Uncorking the limitation-improving dual tasking using transcranial electrical stimulation and task training in the elderly: a systematic review.

Introduction: With aging, dual task (DT) ability declines and is more cognitively demanding than single tasks. Rapidly declining DT performance is regarded as a predictor of neurodegenerative disease. Task training and non-invasive transcranial electrical stimulation (tES) are methods applied to optimize the DT ability of the elderly. Methods: A systematic search was carried out in the PUBMED, TDCS (transcranial direct current stimulation) databases, as well as Web of Science, and a qualitative analysis was conducted in 56 included studies. Aiming to summarize the results of studies that implemented tES, task training, or the combination for improving DT ability and related performance changes in healthy elderly and geriatric patients. For different approaches, the training procedures, parameters, as well as outcomes were discussed. Results: Task training, particularly cognitive-motor DT training, has more notable effects on improving DT performance in the elderly when compared to the neuromodulation method. Discussion: Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (L-DLPFC), or its combination with task training could be promising tools. However, additional evidence is required from aged healthy people and patients, as well as further exploration of electrode montage.

The consequences of the new European reclassification of non-invasive brain stimulation devices and the medical device regulations pose an existential threat to research and treatment: An invited opinion paper.

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment.

Prefrontal theta-gamma transcranial alternating current stimulation improves non-declarative visuomotor learning in older adults.

The rise in the global population of older adults underscores the significance to investigate age-related cognitive disorders and develop early treatment modalities. Previous research suggests that non-invasive transcranial Alternating Current Stimulation (tACS) can moderately improve cognitive decline in older adults. However, non-declarative cognition has received relatively less attention. This study investigates whether repeated (16-day) bilateral theta-gamma cross-frequency tACS targeting the Dorsolateral Prefrontal Cortex (DLPFC) enhances non-declarative memory. Computerized cognitive training was applied alongside stimulation to control for the state-of-the-brain. The Alternating Serial Reaction Time (ASRT) task was employed to assess non-declarative functions such as visuomotor skill and probabilistic sequence learning. Results from 35 participants aged 55-82 indicated that active tACS led to more substantial improvements in visuomotor skills immediately after treatment, which persisted 3 months later, compared to sham tACS. Treatment benefit was more pronounced in older adults of younger age and those with pre-existing cognitive decline. However, neither intervention group exhibited modulation of probabilistic sequence learning. These results suggest that repeated theta-gamma tACS can selectively improve distinct non-declarative cognitive aspects when targeting the DLPFC. Our findings highlight the therapeutic potential of tACS in addressing deficits in learning and retaining general skills, which could have a positive impact on the quality of life for cognitively impaired older individuals by preserving independence in daily activities.

Beyond social engagement: cognitive training leads to greater cognitive improvement in older adults.

Aging is often accompanied by a decline in cognitive functions, with memory being particularly affected. Recent studies suggest that cognitive training sessions that teach memory strategies relevant to daily life may benefit seniors who live in the community. However, it is possible that the cognitive improvement observed in these programs results from the social encounters embedded in them. In this study, we aimed to investigate the effect of a social cognitive training group, which met regularly for an extended period, on enhancing cognitive indices compared to a control group that only received social engagement meetings without training. Sixty-six participants with a mean age of 78 took part in 12 sessions of a social engagement group, with or without strategy training. Cognitive performance was assessed before and after training using four memory tasks, two similar to the trained tasks (near-transfer tasks) and two novel (far-transfer tasks). Both groups showed a slight improvement in most of the evaluation tasks, but the cognitive training combined with social engagement group showed a significant improvement in the Word Recall and Verbal Fluency tests compared to the social engagement group without training. Our findings suggest that cognitive training sessions may be a useful tool in promoting cognitive improvement among older adults living in the community, even beyond the improvement obtained from the social engagement that occurs during the training sessions.Trial registration number:NCT05016336. Date of registration: 20 August 2021. Retrospectively registered.

Why Temporal Inference Stimulation May Fail in the Human Brain: A Pilot Research Study.

