Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields.

We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.

Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

Cerebral hemodynamics underlying ankle force sense modulated by high-definition transcranial direct current stimulation.

This study aimed to investigate the effects of high-definition transcranial direct current stimulation on ankle force sense and underlying cerebral hemodynamics. Sixteen healthy adults (8 males and 8 females) were recruited in the study. Each participant received either real or sham high-definition transcranial direct current stimulation interventions in a randomly assigned order on 2 visits. An isokinetic dynamometer was used to assess the force sense of the dominant ankle; while the functional near-infrared spectroscopy was employed to monitor the hemodynamics of the sensorimotor cortex. Two-way analyses of variance with repeated measures and Pearson correlation analyses were performed. The results showed that the absolute error and root mean square error of ankle force sense dropped more after real stimulation than after sham stimulation (dropped by 23.4% vs. 14.9% for absolute error, and 20.0% vs. 10.2% for root mean square error). The supplementary motor area activation significantly increased after real high-definition transcranial direct current stimulation. The decrease in interhemispheric functional connectivity within the Brodmann's areas 6 was significantly correlated with ankle force sense improvement after real high-definition transcranial direct current stimulation. In conclusion, high-definition transcranial direct current stimulation can be used as a potential intervention for improving ankle force sense. Changes in cerebral hemodynamics could be one of the explanations for the energetic effect of high-definition transcranial direct current stimulation.

Multisession Anodal Transcranial Direct Current Stimulation Enhances Adult Hippocampal Neurogenesis and Context Discrimination in Mice.

Transcranial direct current stimulation (tDCS) is a promising noninvasive neuromodulatory treatment option for multiple neurologic and psychiatric disorders, but its mechanism of action is still poorly understood. Adult hippocampal neurogenesis (AHN) continues throughout life and is crucial for preserving several aspects of hippocampal-dependent cognitive functions. Nevertheless, the contribution of AHN in the neuromodulatory effects of tDCS remains unexplored. Here, we sought to investigate whether multisession anodal tDCS may modulate AHN and its associated cognitive functions. Multisession anodal tDCS were applied on the skull over the hippocampus of adult male mice for 20 min at 0.25 mA once daily for 10 d totally. We found that multisession anodal tDCS enhances AHN by increasing the proliferation, differentiation and survival of neural stem/progenitor cells (NSPCs). In addition, tDCS treatment increased cell cycle reentry and reduced cell cycle exit of NSPCs. The tDCS-treated mice exhibited a reduced GABAergic inhibitory tone in the dentate gyrus compared with sham-treated mice. The effect of tDCS on the proliferation of NSPCs was blocked by pharmacological restoration of GABAB receptor-mediated inhibition. Functionally, multisession anodal tDCS enhances performance on a contextual fear discrimination task, and this enhancement was prevented by blocking AHN using the DNA alkylating agent temozolomide (TMZ). Our results emphasize an important role for AHN in mediating the beneficial effects of tDCS on cognitive functions that substantially broadens the mechanistic understanding of tDCS beyond its well-described in hippocampal synaptic plasticity.SIGNIFICANCE STATEMENT Transcranial direct current stimulation (tDCS) has been shown to effectively enhance cognitive functions in healthy and pathologic conditions. However, the mechanisms underlying its effects are largely unknown and need to be better understood to enable its optimal clinical use. This study shows that multisession anodal tDCS enhances adult hippocampal neurogenesis (AHN) and therefore contributes to enhance context discrimination in mice. Our results also show that the effect of tDCS on AHN is associated with reduced GABAergic inhibition in the dentate gyrus. Our study uncovers a novel mechanism of anodal tDCS to elicit cognitive-enhancing effects and may have the potential to improve cognitive decline associated with normal aging and neurodegenerative disorders.

Neural mechanisms underlying improved new-word learning with high-density transcranial direct current stimulation.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

The relationship between frontal alpha asymmetry and behavioral and brain activity indices of reactive inhibitory control.

