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.

Early Disrupted Neurovascular Coupling and Changed Event Level Hemodynamic Response Function in Type 2 Diabetes: An fMRI Study

“…In patients with stroke it has been shown that the HRF can be altered, which may result in misinterpretation or underestimation of fMRI signal. 17,18 The only way to disentangle vascular from neural impairment-driven changes in the BOLD response is to also use stimuli that are performance matched, thereby using similar neural and cognitive resources.…”

Neurophysiological Markers of Language Recovery in Subacute Stroke

“…After 1s, this changed to a black cross (84 point font) which remained visible until the start of the next trial/event as detailed in Figure 2. A long inter-trial interval (jittered between 10-18s, mean 14s) was employed to allow for the delayed hemodynamic response function observed with stroke patients (Bonakdarpour et al, 2007;Meinzer, Lahiri, Flaisch, Hannemann, & Eulitz, 2009) and to enable future comparison with a planned companion study on individuals with post-stroke aphasia. Order of presentation within each run was pseudorandomised with no more than four items from any one condition (concrete real words, abstract real words and pseudowords) being presented in succession and never more than four words or pseudowords in a row.…”

“…An inter-trial interval (jittered between 10-18s, mean 14s) followed each auditory stimulus presentation. The long interval was designed to allow for future comparison of this data with that of patients with post-stroke aphasia, who can experience a delay in hemodynamic response function (Bonakdarpour et al, 2007). …”

“…In addition, ischaemic infarcts or reduced vascular activity can cause a reduction in the HRF which may affect the BOLD signal detection and create errors in data interpretation. Importantly, delayed HRF has been observed in patients with aphasia (Bonakdarpour, Parrish, & Thompson, 2007) and therefore, it is critical that this issue is considered when designing an experimental paradigm investigating specific cognitive linguistic functions.…”

“…This cross was visible for 1s after which time a black 84 point font appeared on the screen and remained visible until the beginning of the following trial. A long inter-trial interval (jittered between 10-18s, mean 14s) followed each auditory stimulus presentation in order to allow for the delayed hemodynamic response function previously observed in patients with post-stroke aphasia (Bonakdarpour et al, 2007;Meinzer, Lahiri, et al, 2009). …”