Cathodal Stimulation on Left Dorsolateral Prefrontal Cortex Facilitates Restructuring Process Underlying Insight Problem Solving

The cerebellum has an increasingly recognized role in higher order cognition. Advancements in noninvasive neuromodulation techniques allow one to focally create functional alterations in the cerebellum to investigate its role in cognitive functions. To this point, work in this area has been mixed, in part due to varying methodologies for stimulation, and it is unclear whether or not transcranial direct current stimulation (tDCS) effects on the cerebellum are task or load dependent. Here, we employed a between-subjects design using a high definition tDCS system to apply anodal, cathodal, or sham stimulation to the cerebellum or prefrontal cortex (PFC) to examine the role the cerebellum plays in verbal working memory, inhibition, motor learning, and balance performance, and how this interaction might interact with the cortex (i.e., PFC). We predicted performance decrements following anodal stimulation and performance increases following cathodal stimulation, compared with sham. Broadly, our work provides evidence for cerebellar contributions to cognitive processing, particularly in verbal working memory and sequence learning. Additionally, we found the effect of stimulation might be load specific, particularly when applied to the cerebellum. Critically, anodal stimulation negatively impacted performance during effortful processing, but was helpful during less effortful processing. Cathodal stimulation hindered task performance, regardless of simulation region. The current results suggest an effect of stimulation on cognition, perhaps suggesting that the cerebellum is more critical when processing is less effortful but becomes less involved under higher load when processing is more prefrontally dependent.

High-definition transcranial direct current stimulation (HD-tDCS) for the enhancement of working memory – A systematic review and meta-analysis of healthy adults

Falls pose a significant health risk for older adults, with most incidents occurring during dual-task situations—when walking is combined with a secondary cognitive task. Reducing cognitive-motor interference and attentional demands during walking is therefore a key goal in effective fall-prevention and rehabilitation programs. High-definition transcranial direct current stimulation (HD-tDCS) is an emerging neuromodulation technique that may support this goal by enhancing neural efficiency. To date, no studies have directly compared the effects of HD-tDCS targeting different brain regions—such as the left dorsolateral prefrontal cortex (DLPFC), cerebellum, and primary motor cortex (M1)—to identify the most effective site for reducing dual-task cost (DTC) during walking in older adults. Thus, the present study aimed to compare the effects of these HD-tDCS montages on dual-task gait performance in older adults. This study utilized a randomized, double-blind, sham-controlled, counterbalanced crossover design. Each of the 19 older adult participants completed four sessions, with a minimum one-week washout period between sessions. In each session, HD-tDCS was applied for 20 min, targeting either the cerebellum, M1, left DLPFC, or a sham condition, with the order of stimulation counterbalanced across participants. Although the main effect of stimulation site was not significant (P ≥ 0.204), significant interaction effects were found for stride time variability under both single-task (P = 0.023) and dual-task (P < 0.001) conditions. Post hoc analyses showed significant reductions in stride time variability following stimulation of the left DLPFC, M1, and the cerebellum (P ≤ 0.001 for all), but not after sham stimulation (P ≥ 0.646). For the DTC of stride length variability, a significant interaction effect was also observed (P = 0.038), with reductions following M1 (P = 0.007) and cerebellar (P = 0.011) stimulation. Additionally, dual-task gait speed improved significantly after stimulation of the left DLPFC (P = 0.039) and M1 (P = 0.028). No significant effects were found for stride length, stride length variability, or the DTC of gait speed. Although M1, left DLPFC, and cerebellar stimulation showed favorable effects on gait parameters over time, no stimulation target demonstrated clear superiority. These findings suggest that HD-tDCS may modulate dual-task gait performance, but further research is required to confirm site-specific advantages.RCT registration: On the Iranian Registry of Clinical Trials (IRCT20220718055490N1). Registration date: 1/10/2022.

This study investigated the causal role of the human frontopolar cortex (FPC) in managing counterfactual strategies during decision-making under uncertainty. Using a combination of cathodal high-definition transcranial direct current stimulation (HD-tDCS) and computational modeling, we examined how cathodal stimulation, preliminarily simulated with SimNIBS, affects the retrieval of alternative strategies in the task that constantly provokes exploration-exploitation dilemmas. A comparison of resting-state recordings with functional near-infrared spectroscopy (fNIRS) before and after stimulation did not reveal any physiological effect of HD-tDCS. Furthermore, there was no significant difference in participants’ exploratory behavior between the sham and cathodal groups. These results indicate that the employed HD-tDCS protocol may not sufficiently influence FPC function, despite preliminary tDCS simulations with SimNIBS, calling for further refinement of the HD-tDCS protocol used in future research to elucidate the causal role of the FPC in decision-making under uncertainty.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22016-z.

