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Motor control, a ubiquitous part of driving, requires increased cognitive controlled processing in older adults relative to younger adults. However, the influence of aging on motor-related neural mechanisms in the context of driving has rarely been studied. The present study aimed to identify age-related changes in cognitive control and attention allocation during a simulated steering task, using electroencephalography. Midfrontal theta, a marker for cognitive control, and posterior alpha power, a marker for attention allocation, were measured in a total of 26 young, 25 middle-aged, and 28 older adults. By adapting driving speed, the difficulty level of this steering task was individualized for each participant. Results show age-related changes in midfrontal theta power, but not in posterior alpha power, despite similar steering accuracy across age groups. Specifically, only younger and, to a lesser extent, middle-aged adults exhibited increased theta power while driving through more demanding curved segments relative to straight segments. In contrast, theta power upregulation was absent in older adults, suggesting a saturation of cognitive resources while driving, possibly due to a limitation in resource capacity, or less automatic motor-related neural processing.

Interlimb coordination deteriorates as a result of aging. Due to its ubiquity in daily life, a greater understanding of the underlying neurophysiological changes is required. Here, we combined electroencephalography time-frequency spectral power and functional connectivity analyses to provide a comprehensive overview of the neural dynamics underlying the age-related deterioration of interlimb coordination involving all four limbs. Theta, alpha and beta oscillations in the frontal, central and parietal regions were analyzed in twenty younger (18-30 years) and nineteen older adults (65-78 years) during a complex interlimb reaction time task. Reaction time was significantly higher in older adults across all conditions, and the discrepancy between both age groups was largest in the most complex movement condition. Older adults demonstrated enhanced beta event-related desynchronization (i.e., the attenuation of beta power), which further increased along with task complexity and was positively linked to behavioral performance. Theta functional connectivity between frontal, central and parietal regions generally increased with movement complexity, irrespective of age group. In general, frontoparietal alpha band functional connectivity tended to be reduced in older versus younger adults, although these contrasts did not survive multiple comparison corrections. Overall, spectral results suggest that enhanced beta desynchronization in older adults reflects a successful compensatory mechanism to cope with increased difficulty during complex interlimb coordination. Functional connectivity results suggest that theta and alpha band connectivity are prone to respectively task- and age-related modulations. Future work could target these spectral and functional connectivity dynamics through noninvasive brain stimulation to potentially improve interlimb coordination in older adults.

Noninvasive techniques to record and stimulate the brain rely on passing through the tissues in between the scalp and cortex. Currently, there is no method to obtain detailed information about these scalp-to-cortex distance (SCD) tissues. We introduce GetTissueThickness (GTT), an open-source, automated approach to quantify SCD, and unveil how tissue thicknesses differ across age groups, sexes and brain regions (n = 250). We show that men have larger SCD in lower scalp regions and women have similar-to-larger SCD in regions closer to the vertex, with aging resulting in increased SCD in fronto-central regions. Soft tissue thickness varies by sex and age, with thicker layers and greater age-related decreases in men. Compact and spongy bone thickness also differ across sexes and age groups, with thicker compact bone in women in both age groups and an age-related thickening. Older men generally have the thickest cerebrospinal fluid layer and younger women and men having similar cerebrospinal fluid layers. Aging mostly results in grey matter thinning. Concerning SCD, the whole isn’t greater than the sum of its parts. GTT enables rapid quantification of the SCD tissues. The distinctive sensitivity of noninvasive recording and stimulation modalities to different tissues underscores the relevance of GTT.