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal.

Stimulated brains and meditative minds: A systematic review on combining low intensity transcranial electrical stimulation and meditation in humans.

Background: Low intensity transcranial electrical stimulation (tES) and meditation are two promising, yet variable, non-pharmacological interventions. Growing research is investigating combined effects of both techniques on one's cognitive, emotional, and physical health. Objective: This article reviews the current research that combines tES and meditation interventions in healthy and diseased participants. The review considers the intervention parameters and their effects in a well-organized manner. Method: A systematic search for clinical and experimental published studies was conducted in the PubMed, Cochrane, and transcranial direct current stimulation (tDCS) databases using common keywords for tES and for meditation techniques well defined by previous studies. Unpublished ongoing studies were identified with the ClinicalTrials.gov and DRKS.de clinical trial websites. Results: 20 published studies and 13 ongoing studies were included for qualitative analysis. 13 published articles studied patients with chronic pain, psychological disorders, cognitive impairment, and movement disorders. Anodal tDCS was the only tES technique while mindfulness meditation was the most common meditation type. Eight studies had a main group effect, with outcome improvement in the active combined intervention. However, most published studies showed improvements after at least one combined intervention with variable effects. Conclusion: Pairing anodal tDCS with meditation shows promising improvements of the physical, mental, and emotional aspects of daily life. Further studies are required to confirm the relevance of this combination in the clinic.

Distinct cognitive changes in male patients with obstructive sleep apnoea without co-morbidities.

Introduction: Obstructive sleep apnoea (OSA) is a multisystem, debilitating, chronic disorder of breathing during sleep, resulting in a relatively consistent pattern of cognitive deficits. More recently, it has been argued that those cognitive deficits, especially in middle-aged patients, may be driven by cardiovascular and metabolic comorbidities, rather than by distinct OSA-processes, such as are for example ensuing nocturnal intermittent hypoxaemia, oxidative stress, neuroinflammation, and sleep fragmentation. Methods: Thus, we undertook to define cognitive performance in a group of 27 middle-aged male patients with untreated OSA, who had no concomitant comorbidities, compared with seven matched controls (AHI mean ± S.D.: 1.9 ± 1.4 events/h; mean age 34.0 ± 9.3 years; mean BMI 23.8 ± 2.3 kg/m2). Of the 27 patients, 16 had mild OSA (AHI mean ± S.D.:11.7 ± 4.0 events/h; mean age 42.6 ± 8.2 years; mean BMI 26.7 ± 4.1 kg/m2), and 11 severe OSA (AHI 41.8 ± 20.7 events/h; age: 46.9 ± 10.9 years, BMI: 28.0 ± 3.2 kg/m2). Results: In our patient cohort, we demonstrate poorer executive-functioning, visuospatial memory, and deficits in vigilance sustained attention, psychomotor and impulse control. Remarkably, we also report, for the first time, effects on social cognition in this group of male, middle-aged OSA patients. Conclusion: Our findings suggest that distinct, OSA-driven processes may be sufficient for cognitive changes to occur as early as in middle age, in otherwise healthy individuals.

Pain reduction in fibromyalgia syndrome through pairing transcranial direct current stimulation and mindfulness meditation: A randomized, double-blinded, sham-controlled pilot clinical trial.

