High-definition Transcranial Direct Current Stimulation Research Articles

High‐definition transcranial direct current stimulation of the occipital cortices induces polarity dependent effects within the brain regions serving attentional reorientation

Numerous brain stimulation studies have targeted the posterior parietal cortex, a key hub of the attention network, to manipulate attentional reorientation. However, the impact of stimulating brain regions earlier in the pathway, including early visual regions, is poorly understood. In this study, 28 healthy adults underwent three high‐definition transcranial direct current stimulation (HD‐tDCS) visits (i.e., anodal, cathodal, and sham). During each visit, they completed 20 min of occipital HD‐tDCS and then a modified Posner task during magnetoencephalography (MEG). MEG data were transformed into the time‐frequency domain and significant oscillatory events were imaged using a beamformer. Oscillatory response amplitude values were extracted from peak voxels in the whole‐brain maps and were statistically compared. Behaviorally, we found that the participants responded slowly when attention reallocation was needed (i.e., the validity effect), irrespective of the stimulation condition. Our neural findings indicated that cathodal HD‐tDCS was associated with significantly reduced theta validity effects in the occipital cortices, as well as reduced alpha validity effects in the left occipital and parietal cortices relative to anodal HD‐tDCS. Additionally, anodal occipital stimulation significantly increased gamma amplitude in right occipital regions relative to cathodal and sham stimulation. Finally, we also found a negative correlation between the alpha validity effect and reaction time following anodal stimulation. Our findings suggest that HD‐tDCS of the occipital cortices has a polarity dependent impact on the multispectral neural oscillations serving attentional reorientation in healthy adults, and that such effects may reflect altered local GABA concentrations in the neural circuitry serving attentional reorientation.

Prof M. Murugappan Poster Award

Background:In schizophrenia, negative symptoms are often resistant to treatment. Transcranial Direct Current Stimulation (tDCS) to dorsolateral prefrontal cortex (DLPFC) has been tried as an add-on treatment for negative symptoms. High-Definition tDCS (HD-tDCS), an optimized form of tDCS, ensures focalized neuromodulation and delivery of higher current densities. Anodal tDCS has been found to increase N-Acetyl Aspartate (NAA) levels in healthy volunteers and studies have found a relationship between reduced NAA concentration in frontal cortex and severity of negative symptoms.Aim:We aimed to evaluate the efficacy of HD-tDCS over left DLPFC for negative symptoms in schizophrenia and associated changes in NAA levels.Methods:36 patients of schizophrenia with negative symptoms, were enrolled for study. Participants in active group received 10 sessions of HD-tDCS at 2mA for 20min twice daily over 5 days. Magnetic Resonance Spectroscopy was done at baseline, after 2 sessions of HD-tDCS and 6 weeks. Negative symptoms were assessed with SANS and PANSS at baseline, 2 and 6 weeks.Results:Improvement in negative symptoms in active group was statistically significant at 0.05 (p-value) as compared to sham group at 2 weeks. During 6 weeks follow-up, initial reduction in negative symptoms was maintained but no further improvement was noted. There was no significant difference between NAA levels and treatment group over time but there was significant correlation between changes in NAA levels and changes in negative symptoms.Conclusion:HD-tDCS may lead to improvement in negative symptoms and through neuroplastic effects, may alter NAA levels and exert its therapeutic benefits.

High-definition transcranial direct current stimulation modulates performance and alpha/beta parieto-frontal connectivity serving fluid intelligence.