BackgroundElectric field (E-field) modeling is a potent tool to examine the cortical effects of transcranial magnetic and electrical stimulation (TMS and tES, respectively) and to address the high variability in efficacy observed in the literature. However, outcome measures used to report E-field magnitude vary considerably and have not yet been compared in detail.ObjectivesThe goal of this two-part study, encompassing a systematic review and modeling experiment, was to provide an overview of the different outcome measures used to report the magnitude of tES and TMS E-fields, and to conduct a direct comparison of these measures across different stimulation montages.MethodsThree electronic databases were searched for tES and/or TMS studies reporting E-field magnitude. We extracted and discussed outcome measures in studies meeting the inclusion criteria. Additionally, outcome measures were compared via models of four common tES and two TMS modalities in 100 healthy younger adults.ResultsIn the systematic review, we included 118 studies using 151 outcome measures related to E-field magnitude. Structural and spherical regions of interest (ROI) analyses and percentile-based whole-brain analyses were used most often. In the modeling analyses, we found that there was an average of only 6% overlap between ROI and percentile-based whole-brain analyses in the investigated volumes within the same person. The overlap between ROI and whole-brain percentiles was montage- and person-specific, with more focal montages such as 4×1 and APPS-tES, and figure-of-eight TMS showing up to 73%, 60%, and 52% overlap between ROI and percentile approaches respectively. However, even in these cases, 27% or more of the analyzed volume still differed between outcome measures in every analyses.ConclusionsThe choice of outcome measures meaningfully alters the interpretation of tES and TMS E-field models. Well-considered outcome measure selection is imperative for accurate interpretation of results, valid between-study comparisons, and depends on stimulation focality and study goals. We formulated four recommendations to increase the quality and rigor of E-field modeling outcome measures. With these data and recommendations, we hope to guide future studies towards informed outcome measure selection, and improve the comparability of studies.

Bimanual coordination is an important part of everyday life and recruits a large neural network, including the cerebellum. The specific role of the cerebellum in bimanual coordination has not yet been studied in depth, although several studies indicate a differential role of the anterior and posterior cerebellum depending on the complexity of the coordination. An activation likelihood estimation (ALE) meta-analysis was used combining the data of several functional MRI studies involving bimanual coordination tasks with varying complexities to unravel the involvement of the different areas of the cerebellum in simple and complex bimanual coordination. This study confirms the general bimanual network as found by Puttemans et al. (Puttemans et al. in J Neurosci 25:4270-4278, 2005) and highlights the differences between preferred in-phase (simultaneous movements of homologous muscle groups) and anti-phase movement conditions (alternating movements of homologous muscle groups), and more complex, non-preferred bimanual movements (e.g., out-of-phase movements). Our results show a differential role for the anterior and posterior vermis in bimanual coordination, with a role for the anterior vermis in anti-phase and complex bimanual coordination, and an exclusive role for the posterior vermis in complex bimanual movements. In addition, the way complexity was manipulated also seems to play a role in the involvement of the anterior and posterior vermis. We hypothesize that the anterior vermis is involved in sequential/spatial control, while the posterior vermis is involved in temporal control of (bimanual) coordination, though other factors such as (visual) feedback and continuity of the movement also seem to have an impact. More studies are needed to unravel the specific role of the cerebellar vermis in bimanual coordination.

Objective To systematically review how patient characteristics and/or transcranial direct current stimulation (tDCS) parameters influence tDCS effectiveness in respect to upper limb function post-stroke. Methods Three electronic databases were searched for sham-controlled randomised trials using the Fugl-Meyer Assessment for upper extremity as outcome measure. A meta-analysis and nine subgroup-analyses were performed to identify which tDCS parameters yielded the greatest impact on upper limb function recovery in stroke patients. Results Eighteen high-quality studies (507 patients) were included. tDCS applied in a chronic stage yields greater results than tDCS applied in a (sub)acute stage. Additionally, patients with low baseline upper limb impairments seem to benefit more from tDCS than those with high baseline impairments. Regarding tDCS configuration, all stimulation types led to a significant improvement, but only tDCS applied during therapy, and not before therapy, yielded significant results. A positive dose–response relationship was identified for current/charge density and stimulation duration, but not for number of sessions. Conclusion Our results demonstrate that tDCS improves upper limb function post-stroke. However, its effectiveness depends on numerous factors. Especially chronic stroke patients improved, which is promising as they are typically least amenable to recovery. Significance The current work highlights the importance of several patient-related and protocol-related factors regarding tDCS effectiveness.

