Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function161CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465686/2014-1Não tem2014/50909-8; 13/10187–0; 14/10134–7The authors thank the Ministry of Education (MEC), FAPESP - São Paulo Research Foundation, Universidade Estadual de Londrina, Universidade Federal do Rio Grande do Norte and Universidade Federal do ABC for its support. Postdoctoral scholarships to DGSM from the Coordination for the Improvement of Higher Education Personnel (CAPES). Source(s) of financial support: This study was partially funded by grants to MB from NIH (NIH-NIMH 1R01MH111896, NIH-NINDS 1R01NS101362, NIH-NCI U54CA137788/U54CA132378, R03 NS054783) and New York State Department of Health (NYS DOH, DOH01-C31291GG), CEPID/BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology (Process: 13/07559–3) to LML, Brazilian National Research Council (CNPq, Grant # 465686/2014-1) and the São Paulo Research Foundation (Grant # 2014/50909-8) to MSC, and Postdoctoral scholarships to AHO from FAPESP - Sao Paulo Research Foundation (Process: 13/10187–0 and 14/10134–7

Transcranial Electrical Stimulation for Associative Memory Enhancement: State-of-the-Art from Basic to Clinical Research

Associative memory (AM) is the ability to bind new information into complex memory representations. Noninvasive brain stimulation (NIBS), especially transcranial electric stimulation (tES), has gained increased interest in research of associative memory (AM) and its impairments. To provide an overview of the current state of knowledge, we conducted a systematic review following PRISMA guidelines covering basic and clinical research. Out of 374 identified records, 41 studies were analyzed—twenty-nine in healthy young adults, six in the aging population, three comparing older and younger adults, as well as two studies on people with MCI, and one in people with Alzheimer’s dementia. Studies using transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS) as well as oscillatory (otDCS) and high-definition protocols (HD-tDCS, HD-tACS) have been included. The results showed methodological heterogeneity in terms of study design, stimulation type, and parameters, as well as outcome measures. Overall, the results show that tES is a promising method for AM enhancement, especially if the stimulation is applied over the parietal cortex and the effects are assessed in cued recall paradigms

Conventional and HD-tDCS May (or May Not) Modulate Overt Attentional Orienting: An Integrated Spatio-Temporal Approach and Methodological Reflections.

Transcranial Direct Current Stimulation (tDCS) has been employed to modulate visuo-spatial attentional asymmetries, however, further investigation is needed to characterize tDCS-associated variability in more ecological settings. In the present research, we tested the effects of offline, anodal conventional tDCS (Experiment 1) and HD-tDCS (Experiment 2) delivered over the posterior parietal cortex (PPC) and Frontal Eye Field (FEF) of the right hemisphere in healthy participants. Attentional asymmetries were measured by means of an eye tracking-based, ecological paradigm, that is, a Free Visual Exploration task of naturalistic pictures. Data were analyzed from a spatiotemporal perspective. In Experiment 1, a pre-post linear mixed model (LMM) indicated a leftward attentional shift after PPC tDCS; this effect was not confirmed when the individual baseline performance was considered. In Experiment 2, FEF HD-tDCS was shown to induce a significant leftward shift of gaze position, which emerged after 6 s of picture exploration and lasted for 200 ms. The present results do not allow us to conclude on a clear efficacy of offline conventional tDCS and HD-tDCS in modulating overt visuospatial attention in an ecological setting. Nonetheless, our findings highlight a complex relationship among stimulated area, focality of stimulation, spatiotemporal aspects of deployment of attention, and the role of individual baseline performance in shaping the effects of tDCS

Effects of single-session transcranial direct current stimulation on reactive response inhibition

Transcranial direct current stimulation (tDCS) is widely used to explore the role of various cortical regions for reactive response inhibition. In recent years, tDCS studies reported polarity-, time- and stimulation-site dependent effects on response inhibition. Given the large parameter space in which study designs, tDCS procedures and task procedures can differ, it is crucial to systematically explore the existing tDCS literature to increase the current understanding of potential modulatory effects and limitations of different approaches. We performed a systematic review on the modulatory effects of tDCS on response inhibition as measured by the Stop-Signal Task. The final dataset shows a large variation in methodology and heterogeneous effects of tDCS on performance. The most consistent result across studies is a performance enhancement due to anodal tDCS over the right prefrontal cortex. Partially sub-optimal choices in study design, methodology and lacking consistency in reporting procedures may impede valid conclusions and obscured the effects of tDCS on response inhibition in some previous studies. Finally, we outline future directions and areas to improve research