Reactive inhibitory control plays an important role in phenotype of different diseases/different phases of a disease. One candidate electrophysiological marker of inhibitory control is frontal alpha asymmetry (FAA). FAA reflects the relative difference in contralateral frontal brain activity. However, the relationship between FAA and potential behavioral/brain activity indices of reactive inhibitory control is not yet clear. We assessed the relationship between resting-state FAA and indicators of reactive inhibitory control. Additionally, we investigated the effect of modulation of FAA via transcranial direct current stimulation (tDCS). We implemented a randomized sham-controlled design with 65 healthy humans (Mage = 23.93; SDage = 6.08; 46 female). Before and after 2 mA anodal tDCS of the right frontal site (with the cathode at the contralateral site) for 20 minutes, we collected EEG data and reactive inhibitory performance in neutral and food-reward conditions using the Stop Signal Task (SST). There was no support for the effect of tDCS on FAA or any indices of reactive inhibitory control. Our correlation analysis revealed an association between inhibitory brain activity in the food-reward condition and (pre-tDCS) asymmetry. Higher right relative to left frontal brain activity was correlated with reduced early-onset inhibitory activity and in contrast, linked with higher late-onset inhibitory control in the food-reward condition. Similarly, event-related potential analyses showed reduced early-onset and enhanced late-onset inhibitory brain activity over time, particularly in the food-reward condition. These results suggest that there can be a dissociation regarding the lateralization of frontal brain activity and early and late onset inhibitory brain activity.

Complex sequential learning is not facilitated by transcranial direct current stimulation over DLPFC or M1.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique which was found to have a positive modulatory effect on online sequence acquisition or offline motor consolidation, depending on the relative role of the associated brain region. Primary motor regions (M1) and dorsolateral prefrontal cortices (DLPFC) have both been related to sequential learning. However, research so far did not systematically disentangle their differential roles in online and offline learning especially in more complex sequential paradigms. In this study, the influence of anodal M1 leg area-tDCS and anodal DLPFC-tDCS applied during complex sequential learning (online and offline) was investigated using a complex whole body serial reaction time task (CWB-SRTT) in 42 healthy volunteers. TDCS groups did not differ from sham tDCS group regarding their response and reaction time (online) and also not in terms of overnight consolidation (offline). Sequence specific learning and the number of recalled items also did not differ between groups. Results may be related to unspecific parameters such as timing of the stimulation or current intensity but can also be attributed to the relative role of M1 and DLPFC during early complex learning. Taken together, the current study provides preliminary evidence that M1 leg area or DLPFC modulation by means of tDCS does not improve complex sequential skill learning. SIGNIFICANCE STATEMENT: Understanding motor learning is helpful to deepen our knowledge about the human ability to acquire new skills. Complex sequential learning tasks have only been studied, sparsely, but are particularly mimicking challenges of daily living. The present study studied early motor learning in a complex serial reaction time task while transcranial direct current stimulation (tDCS) was either applied to leg primary motor cortex or bilateral dorsolateral prefrontal cortex. TDCS did not affect sequential learning, neither directly during performance nor in terms of sequence consolidation. Results provide preliminary information that M1 or bilateral DLPFC modulation does not improve early complex motor learning.

Transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex reduced attentional bias toward natural emotional sounds.

Previous research has indicated that the left dorsolateral prefrontal cortex (DLPFC) exerts an influence on attentional bias toward visual emotional information. However, it remains unclear whether the left DLPFC also play an important role in attentional bias toward natural emotional sounds. The current research employed the emotional spatial cueing paradigm, incorporating natural emotional sounds of considerable ecological validity as auditory cues. Additionally, high-definition transcranial direct current stimulation (HD-tDCS) was utilized to examine the impact of left dorsolateral prefrontal cortex (DLPFC) on attentional bias and its subcomponents, namely attentional engagement and attentional disengagement. The results showed that (1) compared to sham condition, anodal HD-tDCS over the left DLPFC reduced the attentional bias toward positive and negative sounds; (2) anodal HD-tDCS over the left DLPFC reduced the attentional engagement toward positive and negative sounds, whereas it did not affect attentional disengagement away from natural emotional sounds. Taken together, the present study has shown that left DLPFC, which was closely related with the top-down attention regulatory function, plays an important role in auditory emotional attentional bias.

Higher-order comparative reward processing is affected by noninvasive stimulation of the ventromedial prefrontal cortex.