Few studies have identified the intrahemispheric functional connectivity between the ipsilateral dorsal premotor cortex (PMd) and the primary motor hand area (M1hand) due to technical limitations. In this proof-of-concept study, a novel neuronavigated dsTMS set-up was employed, combining stimulation over left PMd and left M1hand using the edge of a butterfly coil and a small cooled-coil. This arrangement was warranted because coil (over)heating and inter coil distance are limiting factors when investigating connectivity between stimulation targets in close proximity and over a longer duration. The proposed set-up was designed to deal with these limitations. Specifically, the effect of four dual-site transcranial magnetic stimulation (dsTMS) protocols on twenty-eight right-handed participants (12 males) was evaluated. These protocols differed in stimulus order, interstimulus interval and current direction induced in PMd. A structural scan with electric (E-)field modeling was obtained from seven participants prior to dsTMS, demonstrating that PMd and M1hand were effectively stimulated. Results indicate that one protocol, in which a latero-medial current was induced in PMd 2.8 ms prior to stimulation over M1hand, induced a sex-mediated effect. In males, significant inhibition of motor-evoked potentials was identified, whereas females demonstrated a facilitatory effect that did not survive correction for multiple comparisons. E-field simulations revealed that the E-field induced by the coil targeting PMd was maximal in PMd, with weaker E-field strengths extending to regions beyond PMd. Summarizing, the current dsTMS set-up enabled stimulating at an inter-target distance of 35 mm without any indications of coil-overheating.

Older drivers are at a severely higher risk for motor vehicle crash involvement. Due to the global aging of the population, this increased crash risk has a significant impact on society, as well as on an older individual’s quality of life. For this reason, there is a need for understanding how normal age-related changes in cognition and underlying brain dynamics impact driving performance to identify the functional and neurophysiological biomarkers that could be used to design strategies to preserve or improve safe driving behavior in older persons. This review provides an overview of the literature on age-related changes in cognitive functioning and brain dynamics that impact driving simulator performance of healthy persons. A systematic literature search spanning the last ten years was conducted, resulting in 22 eligible studies. Results indicated that various aspects of cognition, most importantly executive function, complex attention, and dual tasking, were associated with driving performance, irrespective of age. However, there was a distinct age-related decline in cognitive and driving performance. Older persons had a more variable, less consistent driving simulator performance, such as more variable speed adaptation or less consistent lane keeping behavior. Only a limited number of studies evaluated the underlying brain dynamics in driving performance. Therefore, future studies should focus on implementing neuroimaging techniques to further unravel the neural correlates of driving performance.

Dual-site transcranial magnetic stimulation (ds-TMS) is well suited to investigate the causal effect of distant brain regions on the primary motor cortex, both at rest and during motor performance and learning. However, given the broad set of stimulation parameters, clarity about which parameters are most effective for identifying particular interactions is lacking. Here, evidence describing inter-and intra-hemispheric interactions during rest and in the context of motor tasks is reviewed. Our aims are threefold: (1) provide a detailed overview of ds-TMS literature regarding inter-and intra-hemispheric connectivity; (2) describe the applicability and contributions of these interactions to motor control, and; (3) discuss the practical implications and future directions. Of the 3659 studies screened, 109 were included and discussed. Overall, there is remarkable variability in the experimental context for assessing ds-TMS interactions, as well as in the use and reporting of stimulation parameters, hindering a quantitative comparison of results across studies. Further studies examining ds-TMS interactions in a systematic manner, and in which all critical parameters are carefully reported, are needed. This work was supported by the KULeuven Special Research Fund grant (C16/15/070), Research Foundation Flanders grant (G089818N and G039821N), and the Excellence of Science grant (EOS 30446199, MEMODYN). SVM (11L9322N) and MH (11F6921N) are funded by a grant from the Research Foundation Flanders. SVM is supported by the UHasselt Special Research Fund grant (BOF21INCENT15).

