Skull conductivity has a substantial influence on EEG and combined EEG and MEG source analysis as well as on optimized transcranial electric stimulation. To overcome the use of standard literature values, we propose a non-invasive two-level calibration procedure to estimate skull conductivity individually in a group study with twenty healthy adults. Our procedure requires only an additional run of combined somatosensory evoked potential and field data, which can be easily integrated in EEG/MEG experiments. The calibration procedure uses the P20/N20 topographies and subject-specific realistic head models from MRI. We investigate the inter-subject variability of skull conductivity and relate it to skull thickness, age and gender of the subjects, to the individual scalp P20/N20 surface distance between the P20 potential peak and the N20 potential trough as well as to the individual source depth of the P20/N20 source. We found a considerable inter-subject variability for (calibrated) skull conductivity (8.44 ± 4.84 mS/m) and skull thickness (5.97 ± 1.19 mm) with a statistically significant correlation between them (rho = 0.52). Age showed a statistically significant negative correlation with skull conductivity (rho = -0.5). Furthermore, P20/N20 surface distance and source depth showed large inter-subject variability of 12.08 ± 3.21 cm and 15.45 ± 4.54 mm, respectively, but there was no significant correlation between them. We also found no significant differences among gender subgroups for the investigated measures. It is thus important to take the inter-subject variability of skull conductivity and thickness into account by means of using subject-specific calibrated realistic head modeling.Non-invasive transcranial stimulation of cerebellum and primary motor cortex (M1) has been shown to enhance motor learning. However, the mechanisms by which stimulation improves learning remain largely unknown. Here, we sought to shed light on the neural correlates of transcranial direct current stimulation (tDCS) during motor learning by simultaneously recording functional magnetic resonance imaging (fMRI). We found that right cerebellar tDCS, but not left M1 tDCS, led to enhanced sequence learning in the serial reaction time task. Performance was also improved following cerebellar tDCS compared to sham in a sequence production task, reflecting superior training effects persisting into the post-training period. These behavioral effects were accompanied by increased learning-specific activity in right M1, left cerebellum lobule VI, left inferior frontal gyrus and right inferior parietal lobule during cerebellar tDCS compared to sham. Despite the lack of group-level changes comparing left M1 tDCS to sham, activity increase in right M1, supplementary motor area, and bilateral middle frontal cortex, under M1 tDCS, was associated with better sequence performance. This suggests that lack of group effects in M1 tDCS relate to inter-individual variability in learning-related activation patterns. We further investigated how tDCS modulates effective connectivity in the cortico-striato-cerebellar learning network.  https://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-2.html  Using dynamic causal modelling, we found altered connectivity patterns during both M1 and cerebellar tDCS when compared to sham. Specifically, during cerebellar tDCS, negative modulation of a connection from putamen to cerebellum was decreased for sequence learning only, effectively leading to decreased inhibition of the cerebellum. These results show specific effects of cerebellar tDCS on functional activity and connectivity in the motor learning network and may facilitate the optimization of motor rehabilitation involving cerebellar non-invasive stimulation.Episodic memory depends decisively on the hippocampus and the parahippocampal gyrus, brain structures that are also prone to exercise-induced neuroplasticity and cognitive improvement. We conducted a randomized controlled trial to investigate the effects of a high-intensity exercise program in twenty-two men resting in bed for 60 days on episodic memory and its neuronal basis. All participants were exposed to 60 days of uninterrupted bed rest. Eleven participants were additionally assigned to a high-intensity interval training that was performed five to six times weekly for 60 days. Episodic memory and its neural basis were determined four days prior to and on the 58th day of bed rest using functional magnetic resonance imaging (fMRI). We found increased BOLD signal in the left hippocampus and parahippocampal gyrus in the non-exercising group compared to the exercising bed rest group whereas the mnemonic performance did not differ significantly. These findings indicate a higher neuronal efficiency in the training group during memory encoding and retrieval and may suggest a dysfunctional mechanism in the non-exercising bed rest group induced by two months of physical inactivity. Our results provide further support for the modulating effects of physical exercise and adverse implications of a sedentary lifestyle and bedridden patients.The thalamus has complex connections with the cortex and is involved in various cognitive processes. However, little is known about the age-related changes of thalamo-cortical connections and their relation to cognitive abilities. The present study analyzed resting-state functional connectivity between the thalamus and nine cortical functional networks (default mode network (DMN), posterior DMN, left/right executive, dorsal attention, salience, motor, visual and auditory network) in a healthy human sample (N = 95, aged 5-25 years). Cognitive abilities, including processing speed, selective attention, and cognitive flexibility were assessed using neuropsychological tests. All nine cortical resting-state networks showed functional connections to the thalamus at rest, with no effect for sex (p > 0.05). For the motor, visual, auditory, DMN, posterior DMN, salience and dorsal attention network, we found mainly bilateral thalamic projections in the mediodorsal nucleus, pulvinar and in nuclei of the lateral group. For the right and left lateralized executive network, corresponding lateralized thalamic projections were found. Thalamo-cortical connectivity strength showed significant age-related changes from distinct sub-nuclei of the thalamus to different cortical networks including the visual, DMN, salience and dorsal attention network. Further, connectivity strength of thalamo-cortical networks was associated with cognitive abilities, including processing speed, selective attention and cognitive flexibility. Better cognitive abilities were associated with increased thalamo-cortical connectivity in the pulvinar, mediodorsal nucleus, intralaminar nucleus, and nuclei from the lateral group. Alterations in the integrity of the thalamo-cortical system seem to be crucial for the development of cognitive abilities during brain maturation.