Correlation Between Speech Repetition Function and the Arcuate Fasciculus in the Dominant Hemisphere Detected by Diffusion Tensor Imaging Tractography in Stroke Patients with Aphasia

Background

About 21–38% of acute stroke patients and 10–18% of chronic stroke patients are reported to have aphasia [1–3]. Repetition disorder is a common symptom of aphasia, such as Wernicke aphasia, Broca aphasia, conduction aphasia, and complete aphasia, and may have various degrees of repetition deficit. Moreover, a repetition disorder could be used as an important criterion for aphasia classification. However, the neurological mechanism underlying repetition disorder in stroke patients with aphasia remains unclear.

Arcuate fasciculus (AF) is a white-matter bundle connecting the frontal, temporal, and parietal cortical areas [4]. The direct pathway (known as the classic pathway, which connects the temporal cortex to the prefrontal cortex) has been linked to phonetics production [5], whereas the indirect pathway (including the anterior segment connecting the inferior parietal cortex and Broca’s area and a posterior segment connecting temporal and parietal regions) has been linked to verbal comprehension (semantic/phonological transcoding, complex syntactic processing) [6]. Most previous research has shown that individuals with impaired repetition have underlying damaged AF in the dominate hemisphere [7–9]. Lichtheim et al. [10] believed that a broken connection between the auditory speech center and the spoken expression center was the physiological basis of the repetition dysfunction and that the main structure connecting the 2 language centers is the AF in the dominant hemisphere. Other researches have shown that preservation of the left AF is associated with positive language outcome [11,12]. However, occasional case reports show that this association between the AF and repetition performance has not been consistently upheld. Selnes et al. reported a patient with dominant hemisphere AF lesion presenting normal repetition performance by diffusion tensor imaging (DTI) [13]. Also, repetition is a complex process in which word repetition and sentence repetition involve different pathways. For example, after speech therapy, a stroke patient with aphasia had significant word repetition function improvement, while sentence repetition improvement was not obvious [14]. Thus, whether repetition deficits are related to a lesion of the AF remains an open question. Furthermore, if there is a correlation between these, which subtypes of the repetition performance (word repetition or sentence repetition) are more easily affected?

DTI, as an effective neuroimaging technique for identification of white-matter fibers in the living brain, can be used to evaluate the integrity of AF in the dominant hemisphere [15]. In this study, we attempted to explore the relationship between the integrity of AF in the dominant hemisphere and repetition function (not only the whole repetition performance, but also including the word repetition and sentence repetition) using DTI technology in poststroke aphasia patients. We also aimed to identify clinical predictors for aphasia stroke patients.

Material and Methods

SUBJECTS:

The stroke patients with poststroke aphasia (the aphasia group) were recruited from the Department of Rehabilitation and the Department of Neurology in the First Affiliated Hospital of Jinan University between 2015 and 2016.

Inclusion criteria were: 1) stroke, as defined by the classification and diagnosis of cerebrovascular diseases in the Fourth National Conference in China on Cerebrovascular Diseases (1995) [16], with DTI examination clearly indicating infarction or bleeding lesions in the AF in the dominant hemisphere (left hemisphere), but not in the nondominant hemisphere; 2) patients diagnosed with aphasia with repetition dysfunction based on the Aphasia Battery of Chinese (ABC) assessment [17]; 3) first-ever stroke(s) within 6 months of onset; 4) between 40 and 75 years old, with education of more than 6 years; 5) all patients were right-handed, as assessed by the Edinburgh Handedness Questionnaire [18]; 6) patients who were able to complete the ABC assessment and MRI image scanning.

Exclusion criteria were: 1) mental illnesses, organic changes, or other diseases affecting brain function; 2) a severe hearing impairment, visual impairment, or dysarthria; 3) contraindications for magnetic resonance examination, such as vascular stents, cardiac pacemakers, and metal implants; 4) unstable condition, such as heart failure and pulmonary insufficiency.

Nine healthy right-handed subjects with age and years of education matched with the patient group participated in this study as the healthy control (HC) group (3 females, 6 males; mean age, 53.4±9.3 years; demographic information shown in Table 1), who could complete the MRI image scanning and had no brain organic disease, history of psychotropic drug abuse, speech disorders, or cognitive impairments.

Our study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Jinan University (No. 2014-022), and informed consent was obtained from all subjects or their families.

REPETITION FUNCTION ASSESSMENT:

The ABC was used to evaluate the language function of 15 patients in our study, which is based on the cultural specificity of the Chinese and the Western Aphasia Battery (WAB) [19]. The reliability and validity testing were well performed in the Chinese population [20]. The ABC includes 9 subdomains for investigating the speech abilities involved in question and answer, comprehension, repetition, naming, reading, writing, structure and space, ability for use, and calculation. The repetition sub-item includes 2 parts: word repetition, and sentence repetition. The scores of total repetition performance (100 points), word repetition performance (24 points), and sentence repetition performance (76 points) were used as observation indicators in our study. All assessments were completed by the same leading speech therapist in our hospital.