Fluid intelligence (Gƒ) includes logical reasoning abilities and is an essential component of normative cognition. Despite the broad consensus that parieto-prefrontal connectivity is critical for Gƒ (e.g. the parieto-frontal integration theory of intelligence, P-FIT), the dynamics of such functional connectivity during logical reasoning remains poorly understood. Further, given the known importance of these brain regions for Gƒ, numerous studies have targeted one or both of these areas with non-invasive stimulation with the goal of improving Gƒ, but to date there remains little consensus on the overall stimulation-related effects. To examine this, we applied high-definition direct current anodal stimulation to the left and right dorsolateral prefrontal cortex (DLPFC) of 24 healthy adults for 20min in three separate sessions (sham, left, and right active). Following stimulation, participants completed a logical reasoning task during magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer, and peak task-induced activity was subjected to dynamic functional connectivity analyses to evaluate the impact of distinct stimulation montages on network activity. We found that participants responded faster following right DLPFC stimulation vs. sham. Moreover, our neural findings followed a similar trajectory of effects such that left parieto-frontal connectivity decreased following right and left DLPFC stimulation compared to sham, with connectivity following right stimulation being significantly correlated with the faster reaction times. Importantly, our findings are consistent with P-FIT, as well as the neural efficiency hypothesis (NEH) of intelligence. In sum, this study provides evidence for beneficial effects of right DLPFC stimulation on logical reasoning. KEY POINTS: Logical reasoning is an indispensable component of fluid intelligence and involves multispectral oscillatory activity in parietal and frontal regions. Parieto-frontal integration is well characterized in logical reasoning; however, its direct neural quantification and neuromodulation by brain stimulation remain poorly understood. High-definition transcranial direct current stimulation of dorsolateral prefrontal cortex (DLPFC) had modulatory effects on task performance and neural interactions serving logical reasoning, with right stimulation showing beneficial effects. Right DLPFC stimulation led to a decrease in the response time (i.e. better task performance) and left parieto-frontal connectivity with a marginal positive association between behavioural and neural metrics. Other modes of targeted stimulation of DLPFC (e.g. frequency-specific) can be employed in future studies.

Mentalizing with the future: Electrical stimulation of the right TPJ increases sustainable decision-making

While many people acknowledge the urgency to drastically change our consumption patterns to mitigate climate change, most people fail to live sustainably. We hypothesized that a lack of sustainability stems from insufficient intergenerational mentalizing (i.e., taking the perspective of people in the future). To causally test our hypothesis, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the temporo-parietal junction (TPJ). We tested participants twice (receiving stimulation at the TPJ or the vertex as control), while they engaged in a behavioral economic paradigm measuring sustainable decision-making, even if sustainability was costly. Indeed, excitatory anodal HD-tDCS increased sustainable decision-making, while inhibitory cathodal HD-tDCS had no effect. These finding cannot be explained by changes in participants’ fairness norms or their estimation of how other people would behave. Shedding light on the neural basis of sustainability, our results could inspire targeted interventions tackling the TPJ and give neuroscientific support to theories on how to construct public campaigns addressing sustainability issues.

Effects of High Definition-Transcranial Direct Current Stimulation on Local GABA and Glutamate Levels Among Older Adults with and without Mild Cognitive Impairment: An Exploratory Study.

Prior research, primarily with young adults, suggests transcranial direct current stimulation (tDCS) effects are driven by the primary excitatory and/or inhibitory neurotransmitters, glutamate, and gamma-aminobutyric acid (GABA), respectively. We examined the neurometabolic mechanisms of tDCS in older adults with and without mild cognitive impairment (MCI). We used data from a double-blind, cross-over, randomized controlled trial (NCT01958437) in 32 older adults to evaluate high definition (HD)-tDCS-induced changes in glutamate and GABA via magnetic resonance spectroscopy (MRS). Participants underwent MRS following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right superior parietal cortex (center anode at P2) and delivered 2mA for 20 minutes. Relative to sham, and when co-varying for MRS voxel overlap and right superior parietal volume, active HD-tDCS significantly increased GABA and decreased the ratio of glutamate to GABA. No changes were observed in a left prefrontal control MRS voxel. Although we did not find a significant correlation between strength of delivered current (measured via MRI-based computational modeling) and neurometabolite change, there was a robust positive relationship between the volume of right superior parietal cortex and neurometabolite change. Our preliminary findings of increased GABA and reduced glutamate/GABA ratio raise the possibility that (HD-)tDCS effects differ by age. Moreover, age- and disease-related regional brain volume loss may be especially important to consider when planning future studies. Replication would emphasize the importance of developing population-specific tDCS parameters that consider structural and physiologic changes associated with "normal" and pathological aging.