in the brain from MR-measurements of the current-induced magnetic field B z. Aim: We test the performance of a standard reconstruction algorithm ("projected current density algorithm", PCD, Jeong et al. 2014) for human brain data. We compare it with current flow simulations using personal-ized head models. Methods: 1. We generated ground-truth data for the TES current flow and Bz-field using a detailed head model and SimNIBS (www.simnibs.org). We applied the PCD algorithm to the B z-field and quantified the reconstruction performance by comparison with the ground-truth current flow. We additionally compared the PCD results with simulations using a simple head model ("3c" with scalp, bone and a homogeneous intracranial compartment). 2. We reconstructed the current flow from in-vivo MRCDI data (G€ oksu et al, 2018) with the PCD algorithm. We also used head models of different complexities ("3c" and "4c": scalp, skull, CSF & brain) and optimized their conductivities to minimize the root-mean-square difference between the measured and simulated B z. Results: 1. For simulated B z data, the PCD algorithm only coarsely reconstructed the true current flow. Even the simple head model performed better. 2. For measured B z data, current flows obtained with personalized head models and fitted conductivities explained the measurements better than the current flow reconstructed with the PCD algorithm. This was already the case for the simple head model (3c). The more detailed model (4c) resulted in further statistically significant improvements. However, for all models, the unexplained variance stayed above the noise floor, indicating remaining differences to unknown true current flow. Conclusions: The PCD algorithm has low accuracy for MRCDI data of the brain. However, MRCDI is useful for evaluations and improvements of current flow simulations with anatomically detailed personalized head models.

uptake after tDCS in the bilateral precentral gyri, the bilateral postcentral gyri, the left cingulate, and the left SMA (p(FWE) < 0.028). These results suggest that perceptions of fatigue and QoL, but not objective performance fatigability, play a prominent role in Post-COVID-19-Fatigue and that tDCS might alter cerebral FDG uptake in fatigue-related brain regions in these patients. Abstract A randomized interventional cross-over trial with transcutaneous auric-ular vagus nerve stimulation (tVNS) was performed on 13 adult Systemic sclerosis (SSc) patients with chronic moderate-to-severe pain from the Scleroderma Unit of Policlinico Hospital in Milan. Patients were randomly assigned to the interventional group with tVNS (25 Hz) or to the control group based on sham stimulation (1 Hz) for 4 not consecutively hours/day for one month. Each group shifted to the opposite arm after a 4-weeks wash-out period. Pain was assessed by Numeric Rating Scale (NRS) and 10-minute ECG was recorded at rest before and after real tVNS and sham. Symbolic Heart Rate Variability (HRV) analysis was performed on ECG to assess the cardiovascular autonomic control. ANCOVA test correcting for baseline values, age, disease duration and month of treatment was used to evaluate NRS or HRV changes after tVNS and sham stimulation. For HRV statistical analysis, cardiac ejection fraction and systolic pulmonary artery pressure were also included as covariates. A linear regression model, correcting for covariates as described above, was performed to evaluate the occurrence of minimal clinically important difference (at least 2 points on NRS). Partial correlation analysis was used to estimate the relationship between NRS and HRV changes after correction for covariates. Statistical analysis showed a significant improvement of NRS score after tVNS with an estimated reduction of 2.051 NRS points (p

It has been argued that age-related changes in the neurochemical and neurophysiological properties of the GABAergic system may underlie increases in reaction time (RT) in older adults. However, the role of GABA levels within the sensorimotor cortices (SMC) in mediating interhemispheric interactions (IHi) during the processing stage of a fast motor response, as well as how both properties explain interindividual differences in RT, are not yet fully understood. In this study, edited magnetic resonance spectroscopy (MRS) was combined with dual-site transcranial magnetic stimulation (dsTMS) for probing GABA+ levels in bilateral SMC and task-related neurophysiological modulations in corticospinal excitability (CSE), and primary motor cortex (M1)-M1 and dorsal premotor cortex (PMd)-M1 IHi, respectively. Both CSE and IHi were assessed during the preparatory and premotor period of a delayed choice RT task. Data were collected from 25 young (aged 18-33 years) and 28 older (aged 60-74 years) healthy adults. Our results demonstrated that older as compared to younger adults exhibited a reduced bilateral CSE suppression, as well as a reduced magnitude of long latency M1-M1 and PMd-M1 disinhibition during the preparatory period, irrespective of the direction of the IHi. Importantly, in older adults, the GABA+ levels in bilateral SMC partially accounted for task-related neurophysiological modulations as well as individual differences in RT. In contrast, in young adults, neither task-related neurophysiological modulations, nor individual differences in RT were associated with SMC GABA+ levels. In conclusion, this study contributes to a comprehensive initial understanding of how age-related differences in neurochemical properties and neurophysiological processes are related to increases in RT. ispartof: NEUROIMAGE vol:243 ispartof: location:United States status: published

