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 min, 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.NEW & NOTEWORTHY This research reveals dissociation between baseline frontal alpha asymmetry and the timing of reactive inhibitory brain activities in food-reward contexts. Whereas inhibitory control performance decreases over time in a stop signal task, electrophysiological indices show reduced early- and heightened late-onset inhibitory brain activity, especially in the reward condition. Additionally, greater right frontal activity correlates with reduced early-onset and increased 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.

The influence of transcranial direct current stimulation to the trigeminal nerve on attention and arousal.

One mechanism by which transcranial direct current stimulation (tDCS) has been proposed to improve attention is by transcutaneous stimulation of cranial nerves, thereby activating the locus coeruleus (LC). Specifically, placement of the electrodes over the frontal bone and mastoid is thought to facilitate current flow across the face as a path of least resistance. The face is innervated by the trigeminal nerve, and the trigeminal nerve is interconnected with the LC. In this study, we tested whether stimulating the trigeminal nerve impacts indices of LC activity and performance on a sustained attention task. We replicated previous research that shows deterioration in task performance, increases in the rate of task-unrelated thoughts, and reduced pupil responses due to time on task irrespective of tDCS condition (sham, anodal, and cathodal stimulation). Importantly, tDCS did not influence pupil dynamics (pretrial or stimulus-evoked), self-reported attention state, nor task performance in active versus sham stimulation conditions. The findings reported here are consistent with theories about arousal centered on a hypothesized link between LC activity indexed by pupil size, task performance, and self-reported attention state but fail to support hypotheses that tDCS over the trigeminal nerve influences indices of LC function.

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.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

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.

The neural structures of theory of mind are valence-sensitive: evidence from three tDCS studies.

Several cortical structures are involved in theory of mind (ToM), including the dorsolateral prefrontal cortex (dlPFC), the ventromedial prefrontal cortex (vmPFC), and the right temporo- parietal junction (rTPJ). We investigated the role of these regions in mind reading with respect to the valence of mental states. Sixty-five healthy adult participants were recruited and received transcranial direct current stimulation (tDCS) (1.5 mA, 20 min) with one week interval in three separate studies. The stimulation conditions were anodal tDCS over the dlPFC coupled with cathodal tDCS over the vmPFC, reversed stimulation conditions, and sham in the first study, and anodal tDCS over the vmPFC, or dlPFC, and sham stimulation, with an extracranial return electrode in the second and third study. During stimulation, participants underwent the reading mind from eyes/voice tests (RMET or RMVT) in each stimulation condition. Anodal left dlPFC/cathodal right vmPFC stimulation increased the accuracy of negative mental state attributions, anodal rTPJ decreased the accuracy of negative and neutral mental state attributions, and decreased the reaction time of positive mental state attributions. Our results imply that the neural correlates of ToM are valence-sensitive.