Functional magnetic resonance imaging suggests automatization of the cortical response to inspiratory threshold loading in humans

https://doi.org/10.1016/j.resp.2013.08.005Get rights and content

Highlights

  • Inspiratory mechanical loading in awake humans is associated with cortical activation.

  • This activation is sustained over time and resists distraction, suggesting automatization.

  • There is a widespread brain BOLD signal in response to single-breath inspiratory loading.

  • In contrast, the continuous inspiratory loading is focused to the supplementary motor area.

  • By analogy with pre-post changes in BOLD responses to learning, this supports automatization of the cortical response to inspiratory loading.

Abstract

Inspiratory threshold loading (ITL) induces cortical activation. It is sustained over time and is resistant to distraction, suggesting automaticity. We hypothesized that ITL-induced changes in cerebral activation may differ between single-breath ITL and continuous ITL, with differences resembling those observed after cortical automatization of motor tasks. We analyzed the brain blood oxygen level dependent (BOLD) signal of 11 naive healthy volunteers during 5 min of random, single-breath ITL and 5 min of continuous ITL. Single-breath ITL increased BOLD in many areas (premotor cortices, bilateral insula, cerebellum, reticular formation of the lateral mesencephalon) and decreased BOLD in regions colocalizing with the default mode network. Continuous ITL induced signal changes in a limited number of areas (supplementary motor area). These differences are comparable to those observed before and after overlearning of motor tasks. We conclude that the respiratory-related cortical activation observed in response to ITL is likely due to automated, attention-independent mechanisms. Also, ITL activates cortical circuits right from the first breath.

Introduction

Breathing is the only autonomic function to depend on motor control extrinsic to the concerned organ. Indeed, ventilation of the lungs is ensured by respiratory muscles innervated by spinal motoneurones relaying a motor drive to breathe that originates in the central nervous system. This organization allows for a permanent interplay between autonomic regulation of breathing (brainstem central pattern generators) and suprapontine respiratory programs producing voluntary respiratory maneuvers and speech-breathing interactions. Volitional breathing is subserved by cortical representations of respiratory muscles (Foerster, 1936, Gandevia and Rothwell, 1987, Maskill et al., 1991, Murphy et al., 1990, Similowski et al., 1996a, Similowski et al., 1996b) and various cortical networks (Colebatch et al., 1991, Evans et al., 1999, Fink et al., 1996, Koritnik et al., 2009, Macefield and Gandevia, 1991, McKay et al., 2003, Ramsay et al., 1993, Raux et al., 2007a, Simonyan et al., 2007; see also meta-analysis in Takai et al., 2010).

In awake humans, experimentally applied inspiratory constraints are “compensated” or “overcompensated”, with maintenance or acceleration of alveolar ventilation (Pengelly et al., 1974, Yanos et al., 1990). During sleep, identical constraints produce hypoventilation (Morrell et al., 2000, Read et al., 1974, Wiegand et al., 1988). This difference between waking and sleeping suggests cortical mechanisms. Respiratory-related cortical activities are indeed observed in response to inspiratory constraints in awake humans (Gozal et al., 1995, Gozal et al., 1996, Isaev et al., 2002, Raux et al., 2007a, Raux et al., 2007b). This phenomenon is sustained over time (Tremoureux et al., 2010) and some of the observed respiratory-related cortical activities are resistant to distraction (Tremoureux et al., 2010). These observations are consistent with cortical automatization, the process that allows a task to be performed without requiring the subject to focus attention on the details of the corresponding motor sequence. Cortical automatization occurs in response to overlearning and is associated with pre-post differences in cortical and subcortical activations (Jansma et al., 2001, Jueptner et al., 1997a, Jueptner et al., 1997b, Lehericy et al., 2005, Poldrack et al., 2005, Wu et al., 2004, Wu et al., 2008). A motor task corresponds to less intense activities after learning, than before learning in the cerebellum, presupplementary motor area, cingulate, premotor, parietal, and prefrontal cortices (Wu et al., 2004). In the basal ganglia, post-learning tasks are associated with less intense activation in the left caudate nucleus than their pre-learning counterpart and with more intense activation in the posterior putamen (Hikosaka et al., 2002, Lehericy et al., 2005). The importance of the selective attention network decreases concomitantly (Wu et al., 2008).

In the present functional magnetic imaging (fMRI) study, we hypothesized that if the respiratory-related cortical activity induced by inspiratory constraints can become automatic, then differences compatible with the learning process described above should be observed between the response to inspiratory load applied to a single breath (single-breath loading) and the response to the same load applied continuously (continuous loading). We tested this hypothesis by comparing the brain blood oxygen level dependent (BOLD) signal obtained during single-breath inspiratory loading and continuous inspiratory loading in normal volunteers. This approach is based on the pioneering work by Gozal et al. (1995) that suggested that the second presentation of a continuous inspiratory load is associated with less intense brain activity than the first presentation.

Section snippets

Ethics board approval

The study complied with the standards defined in the latest revision of the Declaration of Helsinki for human research, and was fully approved by the McGill University Health Center Research Ethics Board. The subjects received detailed information about the methods used and gave their written consent to participate. However, they were initially not informed about the actual purpose of the study, but were told that they would be asked to answer questions about a movie that would be screened

Ventilatory pattern

The effects of inspiratory loading are reported in Table 1. Loading increased the inspiratory time (TI), total respiratory cycle time (TT) and duty cycle (TI/TT), and the magnitude of inspiratory effort, as reflected by greater variations in mouth pressure. Respiratory frequency and mean inspiratory airflow (VT/TI) decreased. Expiratory time (TE) and VT remained globally stable. Ventilation was not affected by inspiratory loading. PETCO2 did not significantly increase or decrease over time,

Discussion

This study confirms that mechanical inspiratory constraints are associated with changes in cortical activity in healthy humans. The pattern of BOLD signal changes induced by inspiratory loading markedly differed between single-breath and continuous loading paradigms. Fewer “activated” and “deactivated” areas were observed during continuous inspiratory loading, with enhanced SMA activity. These changes resemble those observed when a cortical automatization of motor tasks occurs.

Conflict of interest statement

This research was not supported by any industry-funded grant and the authors have no financial conflicts of interest to declare.

Acknowledgments

This research was funded in part by a grant from the Société Française d’Anesthésie Réanimation, a “Legs Poix” grant from the “Chancellerie de l’Université de Paris”, France, grant ANR-11-EMMA-030-01 from the “Agence Nationale de la Recherche”, Paris, France and the program “Investissement d'Avenir ANR-10-AIHU-06” of the French Government.

The authors are indebted to the Pulmonary Function Test laboratory technicians at Royal Victoria Hospital, McGill University Health Center, Montréal, QC for

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