We recorded evoked potentials (EPs) induced by conventional transcutaneous electrical stimulation (TS), laser stimulation (LS) and epidermal electrical stimulation (ES) using a specially made needle electrode. We evaluated the activated fibers by epidermal stimulation by assessing the conduction velocity (CV) of the peripheral nerves. The EPs were recorded from Cz electrode (vertex) of the International 10-20 system in 12 healthy subjects. For the ES, the tip of a stainless steel needle electrode was inserted in the epidermis of the skin (0.2 mm in depth). Distal and proximal sites of the upper limb were stimulated by the LS and ES with an intensity which induced a definite pain sensation. Similar sites were stimulated by TS with an intensity of two times the sensory threshold. A major EP positive response (P1) was obtained by stimulation by all three types of stimuli. The P1 latency for the TS (245+/-22 ms) was significantly shorter than that for the ES (302+/-17 ms, P<0.0001) and LS (341+/-21 ms, P<0.0001) and the peak latency P1 by the LS was also significantly longer, approximately 40 ms, than that by the ES (P<0.0001). The CVs were 15.1, 15.3 and 44.1 m/s obtained by ES, LS and TS, respectively. The CV indicated that the fibers activated by the ES were mainly A fibers, which corresponded to the fibers stimulated by the LS. We considered that the ES with our newly developed needle electrode was a very convenient method for the selective stimulation of the A fibers, since it was very simple, not requiring any special apparatus, did not cause bleeding or burns and caused minimum uncomfortable feeling.

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Healthy aging is associated with structural and functional changes in the brain even in individuals who are free of neurodegenerative diseases. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of participants, we examined cross sectional changes in the functional organization of several large-scale brain networks over the adult lifespan and its potential association with general cognitive performance. Converging results from multiple analyses at the voxel, node, and network levels showed widespread reorganization of functional brain networks with increasing age. Specifically, the primary processing (visual and sensorimotor) and visuospatial (dorsal attention) networks showed diminished network integrity, while the so-called core neurocognitive (executive control, salience, and default mode) and basal ganglia networks exhibited relatively preserved between-network connections. The visuospatial and precuneus networks also showed significantly more widespread increased connectivity with other networks. Graph analysis suggested that this reorganization progressed towards a more integrated network topology. General cognitive performance, assessed by Addenbrooke’s Cognitive Examination-Revised total score, was positively correlated with between-network connectivity among the core neurocognitive and basal ganglia networks and the integrity of the primary processing and visuospatial networks. Mediation analyses further indicated that the observed association between aging and relative decline in cognitive performance could be mediated by changes in relevant functional connectivity measures. Overall, these findings provided further evidence supporting widespread age-related brain network reorganization and its potential association with general cognitive performance during healthy aging.