We studied the effects of rapid-rate transcranial magnetic stimulation (rTMS) of different scalp positions on mood. Ten normal volunteers rated themselves before and after rTMS on five analog scales labeled "Tristeza" (Sadness), "Ansiedad" (Anxiety), "Alegria" (Happiness), "Cansancio" (Tiredness), and "Dolor/Malestar" (Pain/Discomfort). rTMS was applied to the right lateral prefrontal, left prefrontal, or midline frontal cortex in trains of 5 seconds' duration at 10 Hz and 110% of the subject's motor threshold intensity. Each stimulation position received 10 trains separated by a 25-second pause. No clinically apparent mood changes were evoked by rTMS to any of the scalp positions in any subject. However, left prefrontal rTMS resulted in a significant increase in the Sadness ratings (Tristeza) and a significant decrease in the Happiness ratings ("Alegria") as compared with right prefrontal and midfrontal cortex stimulation. These results show differential effects of rTMS of left and right prefrontal cortex stimulation on mood and illustrate the lateralized control of mood in normal volunteers.

High-definition transcranial direct current stimulation (HD-tDCS) is a potential neuromodulation apparatus for stroke rehabilitation. However, its modulatory effects in stroke subjects is still not well understood. In this paper, the offline modulatory effects of HD-tDCS on the ipsilesional primary motor cortex were investigated by performing wrist isometric contraction tasks before and after HD-tDCS in eleven unilateral chronic stroke subjects using a synchronized HD-tDCS and electroencephalogram/electromyography measurement system. This paper is a randomized, single blinded, and sham-controlled crossover study. Each subject randomly received three HD-tDCS (anode, cathode, and sham) with at least one-week washout period. Online feedback-guided medium-level wrist isometric contraction tasks were conducted for the affected upper limbs before stimulation and 10, 30, and 50 min after the end of 10-min 1-mA HD-tDCS. The characteristics of corticomuscular coherence (CMC), cortical oscillation power spectral density, and power spectral entropy were analyzed during tasks and compared across all sessions and stimulation conditions. Anode HD-tDCS induced significant CMC changes in stroke subjects, while cathode and sham stimulation did not induce significant CMC changes. The largest neuromodulation effects were observed at 10 min immediately after anodal HD-tDCS.

Major depressive disorder (MDD) is marked by cognitive and affective dysfunctions associated with altered prefrontal cortical activity. While high-definition transcranial direct current stimulation (HD-tDCS) shows promise in modulating these deficits, little is known about the differential effects of targeting specific prefrontal subregions. This study investigated whether HD-tDCS over the dorsolateral (DLPFC) or ventrolateral (VLPFC) prefrontal cortex produces distinct behavioural and neurophysiological effects in patients with MDD, focusing on cognitive control, mood, and functional brain connectivity. Twenty-six patients with MDD received ten sessions of HD-tDCS over the left DLPFC, left VLPFC, or sham stimulation. Assessments were performed pre-intervention, post-intervention, and at one-month follow-up. Measures included the Beck Depression Inventory (BDI), World Health Organization Quality of Life – BREF (WHOQOL-BREF), and performance on cognitive tasks. A subset underwent resting-state functional near-infrared spectroscopy (fNIRS) to assess changes in prefrontal connectivity. DLPFC stimulation led to early and sustained improvements in depressive symptoms, executive function (e.g., Trail Making Test, Wisconsin Card Sorting Task), and quality of life domains. VLPFC stimulation produced delayed improvements, particularly in inhibitory control (e.g., Attention Network Test). fNIRS revealed no significant within-group changes in global connectivity, but at follow-up, the DLPFC group showed greater prefrontal connectivity than both VLPFC and sham, suggesting lasting functional reorganization. VLPFC stimulation did not alter global connectivity, possibly reflecting more localized or subcortical effects. HD-tDCS can differentially modulate cognitive and affective processes in MDD. DLPFC stimulation promotes broader, earlier, and more durable effects, while VLPFC stimulation may exert more specific, delayed influences. Functional connectivity measures enhance interpretation of neuromodulatory outcomes in clinical research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10548-025-01157-4.