A crucial skill, especially in rapidly changing environments, is to be able to learn efficiently from prior rewards or losses and apply this acquired knowledge in upcoming situations. Often, we must weigh the risks of different options and decide whether an option is worth the risk or whether we should choose a safer option. The ventromedial prefrontal cortex (vmPFC) is suggested as a major hub for basic but also higher-order reward processing. Dysfunction in this region has been linked to cognitive risk factors for depression and behavioral addictions, including reduced optimism and feedback learning. Here, we test whether modulations of vmPFC excitability via noninvasive transcranial direct current stimulation (tDCS) can alter reward anticipation and reward processing. In a financial gambling task, participants chose between a higher and a lower monetary risk option and eventually received feedback whether they won or lost. Simultaneously feedback on the unchosen option was presented as well. Behavioral and magnetoencephalographic correlates of reward processing were evaluated in direct succession of either excitatory or inhibitory tDCS of the vmPFC. We were able to show modulated reward approach behavior (expectancy of greater reward magnitudes) as well as altered reevaluation of received feedback by vmPFC tDCS as indicated by modified choice behavior following the feedback. Thereby, tDCS not only influenced early, rather basic reward processing, but it also modulated higher-order comparative feedback evaluation of gains and losses relative to alternative outcomes. The neural results underline this idea, as stimulation-driven modulations of the basic reward-related effect occurred at rather early time intervals and were followed by stimulation effects related to comparative reward processing. Importantly, behavioral ratings were correlated with neural activity in left frontal areas. Our results imply a dual function of the vmPFC consisting of approaching reward (as indicated by more risky choices) and elaborately evaluating outcomes. In addition, our data suggest that vmPFC activity is associated with adaptive decision-making in the future via modulated behavioral adaptation or reinforcement learning.

Does transcranial direct current stimulation of the primary motor cortex improve implicit motor sequence learning in Parkinson's disease?

Implicit motor sequence learning (IMSL) is a cognitive function that is known to be associated with impaired motor function in Parkinson's disease (PD). We previously reported positive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on IMSL in 11 individuals with PD with mild cognitive impairments (MCI), with the largest effects occurring during reacquisition. In the present study, we included 35 individuals with PD, with (n = 15) and without MCI (n = 20), and 35 age- and sex-matched controls without PD, with (n = 13) and without MCI (n = 22). We used mixed-effects models to analyze anodal M1 tDCS effects on acquisition (during tDCS), short-term (five minutes post-tDCS) and long-term reacquisition (one-week post-tDCS) of general and sequence-specific learning skills, as measured by the serial reaction time task. At long-term reacquisition, anodal tDCS resulted in smaller general learning effects compared to sham, only in the PD group, p = .018, possibly due to floor effects. Anodal tDCS facilitated the acquisition of sequence-specific learning (M = 54.26 ms) compared to sham (M = 38.98 ms), p = .003, regardless of group (PD/controls). Further analyses revealed that this positive effect was the largest in the PD-MCI group (anodal: M = 69.07 ms; sham: M = 24.33 ms), p < .001. Although the observed effect did not exceed the stimulation period, this single-session tDCS study confirms the potential of tDCS to enhance IMSL, with the largest effects observed in patients with lower cognitive status. These findings add to the body of evidence that anodal tDCS can beneficially modulate the abnormal basal ganglia network activity that occurs in PD.

tDCS of right-hemispheric Wernicke's area homologue affects contextual learning of novel lexicon.

Numerous studies have shown robust evidence of the right hemisphere's involvement in the language function, for instance in the processing of intonation, grammar, word meanings, metaphors, etc. However, its role in lexicon acquisition remains obscure. We applied transcranial direct current stimulation (tDCS) over the right-hemispheric homologue of Wernicke's area to assess its putative involvement in the processing of different types of novel semantics. After receiving 15 min of anodal, cathodal, or sham (placebo) tDCS, three groups of healthy participants learnt novel concrete and abstract words in the context of short stories. Learning outcomes were assessed using a battery of tests immediately after this contextual learning session and 24 h later. As a result, an inhibitory effect of cathodal tDCS and a facilitatory effect of anodal tDCS were found for abstract word acquisition only. We also found a significant drop in task performance on the second day of the assessment for both word types in all the stimulation groups, suggesting no significant influence of tDCS on the post-learning consolidation of new memory traces. The results suggest an involvement of Wernicke's right-hemispheric counterpart in initial encoding (but not consolidation) of abstract semantics, which may be explained either by the right hemispheres direct role in processing lexical semantics or by an indirect impact of tDCS on contralateral (left-hemispheric) cortical areas through cross-callosal connections.

Cerebellar Transcranial Direct Current Stimulation Modulates Anticipatory Postural Adjustments in Healthy Adults.

