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Transcranial Direct Current Stimulation (tDCS) is a non‐invasive brain stimulation technique used to modulates cortical brain activity. However, its effects on brain metabolites within the dorsolateral prefrontal cortex (DLPFC), a crucial area targeted for brain stimulation in mental disorders, remain unclear. This study aimed to investigate whether prefrontal tDCS over the left and right DLPFC modulates levels of key metabolites, including gamma‐aminobutyric acid (GABA), glutamate (Glu), glutamine/glutamate (Glx), N‐acetylaspartate (NAA), near to the target region and to explore potential sex‐specific effects on these metabolite concentrations. A total of 41 healthy individuals (19 female, M_age = 25 years, SD = 3.15) underwent either bifrontal active (2 mA for 20 min) or sham tDCS targeting the left (anode: F3) and right (cathode: F4) DLPFC within a 3 Tesla MRI scanner. Magnetic resonance spectroscopy (MRS) was used to monitor neurometabolic changes before, during, and after 40 min of tDCS, with measurements of two 10‐min intervals during stimulation. A single voxel beneath F3 was used for metabolic quantification. Results showed a statistically significant increase in Glx levels under active tDCS compared to the sham condition, particularly during the second 10‐min window and persisting into the post‐stimulation phase. No significant changes were observed in other metabolites, but consistent sex differences were detected. Specifically, females showed lower levels of NAA and GABA under active tDCS compared to the sham condition, while no significant changes were observed in males. E‐field modeling showed no significant differences in field magnitudes between sexes, and the magnitude of the e‐fields did not correlate with changes in Glx levels between active and sham stimulation during the second interval or post‐stimulation. This study demonstrates that a single session of prefrontal tDCS significantly elevates Glx levels in the left DLPFC, with effects persisting post‐stimulation. However, the observed sex differences in the neurochemical response to tDCS were not linked to specific stimulation intervals or variations in e‐field magnitudes, highlighting the complexity of tDCS effects and the need for personalized neuromodulation strategies. Prefrontal transcranial direct current stimulation (tDCS) enhances Glx levels in the left dorsolateral prefrontal cortex, a significant finding for managing disorders characterized by glutamatergic dysregulation. Unchanged levels of GABA, Glu, and NAA and sex‐specific responses highlighting the need for further research.

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.

Speed of Processing (SoP) represents a fundamental limiting step in cognitive performance which may underlie General Intelligence. The measure of SoP is particularly sensitive to aging, neurological or cognitive diseases, and has become a benchmark for diagnosis, cognitive remediation, and enhancement. Neural efficiency of the Dorsolateral Prefrontal Cortex (DLPFC) is proposed to account for individual differences in SoP. However, the mechanisms by which DLPFC efficiency is shaped by training and whether it can be enhanced remain elusive. To address this, we monitored the brain activity of sixteen healthy participants using functional Near Infrared Spectroscopy (fNIRS) while practicing a common SoP task (Symbol Digit Substitution Task) across 4 sessions. Furthermore, in each session, participants received counterbalanced excitatory repetitive transcranial magnetic stimulation (rTMS) during mid-session breaks. Results indicate a significant involvement of the left-DLPFC in SoP, whose neural efficiency is consistently increased through task practice. Active neurostimulation, but not Sham, significantly enhanced the neural efficiency. These findings suggest a common mechanism by which neurostimulation may aid to accelerate learning. •Left-DLPFC activity is associated with Symbol-Digit Performance.•Practice of SDST increases neural efficiency.•Excitatory rTMS to left-DLPFC further increases neural efficiency.•Neuroimaging may help evaluate the effects of neurostimulation paradigms.