Background: Schizophrenia primarily depends on pharmacotherapy, which has demonstrated limited efficacy in enhancing cognitive impairments. High-definition transcranial direct current stimulation (HD-tDCS) and computerized cognitive remediation therapy (CCRT) hold potential for improving cognitive impairments. This study aims to investigate the effects of combining HD-tDCS with CCRT on cognition and to explore the mechanisms of this approach in schizophrenia. Study Design: This is the protocol of a randomized controlled trial. Methods: Schizophrenia patients will be randomly assigned to one of 4 groups: HD-tDCS + CCRT group (Group 1), HD-tDCS group (Group 2), CCRT group (Group 3), and a control group (Group 4). The central electrode will be personalized using magnetic resonance imaging (MRI)-guided localization in the medial prefrontal cortex (mPFC). CCRT includes 6 therapeutic modules and 10 distinct tasks. Both HD-tDCS and CCRT will be administered once daily, 5 days per week, for 4 consecutive weeks, culminating in a total of 20 sessions. Assessments will occur at baseline (T0), after 10 sessions (T1), after 20 sessions (T2), and after 6 months of follow-up (T3). The primary outcome measure is the change in cognition. We will employ multimodal MRI, serum concentrations of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to explore the underlying mechanisms. Expected Results: An involvement of mPFC and synaptic plasticity in response to HD-tDCS and CCRT is hypothesized. Conclusion: The study will provide empirical evidence for the effectiveness of combined therapy at an individual level, explore its mechanisms, and may ultimately result in personalized medicine. Clinical Trial Registration: ChiCTR2500102731, https://www.chictr.org.cn/hvshowprojectEN.html?id=276964&amp;v=1.0.

Background and purposeWorking memory is critical for individuals and has been found to be improved by electrical stimulation of the left dorsolateral prefrontal cortex (DLPFC). However, the effects of different types of transcranial electrical stimulation on working memory are controversial, and the underlying mechanism remains uncertain. In this study, high-definition transcranial direct current stimulation (HD-tDCS) and high-definition transcranial random noise stimulation (HD-tRNS) were applied to the DLPFC to observe the different effects on visual working memory (VWM). The aim was to explore the causal relationship between the electrical activity of the DLPFC and the posterior parietal cortex (PPC) electrical activity and the contralateral delayed activity (CDA).MethodsThirty-three healthy subjects received HD-tDCS, HD-tRNS and sham stimulation in a random order. Stimulation was applied to the left DLPFC for 20 min. The subjects underwent a color change-detection task as our VWM task and an auditory digit span test (DST) immediately after stimulation. Event-related potential (ERP) data were collected during the VWM task.ResultsThe results revealed significant differences between the different types of HD-tES. There was a remarkable increase in VWM capacity following HD-tDCS compared with both HD-tRNS (pa = 0.038) and sham stimulation (pa = 0.038). Additionally, the CDA from the PPC differed after stimulation of the DLPFC. Both HD-tDCS and HD-tRNS expanded the maximum CDA amplitude from set size of 4 to 6, whereas after sham stimulation, the maximum CDA was maintained at a set size of 4. Compared with the sham condition, only HD-tDCS induced a noteworthy increase in CDA amplitude (pa = 0.012). Notably, a significant correlation emerged between the mean CDA amplitude and VWM capacity (p < 0.001, r = − 0.402).ConclusionThese findings underscore the ability of HD-tDCS to target the DLPFC to augment working memory capacity while concurrently amplifying CDA amplitudes in the PPC through the frontoparietal network.Trial registration ChiCTR2300074898.

HD-tDCS in refractory lateral frontal lobe epilepsy patients

Background:Recent disease-modifying treatments for Alzheimer’s disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested.Objectives:To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer’s dementia (AD).Design:Pilot, randomized, double-blind, parallel, sham-controlled studySetting:Clinical research site at UT Southwestern Medical CenterParticipants:Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics.Intervention:Treatment consisted of high definition transcranial direct current stimulation (HD-tDCS) delivered for 20 minutes over the medial prefrontal cortex. Ten sessions of sham, 1 mA, or 2 mA stimulation were received.Measurements:Cognitive outcomes were measured at baseline, after the last HD-tDCS session, and 8-weeks post-treatment. The primary outcome was change in total learning and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) immediately post-treatment and at 8-weeks. Secondary outcomes included measures of language, processing speed, and executive functioning. A multi-stage approach was used to examine cognitive outcomes, which included evaluation of effect sizes, statistical effects, and rate of clinically meaningful responses.Results:In this pilot trial, no statistically significant differences on cognitive outcomes were found between sham and active HD-tDCS immediately post-treatment (p’s > 0.05). However, moderate-to-large effect sizes were identified for enhanced RAVLT total learning (Cohen’s d=0.69–0.93) and phonemic fluency (d=1.08–1.49) for both active HD-tDCS conditions compared to sham, with rates of clinically relevant improvement between 25–33%. Meaningful enhancement persisted to 8 weeks only for the 1 mA condition.Conclusions:Multiple sessions of HD-tDCS over the medial prefrontal cortex appears to have potential to produce meaningful cognitive enhancements in a proportion of patients having AD with improvements maintained for at least 8 weeks in some.