During forward swinging of the arm, the central nervous system must anticipate the effect of upraising upon the body. Little is known about the cerebellar network that coordinates these anticipatory postural adjustments (APAs). Stimulating different cerebellar regions with transcranial direct current stimulation (tDCS) and with different polarities modulated the APAs. We used surface electromyography (sEMG) to measure muscle activities in a bilateral rapid shoulder flexion task. The onset of APAs was altered after tDCS over the vermis, while the postural stability and the kinematics of arm raising were not affected. To our knowledge, this is the first human cerebellar-tDCS (c-tDCS) study to separate cerebellar involvement in core muscle APAs in bilateral rapid shoulder flexion. These data contribute to our understanding of the cerebellar network supporting APAs in healthy adults. Modulated APAs of the erector spinae by tDCS on the vermis may be related to altered cerebellar brain inhibition (CBI), suggesting the importance of the vermal-cerebral connections in APAs regulation.

Investigation of Neuromodulatory Effect of Anodal Cerebellar Transcranial Direct Current Stimulation on the Primary Motor Cortex Using Functional Near-Infrared Spectroscopy.

Cerebellar brain inhibition (CBI), a neural connection between the cerebellum and primary motor cortex (M1), has been researched as a target pathway for neuromodulation to improve clinical outcomes in various neurological diseases. However, conflicting results of anodal cerebellar transcranial direct current stimulation (acb-tDCS) on M1 excitability indicate that additional investigation is required to examine its precise effect. This study aimed to gather evidence of the neuromodulatory effect of acb-tDCS on the M1 using functional near-infrared spectroscopy (fNIRS). Sixteen healthy participants were included in this cross-over study. Participants received real and sham acb-tDCS randomly, with a minimum 1-week washout period between them. The anode and cathode were placed on the right cerebellum and the right buccinator muscle, respectively. Stimulation lasted 20 min at an intensity of 2 mA, and fNIRS data were recorded for 42 min (including a 4-min baseline before stimulation and an 18-min post-stimulation duration) using eight channels attached bilaterally on the M1. acb-tDCS induced a significant decrease in oxyhemoglobin (HbO) concentration (inhibitory effect) in the left (contralateral) M1, whereas it induced a significant increase in HbO concentration (excitatory effect) in the right (ipsilateral) M1 compared to sham tDCS during (p < 0.05) and after stimulation (p < 0.01) in a group level analysis. At the individual level, variations in response to acb-tDCS were observed. Our findings demonstrate the neuromodulatory effects of acb-tDCS on the bilateral M1 in terms of neuronal hemodynamics.

Comparing Cerebellar tDCS and Cerebellar tACS in Neurodegenerative Ataxias Using Wearable Sensors: A Randomized, Double-Blind, Sham-Controlled, Triple-Crossover Trial.

Cerebellar transcranial direct current stimulation (tDCS) represents a promising therapeutic approach for both motor and cognitive symptoms in neurodegenerative ataxias. Recently, transcranial alternating current stimulation (tACS) was also demonstrated to modulate cerebellar excitability by neuronal entrainment. To compare the effectiveness of cerebellar tDCS vs. cerebellar tACS in patients with neurodegenerative ataxia, we performed a double-blind, randomized, sham controlled, triple cross-over trial with cerebellar tDCS, cerebellar tACS or sham stimulation in twenty-six participants with neurodegenerative ataxia. Before entering the study, each participant underwent motor assessment with wearable sensors considering gait cadence (steps/minute), turn velocity (degrees/second) and turn duration (seconds), and a clinical evaluation with the scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). After each intervention, participants underwent the same clinical assessment along with cerebellar inhibition (CBI) measurement, a marker of cerebellar activity. The gait cadence, turn velocity, SARA, and ICARS significantly improved after both tDCS and tACS, compared to sham stimulation (all p<0.010). Comparable effects were observed for CBI (p<0.001). Overall, tDCS significantly outperformed tACS on clinical scales and CBI (p<0.01). A significant correlation between changes of wearable sensors parameters from baseline and changes of clinical scales and CBI scores was detected. Cerebellar tDCS and cerebellar tACS are effective in ameliorating symptoms of neurodegenerative ataxias, with the former being more beneficial than the latter. Wearable sensors may serve as rater-unbiased outcome measures in future clinical trials. ClinicalTrial.gov Identifier: NCT05621200.

Single-Session Cerebellar Transcranial Direct Current Stimulation Improves Postural Stability and Reduces Ataxia Symptoms in Spinocerebellar Ataxia.