Optimising the Application of Transcranial Direct Current Stimulation

The ability of transcranial direct current stimulation (tDCS) to modulate brain activity has vast scientific and therapeutic potential, however, its effects are often variable which limit its utility. Both current flow direction and variance in electric field intensities reaching a cortical target may be vital sources of the variable tDCS effects on neuroplastic change. Controlling for these and exploring the subsequent effects on corticospinal excitability is the aim of this thesis. I here attempted to optimise the delivery of tDCS application by investigating the controlled application of current flow direction and whether through the use of current flow models, we can deliver comparable electric fields with reduced variability across differential montages. To assess whether current flow models are useful, I further investigated if dose-control translates to more consistent physiological outcomes. I demonstrate, firstly, that different current flow directions did not differentially affect the two banks of the central sulcus. Secondly, with the use of dose-control, high-definition tDCS (HD-tDCS) remains focally more advantageous, even with the delivery of comparable electric field intensity and variability as posterior-anterior tDCS (PA-tDCS) to a cortical region. Thirdly, dose-controlled tDCS does not translate to reduced physiological variability. Together, the work presented here suggests that current flow models are useful for informing dose-controlled protocols and montage comparisons for improved tDCS delivery, however, controlling for anatomical differences in the delivery of electric fields to a target is not sufficient to reduce the variability of tDCS effects in physiology. Thus, the methodology for optimised tDCS delivery remains a subject for further improvement and investigation. Advancements in this field may lead to a trusted methodology assisting stroke survivors with a more effective and efficient motor recovery journey

Sex Mediates the Effects of High-Definition Transcranial Direct Current Stimulation on “Mind-Reading”

Sex differences in social cognitive ability are well established, including measures of Theory of Mind (ToM). The aim of this study was to investigate if sex mediates the effects of high-definition transcranial direct current stimulation (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty healthy young adults (18–35 years) were randomly allocated to receive either anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. In each of the two sessions, subjects completed the RMET. Anodal stimulation to the dmPFC increased accuracy on the RMET in females only. To assure regional specificity we performed a follow-up study stimulating the right temporoparietal junction and found no effect in either sex. The current study is the first to show improved performance on the RMET after tDCS to the dmPFC in females only. The polarity-specific effects and use of focal HD-tDCS provide evidence for sex-dependent differences in dmPFC function in relation to the RMET. Future studies using tDCS to study or improve ToM, need to consider sex

The effect of mood in modulating prefrontal transcranial Direct Current Stimulation (tDCS) cognitive outcomes: A systematic review and meta-analysis

