Activation of the dorsal raphe nucleus and locus coeruleus by transcutaneous electrical nerve stimulation in Alzheimer's disease: A reconsideration of stimulation-parameters derived from animal studies

In 1990 a series of studies started in which the effects of Transcutaneous Electrical Nerve Stimulation (TENS) was examined on cognition, behaviour, and the rest-activity rhythm of patients with Alzheimer's disease (AD). In these studies, TENS aimed primarily at stimulating the dorsal raphe nucleus (DRN) and the locus coeruleus (LC) by a combination of low- and high-frequency stimulation (2 Hz and 160 Hz, respectively), a pulse width of 0.1 ms, and an intensity that provokes muscular twitches. TENS was applied 30 min a day, during a six-week period. In order to make reliable comparisons between studies, identical stimulation-parameters were used in all studies thus far. TENS appeared to have a positive effect on cognition, behaviour, and the rest-activity rhythm but the effects disappeared after cessation of stimulation. In order to optimise TENS treatment in AD, the present paper is meant to reconsider the once selected stimulation-parameters by reviewing the relevant literature published since 1991. The results derived from animal experimental studies show that for an optimal stimulation of the LC and DRN, the pulse width should be more than 0.1 ms. Limitations and suggestions for future research will be discussed.