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A small population of brainstem noradrenaline neurons powerfully modulates global brain function, but how they regulate diverse—and at times opposing—functions is not clear. The authors report that a modular organization in this neuromodulatory system, coupled with context-dependent activation modes, controls the balance between opposing emotional and flexible learning states. Noradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell modules with specific anatomical connectivity. An amygdala-projecting ensemble promoted aversive learning, while an independent medial prefrontal cortex-projecting ensemble extinguished aversive responses to enable flexible behavior. LC neurons displayed context-dependent inter-relationships, with moderate, discrete activation of distinct cell populations by fear or safety cues and robust, global recruitment of most cells by strong aversive stimuli. These results demonstrate a modular organization in LC in which combinatorial activation modes are coordinated with projection- and behavior-specific cell populations, enabling adaptive tuning of emotional responding and behavioral flexibility.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.

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.

·This study examined video's effect on friendliness vs. face-to-face using fNIRS.·Face-to-face communication showed increase in friendliness after social tasks.·Video communication elicits fewer feelings of friendliness compared to face-to-face interactions.·Decrement of friendliness through video communication may be related to cognitive effort. Friendliness is essential for the development of stable interpersonal relationships. Video communication is growing rapidly in popularity for initiating and maintaining personal relationships, but it is unknown if video communication is as effective as face-to-face communication for promoting friendliness. This study compared the development of subjective friendliness between video and face-to-face communication sessions and investigated the associated neural correlates. Thirty healthy same-sex pairs were recruited and randomly assigned to face-to-face (Face) and video communication (Video) groups. Both groups performed three communication conditions face-to-face or via the Zoom platform in separate rooms: singing a song alone, singing a song with the other pair, and listening to the other pair sing a song. Activities of the bilateral dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (MPFC) were measured during the condition by functional near-infrared spectroscopy (fNIRS), and subjective friendliness was assessed before and after each condition using the Profile of Mood States 2nd Edition (POMS-F). After each condition, the change in POMS-F score (∆POMS-F) was compared between groups, and correlations were calculated with regional brain activity measures. Face group showed an increase in all conditions in ∆POMS-F, and Video group showed in average a decrease, which results in significant group difference in ∆POMS-F. The Face group showed a significant positive correlation between right DLPFC activity and increase in ∆POMS-F, whereas the Video group showed marginal significant negative correlation. Additionally, left DLPFC activity was significantly higher and MPFC activity was significantly lower in the Video group than in the Face group during all conditions. These findings suggest that subjective feelings of friendliness may be limited during video communication due to a requirement for greater cognitive effort.

Detrimental decision-making is a major problem among violent offenders. Non-invasive brain stimulation offers a promising method to directly influence decision-making and has already been shown to modulate risk-taking in non-violent controls. We hypothesize that anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex beneficially modulates the neural and behavioral correlates of risk-taking in a sample of violent offenders. We expect offenders to show more risky decision-making than non-violent controls and that prefrontal tDCS will induce stronger changes in the offender group. In the current study, 22 male violent offenders and 24 male non-violent controls took part in a randomized double-blind sham-controlled cross-over study applying tDCS over the right dorsolateral prefrontal cortex. Subsequently, participants performed the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging (fMRI). Violent offenders showed significantly less optimal decision-making compared to non-violent controls. Active tDCS increased prefrontal activity and improved decision-making only in violent offenders but not in the control group. Also, in offenders only, prefrontal tDCS influenced functional connectivity between the stimulated area and other brain regions such as the thalamus. These results suggest baseline dependent effects of tDCS and pave the way for treatment options of disadvantageous decision-making behavior in this population.

Neurostimulation techniques, such as continuous theta-burst stimulation (cTBS), over the dorsolateral prefrontal cortex (DLPFC) have been associated with improvements in anxiety symptoms and emotion processing. The aim of this feasibility study was the evaluation of the effectiveness of cTBS over the right DLPFC combined with Attention Modification Training (AMT) on reducing levels of anxiety and attentional bias. A 40s-cTBS session (real or sham) over the right DLPFC was administrated at 8 treatment sessions over a 2-week period, and each cTBS treatment was followed by computer-based AMT (real or control). Eighty-nine participants ( M age = 21.29, SD  = 2.06, 50.56% females) differentiated on levels of anxiety were randomly assigned to the following treatment groups (i) cTBS and AMT, (ii) cTBS and control AMT, and (iii) sham cTBS and AMT. Findings suggested that cTBS combined with AMT treatment was not superior to sham cTBS and AMT on reducing self-reported anxiety symptoms. However, combined cTBS and AMT was associated with increased attention towards positive stimuli and increased gaze fixation in the mouth region of happy facial expressions. Current results provide promising evidence for the effectiveness of AMT in reducing anxiety symptoms and contribute to existing knowledge on how inhibitory stimulation over the right DLPFC combined with AMT may influence emotion processing. Present findings can inform future treatments designed to address the attention mechanisms leading to anxiety symptoms.

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 escalating global burden of age-related neurodegenerative diseases and associated healthcare costs necessitates innovative interventions to stabilize or enhance cognitive functions. Deficits in working memory (WM) are linked to alterations in prefrontal theta–gamma cross-frequency coupling. Low-intensity transcranial alternating current stimulation (tACS) has emerged as a non-invasive, low-cost approach capable of modulating ongoing oscillations in targeted brain areas through entrainment. This study investigates the impact of multi-session peak-coupled theta–gamma cross-frequency tACS administered to the dorsolateral prefrontal cortex (DLPFC) on WM performance in older adults. In a randomized, sham-controlled, triple-blinded design, 77 participants underwent 16 stimulation sessions over six weeks while performing n -back tasks. Signal detection measures revealed increased 2-back sensitivity and robust modulations of response bias, indicating improved WM and decision-making adaptations, respectively. No effects were observed in the 1-back condition, emphasizing dependencies on cognitive load. Repeated tACS reinforces behavioral changes, indicated by increasing effect sizes. This study supports prior research correlating prefrontal theta–gamma coupling with WM processes and provides unique insights into the neurocognitive benefits of repeated tACS intervention. The well-tolerated and highly effective multi-session tACS intervention among the elderly underscores its therapeutic potential in vulnerable populations.

Background and purpose Working 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). Methods Thirty-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. Results The 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 ( p a  = 0.038) and sham stimulation ( p a  = 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 ( p a  = 0.012). Notably, a significant correlation emerged between the mean CDA amplitude and VWM capacity ( p  < 0.001, r  = − 0.402). Conclusion These 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.