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Available pharmacological treatments for Alzheimer disease (AD) have limited effectiveness, are expensive, and sometimes induce side effects. Therefore, alternative or complementary adjuvant therapeutic strategies have gained increasing attention. The development of novel noninvasive methods of brain stimulation has increased the interest in neuromodulatory techniques as potential therapeutic tool for cognitive rehabilitation in AD. In particular, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive approaches that induce prolonged functional changes in the cerebral cortex. Several studies have begun to therapeutically use rTMS or tDCS to improve cognitive performances in patients with AD. However, most of them induced short-duration beneficial effects and were not adequately powered to establish evidence for therapeutic efficacy. Therefore, TMS and tDCS approaches, seeking to enhance cognitive function, have to be considered still very preliminary. In future studies, multiple rTMS or tDCS sessions might also interact, and metaplasticity effects could affect the outcome.

The objective was to investigate if whole-hand mechanical stimulation (MSTIM) in the tapping-flutter frequency range induces outlasting post-stimulus changes in the hand region of the primary motor cortex. MSTIM was delivered to 12 healthy subjects for 20 min using a therapeutic stimulation device (Swisswing BMR 2000). Frequencies of 10 and 25 Hz were tested in separate sessions, and for control additionally the foot sole was stimulated at 25 Hz. Motor evoked potentials (MEPs) after single (recruitment curves) and paired-pulse transcranial magnetic stimulation (TMS) were recorded from FDI and APB muscles of the right hand. TMS assessments were carried out at baseline (T0), immediately after (T1), 30 min (T2), 1 h (T3) and 2 h (T4) after end of MSTIM. After MSTIM with 25 Hz, MEP recruitment curves were increased at all post-stimulation assessments in both muscles. The most significant effect was achieved at T3 (1 h). Intracortical inhibition was decreased within the first hour, while intracortical facilitation was increased at all post-stimulation assessments. No significant effects were found following MSTIM with 10 Hz and following foot vibration. We conclude that 20 min MSTIM with a frequency of 25 Hz induces outlasting plastic changes in the primary motor cortex. Paired-pulse stimulation further confirms that intrinsic intracortical mechanisms are involved in these changes. Spinal adaptation could be excluded (F-wave assessments). These results could be of relevance for hemiplegic patients with motor deficits, to improve the rehabilitation outcome with vibration exercise in combination with motor training.

Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.