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Although, at first sight, one might assume that the human brain is constructed in a roughly symmetric fashion, at closer investigation it becomes apparent that it is inherently asymmetric, i.e., that homotopic brain regions show structural and functional differences [1]. This applies on a structural/anatomical level with, e.g., the right frontal lobe and left occipital lobe tending to protrude over the centerline in a counterclockwise manner called the Yakovlevian torque, but also on the level of brain activity, with certain functions being linked to asymmetric areas of brain activity, such as language which is mainly (but not exclusively) located in the left hemisphere. However, it has been demonstrated that with advancing age, this functional asymmetry of the brain undergoes plastic changes [1]. Over the years, several models have been developed to explain age-related changes in brain asymmetry, such as the Hemispheric Asymmetry Reduction in Older Adults (HAROLD), the right-hemisphere aging, and the Scaffolding Theory of Aging and Cognition (STAC) model ([2] for review). Even though each model succeeds in explaining a subset of brain changes, none accomplishes to serve as an all-encompassing explanation. Therefore, another more recent attempt categorizes the existing evidence on brain aging into three main lines of interpretation, also applicable to brain lateralization: dedifferentiation, neural inefficiency, and compensatory plasticity [3, 4]. In brief, the dedifferentiation model assumes an age-related reduction in the signal-to-noise ratio and specialization of brain regions, resulting in an over-recruitment of task-specific and-unspecific brain regions in older versus younger adults; the neural inefficiency model hypothesizes a diminished signal processing efficiency of the aging brain, leading to a compensatory over-recruitment of task-specific brain regions; and the compensatory neural plasticity model describes (like the dedifferentiation model) an increased task-specific and-unspecific over-recruitment of brain regions with advancing age, however not as the result of malfunctioning but rather of compensatory functional reorganization [4]. As previously stated, advancing age simultaneously impacts lateralization structurally and functionally and a multitude of techniques are employed to study these changes. Structural changes in brain lateralization can be examined using neuroimaging. For example, alterations in the ratio between the two hemispheres' local cortical thickness, gray matter volume (e.g., using voxel-based morphometry analysis) or white matter connectivity (e.g., as assessed with diffusion-weighted imaging) of homologous brain regions can yield information about the brain's structural aging process [4]. At the intersection of brain structure and function, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) are powerful tools to examine the cortex's lateralization. For example, single-pulse (sp)TMS can be used for investigating cortico-spinal excitability (CSE) and the spatial extent and localization of a muscle's cortical motor representation (i.e., motor map) at the primary motor cortex (M1). In addition, dual-site (ds)TMS can be applied to study the interaction of a motor-related brain region and M1 [5]. This can be done at rest or during a task for investigating the chronometry of CSE or an interaction on a temporal scale of milliseconds. While evidence on the lateralization of the brain's motor function using TMS is scarce, our recent work indicated no evidence for age-related differences in lateralization, i.e., in the ratio of the two hemispheres' CSE, motor map size and volume [6]. Lastly, repetitive (r)TMS can temporarily interfere with a brain region's function, resulting in a measurable change of behavior. For example, repetitive stimulation of Broca's area on the left hemisphere interferes with speech, while stimulating the anatomical homologue has no language-related effect. This allows us to study the laterality of a broader set of brain functions such as cognitive tasks [1]. When focusing on brain activation, functional magnetic resonance imaging (fMRI) is a prominent tool to capture the fluctuations in the blood-oxygen-level-dependent (BOLD) signal over time during a task or at rest. Studying task-induced hemodynamic changes in specific brain regions helps to infer their function. More specifically, brain regions engaging synchronously in response to stimuli suggest shared functionality and, altogether, form a connection or network. In the absence of stimuli, i.e., at rest, brain activity is translated into Editorial www.aging-us.com

Using a cross-sectional design, we aimed to identify the effect of aging on sensorimotor function and cortical motor representations of two intrinsic hand muscles, as well as the course and timing of those changes. Furthermore, the link between cortical motor representations, sensorimotor function, and intracortical inhibition and facilitation was investigated. Seventy-seven participants over the full adult lifespan were enrolled. For the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscle, cortical motor representations, GABAA-mediated short-interval intracortical inhibition (SICI), and glutamate-mediated intracortical facilitation (ICF) were assessed using transcranial magnetic stimulation over the dominant primary motor cortex. Additionally, participants' dexterity and force were measured. Linear, polynomial, and piecewise linear regression analyses were conducted to identify the course and timing of age-related differences. Our results demonstrated variation in sensorimotor function over the lifespan, with a marked decline starting around the mid-thirties. Furthermore, an age-related reduction in cortical motor representation volume and maximal MEP of the FDI, but not for ADM, was observed, occurring mainly until the mid-forties. Area of the cortical motor representation did not change with advancing age. Furthermore, cortical motor representations, sensorimotor function, and measures of intracortical inhibition and facilitation were not interrelated. This work was supported by the Research Fund KU Leuven (C16/15/070), the Research Foundation Flanders grant (G089818N), the Excellence of Science grant (EOS 30446199, MEMODYN) and the Hercules fund AUHL/11/01 (R-3987) and I005018N. The authors declare no competing financial interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Cuypers, K (reprint author), Katholieke Univ Leuven, Dept Movement Sci, Grp Biomed Sci, Movement Control & Neuroplastic Res Grp, Leuven, Belgium; Hasselt Univ, REVAL Res Inst, Agoralaan, Diepenbeek, Belgium. koen.cuypers@kuleuven.be