Effects of High-Definition Transcranial Direct Current Stimulation Over the Left Fusiform Face Area on Face View Discrimination Depend on the Individual Baseline Performance.

A basic human visual function is to identify objects from different viewpoints. Typically, the ability to discriminate face views based on in-depth orientation is necessary in daily life. Early neuroimaging studies have identified the involvement of the left fusiform face area (FFA) and the left superior temporal sulcus (STS) in face view discrimination. However, many studies have documented the important role of the right FFA in face processing. Thus, there remains controversy over whether one specific region or all of them are involved in discriminating face views. Thus, this research examined the influence of high-definition transcranial direct current stimulation (HD-tDCS) over the left FFA, left STS or right FFA on face view discrimination in three experiments. In experiment 1, eighteen subjects performed a face view discrimination task before and immediately, 10 min and 20 min after anodal, cathodal and sham HD-tDCS (20 min, 1.5 mA) over the left FFA in three sessions. Compared with sham stimulation, anodal and cathodal stimulation had no effects that were detected at the group level. However, the analyses at the individual level showed that the baseline performance negatively correlated with the degree of change after anodal tDCS, suggesting a dependence of the change amount on the initial performance. Specifically, tDCS decreased performance in the subjects with better baseline performance but increased performance in those with poorer baseline performance. In experiments 2 and 3, the same experimental protocol was used except that the stimulation site was the left STS or right FFA, respectively. Neither anodal nor cathodal tDCS over the left STS or right FFA influenced face view discrimination in group- or individual-level analyses. These results not only indicated the importance of the left FFA in face view discrimination but also demonstrated that individual initial performance should be taken into consideration in future research and practical applications.

Efficacy of transcranial direct current stimulation in people with multiple sclerosis: a review.

Multiple sclerosis (MS) is a chronic inflammatory disease causing a wide range of symptoms including motor and cognitive impairment, fatigue and pain. Over the last two decades, non-invasive brain stimulation, especially transcranial direct current stimulation (tDCS), has increasingly been used to modulate brain function in various physiological and pathological conditions. However, its experimental applications for people with MS were noted only as recently as 2010 and have been growing since then. The efficacy for use in people with MS remains questionable with the results of existing studies being largely conflicting. Hence, the aim of this review is to paint a picture of the current state of tDCS in MS research grounded on studies applying tDCS that have been done to date. A keyword search was performed to retrieve articles from the earliest article identified until 14 February 2021 using a combination of the groups (1) 'multiple sclerosis', 'MS' and 'encephalomyelitis' and (2) 'tDCS' and 'transcranial direct current stimulation'. The analysis of the 30 articles included in this review underlined inconsistent effects of tDCS on the motor symptoms of MS based on small sample sizes. However, tDCS showed promising benefits in ameliorating fatigue, pain and cognitive symptoms. Transcranial direct current stimulation is attractive as a non-drug approach in ameliorating MS symptoms, where other treatment options remain limited. The development of protocols tailored to the individual's own neuroanatomy using high definition tDCS and the introduction of network mapping in the experimental designs might help to overcome the variability between studies.