Background: This double-blinded, randomized and sham-controlled pilot clinical trial aimed to investigate the preliminary clinical efficacy and feasibility of combining mindfulness meditation (MM) and transcranial direct current stimulation (tDCS) for pain and associated symptoms in patients with fibromyalgia syndrome (FMS). Methods: Included FMS patients (age: 33 to 70) were randomized to three different groups to receive either ten daily sessions of anodal tDCS over the left primary motor cortex paired with MM for 20 min (active + MM, n = 10), sham tDCS combined with MM (sham + MM, n = 10) or no intervention (NoT, n = 10). Patients in the bimodal therapy groups received a week of training in MM prior to the stimulation. Participants reported pain intensity, the primary outcome, by filling in a pain diary daily throughout the whole study. They were also evaluated for quality of life, pressure pain sensitivity, psychological wellbeing, sleep quality and sleep quantity. Assessments were performed at three time points (baseline, immediately after treatment and one-month follow-up). Results: Participants in the active + MM group did not exhibit reduced pain intensity following the bimodal therapy compared to controls. Patients in active group demonstrated clinically meaningful and significantly higher quality of life following the therapeutic intervention than other groups. There was no significant difference among groups regarding pressure pain sensitivity, sleep parameters and psychological scales. The combined treatment was well tolerated among participants, with no serious adverse effects. Conclusion: This study was the first to pair these two effective non-pharmacological therapies for pain management in FMS. In the light of an underpowered sample size, repetitive anodal tDCS combined with MM did not improve pain or FMS-associated symptoms. However, patients in the active + MM group reported higher quality of life than the control groups. Studies with more participants and longer follow-ups are required to confirm our findings. Clinical trial registration: [www.drks.de], identifier [DRKS00023490].

Digitalized transcranial electrical stimulation: A consensus statement.

OBJECTIVE: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.

Detection of Transcranial Alternating Current Stimulation Aftereffects Is Improved by Considering the Individual Electric Field Strength and Self-Rated Sleepiness.

Non-invasive electrical stimulation methods, such as transcranial alternating current stimulation (tACS), are increasingly used in human neuroscience research and offer potential new avenues to treat neurological and psychiatric disorders. However, their often variable effects have also raised concerns in the scientific and clinical communities. This study aims to investigate the influence of subject-specific factors on the alpha tACS-induced aftereffect on the alpha amplitude (measured with electroencephalography, EEG) as well as on the connectivity strength between nodes of the default mode network (DMN) [measured with functional magnetic resonance imaging (fMRI)]. As subject-specific factors we considered the individual electrical field (EFIELD) strength at target regions in the brain, the frequency mismatch between applied stimulation and individual alpha frequency (IAF) and as a covariate, subject's changes in mental state, i.e., sleepiness. Eighteen subjects participated in a tACS and a sham session conducted on different days. Each session consisted of three runs (pre/stimulation/). tACS was applied during the second run at each subject's individual alpha frequency (IAF), applying 1 mA peak-to-peak intensity for 7 min, using an occipital bihemispheric montage. In every run, subjects watched a video designed to increase in-scanner compliance. To investigate the aftereffect of tACS on EEG alpha amplitude and on DMN connectivity strength, EEG data were recorded simultaneously with fMRI data. Self-rated sleepiness was documented using a questionnaire. Conventional statistics (ANOVA) did not show a significant aftereffect of tACS on the alpha amplitude compared to sham stimulation. Including individual EFIELD strengths and self-rated sleepiness scores in a multiple linear regression model, significant tACS-induced aftereffects were observed. However, the subject-wise mismatch between tACS frequency and IAF had no contribution to our model. Neither standard nor extended statistical methods confirmed a tACS-induced aftereffect on DMN functional connectivity. Our results show that it is possible and necessary to disentangle alpha amplitude changes due to intrinsic mechanisms and to external manipulation using tACS on the alpha amplitude that might otherwise be overlooked. Our results suggest that EFIELD is really the most significant factor that explains the alpha amplitude modulation during a tACS session. This knowledge helps to understand the variability of the tACS-induced aftereffects.

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

Transcranial magnetic stimulation of the brain: What is stimulated? - A consensus and critical position paper.

Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.

Brain Stimulation for Emotion Regulation in Adolescents With Psychiatric Disorders: Study Protocol for a Clinical-Transdiagnostical, Randomized, Triple-Blinded and Sham-Controlled Neurotherapeutic Trial.

