Effects of electrical brain stimulation on brain indices and presence experience in immersive, interactive virtual reality

The subjective presence experience in virtual reality (VR) is associated with distinct brain activation patterns. Particularly, the dorsolateral prefrontal cortex (DLPFC) seems to play a central role. We investigated the effects of electric brain stimulation (transcranial direct current, tDCS) on the presence experience as well as on brain activity and connectivity. Thirty-eight participants received either anodal (N = 18) or cathodal (N = 20) stimulation of the DLPFC before interacting in an immersive VR as well as sham stimulation. During VR interaction, EEG and heart rate were recorded. After VR interaction, participants rated their subjective presence experience using standardized questionnaires. Cathodal stimulation led to stronger brain connectivity than sham stimulation. Increased brain connectivity was associated with numerically lower levels of subjective presence. Anodal stimulation did not lead to changes in brain connectivity, and no differences in subjective presence ratings were found between the anodal and sham stimulation. These results indicate that cathodal tDCS over the DLPFC leads to a more synchronized brain state, which might hamper the activity in networks, which are generally associated with the evolvement of the subjective presence experience. Our results underline the importance of the DLPFC for the presence experience in VR.

Effects of a single session of cathodal transcranial direct current stimulation primed intermittent theta-burst stimulation on heart rate variability and cortical excitability measures

Objectives: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been used as neuromodulators in neuropsychiatric conditions. This study is aimed to find the effects of a single session of priming cathodal tDCS with intermittent theta-burst stimulation (iTBS) over left dorsolateral prefrontal cortex on heart rate variability (HRV) and cortical excitability parameters before and after perturbation. Materials and Methods: The neuromodulatory techniques used in the study were Cathodal tDCS for 20 min followed by iTBS for 3 min on the left dorsolateral prefrontal cortex (DLPFC). HRV variables and TMS parameters were recorded before and after this intervention of combined neuromodulation in 31 healthy volunteers (20 males and 11 females; age range of 19–35 years with Mean ± SD = 24.2 ± 4.7 years). Results: The results showed an overall increase in cortical excitability and parasympathetic dominance in healthy volunteers. Other measures of cortical excitability and HRV did not change significantly following single session of combined neuromodulation. Conclusion: This study showed that there is an overall increase in cortical excitability and parasympathetic dominance in the cohort of healthy volunteers following a combination of neuromodulation involving cathodal tDCS followed by iTBS over left DLPFC. Future studies exploring the effects of other possible combinations with sham stimulation could be carried out to explore the utility of dual stimulation as add-on therapy in disorders.

Neuroprotection by Transcranial Direct Current Stimulation in Rodent Models of Focal Ischemic Stroke: A Meta-Analysis

Infarct size is associated with stroke severity in clinical studies, so reducing it has become an important target and research hotspot in the treatment of ischemic stroke. Some preclinical studies have shown transcranial direct current stimulation (tDCS) reduced infarct size and improved neurological deficit, but others have not found beneficial effects. Besides, the optimal pattern of tDCS for ischemic stroke remains largely unknown. To shed light on the current circumstance and future research directions, the systematic review evaluated the effect of different tDCS paradigms in reducing infarct size and improving neurological deficit in rodent models of ischemic stroke and assessed the methodological quality of current literature. We searched the MEDLINE (via PubMed), EMBASE, Web of Science, and Scopus from their inception to August 18, 2021, to identify studies evaluating the effects of tDCS in rodent models of ischemic stroke. Eight studies were included, of which seven studies were included in the meta-analysis. The results showed cathodal tDCS, rather than anodal tDCS, reduced infarct size mainly measured by tetrazolium chloride and magnetic resonance imaging (standardized mean difference: −1.13; 95% CI: −1.72, −0.53; p = 0.0002) and improved neurological deficit assessed by a modified neurological severity score (standardized mean difference: −2.10; 95% CI: −3.78, −0.42; p = 0.01) in an early stage of focal ischemic stroke in rodent models. Subgroup analyses showed effects of cathodal tDCS on infarct size were not varied by ischemia duration (ischemia for 1, 1.5, and 2 h or permanent ischemia) and anesthesia (involving isoflurane and ketamine). The overall quality of studies included was low, thus the results must be interpreted cautiously. Published studies suggest that cathodal tDCS may be a promising avenue to explore for augmenting rehabilitation from focal ischemic stroke. Considering the methodological limitations, it is unreliable to blindly extrapolate the animal data to the clinical practice. Future research is needed to investigate the mechanism of tDCS in a randomized and blinded fashion in clinically relevant stroke models, such as elderly animals, female animals, and animals with comorbidities, to find an optimal treatment protocol.