Transcranial direct current stimulation improve symptoms and modulates cortical inhibition in obsessive-compulsive disorder: A TMS-EEG study

BackgroundObsessive-compulsive disorder (OCD) is a disabling condition for which approximately 40% of patients do not respond to first-line treatment. Transcranial direct current stimulation (tDCS) is a safe and accessible technique that modulates cortical excitability and inhibition, but evidence of its efficacy for OCD is insufficient. ObjectiveTo investigate the efficacy of tDCS for OCD and alterations of cortical excitability and inhibition after treatment measured by concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). MethodsTwenty-four OCD patients underwent 10 20-min sessions of 1.5 mA high-definition tDCS with a cathode placed over the right orbitofrontal cortex (OFC) and anode electrodes set around the cathodal electrode. TMS-EEG was performed before and after tDCS treatment. OCD symptom severitys was assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Beck Depression Inventory-Ⅱ (BDI-Ⅱ), and Beck Anxiety Inventory (BAI) were used to assess the severity of depression and anxiety symptoms. Twenty-seven healthy controls were recruited with TMS-EEG recorded. ResultsFollowing tDCS, the Y-BOCS, BDI-Ⅱ, and BAI scores decreased significantly (all p = 0.000). TMS-evoked N100 amplitude, thought to be related to GABAB receptor function, was significantly reduced after tDCS (Z = -2.143, p = 0.032) which was higher in OCD patients than in healthy controls at baseline (Z = -2.151, p = 0.031). LimitationsPharmacotherapy during tDCS treatment may influence the effect of tDCS and EEG. ConclusionsCathodal high-definition tDCS applied over the OFC could improve OCD, depression, and anxiety symptoms along with alleviation of GABAB receptor function.

Somatosensory Cortical Electrical Stimulation After Reperfusion Attenuates Ischemia/Reperfusion Injury of Rat Brain.

Objective: Ischemic stroke is an important cause of death and disability worldwide. Early reperfusion by thrombolysis or thrombectomy has improved the outcome of acute ischemic stroke. However, the therapeutic window for reperfusion therapy is narrow, and adjuvant therapy for neuroprotection is demanded. Electrical stimulation (ES) has been reported to be neuroprotective in many neurological diseases. In this study, the neuroprotective effect of early somatosensory cortical ES in the acute stage of ischemia/reperfusion injury was evaluated.Methods: In this study, the rat model of transient middle cerebral artery occlusion was used to explore the neuroprotective effect and underlying mechanisms of direct primary somatosensory (S1) cortex ES with an electric current of 20 Hz, 2 ms biphasic pulse, 100 μA for 30 min, starting at 30 min after reperfusion.Results: These results showed that S1 cortical ES after reperfusion decreased infarction volume and improved functional outcome. The number of activated microglia, astrocytes, and cleaved caspase-3 positive neurons after ischemia/reperfusion injury were reduced, demonstrating that S1 cortical ES alleviates inflammation and apoptosis. Brain-derived neurotrophic factor (BDNF) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were upregulated in the penumbra area, suggesting that BDNF/TrkB signals and their downstream PI3K/Akt signaling pathway play roles in ES-related neuroprotection.Conclusion: This study demonstrates that somatosensory cortical ES soon after reperfusion can attenuate ischemia/reperfusion injury and is a promising adjuvant therapy for thrombolytic treatment after acute ischemic stroke. Advanced techniques and devices for high-definition transcranial direct current stimulation still deserve further development in this regard.

Engagement of a parieto-cerebellar network in prism adaptation. A double-blind high-definition transcranial direct current stimulation study on healthy individuals

Prism Adaptation (PA) is a non-invasive method to investigate visuomotor control. Recent neurostimulation studies have proposed an interpretation of the mechanisms underlying PA based on functioning of brain networks, instead of focusing on single brain areas.To test the functioning of the network during a classical PA procedure, here we used for the first time High-Definition transcranial Direct Current Stimulation (HD-tDCS) to simultaneously inhibit or facilitate brain activity in two main nodes of the network, namely the parietal cortex and the cerebellum, in healthy individuals.The main results showed that simultaneous anodal HD-tDCS over the two regions reduced terminal errors during exposure to prism glasses as compared to cathodal and sham stimulation. Conversely, cathodal HD-tDCS reduced after-effect as compared to anodal and sham stimulation following prism removal.Overall, these results provide new insights on the network related to the deployment of PA mechanisms and demonstrate the feasibility of using non-invasive HD-tDCS to modulate the adaptive mechanisms of PA.

