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Promoting the modulatory capacity of intracortical inhibition in young and old: interrelation of physical exercise and sleep

English title Promoting the modulatory capacity of intracortical inhibition in young and old: interrelation of physical exercise and sleep
Applicant Taube Wolfgang
Number 197687
Funding scheme Project funding (Div. I-III)
Research institution Département des neurosciences et des sciences du mouvement (NMS) Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Neurophysiology and Brain Research
Start/End 01.11.2020 - 31.10.2024
Approved amount 621'011.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Geriatrics

Keywords (5)

Comparison of young and old; Interrelation of physical activity and sleep; GABAergic system; Plasticity of the cortical inhibitory system; Intervention study

Lay Summary (German)

Lead
“Promoting the modulatory capacity of intracortical inhibition in young and old: interrelation of physical exercise and sleep”
Lay summary

Es ist bekannt, dass das menschliche inhibitorische System eine entscheidende Rolle inne hat für eine normale Entwicklung sowie die Funktion und Plastizität des Gehirns. Dabei nimmt es sowohl auf kognitive als auch auf motorische Prozesse Einfluss. Zudem ist die kortikale Hemmung entscheidend für die Schlafinduktion und Aufrechterhaltung des Schlafes. Der wichtigste inhibitorische Neurotransmitter im Zentralnervensystem ist die Gamma-Aminobuttersäure (GABA). Es gibt erste Hinweise, dass nicht nur das allgemeine Ausmaß der GABAergen Hemmung entscheidend für die motorische Kontrolle und das motorische Lernen ist, sondern auch die Fähigkeit, die GABA-Freisetzung aufgaben- und phasenspezifisch zu modulieren. Diese Modulation der GABA-Freisetzung ist auch wiederum für die Schlafinduktion sowie für die Aufrechterhaltung des Schlafes wichtig. Die meisten pharmakologischen Interventionen, die das Schlafverhalten manipulieren, beinhalten GABAerge Mechanismen. Darüber hinaus haben Studien mit transkranieller Magnetstimulation (TMS) gezeigt, dass die intrakortikale Inhibition während erhöhter Schläfrigkeit hoch- und die kortikospinale Erregbarkeit herunterreguliert wird und dass diese Modulation beim Einschlafen weiter fortschreitet, um dann beim Aufwachen vollständig unterdrückt zu werden. Dies untermauert die Bedeutung des GABAergen Inhibitions-Netzwerks für die Induktion und Aufrechterhaltung des Schlafes. Zudem ist bekannt, dass körperliche Aktivität (unter Einbeziehung von Gleichgewichts-aufgaben) die Schlafqualität verbessert, und dass Schlaf sowohl die motorische Leistungsfähigkeit als auch die Konsolidierung des motorischen Gedächtnisses beeinflussen kann. Das Ziel des aktuellen Projektes ist es daher, den engen wechselseitigen Zusammenhang zwischen körperlicher Aktivität und Schlaf besser zu verstehen und dabei sowohl Verhaltensänderungen als auch die zugrundeliegenden Mechanismen zu untersuchen. Dies ist von grosser Bedeutung, da immer mehr Studien aufzeigen, wie wichtig der Schlaf für das Wohlbefinden und den Gesundheitszustand der Bevölkerung ist.

Direct link to Lay Summary Last update: 19.10.2020

Lay Summary (English)

Lead
“Promoting the modulatory capacity of intracortical inhibition in young and old: interrelation of physical exercise and sleep”
Lay summary
The human cortical inhibitory system is known to play a crucial role for normal brain development, function and plasticity thereby acting on both, cognitive and motor processes. Furthermore, cortical inhibition is crucial for sleep induction and sleep maintenance. The principal inhibitory neurotransmitter in the central nervous system is gamma-aminobutyric acid (GABA). There is first evidence from our lab that not only the general amount of GABAergic inhibition is crucial with respect to motor control and motor learning but rather the capacity to task- and phase-specifically modulate GABA release, i.e. the modulatory range. Furthermore, modulation of GABA release is also vital for sleep induction and sleep maintenance. Most pharmacological interventions manipulating sleep behavior involve GABAergic mechanisms. In addition, studies with transcranial magnetic stimulation (TMS) have demonstrated that short-interval intracortical inhibition (SICI) is up-, and corticospinal excitability is down-regulated during increased sleepiness and that this modulation further proceeds when falling asleep while being entirely suppressed during awakening. Furthermore, it is known that physical activity (e.g. balance exercises) can enhance sleep quality and it is also known that sleep influences motor performance as well as motor memory consolidation. Therefore, the aim of the current study is to investigate the close reciprocal interrelation of physical activity and sleep on the mechanistic and behavioral level. This could be of great significance as there is growing recognition of the importance of sleep to improve population health due to the convincing evidence linking sleep to a range of health outcomes.
Direct link to Lay Summary Last update: 19.10.2020