Spinocerebellar ataxia (SCA) results in balance and coordination impairment, and current treatments have limited efficacy. Recent evidence suggests that combining postural training with cerebellar transcranial direct current stimulation (ctDCS) can improve these symptoms. However, the combined effects of ctDCS and postural training on individuals with spinocerebellar ataxia remain underexplored. Ten volunteers with (SCA type 3) participated in a triple-blind, randomized, crossover study to receive a single session of ctDCS (2 mA for 20 min) and a sham ctDCS session separated by at least one week. The Biodex Balance System was used to assess balance at each session, measuring overall stability index, anteroposterior stability index, and medial-lateral stability index. As secondary outcomes, cerebellar ataxia symptoms were evaluated using the 8-item Scale for Assessment and Rating of Ataxia. The assessments were conducted before and after each session. The results indicated that ctDCS enhanced the overall stability index when compared to sham ctDCS (Z = -2.10, p = 0.03), although it did not significantly affect the anteroposterior or medial-lateral stability indices. Compared to the baseline, a single session of ctDCS reduced appendicular symptoms related to cerebellar ataxia, as evidenced by improvements in the nose-finger test (Z = -2.07, p = 0.04), fast alternating hand movements (Z = -2.15, p = 0.03), and heel-to-shin slide (Z = -1.91, p = 0.05). In conclusion, our study suggests that a single session of ctDCS, in combination with postural training, can enhance balance and alleviate ataxia symptoms in individuals with cerebellar ataxia. This study was approved by the local research ethics committee (No. 2.877.813) and registered on clinicaltrials.org (NCT04039048 - https://www.clinicaltrials.gov/study/NCT04039048 ) on 2019-07-28.

Cerebellar Asymmetry of Motivational Direction: Anger-Dependent Effects of Cerebellar Transcranial Direct Current Stimulation on Aggression in Healthy Volunteers.

It has recently been theorized that the frontal asymmetry of approach- and avoidance-related motivation is mirrored in the posterolateral cerebellum. Accordingly, left-to-right dominant cerebellar activity is associated with avoidance-related motivation, whereas right-to-left dominant cerebellar activity is associated with approach-related motivation. The aim of this study was to examine the cerebellar asymmetry of motivational direction in approach-related behavior in the context of aggression. In this randomized double-blind sham-controlled crossover study, thirty healthy right-handed adult volunteers received 2 mA active or sham left cathodal-right anodal transcranial direct current stimulation (tDCS) to the cerebellum on two separate occasions while engaging in the Point Subtraction Aggression Paradigm (PSAP) task to measure aggressive behavior. Self-reported state anger was assessed before, halfway and immediately after the task, and heart rate and heart rate variability (HRV) were measured during the task. No main effects of tDCS on aggressive behavior, heart rate and HRV were found. Higher state anger before and during the PSAP task was associated with increased aggressive behavior in the active compared to sham tDCS condition. Aggressive behavior was positively correlated with heart rate during active tDCS, while an inverse association was observed during sham tDCS. Results provide support for the cerebellar asymmetry of motivational direction in approach-related behavior and illustrate the importance of affective state-dependency in tDCS-related effects.

The impact of transcranial direct current stimulation on attention bias modification in children with ADHD.

Individuals with attention deficit-hyperactivity disorder (ADHD) struggle with the interaction of attention and emotion. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in this interaction. In the present study, we aimed to explore the effect of stimulation applied over the dlPFC and vmPFC on attention bias in individuals with ADHD. Twenty-three children with ADHD performed the emotional Stroop and dot probe tasks during transcranial direct current stimulation (tDCS) in 3 conditions: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. Findings suggest reduction of attention bias in both real conditions based on emotional Stroop task and not dot probe task. These results were independent of emotional states. The dlPFC and vmPFC are involved in attention bias in ADHD. tDCS can be used for attention bias modification in children with ADHD.

