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.
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•The use of Noninvasive Brain Stimulation in Alzheimer’s Disease is promising.•The rising of precision-medicine strives towards the personalization of protocols.•We review and discuss the most innovative solutions to tailor stimulation interventions.•Multidisciplinary approaches might be the key to increase the efficacy of protocols.
•tES allows to safely modulate brain activity by the means of transcranial electric fields.•tES provides greater anatomical specificity respect to other cognitive enhancer like drugs.•tES shows state ...and trait-dependency effects.•Regulation about tES application outside laboratory environment are needed.
Noninvasive brain stimulation is being widely investigated to understand and modulate human brain function, and offers novel therapeutic approaches to neurologic and psychiatric disorders. Here, we focus on the growing interest in the potential of noninvasive brain stimulation, particularly transcranial Electrical Stimulation (tES), to enhance cognitive abilities in healthy individuals through the modulation of neuronal membrane potentials, specific brain oscillations or the delivery of electrical ‘noise’ to the system. We also emphasize the potential of tailoring tES parameters to individual trait and state characteristics for a personalized-medicine approach. Finally, we address the increasing use of tES by lay people, the ethical issues this raises, and consequently call for appropriate regulation.
In the past several years, the number of studies investigating enhancement of cognitive functions through noninvasive brain stimulation (NBS) has increased considerably. NBS techniques, such as ...transcranial magnetic stimulation and transcranial current stimulation, seem capable of enhancing cognitive functions in patients and in healthy humans, particularly when combined with other interventions, including pharmacologic, behavioral and cognitive therapies. The “net zero-sum model”, based on the assumption that brain resources are subjected to the physical principle of conservation of energy, is one of the theoretical frameworks proposed to account for such enhancement of function and its potential cost. We argue that to guide future neuroenhancement studies, the net-zero sum concept is helpful, but only if its limits are tightly defined.
•Cognitive functions can be enhanced through modulation of brain activity.•The “net zero-sum model” can account for gains and costs of cognitive enhancement.•This model can guide future enhancement studies if its limits are tightly defined.
•687 healthy participant’s TMS data were pooled across 35 studies.•Significant relationships between age and resting motor threshold.•Significant relationships between baseline MEP amplitude and ...SICI/ICF.
This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability.
Authors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data.
687 healthy participant’s data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual’s single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT.
This large-scale analysis has identified a number of factors influencing participants’ responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data.
This study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.
Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the ...understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
Highlights • Non-invasive Brain Stimulation (NIBS) can be applied to the investigation of the autonomic nervous system (ANS) function and, conversely, ANS measures can shed light into the ...neurobiological mechanisms of NIBS. • Significant modification of ANS activity in half of the reported NIBS studies, but the optimal parameters of NIBS and ANS assessments remain unclear. • Based on a review NIBS/ANS studies using a predefined framework, we propose some methodological recommendations for future NIBS studies investigating the ANS.
A single session of isolated repetitive movements of the thumb can alter the response to transcranial magnetic stimulation (TMS), such that the related muscle twitch measured post-training occurs in ...the trained direction. This response is attributed to transient excitability changes in primary motor cortex (M1) that form the early part of learning. We investigated; (1) whether this phenomenon might occur for movements at the wrist, and (2) how specific TMS activation patterns of opposing muscles underlie the practice-induced change in direction.
We used single-pulse suprathreshold TMS over the M1 forearm area, to evoke wrist movements in 20 healthy subjects. We measured the preferential direction of the TMS-induced twitch in both the sagittal and coronal plane using an optical goniometer fixed to the dorsum of the wrist, and recorded electromyographic (EMG) activity from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Subjects performed gentle voluntary movements, in the direction opposite to the initial twitch for 5 minutes at 0.2 Hz. We collected motor evoked potentials (MEPs) elicited by TMS at baseline and for 10 minutes after training.
Repetitive motor training was sufficient for TMS to evoke movements in the practiced direction opposite to the original twitch. For most subjects the effect of the newly-acquired direction was retained for at least 10 minutes before reverting to the original. Importantly, the direction change of the movement was associated with a significant decrease in MEP amplitude of the antagonist to the trained muscle, rather than an increase in MEP amplitude of the trained muscle.
These results demonstrate for the first time that a TMS-twitch direction change following a simple practice paradigm may result from reduced corticospinal drive to muscles antagonizing the trained direction. Such findings may have implications for training paradigms in neurorehabilitation.
Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive ...brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.
Disruption of cortical function can improve behavior. Motor cortex (M1) transcallosal interactions are mainly inhibitory; after unilateral damage to M1, there is increased excitability of the ...unaffected M1. Repetitive transcranial magnetic stimulation (rTMS) of M1 produces a temporary reduction in cortical excitability in the same M1 that outlasts the duration of the rTMS train. The authors hypothesize that reducing cortical excitability of M1 by rTMS may improve motor performance in the ipsilateral hand by releasing the contralateral M1 from transcallosal inhibition.
Sixteen healthy volunteers participated. Using a sequential key-pressing task with the index finger, motor performance was monitored before and after rTMS (1 Hz for 10 minutes with the intensity below motor threshold) applied to the ipsilateral M1, contralateral M1, ipsilateral premotor area, or vertex (Cz).
rTMS of M1 shortened execution time of the motor task with the ipsilateral hand without affecting performance with the contralateral hand. This effect outlasted rTMS by at least 10 minutes, was specific for M1 stimulation, and was associated with increased intracortical excitability in the unstimulated M1.
The authors' results support the concept of an interhemispheric "rivalry." They demonstrate the utility of repetitive transcranial magnetic stimulation to explore the functional facilitation of the unstimulated counterpart motor cortex, presumably via suppression of activity in the stimulated motor cortex and transcallosal inhibition.
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