fMRI signals in white matter rewire gray matter community organization.

Human brain gray matter (GM) has usually been clustered into multiple functional networks. The white matter (WM) fiber bundles are known to interconnect these networks simultaneously, engaging in numerous cognitive functions. However, the exact interconnections between GM and WM are still unclear, whether functional signals in WM rewires GM community organization remains to be explored. In this study, we divided brain functional connections into three types by using edge-centric method, including intra-GM, intra-WM and GM-WM connections, and calculated the edge community evaluation indexes for quantifying GM community engagement. The results showed that the involvement of WM significantly enhanced community entropy in the heteromodal system, while the sensory-attention system remained barely changed. In addition, delta community entropy showed a significant correlation with clinical cognitive scale. Our results suggested that WM rewired GM community organization, enhancing the community engagement of brain regions in the heteromodal system. This involvement was observed to be disrupted in disease groups. Our study revealed that considering the functional signals of GM and WM simultaneously could better understand the brain's functional organization.

Enduring maternal brain changes and their role in mediating motherhood's impact on well-being.

Parenthood, particularly motherhood, is known to impact the structure and function of the brain in the short term, but the long-term effects of parenthood and their impacts on well-being are still poorly understood. This study explores the potential longer-term associations between parenthood and the brain, parenthood and well-being, and the potential role of brain modifications in influencing mothers' well-being. Using data from the UK Biobank, which includes brain imaging information from individuals aged 45-82 at the MRI scanning, we discovered differences in brain structure between mothers and non-mothers, with mothers exhibiting widely distributed higher gray matter density, particularly strong in frontal and occipital regions. No brain changes were observed in fathers. Parents reported a higher sense of life's meaning compared to their childless counterparts. Gray matter changes did not mediate the relationship between motherhood and well-being. This suggests that the alterations in gray matter associated with motherhood do not play a deterministic role in shaping long-term changes in well-being.

Gray matter volume of functionally relevant primary motor cortex is causally related to learning a hand motor task.

Variability in brain structure is associated with the capacity for behavioral change. However, a causal link between specific brain areas and behavioral change (such as motor learning) has not been demonstrated. We hypothesized that greater gray matter volume of a primary motor cortex (M1) area active during a hand motor learning task is positively correlated with subsequent learning of the task, and that the disruption of this area blocks learning of the task. Healthy participants underwent structural MRI before learning a skilled hand motor task. Next, participants performed this learning task during fMRI to determine M1 areas functionally active during this task. This functional ROI was anatomically constrained with M1 boundaries to create a group-level "Active-M1" ROI used to measure gray matter volume in each participant. Greater gray matter volume in the left hemisphere Active-M1 ROI was related to greater motor learning in the corresponding right hand. When M1 hand area was disrupted with repetitive transcranial stimulation (rTMS), learning of the motor task was blocked, confirming its causal link to motor learning. Our combined imaging and rTMS approach revealed greater cortical volume in a task-relevant M1 area is causally related to learning of a hand motor task in healthy humans.

Choir singing is associated with enhanced structural connectivity across the adult lifespan.

The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span.

Relationship between sleep, physical fitness, brain microstructure, and cognition in healthy older adults: A pilot study.

BACKGROUND: There is a critical need for neuroimaging markers of brain integrity to monitor effects of modifiable lifestyle factors on brain health. This observational, cross-sectional study assessed relationships between brain microstructure and sleep, physical fitness, and cognition in healthy older adults. METHODS: Twenty-three adults aged 60 and older underwent whole-brain multi-shell diffusion imaging, comprehensive cognitive testing, polysomnography, and exercise testing. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Diffusion tensor imaging (DTI) was used to quantify axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Relationships between sleep efficiency (SE), time and percent in N3 sleep, cognitive function, physical fitness (VO2 peak) and the diffusion metrics in regions of interest and the whole brain were evaluated. RESULTS: Higher NDI in bilateral white and gray matter was associated with better executive functioning. NDI in the right anterior cingulate and adjacent white matter was positively associated with language skills. Higher NDI in the left posterior corona radiata was associated with faster processing speed. Physical fitness was positively associated with NDI in the left precentral gyrus and corticospinal tract. N3 % was positively associated with NDI in the left caudate and right pre- and postcentral gyri. Higher ODI in the left putamen and adjacent white matter was associated with better executive function. CONCLUSION: NDI and ODI derived from NODDI are potential neuroimaging markers for associations between brain microstructure and modifiable risk factors in aging. If these associations are observable in clinical samples, NODDI could be incorporated into clinical trials assessing the effects of modifiable risk factors on brain integrity in aging and neurodegenerative diseases.