DTI DATA ACQUISITION AND PROCESSING:

DTI was acquired on a 3.0 T Magnetic Resonance Imaging System (General Electric Discovery 750), as well as T1-weighted images and T2-weighted images. Scanning parameters were as follow: T1-weighted images (echo time, 30 ms; rotation angle, 15°; flip time, 4500 ms; slice thickness, 1 mm; voxel, 0.93×0.93×1 mm³; number of slices, 164), T2-weighted images (repetition time, 8000 ms; echo time, 165 ms; slice thickness/slice spacing, 1 mm/1.5 mm); DTI (repetition time/echo time, 5000 ms/68.0 ms; reconstructed to matrix, 128×128; field of view, 25.6×25.6 cm²; number of excitations, 1; b=1000 s/mm²; 25 dispersion-sensitive gradients; slice thickness/slice spacing=3 mm/0 mm).

Functool software (version 9.4.05a, General Electric Medical System) was used for DTI data processing, including three-dimensional reconstruction and the fractional anisotropy (FA) value measurement of the AF on the left hemisphere. The measurement site was placed underneath the inferior limbic gyrus (the position of the AF corner) (Figure 1A). Two regions of interest (ROIs) were selected to track left AF, ROI 1 on the posterior temporal lobe (Figure 1B), and ROI 2 on the posterior parietal lobe in the superior longitudinal fasciculus (Figure 1C) [21]. The area of ROI is 32 mm2. The whole process was performed by the same advanced radiologist. The FA values of the AF in each subject were measured 3 times, and the average was used in the analyses.

STATISTICAL ANALYSIS:

The data were statistically analyzed using SPSS 20.0 software. The continuous variables of 2 groups (the age, educational years, and FA value of AF in the dominant hemisphere) were measured by two-sample t test. The categorical variables (such as handedness and gender) were measured by the chi-square test. The correlation between the FA value of AF in the dominant hemisphere and the repetition performance (the word repetition score, the sentence repetition score, and the total score of repetition) were measured by Spearman correlation analysis. The statistical significance was accepted for P values <0.05.

Results

Fifteen stroke patients with aphasia (2 females and 13 males; mean age, 52.73±11.71 years) and 9 health subjects (3 females and 6 males; mean age, 53.44±9.38 years) were recruited to the aphasia group and control groups, respectively. There were no significant differences in age (P=0.879) and educational level (P=0.345) between the 2 groups. All stroke patients had left hemisphere stroke lesions: 8 were Broca aphasia, 2 were transcortical motor aphasia, 2 were transcortical mixed aphasia, 1 was nominal aphasia, and 2 were complete aphasia. They were all less than 6 months from the first stroke onset (mean time, 2.77±1.26 months). The average FA value of AF in the dominant hemisphere in the patient group was significantly lower than that in the control group (P≤0.001), but no significant difference was found in the nondominant hemisphere between the 2 groups. The demographic information and FA values of AF in the dominant hemisphere of the 2 groups are shown in Table 1.

For the aphasia group, the speech repetition evaluation of ABC assessment (including word repetition scores, sentence repetition scores, and total repetition scores), the stroke types and injured brain regions, and the FA values of the AF in dominate hemisphere of 15 aphasia patients are shown in Table 2. There was a moderate correlation between the total score of repetition evaluation and the FA value of injured AF in the dominant hemisphere (r=0.551, P=0.033) (Figure 2C). Moreover, there was no correlation between the score of word repetition and the FA value of injured AF in the dominant hemisphere (r=0.330, P=0.230) (Figure 2A), whereas there was a strong correlation between the score of sentence repetition and the FA value of injured AF in the dominant hemisphere (r=0.795, P≤0.001) (Figure 2B).

Discussion

LIMITATIONS:

This study has a few limitations. The sample size was relatively small due to a high examination fee for the DTI data collection. Moreover, there was heterogeneity among stroke patients with aphasia recruited in the patient group. Finally, it is hard to completely rule out the effect of eventual physiological improvement on speech performances. Future studies need to recruit more subjects to the patient group and perform hierarchical statistical analysis based on the type of aphasia or degree of repetition deficit.

Conclusions

We found that injured AF in the dominant hemisphere might be related to repetition dysfunction, especially sentence repetition deficit. Our results suggest that facilitation of the AF in the dominant hemisphere could be an important strategy in neuro-rehabilitation for stroke patients with aphasia, so that the patients with the sentence repetition deficit might benefit more than the patients with word repetition deficit.