An Automated Workflow for the Electric Field Modeling of High-definition Transcranial Direct Current Stimulation (HD-tDCS) in Chronic Stroke with Lesions.

Transcranial Direct Current Stimulation is a popular noninvasive brain stimulation (NIBS) technique that modulates brain excitability by means of low-amplitude electrical current (usually <4mA) delivered to the electrodes on the scalp. The NIBS research has gained significant momentum in the past decade, prompting tDCS as an adjunctive therapeutic tool for neuromuscular disorders like stroke. However, due to stroke lesions and the differences in individual neuroanatomy, the targeted brain region may not show the same response upon NIBS across stroke patients. To this end, we conducted a study to test the feasibility of targeted NIBS. The hand motor hotspot (HMH) for each chronic stroke participant was identified using Neuronavigated Transcranial Magnetic Stimulation (TMS). After identifying the HMH as the neural target site, we applied High-definition TDCS with the current delivered at 2mA for 20 minutes. To simulate the effects of HD-tDCS in the brain, especially with stroke lesions, we used the computational modeling tool (ROAST). The lesion mask was identified using an automated tool (LINDA). This paper demonstrates that the stroke lesions can be incorporated in the computational modeling of electric field distribution upon HD-tDCS without manual intervention.

Improving speech and upper limb motor reaction times through high-definition transcranial direct current stimulation of the left ventral motor cortex

Improving speech and upper limb motor reaction times through high-definition transcranial direct current stimulation of the left ventral motor cortex

High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment

High-definition transcranial direct current stimulation enhances network segregation during spatial navigation in mild cognitive impairment

Effect of High-definition Transcranial Direct Current Stimulation on Conditioned Pain Modulation in Healthy Adults: A Crossover Randomized Controlled Trial

The disorder of the conditioned pain modulation (CPM) system is one of the main causes of pain perception in individuals. High-definition transcranial direct current stimulation (HD-tDCS) targeting specific brain areas was indicated to have an analgesic effect possibly by activating the endogenous pain inhibition pathway evident in CPM. However, discrepancies were found in previous limited studies of varied homogeneity and quality. Therefore, the present study applied 2 mA HD-tDCS (20 min) in the left primary motor cortex (M1) among 35 healthy adults with a blinded crossover study design, to investigate its effectiveness on optimizing the analgesic effect in healthy individuals through assessing changes of the CPM. The univariate and multivariate general linear models were used to evaluate the intervention effect between-group on the Δ-value (after-intervention minus before-intervention) during CPM (primary outcome), pressure pain threshold (PPT), and cold pressure threshold (CPT) (secondary outcome), respectively. A significant between-group difference in Δ-CPM was found for active stimulation. HD-tDCS significantly improved the analgesic efficiency of Δ-CPM, compared with the sham control, after adjusting the confounding factors including age, gender, psychological status, as well as the sequence effect. The changes of CPM were positively correlated with the total physical activity volume. In conclusion, our findings provide evidence support to the effectiveness of HD-tDCS on endogenous pain modulation among healthy adults. Further studies are required to explore the analgesic effect of tDCS among patients with chronic pain, thereby facilitating optimal chronic pain management.

The effect of high-definition transcranial direct current stimulation on pain processing in a healthy population: A single-blinded crossover controlled study

Transcranial direct current stimulation (tDCS) is increasingly used in pain treatment. tDCS targeting both primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) may modulate the descending pain inhibitory system, however, it remains controversial regarding the optimal stimulation region for pain modulation. Therefore, this study aimed to explore the effects of high-definition anodic stimulation of M1 and DLPFC on conditioned pain modulation (CPM) and pain thresholds and establish a preferred stimulation setting. Twenty-six healthy adults were randomly assigned to M1-tDCS, DLPFC-tDCS, or sham-tDCS groups. During the three sessions, each participant received an active or sham stimulation of 2 mA for 20 min, with at least 3 days’ interval between sessions. Quantitative sensory tests were performed to obtain pressure pain threshold (PPT), cold pain threshold (CPT), and CPM before and after the tDCS intervention. Only M1-tDCS significantly increased CPM in healthy individuals compared with sham control (P = 0.004). No statistically significant difference was found in PPT and CPT between tDCS vs. sham control (P > 0.05). Our findings further support the important role of M1 as a target in pain regulation. Further large-scale, multicenter studies in chronic pain populations are needed to validate the alterations of distinct target brain regions related to pain and thus for an optimal target stimulation strategy in pain management.