Neural basis responsible for effect of grit on procrastination: The interaction between the self-regulation and motivation neural pathways.

Procrastination has a detrimental impact on academic performance, health, and subjective well-being. Previous studies indicated that grit was negatively related to procrastination. However, the underlying neural basis of this relationship remains unclear. To address this issue, we utilized voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to identify the neural substrates of how is grit linked to procrastination. Behavioral results showed that procrastination was negatively associated with grit. VBM analysis revealed that gray matter volume (GMV) in the left precuneus was positively associated with the consistency of interest (CI), a subcomponent of grit, while the right medial orbital frontal cortex (mOFC) was positively correlated with the perseverance of effort (PE), another subcomponent of grit. Moreover, the RSFC analysis indicated that both precuneus-medial superior frontal gyrus (mSFG) and precuneus-insula connectivity were positively related to CI, while the functional coupling of right mOFC with left anterior cingulate cortex (ACC) was positively related to PE. Importantly, the structural equation modeling (SEM) results were well suited for the influence of grit on procrastination via both self-regulation (mOFC-ACC) and motivation pathways (precuneus-mSFG, precuneus-insula). Together, these findings imply that self-regulation and motivation could be two neural circuits underlying the impact of grit on procrastination.

Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

A semi-automated pipeline for finite element modeling of electric field induced in nonhuman primates by transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) is used to treat a range of brain disorders by inducing an electric field (E-field) in the brain. However, the precise neural effects of TMS are not well understood. Nonhuman primates (NHPs) are used to model the impact of TMS on neural activity, but a systematic method of quantifying the induced E-field in the cortex of NHPs has not been developed. NEW METHOD: The pipeline uses statistical parametric mapping (SPM) to automatically segment a structural MRI image of a rhesus macaque into five tissue compartments. Manual corrections are necessary around implants. The segmented tissues are tessellated into 3D meshes used in finite element method (FEM) software to compute the TMS induced E-field in the brain. The gray matter can be further segmented into cortical laminae using a volume preserving method for defining layers. RESULTS: Models of three NHPs were generated with TMS coils placed over the precentral gyrus. Two coil configurations, active and sham, were simulated and compared. The results demonstrated a large difference in E-fields at the target. Additionally, the simulations were calculated using two different E-field solvers and were found to not significantly differ. COMPARISON WITH EXISTING METHODS: Current methods segment NHP tissues manually or use automated methods for only the brain tissue. Existing methods also do not stratify the gray matter into layers. CONCLUSION: The pipeline calculates the induced E-field in NHP models by TMS and can be used to plan implant surgeries and determine approximate E-field values around neuron recording sites.

The Important Role of the Right Dorsolateral Prefrontal Cortex in Conflict Adaptation: A Combined Voxel-Based Morphometry and Continuous Theta Burst Stimulation Study.

Humans can flexibly adjust their executive control to resolve conflicts. Conflict adaptation and conflict resolution are crucial aspects of conflict processing. Functional neuroimaging studies have associated the dorsolateral prefrontal cortex (DLPFC) with conflict processing, but its causal role remains somewhat controversial. Moreover, the neuroanatomical basis of conflict processing has not been thoroughly examined. In this study, the Stroop task, a well-established measure of conflict, was employed to investigate (1) the neuroanatomical basis of conflict resolution and conflict adaptation with the voxel-based morphometry analysis, (2) the causal role of DLPFC in conflict processing with the application of the continuous theta burst stimulation to DLPFC. The results revealed that the Stroop effect was correlated to the gray matter volume of the precuneus, postcentral gyrus, and cerebellum, and the congruency sequence effect was correlated to the gray matter volume of superior frontal gyrus, postcentral gyrus, and lobule paracentral gyrus. These findings indicate the neuroanatomical basis of conflict resolution and adaptation. In addition, the continuous theta burst stimulation over the right DLPFC resulted in a significant reduction in the Stroop effect of RT after congruent trials compared with vertex stimulation and a significant increase in the Stroop effect of accuracy rate after incongruent trials than congruent trials, demonstrating the causal role of right DLPFC in conflict adaptation. Moreover, the DLPFC stimulation did not affect the Stroop effect of RT and accuracy rate. Overall, our study offers further insights into the neural mechanisms underlying conflict resolution and adaptation.