Mind wandering is a common phenomenon in our daily lives and can have both an adaptive and detrimental impact. Recently, a dynamic framework has been proposed to characterise the heterogeneity of internal thoughts, suggesting there are three distinct thought types which can change over time – freely moving, deliberately constrained, and automatically constrained (thoughts). There is currently very little evidence on how different types of dynamic thought are represented in the brain. Previous research has applied non-invasive transcranial direct current stimulation (tDCS) to causally implicate the prefrontal cortex and inferior parietal lobule in mind wandering. However, a more recently developed and nuanced technique, high-definition tDCS (HD-tDCS), delivers more focal stimulation able to target specific brain regions. Therefore, the current study investigated the effect of anodal HD-tDCS applied to the left prefrontal and right inferior parietal cortices (with the occipital cortex included as an active control) on mind wandering, and specifically, the causal neural substrates of the three internal dynamic thought types. This was a single session study using a novel task which allows investigation into how dynamic thoughts are associated with behavioural variability and the recruitment of executive control operations across the three brain regions. There was no evidence to support our hypothesised effect of stimulation reducing task unrelated thought. Furthermore, the hypothesis driven analyses found no evidence of stimulation affecting the dynamic thought types, nor any evidence for our hypothesised effects of stimulation reducing behavioural variability and increasing randomness. There was only evidence for a relationship between these two measures of performance when participants thoughts were freely moving. However, there was evidence from our exploratory analyses that anodal stimulation to the prefrontal cortex decreased freely moving thought and anodal stimulation to the parietal lobule decreased deliberately constrained thought, relative to the sham conditions. The exploratory analyses also suggested stimulation may increase freely moving thought in the occipital cortex. Overall, these findings suggest stimulation does not affect the dynamic thought types, however there is preliminary evidence to support the heterogenous nature of mind wandering, whereby different brain regions may be causally implicated in distinct dynamic thought types.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33years) for 20min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

ABSTRACTThis study was designed to examine the effect of frontal hemispheric asymmetry (FHA) on effort‐related cardiovascular responses. High‐definition transcranial direct current stimulation (HD‐tDCS) was applied to the dorsolateral prefrontal cortex (dlPFC) to manipulate FHA and investigate its impact on cardiovascular reactivity. The sample consisted of 45 female and 44 male participants, who received either left or right cathodal stimulation. Following stimulation, participants performed two types of task demands: one fixed and easy, the other unfixed. In both tasks, participants could earn a moderate monetary reward. We measured pre‐ejection period (PEP), heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Drawing on motivation intensity theory (MIT), we predicted that right cathodal stimulation (left FHA) would lead to higher perceived success importance to get the reward determining higher effort in the unfixed task demand compared to the left cathodal stimulation and both stimulation conditions in the fixed task. As predicted, PEP reactivity was stronger in the unfixed condition following right cathodal stimulation compared to left cathodal stimulation and both stimulation conditions in the fixed task. Importantly, this effect was observed across both female and male participants, extending earlier neuromodulation findings (previously shown only in female samples) to both sexes. Overall, the results indicate that dlPFC neuromodulation can lead to higher effort by shifting frontal asymmetry and enhancing the perceived success importance in reward‐driven tasks.

This study investigated the effect of the high-definition transcranial direct current stimulation (HD-tDCS) on sustained attention reaction. The HD-tDCS was applied to the right dorsolateral prefrontal cortex (DLPFC) and the EEG signal was recorded simultaneously. We found that HD-tDCS could be used to enhance the reaction time and the N2 amplitude in response to the flanker stimuli changed significantly after the HD-tDCS stimulation. Moreover, the behavior enhancement was in accordance with the neural response. The HD-tDCS on DLPFC provides a way to enhance the subject’s attention to both the target task and the target task accompanied by distractors. The investigated approach may find application for digital medication in patients with attention problems, such as attention deficit hyperactivity disorder (ADHD).KeywordsHD-tDCSEEGReactionERP