Effects of Transcranial Direct Current Stimulation and High-Definition Transcranial Direct Current Stimulation Enhanced Motor Learning on Robotic Transcranial Magnetic Stimulation Motor Maps in Children.

Introduction: Conventional transcranial direct current stimulation (tDCS) and high-definition tDCS (HD-tDCS) may improve motor learning in children. Mechanisms are not understood. Neuronavigated robotic transcranial magnetic stimulation (TMS) can produce individualised maps of primary motor cortex (M1) topography. We aimed to determine the effects of tDCS- and HD-tDCS-enhanced motor learning on motor maps.Methods: Typically developing children aged 12–18 years were randomised to right M1 anodal tDCS, HD-tDCS, or Sham during training of their left-hand on the Purdue Pegboard Task (PPT) over 5 days. Bilateral motor mapping was performed at baseline (pre), day 5 (post), and 6-weeks retention time (RT). Primary muscle was the first dorsal interosseous (FDI) with secondary muscles of abductor pollicis brevis (APB) and adductor digiti minimi (ADM). Primary mapping outcomes were volume (mm2/mV) and area (mm2). Secondary outcomes were centre of gravity (COG, mm) and hotspot magnitude (mV). Linear mixed-effects modelling was employed to investigate effects of time and stimulation type (tDCS, HD-tDCS, Sham) on motor map characteristics.Results: Twenty-four right-handed participants (median age 15.5 years, 52% female) completed the study with no serious adverse events or dropouts. Quality maps could not be obtained in two participants. No effect of time or group were observed on map area or volume. LFDI COG (mm) differed in the medial-lateral plane (x-axis) between tDCS and Sham (p = 0.038) from pre-to-post mapping sessions. Shifts in map COG were also observed for secondary left-hand muscles. Map metrics did not correlate with behavioural changes.Conclusion: Robotic TMS mapping can safely assess motor cortex neurophysiology in children undergoing motor learning and neuromodulation interventions. Large effects on map area and volume were not observed while changes in COG may occur. Larger controlled studies are required to understand the role of motor maps in interventional neuroplasticity in children.

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans

Transcranial direct current stimulation (tDCS) has been shown to evoke hemodynamics response; however, the mechanisms have not been investigated systematically using systems biology approaches. Our study presents a grey-box linear model that was developed from a physiologically detailed multi-compartmental neurovascular unit model consisting of the vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. Then, model linearization was performed on the physiologically detailed nonlinear model to find appropriate complexity (Akaike information criterion) to fit functional near-infrared spectroscopy (fNIRS) based measure of blood volume changes, called cerebrovascular reactivity (CVR), to high-definition (HD) tDCS. The grey-box linear model was applied on the fNIRS-based CVR during the first 150 seconds of anodal HD-tDCS in eleven healthy humans. The grey-box linear models for each of the four nested pathways starting from tDCS scalp current density that perturbed synaptic potassium released from active neurons for Pathway 1, astrocytic transmembrane current for Pathway 2, perivascular potassium concentration for Pathway 3, and voltage-gated ion channel current on the smooth muscle cell for Pathway 4 were fitted to the total hemoglobin concentration (tHb) changes from optodes in the vicinity of 4x1 HD-tDCS electrodes as well as on the contralateral sensorimotor cortex. We found that the tDCS perturbation Pathway 3 presented the least mean square error (MSE, median <2.5%) and the lowest Akaike information criterion (AIC, median -1.726) from the individual grey-box linear model fitting at the targeted-region. Then, minimal realization transfer function with reduced-order approximations of the grey-box model pathways was fitted to the ensemble average tHb time series. Again, Pathway 3 with nine poles and two zeros (all free parameters), provided the best Goodness of Fit of 0.0078 for Chi-Square difference test of nested pathways. Therefore, our study provided a systems biology approach to investigate the initial transient hemodynamic response to tDCS based on fNIRS tHb data. Future studies need to investigate the steady-state responses, including steady-state oscillations found to be driven by calcium dynamics, where transcranial alternating current stimulation may provide frequency-dependent physiological entrainment for system identification. We postulate that such a mechanistic understanding from system identification of the hemodynamics response to transcranial electrical stimulation can facilitate adequate delivery of the current density to the neurovascular tissue under simultaneous portable imaging in various cerebrovascular diseases.

