups. Mean connection strength (normalized correlation coefficient, r′) (top) and mean speech-related activity (effect size) (bottom) in the Connec(+), Connec(−) and normal groups. In the aphasic subgroups, data relating to the LIFG regions of interest are based on the five Connec(+) subjects and seven Connec(−) subjects with lesions sparing this region; data relating to all other regions are based on the full number of eight subjects in each subgroup. Normal data are identical to that in Fig. 2A. Units of measurement for effect size are arbitrary. Error bars represent standard error of the mean. Significant between-group differences are indicated: ***P < 0.0005; **P < 0.01, *P < 0.05 (see text for exact P-values).

Figure 5

Lesion distribution in the aphasic subgroups. (A) T₁-weighted structural images from aphasic patients in the Connec(+) and Connec(−) groups are displayed in the coronal plane at the level of the anterior commissure in order to demonstrate the structural integrity of interhemispheric white matter projections from anterolateral STC via the anterior commissure. Structural images have been normalized into MNI stereotactic brain space to facilitate identification of the anterior commissure, which is located at the image origin in MNI space. Images outlined in grey show lesion involvement of the temporal stem at the level of the anterior commissure, and therefore probable disruption of white matter tracts projecting from anterolateral STC to right hemispheric homotopic cortex. (B) Lesion overlap in the Connec(+) and Connec(−) patient subgroups, displayed as normalized lesion images in the same manner as in Fig. 1C. Ant = anterior.