Multimodal neural correlates of dispositional resilience among healthy individuals.

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience's neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.

Narcissus reflected: Grey and white matter features joint contribution to the default mode network in predicting narcissistic personality traits.

Despite the clinical significance of narcissistic personality, its neural bases have not been clarified yet, primarily because of methodological limitations of the previous studies, such as the low sample size, the use of univariate techniques and the focus on only one brain modality. In this study, we employed for the first time a combination of unsupervised and supervised machine learning methods, to identify the joint contributions of grey matter (GM) and white matter (WM) to narcissistic personality traits (NPT). After preprocessing, the brain scans of 135 participants were decomposed into eight independent networks of covarying GM and WM via parallel ICA. Subsequently, stepwise regression and Random Forest were used to predict NPT. We hypothesized that a fronto-temporo parietal network, mainly related to the default mode network, may be involved in NPT and associated WM regions. Results demonstrated a distributed network that included GM alterations in fronto-temporal regions, the insula and the cingulate cortex, along with WM alterations in cerebellar and thalamic regions. To assess the specificity of our findings, we also examined whether the brain network predicting narcissism could also predict other personality traits (i.e., histrionic, paranoid and avoidant personalities). Notably, this network did not predict such personality traits. Additionally, a supervised machine learning model (Random Forest) was used to extract a predictive model for generalization to new cases. Results confirmed that the same network could predict new cases. These findings hold promise for advancing our understanding of personality traits and potentially uncovering brain biomarkers associated with narcissism.

The anatomical structure of sex differences in trust propensity: A voxel-based morphometry study.

Trust is a key component of human relationships. Sex differences in trust behavior have been elucidated by parental investment theory and social role theory, attributing men's higher trust propensity to their increased engagement in physically and socially risky activities aimed at securing additional resources. Although sex differences in trust behavior exist and the neuropsychological signatures of trust are known, the underlying anatomical structure of sex differences is still unexplored. Our study aimed to investigate the anatomical structure of sex differences in trust behavior toward strangers (i.e., trust propensity, TP) by employing voxel-based morphometry (VBM) in a sample of healthy young adults. We collected behavioral data for TP as measured with participants in the role of trustors completing the one-shot trust game (TG) with anonymous partners as trustees. We conducted primary region of interest (ROI) and exploratory whole-brain (WB) VBM analyses of high-resolution structural images to test for the association between TP and regional gray matter volume (GMV) associated with sex differences. Confirming previous studies, our behavioral results demonstrated that men trusted more than women during the one-shot TG. Our WB analysis showed a greater GMV related to TP in men than women in the precuneus (PreC), whereas our ROI analysis in regions of the default-mode network (dorsomedial prefrontal cortex [dmPFC], PreC, superior temporal gyrus) to simulate the partner's trustworthiness, central-executive network (ventrolateral PFC) to implement a calculus-based trust strategy, and action-perception network (precentral gyrus) to performance cost-benefit calculations, as proposed by a neuropsychoeconomic model of trust. Our findings advance the neuropsychological understanding of sex differences in TP, which has implications for interpersonal partnerships, financial transactions, and societal engagements.

Challenges in replication: Does amygdala gray matter volume relate to social network size?

In this work, we tried to replicate and extend prior research on the relationship between social network size and the volume of the amygdala. We focused on the earliest evidence for this relationship (Bickart et al., Nature Neuroscience 14(2), 163-164, 2011) and another methodologically unique study that often is cited as a replication (Kanai et al., Proceedings of the Royal Society B: Biological Sciences, 279(1732), 1327-1334, 2012). Despite their tight link in the literature, we argue that Kanai et al. (Proceedings of the Royal Society B: Biological Sciences, 279(1732), 1327-1334, 2012) is not a replication of Bickart et al. Nature Neuroscience 14(2), 163-164 (2011), because it uses different morphometric measurements. We collected data from 128 participants on a 7-Tesla MRI and examined variations in gray matter volume (GMV) in the amygdala and its nuclei. We found inconclusive support for a correlation between measures of real-world social network and amygdala GMV, with small effect sizes and only anecdotal evidence for a positive relationship. We found support for the absence of a correlation between measures of online social network and amygdala GMV. We discuss different challenges faced in replication attempts for small effects, as initially reported in these two studies, and suggest that the results would be most helpful in the context of estimation and future meta-analytical efforts. Our findings underscore the value of a narrow approach in replication of brain-behavior relationships, one that is focused enough to investigate the specifics of what is measured. This approach can provide a complementary perspective to the more popular "thematic" alternative, in which conclusions are often broader but where conclusions may become disconnected from the evidence.

