Regional changes in word-production laterality after a naming treatment designed to produce a rightward shift in frontal activity

Abstract

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying assumption regarding re-lateralization, patients participated in fMRI of category-member generation before and after treatment. Generally, the four patients who improved during treatment showed reduced frontal activity from pre- to post-treatment fMRI with increasing concentration of activity in the right posterior frontal lobe (motor/premotor cortex, pars opercularis), demonstrating a significant shift in lateraliity toward the right lateral frontal lobe, as predicted. Three of these four patients showed no left frontal activity by completion of treatment, indicating that right posterior lateral frontal activity supported category-member generation. Patients who improved in treatment showed no difference in lateralization of lateral frontal activity from normal controls pre-treatment, but post-treatment, their lateral frontal activity during category-member generation was significantly more right lateralized than that of controls. Patterns of activity pre- and post-treatment suggested increasing efficiency of cortical processing as a result of treatment in the four patients who improved. The one patient who did not improve during treatment showed a leftward shift in lateral frontal lateralization that was significantly different from the four patients who did improve. Neither medial frontal nor posterior perisylvian re-lateralization from immediately pre- to immediately post-treatment images was a necessary condition for significant treatment gains or shift in lateral frontal lateralization. Of the three patients who improved and in whom posterior perisylvian activity could be measured at post-treatment fMRI, all maintained equal or greater amounts of left-hemisphere perisylvian activity as compared to right. This finding is consistent with reviews suggesting both hemispheres are involved in recovery of language in aphasia patients.

Figures

Figure 1

Axial slices and left-hemisphere sagittal cuts from T1-weighted MRI images, after deformation to the Talairach atlas. For each subject, the top row of images (a) contains eight 1mm-thick axial slices with a separation of 8mm from center to center. Images proceed from inferior on the left side to superior on the right side. Axial coordinates vary from patient to patient to best illustrate their lesion. The bottom row of images for each subject (b) shows a lateral view of the left hemisphere from a whole brain image (left-most image), with each successive image from left to right incrementally cutting away 5 mm in the sagittal plane. The purpose of the images is to demonstrate damage to left perisylvian regions, including cortex within sulci and underlying white matter. 02-030’s lesion, at 8 months post-stroke, occupies the inferior two thirds of the left sensory-motor region, extending forward inferiorly to encompass pars opercularis and especially its underlying white matter and undercutting white matter for premotor cortex above the inferior frontal gyrus and in the posterior half of the middle frontal gyrus. Medially, the lesion damaged most of the insula, but left the basal ganglia and thalamus are virtually untouched. 03-031’s lesion, at 83 months post-stroke, is primarily subcortical. It centers on the insula, extending laterally to encompass white matter underlying the operculum and extending medially to border of the lateral ventricle (sparing most of the medial subcallosal fasciculus deep to Broca’s area, but including periventricular white matter deep to sensorimotor cortex area for mouth, at body of the lateral ventricle). Most of the basal ganglia are subsumed by the lesion, but most of the head of the caudate nucleus and the posterior and the superior thalamus are largely intact. White matter underlying the entire frontal lobe and the inferior parietal lobule (deep to the angular and supramarginal gyri), and the superior temporal lobe are compromised. There is also some high, fronto-parietal supraventricular white matter damage. There is small degree of white matter compromise in portions of the superior temporal lobe. 00-008 (48 months post-stroke) has a large subcortical lesion with some cortical compromise. The lesion damaged white matter underlying pars opercularis, but also to some degree beneath pars orbitalis and pars triangularis. Patchy lesion is present in the medial subcallosal fasciculus, antero-lateral to the left frontal horn (deep to Broca’s area). White matter beneath both the inferior parietal lobule and to some degree in the superior temporal lobe is compromised. Medially, the lesion destroyed the insula and basal ganglia. Portions of the thalamus were spared. Wernicke’s area (region of the posterior, superior temporal gyrus) is largely spared. 02-036’s lesion, at15 months post-stroke, destroyed the posterior two thirds of the temporal lobe, including all of Wernicke’s area, sparing only the anterior temporal lobe and those medial structures supplied by the PCA. The entire inferior parietal lobule, most of the superior parietal lobule, and the entire lateral occipital cortex were damaged. Lesion is present in the posterior thalamus, including the pulvinar. The lesion extends minimally into pars opercularis and its underlying white matter. The lesion impinges on the posterior putamen and caudate tail, but the basal ganglia and thalamus are otherwise spared. At the level of the body of the lateral ventricle, lesion of the sensorimotor cortex (most likely at the level of the mouth representation) extends toward the periventricular white matter. The extent of lesion in periventricular white matter adjacent to the body of the lateral ventricle is difficult to assess, however, due to large ventricular dilation in the body of the lateral ventricle, especially in the posterior portion. The deep white matter lesion, immediately posterolateral to the body of the lateral ventricle likely interrupts posterior interhemispheric connections, including auditory pathways which may in part account for the patient’s poor auditory comprehension. 03-004 had two lesions. The anterior, subcortical component of hemorrhagic origin is centered in the putamen, with a posterior white matter extension that may interrupt auditory geniculocortical fibers in the region of the temporal isthmus. The posterior, ischemic component in the area of the supramarginal gyrus extends medially and variably to the posterolateral body of the lateral ventricle. The location of the medial extension, in combination with the temporal isthmus lesion, may account for the auditory comprehension deficit.

