Scalp-based, noninvasive modalities such as electroencephalography (EEG), magnetoencephalography (MEG), transcranial electrical stimulation (tES), and transcranial magnetic stimulation (TMS) offer valuable avenues to investigate and manipulate the effects of aging on the brain. For instance, changes in EEG and MEG features have been associated with age-related cognitive and motor performance declines (Kardos et al., 2014, Trammell et al., 2017, Van Hoornweder et al., 2022, Xifra-Porxas et al., 2021, Xifra-Porxas et al., 2019). Likewise, TMS and tES research has provided unique insights into the neural mechanisms underlying age-related changes in the brain (Bhandari et al., 2016, Ghasemian-Shirvan et al., 2020, Ghasemian-Shirvan et al., 2022, Verstraelen et al., 2020).

Although each scalp-based technique has a distinct mechanism of action, they all involve traversing from the scalp to the cortex, or vice versa (Bikson et al., 2012, di Biase et al., 2019, Fitzgerald and Daskalakis, 2022, Giordano et al., 2017, Klomjai et al., 2015, Nitsche and Paulus, 2000, Nunez and Srinivasan, 2006, Reich, 2005, Singh, 2014). Notably, the sensitivity of these techniques to different scalp-to-cortex tissues varies. Electromagnetic field-based methods, such as TMS and MEG, are particularly influenced by the scalp-to-cortex distance (SCD) as the electromagnetic field strength strongly depends on the distance from the source (Hanlon et al., 2019, Herbsman et al., 2009, Julkunen et al., 2012, Kozel et al., 2000, McConnell et al., 2001, Nahas et al., 2001, Nathou et al., 2015). Conversely, techniques relying on electric current conduction, such as tES and EEG, are more affected by tissues such as the compact bone (Butler et al., 2019, Hagemann et al., 2008, Nunez and Srinivasan, 2006, Opitz et al., 2015, Truong et al., 2013).

The aging process not only impacts the brain but also affects the overlying tissues, with some studies demonstrating higher SCD values in older adults, and other research showing no age-related impact on SCD (Kozel et al., 2000; H. N. Lu et al., 2019; Lu et al., 2021; McConnell et al., 2001). A partially overlooked aspect of previous work is that the influence of aging on the tissues comprising SCD is multifaceted. Generally, the soft tissue and compact bone layers decrease in thickness with age, while spongy bone and cerebrospinal fluid (CSF) thickness tend to increase (Akiyama et al., 1997, Blatter et al., 1995, Greenberg et al., 2008, Hatipoglu et al., 2008, Lillie et al., 2016, Makrantonaki and Zouboulis, 2007, Royle et al., 2013, Sabancıoğulları et al., 2012, Ungar et al., 2018). However, the overall impact of aging on SCD tissues remains to be fully understood, as previous studies primarily focused on isolated tissues.

Gaining a more holistic understanding of how aging impacts the SCD tissues is crucial, given their influence on all scalp-based neuroimaging and brain stimulation techniques. Therefore, we developed GetTissueThickness (GTT), which leverages recent advancements in automated segmentation and meshing of MRI scans to determine tissue thicknesses at a user-specified region of interest (ROI) (Huang et al., 2019, Nielsen et al., 2018, Provencher et al., 2016, Puonti et al., 2020, Thielscher et al., 2015, Zarei et al., 2013). As previous research has demonstrated that sex also influences the SCD tissues and that age-related differences may be region-specific, our objective is to investigate differences between age groups in light of sex and scalp-region (Anand Meundi and David, 2019, Blatter et al., 1995, Calisan et al., 2021, Greenberg et al., 2008, Hanlon and McCalley, 2022, Hatipoglu et al., 2008, Indahlastari et al., 2020, Lillie et al., 2016, Makrantonaki and Zouboulis, 2007, McCalley and Hanlon, 2021, Royle et al., 2013, Sabancıoğulları et al., 2012). Furthermore, we will assess whether representing regions in spherical or cartesian coordinates, as opposed to categorical ROIs (i.e., the EEG 10-20 system), can better explain potential variations in tissue thickness related to age and sex. If so, adopting spherical and/or cartesian representations offers the advantage of a more heuristic understanding. Our findings may have important implications specific to each noninvasive neuroimaging and brain stimulation modality, as divergent tissue profiles among age groups and between sexes may result in systematically different outcomes.

Based on previous literature (cf., previous paragraphs), we hypothesize that compared to younger adults, older adults will exhibit thinner soft tissues, thicker compact bone, thicker spongy bone and thicker CSF, minor-to-no increases in SCD, and a slightly thinner grey matter layer (Frangou et al., 2022). Regarding sex, our hypotheses are as follows: men are expected to have higher SCD values, with smaller differences between sexes in channels near the vertex where less soft tissues are present. In contrast to the expected thicker soft tissue layer in men, we anticipate that women will have thicker compact bone layers. For spongy bone, CSF, and grey matter, our hypothesis is that minor-to-no differences between both sexes will be found.