In most people the left hemisphere of the brain is dominant for language. Because of the increased incidence of atypical right-hemispheric language in left-handed neurological patients, a systematic association between handedness and dominance has long been suspected. To clarify the relationship between handedness and language dominance in healthy subjects, we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task. The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-handedness, from 4% in strong right-handers (handedness = 100) to 15% in ambidextrous individuals and 27% in strong left-handers (handedness = -100). The relationship could be approximated by the formula: f1.gif" BORDER="0">. These results clearly demonstrate that the relationship between handedness and language dominance is not an artefact of cerebral pathology but a natural phenomenon.

Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind, Sham-controlled, crossover study was designed to test the hypothesis that non-invasive stimulation of the motor cortex could improve motor function in the paretic hand of patients with chronic stroke. Hand function was measured using the Jebsen-Taylor Hand Function Test (JTT), a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measured in the paretic hand improved significantly with non-invasive transcranial direct current stimulation (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphere, expressed as increased recruitment curves (RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-invasive cortical stimulation on a set of hand functions that mimic activities of daily living in the paretic hand of patients with chronic stroke, and suggest that this interventional strategy in combination with customary rehabilitative treatments may play an adjuvant role in neurorehabilitation.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity ‘conventional’ TES defined as <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10 mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6–7, 2016 and were refined thereafter by email correspondence.

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Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m2) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < −0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age

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Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanismsunderlyingthiseffect.Twenty-threehealthyoverweightolderindividualsthatsuccessfullycompleted26weeksofresveratrolintake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n ϭ 46, 18 females, 50 -75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p ϭ 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p Ͻ 0.05). Increases in FC between the left posterior hippocampus and the medial prefrontal cortex correlated with increases in retention scores and with decreases in HbA1c (all p Ͻ 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging.

The rising proportion of elderly people worldwide will yield an increased incidence of age-associated cognitive impairments, imposing major burdens on societies. Consequently, growing interest emerged to evaluate new strategies to delay or counteract cognitive decline in aging. Here, we assessed immediate effects of anodal transcranial direct current stimulation (atDCS) on cognition and previously described detrimental changes in brain activity attributable to aging. Twenty healthy elderly adults were assessed in a crossover shamcontrolled design using functional magnetic resonance imaging (fMRI) and concurrent transcranial DCS administered to the left inferior frontal gyrus. Effects on performance and task-related brain activity were evaluated during overt semantic word generation, a task that is negatively affected by advanced age. Task-absent resting-state fMRI (RS-fMRI) assessed atDCS-induced changes at the network level independent of performance. Twenty matched younger adults served as controls. During sham stimulation, task-related fMRI demonstrated that enhanced bilateral prefrontal activity in older adults was associated with reduced performance. RS-fMRI revealed enhanced anterior and reduced posterior functional brain connectivity. atDCS significantly improved performance in older adults up to the level of younger controls; significantly reduced task-related hyperactivity in bilateral prefrontal cortices, the anterior cingulate gyrus, and the precuneus; and induced a more "youth-like" connectivity pattern during RS-fMRI. Our results provide converging evidence from behavioral analysis and two independent functional imaging paradigms that a single session of atDCS can temporarily reverse nonbeneficial effects of aging on cognition and brain activity and connectivity. These findings may translate into novel treatments to ameliorate cognitive decline in normal aging in the future.