The role of the dorsolateral prefrontal cortex (DLPFC) in the regulation of bimanual coordination appears to become crucial with aging. Age-related changes in the involvement of the DLPFC in bimanual coordination were studied by using disruptive repetitive TMS (rTMS), inducing a transient lesion in this brain structure. Neurophysiological as well as behavioral effects of suppressing DLPFC during the preparation and execution of a bimanual task were studied in 41 healthy adults (young and old). Specifically, we combined short-train rTMS with single pulse TMS to examine the effect of DLPFC suppression on the interhemispheric projection to the contralateral primary motor cortex (M1) during motor preparation. Findings revealed that compromised interhemispheric DLPFC-M1 disinhibition during motor preparation in older adults resulted in less accurate bimanual performance. The altered DLPFC-M1 interaction in older adults appeared to result from a decline in local inhibitory mechanisms in the DLPFC. In addition, the induction of DLPFC suppression affected task accuracy, but not movement stability in both age groups. Taken together, these results suggest that DLPFC acts as a key regulator in the control of bimanual movement coordination.

Introduction Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain. Previous literature revealed a decline in GABA concentration in frontal and parietal regions as a result of age (Gao et al., 2013; Porges et al., 2017). Nevertheless, it is not clear whether this age-related decline in GABA concentration is specific to these regions or a widespread effect. Therefore, we aimed to investigate age-related changes in GABA concentrations within several cortical and subcortical regions. Since regional GABA concentration has been found to be correlated with various behavioral measures (Puts & Edden, 2012; Stagg, 2014), insight into the effect of healthy aging on brain chemistry may increase our understanding of the underlying neural mechanisms that contribute to cognitive and motor deficits in older adults. Methods A total of 30 healthy right-handed young (14 men, mean age = 23.2) and 29 healthy right-handed older adults (13 men, mean age = 67.5) participated in this study. GABA+ concentrations were acquired in nine different voxels using the MEGA-PRESS spectral editing method on a Philips 3T Achieva Magnetic Resonance scanner (Philips Healthcare, The Netherlands) with a 32 channel receiver head coil. The following acquisition parameters were used: 14 ms editing pulses at 7.5 ppm (edit-OFF) and 1.9 ppm (edit-ON), TE = 68 ms, TR = 2 s, 320 averages, 2 kHz spectral width, MOIST water suppression. Voxels of interest were bilateral primary motor cortex (3x3x3cm³), bilateral dorsal premotor cortex (4x2.5x2.5cm³), bilateral striatum (3x3x3cm³), presupplementary motor area (3x3x3cm³), right inferior frontal cortex (4x2.5x2.5cm³) and occipital cortex (3x3x3cm³). Additionally, a T1 scan was acquired in order to calculate the cerebrospinal fluid (CSF) fraction of each voxel. The obtained MRS spectra were analyzed using the Gannet software toolkit (Edden, Puts, Harris, Barker, & Evans, 2013) and GABA+ concentrations were calculated relative to water. Differences in GABA+ concentrations between young and older adults were tested with a mixed model with age group and voxel as fixed factor, participant as random factor and CSF as covariate (JMP Pro 12). Significant interaction effects were further investigated using unpaired student’s t-tests with Bonferroni correction. Results Older adults had lower GABA+ concentrations in all voxels in comparison with young adults (Figure 1). Statistical analysis however indicated that there was no effect of age on GABA+ concentrations (F1,106.4 = 0.317, p = .574), but there was an interaction between age and voxel (F8, 404.8 = 2.009, p = .0442). Between-group post hoc analysis showed lower GABA+ concentrations within right striatum in older adults compared to young adults (t = -2.86, p = .0045). GABA+ concentrations did not significantly differ between young and older adults in all other voxels (all p ≥ .1604). Conclusions In the present study, we found a decline in GABA+ concentrations with age, however, this decline was only present within right striatum. Within bilateral primary motor cortex, bilateral dorsal premotor cortex, left striatum, presupplementary motor area, right inferior frontal cortex and occipital cortex, the decline in GABA+ concentrations was not significant. This suggests that biochemical changes as a result of healthy aging are not uniform across the human brain. However, it is possible that the regional concentration of macromolecules (i.e. part of the edited GABA+ signal) changes as a function of age, thereby masking the decline in GABA concentrations.