Electrical stimulation of the ventromedial prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure.

We recently showed that transcranial alternating current stimulation of the dorsolateral prefrontal cortex modulates spontaneous bursts of muscle sympathetic nerve activity, heart rate, and blood pressure (Sesa-Ashton G, Wong R, McCarthy B, Datta S, Henderson LA, Dawood T, Macefield VG. Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans. Cereb Cortex Comm. 2022:3:2tgac017.). Stimulation was delivered between scalp electrodes placed over the nasion and electroencephalogram (EEG) electrode site F3 (left dorsolateral prefrontal cortex) or F4 (right dorsolateral prefrontal cortex), and therefore the current passed within the anatomical locations underlying the left and right ventromedial prefrontal cortices. Accordingly, we tested the hypothesis that stimulation of the left and right ventromedial prefrontal cortices would also modulate muscle sympathetic nerve activity, although we predicted that this would be weaker than that seen during dorsolateral prefrontal cortex stimulation. We further tested whether stimulation of the right ventromedial prefrontal cortices would cause greater modulation of muscle sympathetic nerve activity, than stimulation of the left ventromedial prefrontal cortices. In 11 individuals, muscle sympathetic nerve activity was recorded via microelectrodes inserted into the right common peroneal nerve, together with continuous blood pressure, electrocardiogram, and respiration. Stimulation was achieved using transcranial alternating current stimulation, +2 to -2 mA, 0.08 Hz, 100 cycles, applied between electrodes placed over the nasion, and EEG electrode site FP1, (left ventromedial prefrontal cortices) or FP2 (right ventromedial prefrontal cortices); for comparison, stimulation was also applied over F4 (right dorsolateral prefrontal cortex). Stimulation of all three cortical sites caused partial entrainment of muscle sympathetic nerve activity to the sinusoidal stimulation, together with modulation of blood pressure and heart rate. We found a significant fall in mean blood pressure of ~6 mmHg (P = 0.039) during stimulation of the left ventromedial prefrontal cortices, as compared with stimulation of the right. We have shown, for the first time, that transcranial alternating current stimulation of the ventromedial prefrontal cortices modulates muscle sympathetic nerve activity and blood pressure in awake humans at rest. However, it is unclear if this modulation occurred through the same brain pathways activated during transcranial alternating current stimulation of the dorsolateral prefrontal cortex.

A new perspective for evaluating the efficacy of tACS and tDCS in improving executive functions: A combined tES and fNIRS study.

BACKGROUND: Executive function enhancement is considered necessary for improving the quality of life of patients with neurological or psychiatric disorders, such as attention-deficit/hyperactivity disorder, obsessive-compulsive disorder and Alzheimer's disease. Transcranial electrical stimulation (tES) has been shown to have some beneficial effects on executive functioning, but the quantification of these improvements remains controversial. We aimed to explore the potential beneficial effects on executive functioning induced by the use of transcranial alternating current stimulation (tACS)/transcranial direct current stimulation (tDCS) on the right inferior frontal gyrus (IFG) and the accompanying brain function variations in the resting state. METHODS: We recruited 229 healthy adults to participate in Experiments 1 (105 participants) and 2 (124 participants). The participants in each experiment were randomly divided into tACS, tDCS, and sham groups. The participants completed cognitive tasks to assess behavior related to three core components of executive functions. Functional near-infrared spectroscopy (fNIRS) was used to monitor the hemodynamic changes in crucial cortical regions in the resting state. RESULTS: Inhibition and cognitive flexibility (excluding working memory) were significantly increased after tACS/tDCS, but there were no significant behavioral differences between the tACS and tDCS groups. fNIRS revealed that tDCS induced decreases in the functional connectivity (increased neural efficiency) of the relevant cortices. CONCLUSIONS: Enhancement of executive function was observed after tES, and the beneficial effects of tACS/tDCS may need to be precisely evaluated via brain imaging indicators at rest. tDCS revealed better neural benefits than tACS during the stimulation phase. These findings might provide new insights for selecting intervention methods in future studies and for evaluating the clinical efficacy of tES.

Posture enhancement with cerebellum transcranial electrical stimulation: a systematic review of current methods and findings.

Recently, transcranial electrical stimulation (tES) has gained increasing popularity among researchers, especially for recovery and improvement, but interpretation of these results is difficult due to variations in study methods and outcome measurements. The main goal of this study was to better understand the postural and balance indicators affected by cerebellar tES, as the cerebellum is the main brain region responsible for controlling balance. For this systematic literature review, three databases were searched for articles where the cerebellum was stimulated by any type of tES in either healthy participants or those with neurologic disorders. Postural, dynamic, and/or static stability measurements were recorded, and risk of bias was assessed on the PEDro scale. A total of 21 studies were included in the analysis. 17 studies reported improvements after application of tES. 14 studies stimulated the cerebellum unilaterally and 15 used this modality for 20 min. Moreover, all studies exclusively used transcranial direct current as the type of stimulation. Evaluation of PEDro results showed that studies included in the analysis utilized good methodology. Although there were some inconsistencies in study results, overall, it was demonstrated that tES can improve balance and postural index under both healthy and neurological conditions. Further research of bilateral cerebellar stimulation or the use of transcranial alternating current stimulation, transcranial random noise stimulation, and transcranial pulsed current stimulation is needed for a more comprehensive assessment of the potential positive effects of cerebellar tES on the balance system.