Background: Anxiety, conduct and depressive disorders represent three highly prevalent psychiatric conditions in adolescents. A shared underpinning of these disorders is a shortcoming in emotion regulation, connected to the functioning of the ventromedial prefrontal cortex. Thus, an intervention able to target the suggested neural correlate seems to be highly desirable, aiming to hinder a maladaptive development of emotion regulation abilities and chronification of associated psychiatric disorders. As transcranial direct current stimulation (tDCS) was repeatedly demonstrated as a safe and non-invasive method to modulate specific brain activity, research is in demand to evaluate neurotherapeutic applications in adolescents with psychiatric disorders. Method: This transdiagnostic, randomized, triple-blind and sham-controlled clinical neurostimulation trial primary aims to investigate if emotion regulation abilities are increased after tDCS in adolescents with psychiatric disorders. Secondly, disorder-specific changes in the anxiety, depression or conduct disorder will be investigated, as well as changes in quality of life, and cognitive and emotional functioning after tDCS intervention. We will include 108 adolescents with psychiatric disorders, displaying a substantial deficit in emotion regulation. Of these, one third each has to be primarily diagnosed with a depressive, anxiety or conduct disorder, respectively. Participants will be randomized to the experimental group (n = 54) receiving real anodal tDCS, or to the control group (n = 54) receiving sham tDCS. Brain stimulation will be applied for 20 min on five consecutive days twice targeting the ventromedial prefrontal cortex (vmPFC). Changes in emotion regulation, together with changes in disorder-specific clinical symptoms will be recorded by multi-informant psychological ratings. To inspect changes in behavior and gaze, computerized tasks and an eye tracker system will be used. Changes in brain responses to emotional and cognitive stimuli will be examined with three functional magnetic resonance imaging (fMRI) paradigms. In addition, a resting state MRI will be acquired to investigate possible changes in brain connectivity. Discussion: By investigating "emotion regulation" as transdiagnostic treatment target, this project is oriented toward the Research Domain Criteria framework with a dimensional view on mental illness. The study aims at investigating the potential of tDCS as non-invasive intervention for depressive, anxiety and conduct disorders in adolescents and broadening the scientific foundation for its clinical application. Clinical Trial Registration: The study is ongoing and has been registered in the German Registry of Clinical Trials (DRKS-ID: DRKS00025601X) on the 28.06.2021.

The role of the TMS parameters for activation of the corticospinal pathway to the diaphragm.

OBJECTIVE: The influence of the TMS-parameters on the efficacy and reliability to induce diaphragmatic motor-evoked potentials (diMEPs) has not been studied so far. Therefore, the objective of the present research is to probe the role of TMS- waveform (monophasic- [Mo] vs. biphasic-pulses [Bi]) and current direction (posterior-anterior [Pa] vs. anterior-posterior [Ap]) in the activation of the diaphragm. METHODS: Four different pulse-configurations (Mo-Ap, Mo-Pa, Bi-Ap, Bi-Pa) were applied by means of neuronavigated-TMS and surface MEP-recordings at relaxed end-expiration in 19 healthy subjects. The parameters resting motor threshold (RMT), diMEP-amplitude and -latency, as well as best stimulation site (motor hotspot) and central motor conduction time were studied. Diaphragm movements were simultaneously recorded via ultrasound. To control for possible signal contamination the MEPs of muscles neighboring the diaphragm were also obtained. RESULTS: The motor hotspots of the diaphragm showed similar spatial distribution for the Mo-Ap, Mo-Pa, Bi-Ap and Bi-Pa. The biphasic-pulses yielded significantly lower RMTs and higher diMEP-amplitudes as the monophasic-pulses. Anterior to posterior oriented Bi- and Mo-pulses evoked significantly shorter diMEP-latencies than the posterior-anterior oriented ones. CONCLUSIONS: The present research demonstrates that biphasic- as compared to monophasic-pulses require significantly less charge and time for inducing diMEPs. SIGNIFICANCE: The biphasic-TMS is best suited for the demanding stimulation of the diaphragm.

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.

Adaptive and Maladaptive Brain Functional Network Reorganization After Stroke in Hemianopia Patients: An Electroencephalogram-Tracking Study.