Neural basis underlying the association between thought control ability and happiness: The moderating role of the amygdala.

Thought control ability (TCA) plays an important role in individuals' health and happiness. Previous studies demonstrated that TCA was closely conceptually associated with happiness. However, empirical research supporting this relationship was limited. In addition, the neural basis underlying TCA and how this neural basis influences the relationship between TCA and happiness remain unexplored. In the present study, the voxel-based morphometry (VBM) method was adopted to investigate the neuroanatomical basis of TCA in 314 healthy subjects. The behavioral results revealed a significant positive association between TCA and happiness. On the neural level, there was a significant negative correlation between TCA and the gray matter density (GMD) of the bilateral amygdala. Split-half validation analysis revealed similar results, further confirming the stability of the VBM analysis findings. Furthermore, gray matter covariance network and graph theoretical analyses showed positive association between TCA and both the node degree and node strength of the amygdala. Moderation analysis revealed that the GMD of the amygdala moderated the relationship between TCA and happiness. Specifically, the positive association between TCA and self-perceived happiness was stronger in subjects with a lower GMD of the amygdala. The present study indicated the neural basis underlying the association between TCA and happiness and offered a method of improving individual well-being.

Long-term abacus training gains in children are predicted by medial temporal lobe anatomy and circuitry.

Abacus-based mental calculation (AMC) is a widely used educational tool for enhancing math learning, offering an accessible and cost-effective method for classroom implementation. Despite its universal appeal, the neurocognitive mechanisms that drive the efficacy of AMC training remain poorly understood. Notably, although abacus training relies heavily on the rapid recall of number positions and sequences, the role of memory systems in driving long-term AMC learning remains unknown. Here, we sought to address this gap by investigating the role of the medial temporal lobe (MTL) memory system in predicting long-term AMC training gains in second-grade children, who were longitudinally assessed up to fifth grade. Leveraging multimodal neuroimaging data, we tested the hypothesis that MTL systems, known for their involvement in associative memory, are instrumental in facilitating AMC-induced improvements in math skills. We found that gray matter volume in bilateral MTL, along with functional connectivity between the MTL and frontal and ventral temporal-occipital cortices, significantly predicted learning gains. Intriguingly, greater gray matter volume but weaker connectivity of the posterior parietal cortex predicted better learning outcomes, offering a more nuanced view of brain systems at play in AMC training. Our findings not only underscore the critical role of the MTL memory system in AMC training but also illuminate the neurobiological factors contributing to individual differences in cognitive skill acquisition. A video abstract of this article can be viewed at https://youtu.be/StVooNRc7T8. RESEARCH HIGHLIGHTS: We investigated the role of medial temporal lobe (MTL) memory system in driving children's math learning following abacus-based mental calculation (AMC) training. AMC training improved math skills in elementary school children across their second and fifth grade. MTL structural integrity and functional connectivity with prefrontal and ventral temporal-occipital cortices predicted long-term AMC training-related gains.

Whole-brain, gray, and white matter time-locked functional signal changes with simple tasks and model-free analysis.

Recent studies have revealed the production of time-locked blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to tasks, challenging the existence of sparse and localized brain functions and highlighting the pervasiveness of potential false negative fMRI findings. "Whole-brain" actually refers to gray matter, the only tissue traditionally studied with fMRI. However, several reports have demonstrated reliable detection of BOLD signals in white matter, which have previously been largely ignored. Using simple tasks and analyses, we demonstrate BOLD signal changes across the whole brain, in both white and gray matters, in similar manner to previous reports of whole brain studies. We investigated whether white matter displays time-locked BOLD signals across multiple structural pathways in response to a stimulus in a similar manner to the cortex. We find that both white and gray matter show time-locked activations across the whole brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that, just like all gray matter, essentially all white matter in the brain shows time-locked BOLD signal changes in response to multiple stimuli, challenging the idea of sparse functional localization and the prevailing wisdom of treating white matter BOLD signals as artifacts to be removed.

Intracranial electrophysiological and structural basis of BOLD functional connectivity in human brain white matter.

