Hemodynamic response function in patients with stroke-induced aphasia: implications for fMRI data analysis

Abstract

Functional MRI is based on changes in cerebral microvasculature triggered by increased neuronal oxidative metabolism. This change in blood flow follows a pattern known as the hemodynamic response function (HRF), which typically peaks 4-6 s following stimulus delivery. However, in the presence of cerebrovascular disease the HRF may not follow this normal pattern, due to either the temporal signal to noise (tSNR) ratio or delays in the HRF, which may result in misinterpretation or underestimation of fMRI signal. The present study examined the HRF and SNR in five individuals with aphasia resulting from stroke and four unimpaired participants using a lexical decision task and a long trial event-related design. T1-weighted images were acquired using an MP-RAGE sequence and BOLD T2*-weighted images were acquired using Echo Planar Imaging to measure time to peak (TTP) in the HRF. Data were analyzed using Brain Voyager in four anatomic regions known to be involved in language processing: Broca's area and the posterior perisylvian network (PPN) (including Wernicke's area, the angular and supramarginal gyri) and right hemisphere homologues of these regions. The occipital area also was examined as a control region. Analyses showed that the TTP in three out of five patients in the left perisylvian area was increased significantly as compared to normal individuals and the left primary visual cortex in the same patients. In two other patients no significant delays were detected. We also found that the SNR for BOLD signal detection may by insufficient in damaged areas. These findings indicate that obtaining physiologic (TTP) and quality assurance (tSNR) information is essential for studying activation patterns in brain-damaged patients in order to avoid errors in interpretation of the data. An example of one such misinterpretation and the need for alternative data analysis strategies is discussed.

Fig. 1

The BOLD signal time courses for a patient with right internal carotid artery occlusion. Event-related paradigm curves show the HRFs for the right (black curve) and left motor cortex (gray curve). The black box denotes the timing of the stimulus (Stim). A decrease in amplitude and delay in onset of the hemodynamic response function exists in the hemisphere ipsilateral to the occlusion (black curve). (source: Carusone et al., 2002; used with the permission from the American Journal of Neuroradiology).

Fig. 2

Axial anatomical T1 MRI scans from selected perisylvian slices in five patients who participated in the study. See text for details regarding lesion boundaries.

Fig. 3

Regions of interest for patient A1. In the anterior region remaining tissue in Broca’s area was examined. The posterior region included spared pSTG, pMTG, left angular gyrus and left supramarginal gyrus. Homologues of the same areas were used as ROIs in the right hemisphere. Also shown is primary visual cortex which was used as a control region.

Fig. 4

Linear correlation lag maps at a threshold of r = 0.12 in patient A1 (left side of figure) and a normal participant (right side of figure). Plots show BOLD signal peaks at 18 s post-stimulus onset in Broca’s Area and 12 s post-stimulus onset in the PPN for the patient, as compared to the normal subject, who showed a peak at 6–8 s in both regions. The color bar shows the lag time, with red being zero delay and green being a 24-s delay.

Fig. 5

Measured HRF data for two aphasic patients (A2, A5), who showed no delay compared to the normal subjects. In each plot above, the grey curve shows the average HRF plot from the four control participants. The PPN in this study included Wernicke’s area, posterior middle temporal gyrus, angular gyrus and supramarginal gyrus. Note: TTP = time to peak.

Fig. 6

Measured HRF data from three aphasic patients who showed a significant delay compared to normal control participants. In each plot above, the grey curve shows the average HRF plot from the four controls. The PPN included Wernicke’s area, posterior middle temporal gyrus, angular gyrus and supramarginal gyrus. Note the prolonged dip in Broca’s area in patients A1, A3, A5 and also in the PPN area in patient A3.

Fig. 7

An example of different activation patterns with and without consideration of the patient’s HRF pattern. No significant activation was detected in Broca’s area using a general linear model analysis modeled after the canonical HRF. However, activation was detected when the HRF was modeled after the patient’s own hemodynamic pattern.