Objective: Hemianopia after occipital stroke is believed to be mainly due to local damage at or near the lesion site. However, magnetic resonance imaging studies suggest functional connectivity network (FCN) reorganization also in distant brain regions. Because it is unclear whether reorganization is adaptive or maladaptive, compensating for, or aggravating vision loss, we characterized FCNs electrophysiologically to explore local and global brain plasticity and correlated FCN reorganization with visual performance. Methods: Resting-state electroencephalography (EEG) was recorded in chronic, unilateral stroke patients and healthy age-matched controls (n = 24 each). This study was approved by the local ethics committee. The correlation of oscillating EEG activity was calculated with the imaginary part of coherence between pairs of regions of interest, and FCN graph theory metrics (degree, strength, clustering coefficient) were correlated with stimulus detection and reaction time. Results: Stroke brains showed altered FCNs in the alpha- and low beta-band in numerous occipital, temporal brain structures. On a global level, FCN had a less efficient network organization whereas on the local level node networks were reorganized especially in the intact hemisphere. Here, the occipital network was 58% more rigid (with a more "regular" network structure) whereas the temporal network was 32% more efficient (showing greater "small-worldness"), both of which correlated with worse or better visual processing, respectively. Conclusions: Occipital stroke is associated with both local and global FCN reorganization, but this can be both adaptive and maladaptive. We propose that the more "regular" FCN structure in the intact visual cortex indicates maladaptive plasticity, where less processing efficacy with reduced signal/noise ratio may cause the perceptual deficits in the intact visual field (VF). In contrast, reorganization in intact temporal brain regions is presumably adaptive, possibly supporting enhanced peripheral movement perception.

Toward noninvasive brain stimulation 2.0 in Alzheimer's disease.

Noninvasive brain stimulation techniques (NiBS) have gathered substantial interest in the study of dementia, considered their possible role in help defining diagnostic biomarkers of altered neural activity for early disease detection and monitoring of its pathophysiological course, as well as for their therapeutic potential of boosting residual cognitive functions. Nevertheless, current approaches suffer from some limitations. In this study, we review and discuss experimental NiBS applications that might help improve the efficacy of future NiBS uses in Alzheimer's Disease (AD), including perturbation-based biomarkers for early diagnosis and disease tracking, solutions to enhance synchronization of oscillatory electroencephalographic activity across brain networks, enhancement of sleep-related memory consolidation, image-guided stimulation for connectome control, protocols targeting interneuron pathology and protein clearance, and finally hybrid-brain models for in-silico modeling of AD pathology and personalized target selection. The present work aims to stress the importance of multidisciplinary, translational, model-driven interventions for precision medicine approaches in AD.

New Methods, Old Brains-A Systematic Review on the Effects of tDCS on the Cognition of Elderly People.

The world's population is aging. With this comes an increase in the prevalence of age-associated diseases, which amplifies the need for novel treatments to counteract cognitive decline in the elderly. One of the recently discussed non-pharmacological approaches is transcranial direct current stimulation (tDCS). TDCS delivers weak electric currents to the brain, thereby modulating cortical excitability and activity. Recent evidence suggests that tDCS, mainly with anodal currents, can be a powerful means to non-invasively enhance cognitive functions in elderly people with age-related cognitive decline. Here, we screened a recently developed tDCS database (http://tdcsdatabase.com) that is an open access source of published tDCS papers and reviewed 16 studies that applied tDCS to healthy older subjects or patients suffering from Alzheimer's Disease or pre-stages. Evaluating potential changes in cognitive abilities we focus on declarative and working memory. Aiming for more standardized protocols, repeated tDCS applications (2 mA, 30 min) over the left dorso-lateral prefrontal cortex (LDLPFC) of elderly people seem to be one of the most efficient non-invasive brain stimulation (NIBS) approaches to slow progressive cognitive deterioration. However, inter-subject variability and brain state differences in health and disease restrict the possibility to generalize stimulation methodology and increase the necessity of personalized protocol adjustment by means of improved neuroimaging techniques and electrical field modeling.