openIn recent years, several studies in cognitive neuroscience investigated the impact of prefrontal transcranial Direct Current Stimulation (tDCS) on executive functioning. However, the mixed results obtained so far suggest the need for meta-analytic approaches and meta-regression methods, aimed to both synthesize outcomes across studies and potentially identify the reasons for their variability. The present work aimed to test the hypothesis of mood as a possible moderating factor in the effect of prefrontal tDCS on executive functions. This hypothesis stems from the evidence showing that the region targeted by tDCS studies on executive functions, i.e. the dorsolateral prefrontal cortex (dlPFC), is also involved in mood and emotional regulation. Hence, our hypothesis suggests that dlPFC is the shared neural underpinnings of the circuits of mood and executive functioning, and that mood influences the performance of cognitive tasks. Mood disturbances are often linked to cognitive deficits, and there is some evidence in research that suggests that mood states could influence cognitive performance. Moreover, different models attempt to explain how mood modulates cognition, for example by making some contents more available or by triggering different process strategies during cognitive tasks. To test this hypothesis, a systematic review and meta-analysis have been conducted by selecting anodal tDCS studies targeting the dlPFC. The included articles were 19 within-group, sham-controlled and single-session experiments. Every article included at least a mood measurement at baseline and a cognitive task performed after or during stimulation. In this study, both clinical and healthy populations were included. Results discarded mood as a modulating factor of cognitive performance in dlPFC-tDCS. Furthermore, tDCS led to no effect on cognitive outcomes. In conclusion, our analysis adds to the literature by supporting the evidence for a lack of relevant effect of dlPFC-tDCS on bettering cognitive performance, as well as ruling out the mood as a potential factor that explains the variety of findings.In recent years, several studies in cognitive neuroscience investigated the impact of prefrontal transcranial Direct Current Stimulation (tDCS) on executive functioning. However, the mixed results obtained so far suggest the need for meta-analytic approaches and meta-regression methods, aimed to both synthesize outcomes across studies and potentially identify the reasons for their variability. The present work aimed to test the hypothesis of mood as a possible moderating factor in the effect of prefrontal tDCS on executive functions. This hypothesis stems from the evidence showing that the region targeted by tDCS studies on executive functions, i.e. the dorsolateral prefrontal cortex (dlPFC), is also involved in mood and emotional regulation. Hence, our hypothesis suggests that dlPFC is the shared neural underpinnings of the circuits of mood and executive functioning, and that mood influences the performance of cognitive tasks. Mood disturbances are often linked to cognitive deficits, and there is some evidence in research that suggests that mood states could influence cognitive performance. Moreover, different models attempt to explain how mood modulates cognition, for example by making some contents more available or by triggering different process strategies during cognitive tasks. To test this hypothesis, a systematic review and meta-analysis have been conducted by selecting anodal tDCS studies targeting the dlPFC. The included articles were 19 within-group, sham-controlled and single-session experiments. Every article included at least a mood measurement at baseline and a cognitive task performed after or during stimulation. In this study, both clinical and healthy populations were included. Results discarded mood as a modulating factor of cognitive performance in dlPFC-tDCS. Furthermore, tDCS led to no effect on cognitive outcomes. In conclusion, our analysis adds to the literature by supporting the evidence for a lack of relevant effect of dlPFC-tDCS on bettering cognitive performance, as well as ruling out the mood as a potential factor that explains the variety of findings

A Comprehensive View of Electrosleep: The History, Finite Element Models and Future Directions

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. This is concluded with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES. Despite this history, questions regarding the efficacy of ES remain including optimal dose (electrode placement and waveform). An investigation into brain electric field and current density produced by various montages that are historically relevant to ES was done to evaluate how these montages effect the brain. MRI-derived head models that were segmented using an automated segmentation algorithm and manual corrections were solved for four different electrode montages. The montages that were used are as follows: Sponge electrode on left and right eyes (active), Sponge electrodes over left and right mastoids (return); Sponge electrodes above left and right eyes (active), Sponge electrodes over left and right mastoids (return); High-Definition (HD) electrodes on AF3 and AF4 (active), 5x7 cm sponge on neck (return); HD electrodes on AF3 and AF4 (active), 5x7 sponge electrode on Iz (return). A high concentration of electric field was found on the optic nerve, with levels lowered as the electrodes moved further away from the eyes. There was also a moderate current density on the amygdala, a center involved with anxiety, as well as high electric fields on the brain stem which are centers for sleep. Using the models that were run for the electrosleep inspired montages the montage that was selected for the proposed experiment was to use anodes on AF3 and AF4 with the cathode on Iz. The anodes will be HD electrodes while the cathode will be a 5x7 cm sponge. Subjects will be split into 4 groups of 8 people each and will receive two legs of stimulation spaced one week apart. One leg will have current of 2 mA, 1 mA, 0.5 mA or sham while the other leg is all sham and the order in which they receive it will be randomized. Subjects will be stimulated for 20 minutes at 100 Hz and will spend a total of 40 minutes during the experiment where they will have their eyes recorded with an IR sensitive camera and they will be required to perform an odd-tone response task. Subjects are expected to fall asleep faster with higher levels of current and there is no added effect from baseline expected for subjects who receive sham stimulatio