•TMS-EEG identified neural markers of craving vulnerability in the DLPFC.•High cravers showed distinct early inhibitory and sustained cortical responses.•Cortical reactivity varied with cue salience and craving trait level.•TEPs offer biomarkers for state-dependent craving regulation and targeting.•Findings support temporally specific targets for neuromodulatory intervention. This study investigated the neural mechanisms underlying food-related motivational salience by integrating transcranial magnetic stimulation with electroencephalography (TMS–EEG) in a visual cue paradigm. By aligning TMS-evoked potentials (TEPs) with classical event-related potential (ERP) components, we aimed to characterize cortical excitability and inhibitory dynamics during early and sustained stages of stimulus processing. TEPs were recorded over the left dorsolateral prefrontal cortex (DLPFC) at two latencies—immediately (0 ms) and 300 ms after the onset of food-related and neutral images. Thirty-nine participants were classified as high or normal cravers based on composite craving scores derived from questionnaire and visual analog ratings. At 0 ms, high cravers exhibited greater early inhibitory (N40) and excitatory (P60) responses to food cues, together with enhanced N280 amplitudes, indicating stronger early cortical engagement. At 300 ms, larger P185 amplitudes reflected prolonged processing in high cravers. Within the high-craver group, P60 amplitudes were positively correlated with post-task craving ratings, suggesting a link between early cortical excitability and subjective motivational state. These findings demonstrate that TMS–EEG can resolve temporally distinct neural signatures of excitatory and inhibitory processing in response to salient cues. The observed TEP patterns, particularly in components associated with GABAergic inhibition (N40, N100), reveal individual variability in prefrontal control of appetitive stimuli. By bridging ERP and TMS–EEG approaches, this study provides mechanistic insight into the temporal dynamics of prefrontal regulation under motivational challenge and identifies potential neurophysiological markers for targeted neuromodulation of cue reactivity in health and disorder.

In the last few years, transcranial direct current stimulation (tDCS) has emerged as an appealing therapeutic option to improve brain functions. Promising data support the role of prefrontal tDCS in augmenting cognitive performance and ameliorating several neuropsychiatric symptoms, namely pain, fatigue, mood disturbances, and attentional impairment. Such symptoms are commonly encountered in patients with multiple sclerosis (MS). The main objective of the current work was to evaluate the tDCS effects over the left dorsolateral prefrontal cortex (DLPFC) on pain in MS patients.Our secondary outcomes were to study its influence on attention, fatigue, and mood. Sixteen MS patients with chronic neuropathic pain were enrolled in a randomized, sham-controlled, and cross-over study.Patients randomly received two anodal tDCS blocks (active or sham), each consisting of three consecutive daily tDCS sessions, and held apart by 3 weeks. Evaluations took place before and after each block. To evaluate pain, we used the Brief Pain Inventory (BPI) and the Visual Analog Scale (VAS). Attention was assessed using neurophysiological parameters and the Attention Network Test (ANT). Changes in mood and fatigue were measured using various scales. Compared to sham, active tDCS yielded significant analgesic effects according to VAS and BPI global scales.There were no effects of any block on mood, fatigue, or attention. Based on our results, anodal tDCS over the left DLPFC appears to act in a selective manner and would ameliorate specific symptoms, particularly neuropathic pain. Analgesia might have occurred through the modulation of the emotional pain network. Attention, mood, and fatigue were not improved in this work. This could be partly attributed to the short protocol duration, the small sample size, and the heterogeneity of our MS cohort. Future large-scale studies can benefit from comparing the tDCS effects over different cortical sites, changing the stimulation montage, prolonging the duration of protocol, and coupling tDCS with neuroimaging techniques for a better understanding of its possible mechanism of action.

Transcranial magnetic stimulation (TMS) holds potential promise as a therapeutic modality for disorders of addiction. Our previous findings indicate that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsal-lateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC can reduce drug craving for methamphetamine. One major issue with rTMS is the duration of treatment and hence potential dropout rate. Theta burst stimulation (TBS) has been recently shown to be non-inferior relative to repetitive transcranial magnetic stimulation for major depression. Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left or right dorsolateral prefrontal cortex on methamphetamine craving in abstinent-dependent subjects. In this randomized single-blind pilot study, 83 abstinent methamphetamine-dependent subjects from a long-term residential treatment program were randomly allocated into three groups: intermittent theta burst stimulation (iTBS) over the left DLPFC (active group), continuous theta burst stimulation (cTBS) over the left DLPFC (active control group), or cTBS over the right DLPFC (active group) was administered twice daily over 5 days for a total of 10 sessions. We measured the primary outcome of cue-induced craving and secondarily sleep quality, depression, anxiety, impulsivity scores, and adverse effects. We show a pre- vs. postintervention effect on craving, which, on paired tests, showed that the effect was driven by iTBS of the left DLPFC and cTBS of the right DLPFC, reducing cue-induced craving but not cTBS of the left DLPFC. We did not show the critical group-by-time interaction. The secondary outcomes of depression, anxiety, and sleep were unrelated to the improvement in craving in the left iTBS and right cTBS group. In the first two sessions, self-reported adverse effects were higher with left iTBS when compared to right cTBS. The distribution of craving change suggested greater clinical response (50% improvement) with right cTBS and a bimodal pattern of effect with left iTBS, suggesting high interindividual variable response in the latter. Accelerated twice-daily TBS appears feasible and tolerable at modulating craving and mood changes in abstinent methamphetamine dependence critically while reducing session length. We emphasize the need for a larger randomized controlled trial study with a sham control to confirm these findings and longer duration of clinically relevant follow-up. Chinese Clinical Trial Registry number, 17013610.