Control of Transcranial Direct Current Stimulation Duration by Assessing Functional Connectivity of Near-Infrared Spectroscopy Signals.

Transcranial direct current stimulation (tDCS) has been shown to create neuroplasticity in healthy and diseased populations. The control of stimulation duration by providing real-time brain state feedback using neuroimaging is a topic of great interest. This study presents the feasibility of a closed-loop modulation for the targeted functional network in the prefrontal cortex. We hypothesize that we cannot improve the brain state further after reaching a specific state during a stimulation therapy session. A high-definition tDCS of 1[Formula: see text]mA arranged in a ring configuration was applied at the targeted right prefrontal cortex of 15 healthy male subjects for 10[Formula: see text]min. Functional near-infrared spectroscopy was used to monitor hemoglobin chromophores during the stimulation period continuously. The correlation matrices obtained from filtered oxyhemoglobin were binarized to form subnetworks of short- and long-range connections. The connectivity in all subnetworks was analyzed individually using a new quantification measure of connectivity percentage based on the correlation matrix. The short-range network in the stimulated hemisphere showed increased connectivity in the initial stimulation phase. However, the increase in connection density reduced significantly after 6[Formula: see text]min of stimulation. The short-range network of the left hemisphere and the long-range network gradually increased throughout the stimulation period. The connectivity percentage measure showed a similar response with network theory parameters. The connectivity percentage and network theory metrics represent the brain state during the stimulation therapy. The results from the network theory metrics, including degree centrality, efficiency, and connection density, support our hypothesis and provide a guideline for feedback on the brain state. The proposed neuro-feedback scheme is feasible to control the stimulation duration to avoid overdosage.

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer's Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position.

The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer's disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. To measure the effect of individualized HD-tDCS in AD patients. Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient's brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

Distinct Causal Influences of Dorsolateral Prefrontal Cortex and Posterior Parietal Cortex in Multiple-Option Decision Making.

Our knowledge about neural mechanisms underlying decision making is largely based on experiments that involved few options. However, it is more common in daily life to choose between many options, in which processing choice information selectively is particularly important. The current study examined whether the dorsolateral prefrontal cortex (dlPFC) and posterior parietal cortex (PPC) are of particular importance to multiple-option decision making. Sixty-eight participants received anodal high definition-transcranial direct current stimulation (HD-tDCS) to focally enhance dlPFC or PPC in a double-blind sham-controlled design. Participants then performed a multiple-option decision making task. We found longer fixations on poorer options were related to less optimal decisions. Interestingly, this negative impact was attenuated after applying anodal HD-tDCS over dlPFC, especially in choices with many options. This suggests that dlPFC has a causal role in filtering choice-irrelevant information. In contrast, these effects were absent after participants received anodal HD-tDCS over PPC. Instead, the choices made by these participants were more biased towards the best options presented on the side contralateral to the stimulation. This suggests PPC has a causal role in value-based spatial selection. To conclude, the dlPFC has a role in filtering undesirable options, whereas the PPC emphasizes the desirable contralateral options.