Dose-dependent response of prefrontal transcranial direct current stimulation on the heart rate variability: An electric field modeling study.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) modulates the autonomic nervous system by activating deeper brain areas via top-down pathway. However, effects on the nervous system are heterogeneous and may depend on the amount of current that penetrates. Therefore, we aimed to investigate the variable effects of tDCS on heart rate variability (HRV), a measure of the functional state of the autonomic nervous system. Using three prefrontal tDCS protocols (1.5, 3 mA and sham), we associated the simulated individual electric field (E-field) magnitude in brain regions of interest with the HRV effects. This was a randomized, double-blinded, sham-controlled and within-subject trial, in which healthy young-adult participants received tDCS sessions separated by 2 weeks. The brain regions of interest were the dorsolateral PFC (DLPFC), anterior cingulate cortex, insula and amygdala. Overall, 37 participants were investigated, corresponding to a total of 111 tDCS sessions. The findings suggested that HRV, measured by root mean squared of successive differences (RMSSD) and high-frequency HRV (HF-HRV), were significantly increased by the 3.0 mA tDCS when compared to sham and 1.5 mA. No difference was found between sham and 1.5 mA. E-field analysis showed that all brain regions of interest were associated with the HRV outcomes. However, this significance was associated with the protocol intensity, rather than inter-individual brain structural variability. To conclude, our results suggest a dose-dependent effect of tDCS for HRV. Therefore, further research is warranted to investigate the optimal current dose to modulate HRV.

Computer-aided cognitive training combined with tDCS can improve post-stroke cognitive impairment and cerebral vasomotor function: a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is the focus and difficulty of poststroke rehabilitation intervention with an incidence of up to 61%, which may be related to the deterioration of cerebrovascular function. Computer-aided cognitive training (CACT) can improve cognitive function through scientific training targeting activated brain regions, becoming a popular training method in recent years. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, can regulate the cerebral vascular nerve function, and has an effect on the rehabilitation of cognitive dysfunction after stroke. This study examined the effectiveness of both CACT and tDCS on cognitive and cerebrovascular function after stroke, and explored whether CACT combined with tDCS was more effective. METHODS: A total of 72 patients with PSCI were randomly divided into the conventional cognitive training (CCT) group (n = 18), tDCS group (n = 18), CACT group (n = 18), and CACT combined with tDCS group (n = 18). Patients in each group received corresponding 20-minute treatment 15 times a week for 3 consecutive weeks. Montreal Cognitive Assessment (MoCA) and the Instrumental Activities of Daily Living Scale (IADL) were used to assess patients' cognitive function and the activities of daily living ability. Transcranial Doppler ultrasound (TCD) was used to assess cerebrovascular function, including cerebral blood flow velocity (CBFV), pulse index (PI), and breath holding index (BHI). These outcome measures were measured before and after treatment. RESULTS: Compared with those at baseline, both the MoCA and IADL scores significantly increased after treatment (P < 0.01) in each group. There was no significantly difference in efficacy among CCT, CACT and tDCS groups. The CACT combined with tDCS group showed greater improvement in MoCA scores compared with the other three groups (P < 0.05), especially in the terms of visuospatial and executive. BHI significantly improved only in CACT combined with tDCS group after treatment (p ≤ 0.05) but not in the other groups. Besides, no significant difference in CBFV or PI was found before and after the treatments in all groups. CONCLUSION: Both CACT and tDCS could be used as an alternative to CCT therapy to improve cognitive function and activities of daily living ability after stroke. CACT combined with tDCS may be more effective improving cognitive function and activities of daily living ability in PSCI patients, especially visuospatial and executive abilities, which may be related to improved cerebral vasomotor function reflected by the BHI. TRIAL REGISTRATION NUMBER: The study was registered in the Chinese Registry of Clinical Trials (ChiCTR2100054063). Registration date: 12/08/2021.

Transcranial direct current stimulation facilitates backward walking training.

Backward walking training presents a great challenge to the physical and neural systems, which may result in an improvement in gait performance. Transcranial direct current electrical stimulation (tDCS), which can non-invasively enhance cortical activity, has been reported to strengthen corticomotor plasticity. We investigated whether excitatory tDCS over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) enhances the effects of backward walking training in healthy participants. Thirty-six healthy participants (16 men and 20 women, mean age 21.3 ± 1.4 years) participated in this study. The participants were randomly assigned to one of the three tDCS groups (M1, DLPFC, and sham). They performed 5 min of backward walking training during 15 min of tDCS. We evaluated dual-task forward and backward walking performance before and after training. Both tDCS groups increased walking speed in the backward condition, but the DLPFC group increased the dual-task backward walking speed more than the M1 group. The M1 group showed decreased gait variability in dual-task backward walking, whereas the DLPFC group showed increased gait variability. Backward walking training combined with M1 stimulation may increase the backward walking speed by reducing gait variability. Backward walking training combined with DLPFC stimulation may prioritize walking speed over gait stability. Our results indicate that backward walking training combined with tDCS may be extended to other rehabilitation methods to improve gait performance.