Modulating the Activity of the VMPFC With tDCS Alters the Social Framing Effect

Numerous experimental studies have replicated the social framing effect-the observation that people’s decisions related to economic benefits and feelings depend on the method of presentation. Previous neuroimaging studies have shown that the ventromedial prefrontal cortex (VMPFC) plays a part in the influence of framing and how individuals think about the feelings of others. Based on this, we used transcranial direct current stimulation (tDCS) to modulate neuronal activity in the VMPFC to determine the likelihood of a direct association between VMPFC activity and the social framing effect. Subsequently, in three stimulation treatments, we assessed the presence of the social framing effect, as demonstrated by a disparity between harm degree and help degree. The findings revealed a social framing effect in the participants in the control group and the sham treatment but no social framing effect in the participants in the anodal or cathodal treatments. Furthermore, sex differences were observed in the sham treatment’s social framing effect, whereas no sex differences were observed in the anodal or cathodal treatments. The participants tended to harm the victim after receiving anodal or cathodal tDCS over the VMPFC and did not change their helping behaviour in any stimulations. Consequently, a clear causal link between the behaviour of the VMPFC and the social framing effect was found in the present research.

Contralesional Cathodal Transcranial Direct Current Stimulation Does Not Enhance Upper Limb Function in Subacute Stroke: A Pilot Randomized Clinical Trial

Transcranial direct current stimulation (tDCS) has the potential to improve upper limb motor outcomes after stroke. According to the assumption of interhemispheric inhibition, excessive inhibition from the motor cortex of the unaffected hemisphere to the motor cortex of the affected hemisphere may worsen upper limb motor recovery after stroke. We evaluated the effects of active cathodal tDCS of the primary motor cortex of the unaffected hemisphere (ctDCSM1UH) compared to sham, in subjects within 72 hours to 6 weeks post ischemic stroke. Cathodal tDCS was intended to inhibit the motor cortex of the unaffected hemisphere and hence decrease the inhibition from the unaffected to the affected hemisphere and enhance motor recovery. We hypothesized that motor recovery would be greater in the active than in the sham group. In addition, greater motor recovery in the active group might be associated with bigger improvements in measures in activity and participation in the active than in the sham group. We also explored, for the first time, changes in cognition and sleep after ctDCSM1UH. Thirty subjects were randomized to six sessions of either active or sham ctDCSM1UH as add-on interventions to rehabilitation. The NIH Stroke Scale (NIHSS), Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA), Barthel Index (BI), Stroke Impact Scale (SIS), and Montreal Cognitive Assessment (MoCA) were assessed before, after treatment, and three months later. In the intent-to-treat (ITT) analysis, there were significant GROUP*TIME interactions reflecting stronger gains in the sham group for scores in NIHSS, FMA, BI, MoCA, and four SIS domains. At three months post intervention, the sham group improved significantly compared to posttreatment in FMA, NIHSS, BI, and three SIS domains while no significant changes occurred in the active group. Also at three months, NIHSS improved significantly in the sham group and worsened significantly in the active group. FMA scores at baseline were higher in the active than in the sham group. After adjustment of analysis according to baseline scores, the between-group differences in FMA changes were no longer statistically significant. Finally, none of the between-group differences in changes in outcomes after treatment were considered clinically relevant. In conclusion, active CtDCSM1UH did not have beneficial effects, compared to sham. These results were consistent with other studies that applied comparable tDCS intensities/current densities or treated subjects with severe upper limb motor impairments during the first weeks post stroke. Dose-finding studies early after stroke are necessary before planning larger clinical trials.