Children with attention deficit-hyperactivity disorder (ADHD) have impaired hot and cold executive functions, which is thought to be related to impaired ventromedial and dorsolateral prefrontal cortex (vmPFC and dlPFC) functions. The present study aimed to assess the impact concurrent stimulation of dlPFC and vmPFC through transcranial random noise stimulation (tRNS), a non-invasive brain stimulation tool which enhances cortical excitability via application of alternating sinusoidal currents with random frequencies and amplitudes over the respective target regions on hot and cold executive functions. Eighteen children with ADHD received real and sham tRNS over the left dlPFC and the right vmPFC in two sessions with one week interval. The participants performed Circle Tracing, Go/No-Go, Wisconsin Card Sorting, and Balloon Analogue Risk Tasks during stimulation in each session. The results showed improved ongoing inhibition, prepotent inhibition, working memory, and decision making, but not set-shifting performance, during real, as compared to sham stimulation. This indicates that simultaneous stimulation of the dlPFC and the vmPFC improves hot and cold executive functions in children with ADHD.

Preclinical findings suggest that transcranial infrared laser stimulation (TILS) improves fear extinction learning and cognitive function by enhancing prefrontal cortex (PFC) oxygen metabolism. These findings prompted our investigation of treating pathological fear using this non-invasive stimulation approach either alone to the dorsolateral PFC (dlPFC), or to the ventromedial PFC (vmPFC) in combination with exposure therapy. Volunteers with pathological fear of either enclosed spaces, contamination, public speaking, or anxiety-related bodily sensations were recruited for this randomized, single-blind, sham-controlled trial with four arms: (a) Exposure + TILS_vmPFC ( = 29), (b) Exposure + sham TILS_vmPFC ( = 29), (c) TILS_dlPFC alone ( = 26), or (d) Sham TILS _dlPFC alone ( = 28). Post-treatment assessments occurred immediately following treatment. Follow-up assessments occurred 2 weeks after treatment. A total of 112 participants were randomized [age range: 18-63 years; 96 females (85.71%)]. Significant interactions of Group × Time and Group × Context indicated differential treatment effects on retention (i.e. between time-points, averaged across contexts) and on generalization (i.e. between contexts, averaged across time-points), respectively. Among the monotherapies, TILS_dlPFC outperformed SHAM_dlPFC in the initial context, = -13.44, 95% CI (-25.73 to -1.15), = 0.03. Among the combined treatments, differences between EX + TILS_vmPFC and EX + SHAM_vmPFC were non-significant across all contrasts. TILS to the dlPFC, one of the PFC regions implicated in emotion regulation, resulted in a context-specific benefit as a monotherapy for reducing fear. Contrary to prediction, TILS to the vmPFC, a region implicated in fear extinction memory consolidation, did not enhance exposure therapy outcome.

Introduction It is widely demonstrated that high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has facilitative effects and is therefore capable to inducing changes in motor responses. One of the most investigated areas is the dorsolateral prefrontal cortex (DLPFC) as it plays a special executive attention role in actively preserving access to stimulus representations and objectives in environments with plenty of distraction such as those of team sports. Volleyball is a team sport in which the attention and coordination components are essential for achieving performance. Thus, the aim of this study was to investigate if HF rTMS at DLPFC in volleyball players can improve homolateral motor coordination and cortical excitability. Results This study was a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study and were randomly assigned either the active rTMS (n = 10) or the sham stimulation group (n = 10). The stimulation was performed in one session with 10 Hz, 80% of the resting motor threshold (RMT) of the right first dorsal interosseous muscle, 5 s of stimulation, and 15 s of rest, for a total of 1500 pulses. Before and after stimulation, the coordination and the cortical excitability were evaluated. The significant finding of this paper was that HF-rTMS of the DLPFC improved performance in terms of the homolateral interlimb coordination, with a significantly decreased in resting motor threshold and MEP latency of the ipsilateral motor cortex. It seem that HF-rTMS could increase coordination performances when the velocity of the execution is higher (120 bpm and 180 bpm). Conclusion Moreover, in active rTMS group significant differences emerged after stimulation in RMT and in MEP latency, while no differences emerged after stimulation in MEP amplitude. In conclusion we believe that these results may be of great interest to the scientific community and may also have practical implications in the future.

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.