Non-additive effects of electrical stimulation of the dorsolateral prefrontal cortex and the vestibular system on muscle sympathetic nerve activity in humans.

Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes.

The role of the dorsolateral prefrontal cortex in control of skin sympathetic nerve activity in humans.

The dorsolateral prefrontal cortex (dlPFC) is primarily involved in higher order executive functions, with there being evidence of lateralization. Brain imaging studies have revealed its link to the generation of skin sympathetic nerve activity (SSNA), which is elevated in states of emotional arousal or anxiety. However, no studies have directly explored dlPFC influences on SSNA. Transcranial alternating current stimulation (-2 to 2 mA, 0.08 Hz, 100 cycles) was applied between the left or right dlPFC and nasion via surface electrodes. Spontaneous bursts of SSNA were recorded from the common peroneal nerve via a tungsten microelectrode in 21 healthy participants. The modulation index was calculated for each stimulation paradigm by constructing cross-correlation histograms between SSNA and the sinusoidal stimulus. Stimulation of the dlPFC caused significant modulation of SSNA, but there was no significant difference in the median modulation index across sides. Stimulation also caused cyclic modulation of skin blood flow and sweat release. We have shown for the first time that stimulation of the dlPFC causes modulation of SSNA, also reflected in the effector-organ responses. This supports a role for the dlPFC in the control of SSNA, which likely contributes to the ability of emotions to bring about cutaneous vasoconstriction and sweat release.

Application of Transcranial Direct and Alternating Current Stimulation (tDCS and tACS) on Major Depressive Disorder.

The exploration of brain stimulation methods offers a promising avenue to overcome the shortcomings of traditional drug therapies and psychological treatments for major depressive disorder (MDD). Over the past years, there has been an increasing focus on transcranial electrical stimulation (tES), notably for its ease of use and potentially fewer side effects. This chapter delves into the use of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), which are key components of tES, in managing depression. It begins by introducing tDCS and tACS, summarizing their action mechanisms. Following this introduction, the chapter provides an in-depth analysis of existing meta-analyses, systematic reviews, clinical studies, and case reports that have applied tES in MDD treatment. It also considers the role of tES in personalized medicine by looking at specific patient groups and evaluating research on possible biomarkers that could predict how patients with MDD respond to tES therapy.

Pilot study of using transcranial temporal interfering theta-burst stimulation for modulating motor excitability in rat.

Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity.

Cognitive enhancement through technology: A review of transcranial electrical stimulation (TES) interventions in children and adolescents with specific learning disabilities.

BACKGROUND: In recent years, the exploration of innovative interventions for addressing problems of children and adolescents with specific learning disabilities (SLD) has garnered significant attention within the realm of neurocognitive research. Transcranial electrical stimulation (TES) has emerged as a promising tool for enhancing cognitive skills in children, offering a non-invasive and safe method that may particularly benefit those with learning difficulties. We aimed to appraise the extent and the quality of studies about impact of TES on cognitive skills including academic skills in children and adolescents with SLD. METHODS: A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published between January 2000 and January 2024 were searched in PubMed, Embase, Scopus, Web of Science and Google Scholar. The study eligibility criteria were previously established according to the PICO model. The Physiotherapy Evidence Database (PEDro) scale and Cochrane Collaboration tool (ROB2) were used to assess the methodological quality and the risk of bias of the included studies, respectively. RESULTS: The initial search yielded 1571 studies among which 30 studies were systematically reviewed. The total number of participants was 224 individuals (intervention: 114; control: 110). Findings showed significant improvements in reading skills such as text reading, high-frequency word reading speed and efficiency and mathematical skills. Conversely, other cognitive skills such as working memory were not improved in people with dyslexia and dyscalculia. DISCUSSION: TES interventions can positively affect cognitive skills in children and adolescents with SLD; However, due to the small number of studies, medium methodological quality and high risk of bias, caution should be taken when interpreting the results.

Updated review on the use of neuromuscular blockade during intraoperative motor-evoked potential monitoring in the modern anesthesia era.

Transcranial electrical stimulation motor-evoked potentials (Tc-MEP) monitoring is a common practice in neurosurgery to prevent postoperative neurological damage. However, the use of neuromuscular blocking agents (NMBAs) during Tc-MEP monitoring is a subject of controversy. In addition, the effectiveness of sugammadex, a selective reversal agent, in the context of Tc-MEP monitoring requires further investigation. This review aimed to clarify the considerations involved in achieving optimal Tc-MEP monitoring while ensuring patient safety. Preoperative patient selection, comorbidity assessment, motor power evaluation, and the nature of the planned surgery are critical factors. Accurate paralysis assessment, continuous NMBA infusion, and post-tetanic stimulation techniques are essential for achieving optimal partial NMB. The decision to administer an NMB during Tc-MEP monitoring necessitates a careful evaluation of the balance between accuracy and potential complications. This review emphasizes the challenges associated with NMB administration during Tc-MEP monitoring and highlights the need for personalized patient assessment.

Attention improvement to transcranial alternating current stimulation at gamma frequency over the right frontoparietal network: a preliminary report.

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate (p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.