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Abstract

BACKGROUND: The human cortical inhibitory system is known to play a crucial role for normal brain development, function and plasticity thereby acting on both cognitive and motor processes. Furthermore, cortical inhibition is crucial for sleep induction and sleep maintenance. The principal inhibitory neurotransmitter in the central nervous system is gamma-aminobutyric acid (GABA). There is first evidence from our lab that not only the general amount of GABAergic inhibition is crucial with respect to motor control and motor learning but rather the capacity to task- and phase-specifically modulate GABA release, i.e. the modulatory range. Yet unpublished, but prize-awarded data of our group demonstrate for the first time increases of GABA-mediated intracortical inhibition after learning balance tasks in elderly subjects and a decrease after strength training in young subjects. Furthermore, in a small subsample, sleep was monitored and these data support the idea that balance training improves not only motor function but also sleep quality.Modulation of GABA release is also important for sleep induction and sleep maintenance. Most pharmacological interventions manipulating sleep behavior involve GABAergic mechanisms. In addition, studies with transcranial magnetic stimulation (TMS) have demonstrated that short-interval intracortical inhibition (SICI) is up-, and corticospinal excitability is down-regulated during increased sleepiness and that this modulation further proceeds when falling asleep to be then entirely suppressed during awakening. This and other findings highlight the importance of the GABAergic inhibitory network for the initiation and maintenance of sleep. WORKING HYPOTHESIS: We hypothesize that at the mechanistic level, the strong dependency on the GABAergic system is one reason for the close reciprocal interrelation of physical activity and sleep. It is known that physical activity (incorporating balance exercises) can enhance sleep quality and it is also known that sleep influences motor performance as well as motor memory consolidation. So far, however, there is no unequivocal demonstration that improvements in the modulatory capacity of the inhibitory system induced by physical activity may translate into better modulation of GABA release during sleep. EXPERIMENTAL DESIGN & METHODS: We will recruit 60 young and 60 elderly people which will be assigned into balance training, strength training and a non-active control group. The balance and the strength training will last for 3 months. The comparison of young and elderly people has the great advantage that young subjects serve as the ‘gold standard’ whereas elderly people constitute a ‘model of reduced inhibitory capacity’. TMS will be used to test the capacity to modulate inhibitory mechanisms during a) the process of falling asleep, sleep and waking up (afternoon nap) and b) during postural tasks before and after the intervention. GABA-levels will be measured with magnetic resonance spectroscopy (MRS) in a) the thalamus (“sleep area”) and b) sensorimotor cortex (“motor control area”) as well as in a non-affected control region (visual cortex). Sleep quality will be assessed during normal sleep at night with questionnaires and mobile EEG. The AIM of the current project is to investigate the close reciprocal interrelation of physical activity and sleep on the mechanistic and behavioral level. We hypothesize that:•improvements in the modulatory capacity of the inhibitory system induced by physical activity (i.e. balance exercises) translate to better modulation of GABA release during sleep and better sleep quality.•young adults demonstrate better ability to modulate intracortical inhibition during sleep and motor tasks than elderly subjects and reveal higher levels of extrasynaptic GABA.•the increase in intracortical inhibition after balance training in the elderly goes along with reductions in cortical overactivation so that brain activation patterns in the elderly approach the ones in young adults. The multimodal approach including TMS, MRS, magnetic resonance imaging (MRI), electroencephalography (EEG) and kinematic analyses further allows to: •relate physiological (GABA, MRS, EEG), neurophysiological (intracortical inhibition, TMS), and behavioral changes (sleep behavior, kinematics).•detect the functional relevance of intra- (SICI with 2 ms) and extrasynaptic inhibition (MRS and SICI with 1 ms ISI) and their changes with i) age and ii) coordinative balance exercises.•link functional (TMS, MRS, EEG) with structural brain changes (MRI).
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