Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.     

Effects of transcranial direct current stimulation on cognitive dysfunction in multiple sclerosis

BackgroundAround 40%–70% of patients with multiple sclerosis (MS) may experience cognitive impairments during the course of their disease with detrimental effects on social and occupational activities. Transcranial direct current stimulation (tDCS has been investigated in pain, fatigue, and mood disorders related to MS, but to date, few studies have examined effects of tDCS on cognitive performance in MS.ObjectiveThe current study aimed to investigate the effects of a multi-session tDCS protocol on cognitive performance and resting-state brain electrical activities in patients with MS.MethodsTwenty-four eligible MS patients were randomly assigned to real (anodal) or sham tDCS groups. Before and after 8 consecutive daily tDCS sessions over the left dorsolateral prefrontal cortex (DLPFC), patients’ cognitive performance was assessed using the Cambridge Brain Sciences-Cognitive Platform (CBS-CP). Cortical electrical activity was also evaluated using quantitative electroencephalography (QEEG) analysis at baseline and after the intervention.ResultsCompared to the sham condition, significant improvement in reasoning and executive functions of the patients in the real tDCS group was observed. Attention was also improved considerably but not statistically significantly following real tDCS. However, no significant changes in resting-state brain activities were observed after stimulation in either group.ConclusionAnodal tDCS over the left DLPFC appears to be a promising therapeutic option for cognitive dysfunction in patients with MS. Larger studies are required to confirm these findings and to investigate underlying neuronal mechanisms.     

Improving working memory: Exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex

Objective

The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham.

Methods

Ten participants undertook three experimental sessions in which they received 10 min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1 week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task.

Results

There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding.

Conclusions

The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed.

Significance

Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia.     

Pre-treatment attentional processing speed and antidepressant response to transcranial direct current stimulation: Results from an international randomized controlled trial

Background

Transcranial direct current stimulation (tDCS) has promising antidepressant effects, however, clinical trials have shown variable efficacy. Pre-treatment neurocognitive functioning has previously been identified as an inter-individual predictor of tDCS antidepressant efficacy.

Modulation of creativity by transcranial direct current stimulation

BackgroundCreativity is the use of original ideas to accomplish something innovative. Previous research supports the notion that creativity is facilitated by an activation of the right and/or a deactivation of the left prefrontal cortex. In contrast, recent brain imaging studies suggest that creativity improves with left frontal activation.ObjectiveThe present study was designed to further elucidate the neural basis of and ways to modulate creativity, based on the modulation of prefrontal cortical activity through the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS).MethodsNinety healthy University students performed three tasks on major aspects of creativity: conceptual expansion (Alternate Uses Task, AUT), associative thinking (Compound Remote Associate Task, CRA), and set shifting ability (Wisconsin Card Sorting Task, WCST). Simultaneously, they received cathodal stimulation of the left and anodal stimulation of the right inferior frontal gyrus (IFG), the reverse protocol, or sham stimulation.ResultsThe main pattern of results was a superior performance with bilateral left cathodal/right anodal stimulation, and an inferior performance in the reversed protocol compared to sham stimulation. As a potential underlying physiological mechanism, resting state EEG beta power, indicative of enhanced cortical activity, in the right frontal area increased with anodal stimulation and was associated with better performance.ConclusionThe findings provide new insights into ways of modulating creativity, whereby a deactivation of the left and an activation of the right prefrontal cortex with tDCS is associated with increased creativity. Potential future applications might include tDCS for patients with mental disorders and for healthy individuals in creative professions.     

