Neural representation of swallowing is retained with age. A functional neuroimaging study validated by classical and Bayesian inference

Highlights

• We studied cortical activation of swallowing in healthy young adults and healthy seniors using fMRI.

• Differences in the swallowing network between seniors vs. young participants were found in BA10 only using Bayesian inference.

• Seniors showed increased swallowing latency and higher skin conductance response (SCR).

• fMRI-activation in seniors was positively associated with SCR in areas processing sensorimotor performance, arousal and emotional perception.

Abstract

We investigated the neural representation of swallowing in two age groups for a total of 51 healthy participants (seniors: average age 64 years; young adults: average age 24 years) using high spatial resolution functional magnetic resonance imaging (fMRI). Two statistical comparisons (classical and Bayesian inference) revealed no significant differences between subject groups, apart from higher cortical activation for the seniors in the frontal pole 1 of Brodmann's Area 10 using Bayesian inference. Seniors vs. young participants showed longer reaction times and higher skin conductance response (SCR) during swallowing. We found a positive association of SCR and fMRI-activation only among seniors in areas processing sensorimotor performance, arousal and emotional perception. The results indicate that the highly automated swallowing network retains its functionality with age. However, seniors with higher SCR during swallowing appear to also engage areas involved in attention control and emotional regulation, possibly suggesting increased attention and emotional demands during task performance.

Introduction

Swallowing is a complex sensorimotor event that has been investigated via several imaging methods such as functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), positron emission tomography (PET), transcranial magnetic stimulation (TMS) and electroencephalography (EEG). However, little research has been dedicated to healthy older subjects [26], [33], [34], [36], [58] despite the fact that swallowing difficulties are more prevalent among seniors. Age is a major risk factor for the most common neurogenic causes of dysphagia such as stroke [22], Morbus Parkinson and dementia [55] leading to as much as 38% of older people affected by dysphagia [53]. Even without the presence of disease, the swallowing process changes with age (presbyphagia) [27] and studying such changes is of utmost importance [27], [33]. Compared to young healthy participants, studies of older people have shown age-related changes in the swallowing process such as delayed initiation of swallowing, prolonged oral phase [9], [26], [52], [54] declining laryngo-pharyngeal sensitivity [3], reduced lingual and pharyngeal pressure [18], [27] accompanied by increased rates of laryngeal penetration [15]. Moreover, a good understanding of the neural control of swallowing in elderly allows a comparison of same age dysphagic patients. This may lead to a better understanding of cortical reorganization after dysphagia, enabling possible increased therapeutic efficacy.

Previous fMRI studies investigating the neural representation of swallowing in older populations reported inconsistent results. Martin and colleagues described increased neural representation for seniors in the lateral pericentral, perisylvian and anterior cingulate cortex [36]. Humbert et al. [26] described similar findings with increased blood oxygenation level dependent (BOLD)-magnitude in seniors compared to young healthy volunteers in primary and secondary motor areas such as the right pre- and post-central gyri, bilateral frontal lobe, bilateral parietal regions and right superior temporal gyrus. They also reported increased lateralization only in young participants to the left hemisphere in the primary sensorimotor cortex (MS1) and supplementary motor area (SMA). Using MEG Teismann and colleagues found elevated bilateral amplitudes over the pre- and post-central gyrus in seniors, which was interpreted as increased demand in neural processing with decreasing sensorimotor functionality [58].

Contrary to the studies stated above, Malandraki and colleagues used fMRI and found reduced cortical activity in seniors compared to young adults in the somatosensory cortex, and no significant differences in primary motor or other brain areas [34]. In another fMRI-study, the same group reported more symmetrical activation and less lateralization to the dominant hemisphere in seniors during swallowing of water [33], and reported no other significant differences between the senior and younger group.

Common to all above mentioned studies is the suggestion that older people need compensatory mechanisms in the execution of swallowing. In a study measuring performance of complex motor tasks in older subjects, Loibl et al. [31] found that those participants who show early increased recruitment in simple motor tasks decompensate in motor performance with increasing motor complexity. In swallowing, however, it is unclear whether increased neural activation in seniors is an indicator of higher arousal and attentional demand specific to swallowing or less overall efficiency [26].

In general, a missing between group effect and inconsistent findings in age-related swallowing studies might be the result of underpowered study designs (group sizes 9–11 subjects). Based on different paradigms, the recommendation for random effects statistics is at least 20 participants; more optimal would be about 27 participants [60]. Also, different methodological approaches might also account for discrepant results. Teismann et al. [58] used MEG where swallowing took place in an upright position whereas in the case of the fMRI studies participants had to swallow in a supine position. Humbert et al. [26] restricted the analysis to preselected cortical regions and did not correct for multiple comparisons. Martin and colleagues analyzed neural activity on a voxel-by-voxel basis with a fixed-effects model [36]. Malandraki et al. [33] used Z statistics by employing cluster significance thresholding with an analysis focused on Regions of Interests (ROI). Additionally, different amounts of water have been used ranging from 3 to 5 ml per swallow or even with a continuous water delivery of 8–12 ml/min in the MEG-study by Teismann et al. [58]. Also, different interstimulus intervals have been used between the swallows (between 11 and 40 s). Furthermore, age ranges differ among studies from 60 to 85 (mean ages vary between 64.8 and 74.2 years) making it potentially difficult to compare results properly.

In order to complement the previous studies, we aimed to characterize the neural representation of swallowing in healthy seniors compared to healthy young participants with a large sample size (24 young and 27 senior volunteers), high resolution functional imaging methods, and motor performance during imaging. Furthermore, we wanted to quantify physiological parameters in order to examine possible changes with age in task performance and arousal. Swallowing performance and latency was measured using a pneumatic control of the larynx movement. To monitor arousal during swallowing while the subject was in the scanner, we measured skin conductance responses (SCR; [30], [41]) as has been done in an earlier swallowing study [40]. SCRs have been used as a psychophysiological measurement of arousal and controllability [44], [64] and are described as a useful measure of distress and effort in recent studies [41], [56], [57] with increased BOLD-effects in motor areas during increased task challenge [41], [66]. A higher SCR has also been associated with task-related changes in arousal [25], [64]. Since seniors report more swallowing difficulties and swallowing disorders, we aimed to evaluate if swallowing difficulties are also associated with increased arousal. In order to detect neural representation differences between seniors and young healthy participants, we applied two different robust statistical methods in data evaluation, both of which are based on the general linear model (GLM) – classical and Bayesian inference – to exclude statistical processing dependent effects and ensure high statistical validity of our results. The classical approach is more conservative while Bayesian inference is more specific and avoids the multiple comparison problem [19]. By using multiple regression analysis, we looked for associations between BOLD-magnitude during swallowing, age, changes in arousal measured by SCR, and changes in performance measured by swallowing latency.

We hypothesized that seniors show an overall greater bilateral cortical activation in primary and secondary motor areas, Brodmann Area 44/45 and cerebellum compared to young participants as reported in previous studies. Secondly, we expected a more specific representation and higher sensitivity of activation related to swallowing using Bayesian inference. Additionally, we assumed increased activation in elderly accompanied by prolonged swallowing latency and an increased skin conductance response.