The results of this study suggest that specific supratentorial lesions are associated with decreased VC function in patients diagnosed with stroke, confirming previous studies [6, 7, 10] implicating both cortical and subcortical regions in the control of VC. Our findings establish the role of supratentorial lesions in the frontal sub-gyral area, STG, some parts of the parietal lobes, and superior corona radiata. In addition, the SLF showed significant association. Knowledge of these brain sites involved in poor VC may facilitate early identification of patients with poor coughing function.
Due to disruption of the cortical and medullary area associated with cough generation [28] both the RC and VC may be affected after stroke [9]. These two types of cough share common features, including a 3-phase inspiration pattern compressed with glottic adduction followed by expulsion via contraction of the respiratory muscles [29]. They also share the same afferents and efferents. In line with these similarities, a few lesions from our study overlapped with those known to be involved in poor RC [8]. The overlapping lesions include the temporal lobe and STG areas, which are also crucial components in the swallowing mechanism. The supramarginal gyrus and temporal area represent sensorimotor regions are known to associated with impaired swallowing and also with impaired motor reaction in RC [8]. The similarities of the muscle activation and output between RC and VC suggest a possible role of the temporal, STG and suprmarginal gyrus lesions in the motor components of cough, and their potential crucial roles in airway protection during swallowing.
Despite these similarities, the underlying musculoskeletal mechanisms and motor patterns of these two coughs differ considerably [29] with different stroke sites resulting in distinct cough impairment. Specific brain lesions that were exclusively investigated in this study; include the frontal lobe, the posterior corona radiate, and the sub-gyral area, which consist of the descending cortico-respiratory projections located within the pyramidal tract [11]. These cortico-respiratory projections are frequently affected in patients with hemiparesis due to stroke [6, 7]. These regions have not been strongly implicated in RC impairment in previous studies [8]. Our findings support the clinical role of these regions in the diminished ability to generate a VC due to direct involvement of the cortico-respiratory tract.
The frontal subgyral region and the frontal cortex may correspond closely to the cortical “hotspot” sites identified by electrophysiological studies using the transcranial magnetic stimulation [5, 6, 11]. Furthermore, the cortical representation of the inspiratory muscles is known to lie close to the vertex [30]. The corona radiata is part of the descending cortico-respiratory projection located within the pyramidal tract [11], and is also associated with increased risk of aspiration [31]. Although swallowing has been related to the superior or anterior portion of the corona radiata, our results indicate the involvement of the posterior part. The corona radiata is somatotopically arranged and while the anterior part involves the corticobulbar tract, the posterior portion controls the truncal muscles [31]. Since the role of the truncal and abdominal muscles is related not only to truncal control, but also to the control of the respiratory pump muscles and ventilation [32], it is plausible that the posterior portion of the corona radiata may reflect the involvement of respiratory muscles in VC. Thus, though not directly part of the corticobulbar tract involved in the act of swallowing, our results further suggest that these posterior corona radiata regions are crucial regions in airway protection.
An unexpected finding was the SLF, which is not part of the cortico-respiratory projections, to show positive association with VC. The SLF, which consists of longitudinal fibers that connect the dorsolateral frontal and parietal cortices [33], mediates the spatial coordination of the trunk and limbs and contributes to the preparatory sages of movement planning [34]. Therefore, the SLF may contribute to the preparatory truncal function related to the respiratory muscles, such as the abdomen and respiratory muscles required for cough. The SLF also plays an important role in swallowing and its temporal part has been implicated in impaired RC [8]. In addition to these past findings, our results demonstrate that the lesions in the SLF may also interfere with airway protection by limiting VC.
Though swallowing and coughing are independent behaviors, both these two actions are strongly coordinated structural movements that require reconfiguration of the ventilatory breathing pattern [2]. Apparently, a few brain lesions already known to be involved in swallowing such as the STG [8] and the SLF [31] overlap with lesions that were associated with weak cough in this study. Therefore, it is not surprising that the PCF values showed strong correlations with swallowing parameters, suggesting that swallowing and coughing are closely linked. Coordination of these two behaviors is vital to protect the airway from aspiration. Therefore, further studies are needed to understand coughing and swallowing as both independent and as a coordinated response to aspiration events [35].
Post-stroke patients are known to carry impaired contralateral corticodiaphragmatic pathways and may manifest abnormal motion of the diaphragm. Patients diagnosed with dysphagia after stroke are known to exhibit a greater degree of diaphragm weakness than those without swallowing disturbance [3]. Accordingly, patients with stroke-related dysphagia are known to produce low PCF during VC compared to stroke patients without dysphagia and healthy controls [36]. In accordance, our results showed that those with PCF below 80 L/min showed increased severity of dysphagia and more respiratory infections. These results indicate that weakness of cough strength based on the measurement of cough flow can be used as an indicator of pneumonia risk and in acute stroke [37].
Increased lesion volume has been linked to severe dysphagia in previous studies [31]. In contrast, our results failed to show significant association between brain volume and PCF, obviating the need for adjustment of stroke lesion volume in our analysis. Though the functional parameters were affected by the total stroke volume, PCF was more specific to the lesion location rather than the total volume per se.
The study limitations are as follows. First, it was a retrospective study and many subjects who were either too ill to undergo spirometry may not have been included. Second, the PCF and PAS scores were poorly correlated. Nevertheless, patients with a lower PCF showed an increased incidence of respiratory complications, which was consistent with the results of multiple regression analysis reported by Sohn et al. [22], suggesting that PAS per se was not a predictor of respiratory complications. Third, no laterality was considered in this study with all the lesions flipped to one side. Past studies have shown that the majority of patients with left MCA [13] show weak or absent VC and suggested laterality in VC with the left cerebral hemisphere playing a dominant role in the voluntary control of cough. However, other studies failed to associate RC with a specific hemisphere [8, 38]. Indeed, right supratentorial stroke patients were also identified in our study. The discrepancies of our findings to those that suggested left laterality may be attributed to varying number of cases and different assessment methods for defining weak cough, where subjective classification of cough as either weak or absent, was used in the previous report [13]. All our cases were first screened by the physiotherapist to have a weak cough based on the same subjective classification as above, and then had undergoen full objective measurements of the PCF. The mean PCF in our study, are lower than those reported from post-stroke patients with no coughing dysfunction(mean195 ± 67.1 L/min) or from healthy participants (253.2 ± 90.8 L/min)[3], confirming that all those in our analysis had impairment in VC. In addition, one has to consider that the diaphragm and voluntary respiratory movement are under the control of both hemispheres of the brain with no dominance [39]. Finally, it should be investigated whether the proposed lesions were specific to coughing alone given the overlap of patients with both dysphagia and cough dysfunction. However, our results did not reveal obvious lesions that are hallmarks of dysphagia, such as the insula or thalamus. Instead the lesions in our study closely correspond to the cortico-respiratory pathways [5, 11, 40].
In conclusion, this study provides novel insight into the cortical and subcortical dimensions of VC. The lesions defined in this study may facilitate stratification of patients at risk of impaired VC and respiratory complications, and thus identify candidates for respiratory training [41] along with conventional rehabilitation therapy after stroke.