Figure 1

Axial slices and left-hemisphere sagittal cuts from T1-weighted MRI images, after deformation to the Talairach atlas. For each subject, the top row of images (a) contains eight 1mm-thick axial slices with a separation of 8mm from center to center. Images proceed from inferior on the left side to superior on the right side. Axial coordinates vary from patient to patient to best illustrate their lesion. The bottom row of images for each subject (b) shows a lateral view of the left hemisphere from a whole brain image (left-most image), with each successive image from left to right incrementally cutting away 5 mm in the sagittal plane. The purpose of the images is to demonstrate damage to left perisylvian regions, including cortex within sulci and underlying white matter. 02-030’s lesion, at 8 months post-stroke, occupies the inferior two thirds of the left sensory-motor region, extending forward inferiorly to encompass pars opercularis and especially its underlying white matter and undercutting white matter for premotor cortex above the inferior frontal gyrus and in the posterior half of the middle frontal gyrus. Medially, the lesion damaged most of the insula, but left the basal ganglia and thalamus are virtually untouched. 03-031’s lesion, at 83 months post-stroke, is primarily subcortical. It centers on the insula, extending laterally to encompass white matter underlying the operculum and extending medially to border of the lateral ventricle (sparing most of the medial subcallosal fasciculus deep to Broca’s area, but including periventricular white matter deep to sensorimotor cortex area for mouth, at body of the lateral ventricle). Most of the basal ganglia are subsumed by the lesion, but most of the head of the caudate nucleus and the posterior and the superior thalamus are largely intact. White matter underlying the entire frontal lobe and the inferior parietal lobule (deep to the angular and supramarginal gyri), and the superior temporal lobe are compromised. There is also some high, fronto-parietal supraventricular white matter damage. There is small degree of white matter compromise in portions of the superior temporal lobe. 00-008 (48 months post-stroke) has a large subcortical lesion with some cortical compromise. The lesion damaged white matter underlying pars opercularis, but also to some degree beneath pars orbitalis and pars triangularis. Patchy lesion is present in the medial subcallosal fasciculus, antero-lateral to the left frontal horn (deep to Broca’s area). White matter beneath both the inferior parietal lobule and to some degree in the superior temporal lobe is compromised. Medially, the lesion destroyed the insula and basal ganglia. Portions of the thalamus were spared. Wernicke’s area (region of the posterior, superior temporal gyrus) is largely spared. 02-036’s lesion, at15 months post-stroke, destroyed the posterior two thirds of the temporal lobe, including all of Wernicke’s area, sparing only the anterior temporal lobe and those medial structures supplied by the PCA. The entire inferior parietal lobule, most of the superior parietal lobule, and the entire lateral occipital cortex were damaged. Lesion is present in the posterior thalamus, including the pulvinar. The lesion extends minimally into pars opercularis and its underlying white matter. The lesion impinges on the posterior putamen and caudate tail, but the basal ganglia and thalamus are otherwise spared. At the level of the body of the lateral ventricle, lesion of the sensorimotor cortex (most likely at the level of the mouth representation) extends toward the periventricular white matter. The extent of lesion in periventricular white matter adjacent to the body of the lateral ventricle is difficult to assess, however, due to large ventricular dilation in the body of the lateral ventricle, especially in the posterior portion. The deep white matter lesion, immediately posterolateral to the body of the lateral ventricle likely interrupts posterior interhemispheric connections, including auditory pathways which may in part account for the patient’s poor auditory comprehension. 03-004 had two lesions. The anterior, subcortical component of hemorrhagic origin is centered in the putamen, with a posterior white matter extension that may interrupt auditory geniculocortical fibers in the region of the temporal isthmus. The posterior, ischemic component in the area of the supramarginal gyrus extends medially and variably to the posterolateral body of the lateral ventricle. The location of the medial extension, in combination with the temporal isthmus lesion, may account for the auditory comprehension deficit.

Figure 2

Treatment response is shown for all five patients. Data points represent percent correct for daily probe items (see text for explanation of probes). Phases are color coded. Also represented are trend lines for baseline projected into treatment days (see text for details) and, for the modified Conservative Dual Criterion test (MCDC), a line indicating the mean baseline percent correct + .25 SD and the trend line + .25 SD for phase 3. The equations for the trend lines (linear or natural log) are included. Results of Tryon’s C statistic, effect size, and the mCDC are included in Table 2. All patients except for 03-004 showed a significant response to treatment by all three criteria; 03-004 did not show significant improvement by any of the criteria.

Figure 3

Pre- and post-intention treatment whole-brain images are shown for each of the five patients in the study. A conservative statistical threshold was used to ensure that false positive activity would be excluded. For purposes of anatomic localization of activity at the boundaries of regions of interest, no spatial smoothing was performed on images. For each image set, the frontal lobes are facing the viewer (thus, the left side of the image represents the right side of the brain), and the whole-brain image is sliced axially into three slabs and tilted toward the viewer to best visualize frontal activity in the axial cut. Slice levels may vary between pre- and post-treatment images of an individual patient dependent upon location of frontal activity.