Effects of tDCS on the attentional blink revisited: A statistical evaluation of a replication attempt

The attentional blink (AB) phenomenon reveals a bottleneck of human information processing: the second of two targets is often missed when they are presented in rapid succession among distractors. A recent study by London & Slagter (Journal of Cognitive Neuroscience, 33, 756 to 768, 2021) showed that the size of the AB can be changed by applying transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC). Although AB size at the group level remained unchanged, the effects of anodal and cathodal tDCS were negatively correlated: if a given individuals AB size decreased from baseline during anodal tDCS, their AB size would increase during cathodal tDCS, and vice versa. Here, we attempted to replicate this finding. Like London & Slagter, we found no group effects of tDCS, but also no longer found a significant negative correlation. We present a series of statistical measures of replication success, all of which confirm that both studies are not in agreement. First, the correlation here is significantly smaller than a conservative estimate of the original correlation. Second, the difference between the correlations is greater than expected due to sampling error, and our data are more consistent with a zero effect than with the original estimate. Finally, the overall effect when combining both studies is small and not significant. Our findings thus indicate that the effects of lDPLFC tDCS on the AB are less substantial than observed by London & Slagter (2021). Although this should be quite a common scenario, null findings can be difficult to interpret and are still under represented in the brain stimulation and cognitive neuroscience literatures. An important auxiliary goal of this paper is therefore to provide a tutorial for other researchers, to maximize the evidential value from null findings.

Filthiness of Immorality: Manipulating Disgust and Moral Rigidity Through Noninvasive Brain Stimulation as a Promising Therapeutic Tool for Obsessive Compulsive Disorder

The study was designed to test the hypothesis that indirect inhibition of the insula via cathodal transcranial direct current stimulation (tDCS) would decrease disgust and moral rigidity in 36 healthy individuals undergoing 15 min of tDCS over the temporal lobe. To obtain a comprehensive assessment of disgust, we used subjective (affect rating), physiological (heart rate variability [HRV]), and implicit measures (word-fragment completion), and moral judgment was assessed by asking participants to rate the deontological and altruistic moral wrongness of a revised version of the moral foundations vignettes. We found anodal and cathodal stimulations to, respectively, enhance and decrease self-reported disgust, deontological morality, and HRV. Note that these effects were stronger in individuals with higher levels of obsessive compulsive (OC) traits. Because disgust and sensitivity to deontological guilt are among the most impairing features in OC disorder, it is auspicious that cathodal tDCS could be implemented to reduce such symptoms.

Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability

Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain’s descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.

Verbal Fluency in Mild Alzheimer’s Disease: Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex

Background: Recent studies showed that in healthy controls and in aphasic patients, inhibitory trains of repetitive transcranial magnetic stimulation (rTMS) over the right prefrontal cortex can improve phonemic fluency performance, while anodal transcranial direct current stimulation (tDCS) over the left prefrontal cortex can improve performance in naming and semantic fluency tasks. Objective: This study aimed at investigating the effects of cathodal tDCS over the left or the right dorsolateral prefrontal cortex (DLPFC) on verbal fluency tasks (VFT) in patients with mild Alzheimer’s disease (AD). Methods: Forty mild AD patients participated in the study (mean age 73.17±5.61 years). All participants underwent cognitive baseline tasks and a VFT twice. Twenty patients randomly received cathodal tDCS to the left or the right DLPFC, and twenty patients were assigned to a control group in which only the two measures of VFT were taken, without the administration of the tDCS. Results: A significant improvement of performance on the VFT in AD patients was present after tDCS over the right DLPFC (p = 0.001). Instead, no difference was detected between the two VFTs sessions after tDCS over the left DLPFC (p = 0.42). Furthermore, these results cannot be related to task learning effects, since no significant difference was found between the two VFT sessions in the control group (p = 0.73). Conclusion: These data suggest that tDCS over DLPFC can improve VFT performance in AD patients. A hypothesis is that tDCS enhances adaptive patterns of brain activity between functionally connected areas.