While functional MRI (fMRI) studies have mainly focused on gray matter, recent studies have consistently found that blood-oxygenation-level-dependent (BOLD) signals can be reliably detected in white matter, and functional connectivity (FC) has been organized into distributed networks in white matter. Nevertheless, it remains unclear whether this white matter FC reflects underlying electrophysiological synchronization. To address this question, we employ intracranial stereotactic-electroencephalography (SEEG) and resting-state fMRI data from a group of 16 patients with drug-resistant epilepsy. We find that BOLD FC is correlated with SEEG FC in white matter, and this result is consistent across a wide range of frequency bands for each participant. By including diffusion spectrum imaging data, we also find that white matter FC from both SEEG and fMRI are correlated with white matter structural connectivity, suggesting that anatomical fiber tracts underlie the functional synchronization in white matter. These results provide evidence for the electrophysiological and structural basis of white matter BOLD FC, which could be a potential biomarker for psychiatric and neurological disorders.

The functional connectivity between left insula and left medial superior frontal gyrus underlying the relationship between rumination and procrastination.

Procrastination is regarded as a prevalent problematic behavior that impairs people's physical and mental health. Although previous studies have indicated that trait rumination is robustly positively correlated with procrastination, it remains unknown about the neural substrates underlying the relationship between trait rumination and procrastination. To address this issue, we used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) approaches to explore the neural basis of the relationship between trait rumination and procrastination. Our behavior results found that trait rumination was significantly positively correlated to procrastination, while the VBM analysis showed that trait rumination was negatively correlated with gray matter volume of the insula. Furthermore, the RSFC results revealed a negative association of the left insula-lmSFG (left medial superior frontal gyrus) functional connectivity with trait rumination. More importantly, the mediation analysis showed that trait rumination could completely mediate the relationship between left insula-lmSFG functional connectivity and procrastination. These results suggest that the left insula-lmSFG functional connectivity involved in emotion regulation modulates the association between trait rumination and procrastination, which provides neural evidence for the relationship between trait rumination and procrastination.

Hippocampal and motor regions contribute to memory benefits after enacted encoding: cross-sectional and longitudinal evidence.

The neurobiological underpinnings of action-related episodic memory and how enactment contributes to efficient memory encoding are not well understood. We examine whether individual differences in level (n = 338) and 5-year change (n = 248) in the ability to benefit from motor involvement during memory encoding are related to gray matter (GM) volume, white matter (WM) integrity, and dopamine-regulating genes in a population-based cohort (age range = 25-80 years). A latent profile analysis identified 2 groups with similar performance on verbal encoding but with marked differences in the ability to benefit from motor involvement during memory encoding. Impaired ability to benefit from enactment was paired with smaller HC, parahippocampal, and putamen volume along with lower WM microstructure in the fornix. Individuals with reduced ability to benefit from encoding enactment over 5 years were characterized by reduced HC and motor cortex GM volume along with reduced WM microstructure in several WM tracts. Moreover, the proportion of catechol-O-methyltransferase-Val-carriers differed significantly between classes identified from the latent-profile analysis. These results provide converging evidence that individuals with low or declining ability to benefit from motor involvement during memory encoding are characterized by low and reduced GM volume in regions critical for memory and motor functions along with altered WM microstructure.

Modelling the differential effects of age on transcranial magnetic stimulation induced electric fields.

Objective. The therapeutic application of noninvasive brain stimulation modalities such as transcranial magnetic stimulation (TMS) has expanded in terms of indications and patient populations. Often neurodevelopmental and neurodegenerative changes are not considered in research studies and clinical applications. This study sought to examine TMS dosing across time points in the life cycle.Approach. TMS induced electric fields with a figure-of-eight coil was simulated at left dorsolateral prefrontal cortex regions and taken in vertex as a control region. Realistic magnetic resonance imaging-based head models (N= 48) were concurrently examined in a cross-sectional study of three different age groups (children, adults, and elderlies).Main results. Age had a negative correlation with electric field peaks in white matter, grey matter and cerebrospinal fluid (P< 0.001). Notably, the electric field map in children displayed the widest cortical surface spread of TMS induced electric fields.Significance. Age-related anatomical geometry beneath the coil stimulation site had a significant impact on the TMS induced electric fields for different age groups. Safety considerations for TMS applications and protocols in children are warranted based on the present electric field findings.