Enhancing cognitive control training with transcranial direct current stimulation: a systematic parameter study

BackgroundCognitive control (CC) is an important prerequisite for goal-directed behaviour and efficient information processing. Impaired CC is associated with reduced prefrontal cortex activity and various mental disorders, but may be effectively tackled by transcranial direct current stimulation (tDCS)-enhanced training. However, study data are inconsistent as efficacy depends on stimulation parameters whose implementations vary widely between studies.ObjectiveWe systematically tested various tDCS parameter effects (anodal/cathodal polarity, 1/2 mA stimulation intensity, left/right prefrontal cortex hemisphere) on a six-session CC training combined with tDCS.MethodsNine groups of healthy humans (male/female) received either anodal/cathodal tDCS of 1/2 mA over the left/right PFC or sham stimulation, simultaneously with a CC training (modified adaptive Paced Auditory Serial Addition Task [PASAT]). Subjects trained thrice per week (19 min each) for two weeks. We assessed performance progress in the PASAT before, during, and after training. Using a hierarchical approach, we incrementally narrowed down on optimal stimulation parameters supporting CC. Long-term CC effects as well as transfer effects in a flanker task were assessed after the training period as well as three months later.ResultsCompared to sham stimulation, anodal but not cathodal tDCS improved performance gains. This was only valid for 1 mA stimulation intensity and particularly detected when applied to the left PFC.ConclusionsOur results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions.     

Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task

ObjectiveThe aim of this study was to test the hypothesis that dual-hemisphere transcranial direct current stimulation (tDCS) over the primary somatosensory cortex (S1) could improve performance in a tactile spatial discriminative task, compared with uni-hemisphere or sham tDCS.MethodsNine healthy adults participated in this double-blind, sham-controlled, and cross-over design study. The performance in a grating orientation task (GOT) in the right index finger was evaluated before, during, immediately after and 30 min after the dual-hemisphere, uni-hemisphere (1 mA, 20 min), or sham tDCS (1 mA, 30 s) over S1. In the dual-hemisphere and sham conditions, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the right S1. In the uni-hemisphere condition, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the contralateral supraorbital front.ResultsThe percentage of correct responses on the GOT during dual-hemisphere tDCS was significantly higher than that in the uni-hemisphere or sham tDCS conditions when the grating width was set to 0.75 mm (all p < 0.05).ConclusionsDual-hemisphere tDCS over S1 improved performance in a tactile spatial discrimination task in healthy volunteers.SignificanceDual-hemisphere tDCS may be a useful strategy to improve sensory function in patients with sensory dysfunctions.     

Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with potential for cost-effective therapeutic neuromodulation. Although positive therapeutic effects were found by stimulating the dorsolateral prefrontal cortex (DLPFC), few studies have investigated physiological effects of DLPFC-tDCS.

Effects of transcranial direct current stimulation on experimental pain perception: A systematic review and meta-analysis

ObjectiveMany studies have examined the effectiveness of transcranial direct current stimulation (tDCS) on human pain perception in both healthy populations and pain patients. Nevertheless, studies have yielded conflicting results, likely due to differences in stimulation parameters, experimental paradigms, and outcome measures. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds present in clinical data. This study aimed to assess the robustness of tDCS effects on experimental pain perception among healthy populations.MethodsWe conducted three meta-analyses that analyzed tDCS effects on ratings of perceived pain intensity to suprathreshold noxious stimuli, pain threshold and tolerance.ResultsThe meta-analyses showed a statically significant tDCS effect on attenuating pain-intensity ratings to suprathreshold noxious stimuli. In contrast, tDCS effects on pain threshold and pain tolerance were statistically non-significant. Moderator analysis further suggested that stimulation parameters (active electrode size and current density) and experimental pain modality moderated the effectiveness of tDCS in attenuating pain-intensity ratings.ConclusionThe effectiveness of tDCS on attenuating experimental pain perception depends on both stimulation parameters of tDCS and the modality of experimental pain.SignificanceThis study provides some theoretical basis for the application of tDCS in pain management.     

Combined transcranial direct current stimulation with virtual reality exposure for posttraumatic stress disorder: Feasibility and pilot results

Background

Facilitating neural activity using non-invasive brain stimulation may improve extinction-based treatments for posttraumatic stress disorder (PTSD).

Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients

Cortical excitability changes induced by tDCS and revealed by TMS, are increasingly being used as an index of neuronal plasticity in the human cortex. The aim of this paper is to summarize the partially adverse effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) from the last 2 years, on work performed in our laboratories. One-hundred and two of our subjects who participated in our tDCS studies completed a questionnaire. The questionnaire contained rating scales regarding the presence and severity of headache, difficulties in concentrating, acute mood changes, visual perceptual changes and any discomforting sensation like pain, tingling, itching or burning under the electrodes, during and after tDCS. Participants were healthy subjects (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus patients (9.8%). During tDCS a mild tingling sensation was the most common reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the subjects, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. In addition, the incidence of the itching sensation (p=0.02) and the intensity of tingling sensation (p=0.02) were significantly higher during tDCS in the group of the healthy subjects, in comparison to patients; whereas the occurrence of headache was significantly higher in the patient group (p=0.03) after the stimulation. Our results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders.     

A Comparison of the Effects of Transcranial Direct Current Stimulation and Caffeine on Vigilance and Cognitive Performance During Extended Wakefulness

BackgroundSleep deprivation from extended duty hours is a common complaint for many occupations. Caffeine is one of the most common countermeasures used to combat fatigue. However, the benefits of caffeine decline over time and with chronic use.ObjectiveOur objective was to evaluate the efficacy of anodal transcranial direct current stimulation (tDCS) applied to the pre-frontal cortex at 2 mA for 30 min to remediate the effects of sleep deprivation and to compare the behavioral effects of tDCS with those of caffeine.MethodsThree groups of 10 participants each received either active tDCS with placebo gum, caffeine gum with sham tDCS, or sham tDCS with placebo gum during 30 h of extended wakefulness.ResultsOur results show that tDCS prevented a decrement in vigilance and led to better subjective ratings for fatigue, drowsiness, energy, and composite mood compared to caffeine and control in sleep-deprived individuals. Both the tDCS and caffeine produced similar improvements in latencies on a short-term memory task and faster reaction times in a psychomotor task when compared to the placebo group. Interestingly, changes in accuracy for the tDCS group were not correlated to changes in mood; whereas, there was a relationship for the caffeine and sham groups.ConclusionOur data suggest that tDCS could be a useful fatigue countermeasure and may be more beneficial than caffeine since boosts in performance and mood last several hours.     

Effects of direct current stimulation on synaptic plasticity in a single neuron

BackgroundTranscranial direct current stimulation (DCS) has lasting effects that may be explained by a boost in synaptic long-term potentiation (LTP). We hypothesized that this boost is the result of a modulation of somatic spiking in the postsynaptic neuron, as opposed to indirect network effects. To test this directly we record somatic spiking in a postsynaptic neuron during LTP induction with concurrent DCS.MethodsWe performed rodent in-vitro patch-clamp recordings at the soma of individual CA1 pyramidal neurons. LTP was induced with theta-burst stimulation (TBS) applied concurrently with DCS. To test the causal role of somatic polarization, we manipulated polarization via current injections. We also used a computational multi-compartment neuron model that captures the effect of electric fields on membrane polarization and activity-dependent synaptic plasticity.ResultsTBS-induced LTP was enhanced when paired with anodal DCS as well as depolarizing current injections. In both cases, somatic spiking during the TBS was increased, suggesting that evoked somatic activity is the primary factor affecting LTP modulation. However, the boost of LTP with DCS was less than expected given the increase in spiking activity alone. In some cells, we also observed DCS-induced spiking, suggesting DCS also modulates LTP via induced network activity. The computational model reproduces these results and suggests that they are driven by both direct changes in postsynaptic spiking and indirect changes due to network activity.ConclusionDCS enhances synaptic plasticity by increasing postsynaptic somatic spiking, but we also find that an increase in network activity may boost but also limit this enhancement.     

Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease

BackgroundAlthough single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated.ObjectiveThis study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients.MethodsPatients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups.ResultsCompared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001).ConclusionsDaily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.     

Treatment of depression with transcranial direct current stimulation (tDCS): A Review

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.     

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.