Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a serious mental illness with complex pathology, including abnormalities in the glutamate system. Glutamate is rapidly removed from the synapse by excitatory amino acid transporters (EAATs). Changes in the expression and localization of the primary glutamate transporter EAAT2 are found in the brain in central nervous system (CNS) disorders including SCZ. We hypothesize that neuronal expression and function of EAAT2 are increased in the frontal cortex in subjects diagnosed with SCZ. STUDY DESIGN: EAAT2 protein expression and glutamate transporter function were assayed in synaptosome preparations from the dorsolateral prefrontal cortex (DLPFC) of SCZ subjects and age- and sex-matched nonpsychiatrically ill controls. EAAT2 splice variant transcript expression was assayed in enriched populations of neurons and astrocytes from the DLPFC. Pathway analysis of publicly available transcriptomic datasets was carried out to identify biological changes associated with EAAT2 perturbation in different cell types. RESULTS: We found no significant changes in EAAT2 protein expression or glutamate uptake in the DLPFC in SCZ subjects compared with controls (n = 10/group). Transcript expression of EAAT2 and signaling molecules associated with EAAT2b trafficking (CaMKIIa and DLG1) were significantly altered in enriched populations of astrocytes and pyramidal neurons (P < .05) in SCZ (n = 16/group). These changes were not associated with antipsychotic medications. Pathway analysis also identified cell-type-specific enrichment of biological pathways associated with perturbation of astrocyte (immune pathways) and neuronal (metabolic pathways) EAAT2 expression. CONCLUSIONS: Overall, these data support the growing body of evidence for the role of dysregulation of the glutamate system in the pathophysiology of SCZ.

Effects of age and flight experience on prefrontal cortex activity in airline pilots: An fNIRS study.

It is essential for airlines to have a deep understanding of the cognitive impact of aging among pilots. The current literature on executive function indicates that compensatory mechanisms in the brain may counteract age-related cognitive decline, at least up to certain task load levels. However, few studies have been administered to evaluate changes in aircrew competence as they age. The present study focuses on dorsolateral prefrontal cortex (DLPFC) activity as it is implicated in cognitive performance and working memory, which are associated with skill proficiency. We measured the DLPFC activity for airline pilots, including trainees, during maneuvering using a flight simulator. Our preliminary results indicated that only expert (aged) pilots demonstrated higher activity of the left DLPFC than the right one. However, for youth trainees, not only was the error rate high while using the flight simulator, but the activity of the DLFPC was also lower than that of the expert pilots, and there was no statistically significant difference between the left and right DLPFC. Although these findings partially differ from those reported in previous studies on age-related changes, it is evident that training as an airline pilot for over 20 years may affect such results. We believe that this noninvasive approach to objective quantification of skill will facilitate the development of effective assessment competence in aging.

Neural correlates of stress-reactive rumination in depression - The role of childhood trauma and social anxiety.

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.

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.

Trajectories of suicidal ideation during rTMS for treatment-resistant depression.

BACKGROUND: rTMS is a safe and effective intervention for treatment-resistant depression (TRD). However, there is limited data on its specific impact on suicidal ideation (SI), and the trajectory of SI over the treatment course. OBJECTIVE: This open-label clinical trial investigated SI outcomes and trajectories in patients with TRD receiving low-frequency rTMS (LFR) to the right dorsolateral prefrontal cortex (DLPFC; N = 55). METHODS: A latent class mixed-effect model was used to identify response trajectories for SI as well as core mood symptoms. Logistic regression analyses investigated risk factors associated with identified trajectories. RESULTS: For each symptom domain, we identified two distinct trajectories during LFR, one tracking improvement (SI: n = 35, 60 %; mood: n = 29, 53 %) and the other tracking no improvement (SI: n = 20, 40 %; mood: n = 26, 47 %). Male sex, higher baseline anxiety, and higher baseline SI were risk factors for no improvement of SI; while higher baseline anxiety and benzodiazepine use were risk factors for no improvement of mood. Mediation analyses showed that anxiety was a risk factor for no improvement of SI and mood independent of benzodiazepine treatment. CONCLUSIONS: This is the first study to investigate trajectories of response to LFR to the right DLPFC. SI and mood improved with LFR in most patients but the severity of anxiety symptoms was a factor of poor prognosis for both. Nuanced characterization of SI response to rTMS may lead to critical insights for individualized targeting strategies.

A comparative study of the dorsolateral prefrontal cortex targeting approaches for transcranial magnetic stimulation treatment: Insights from the healthy control data.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for medication-resistant depression. Several targeting methods for the left DLPFC have been proposed including identification with resting-state functional magnetic resonance imaging (rs-fMRI) neuronavigation, stimulus coordinates based on structural MRI, or electroencephalography (EEG) F3 site by Beam F3 method. To date, neuroanatomical and neurofunctional differences among those approaches have not been investigated on healthy subjects, which are structurally and functionally unaffected by psychiatric disorders. This study aimed to compare the mean location, its dispersion, and its functional connectivity with the subgenual cingulate cortex (SGC), which is known to be associated with the therapeutic outcome in depression, of various approaches to target the DLPFC in healthy subjects. Fifty-seven healthy subjects underwent MRI scans to identify the stimulation site based on their resting-state functional connectivity and were measured their head size for targeting with Beam F3 method. In addition, we included two fixed stimulus coordinates over the DLPFC in the analysis, as recommended in previous studies. From the results, the rs-fMRI method had, as expected, more dispersed target sites across subjects and the greatest anticorrelation with the SGC, reflecting the known fact that personalized neuronavigation yields the greatest antidepressant effect. In contrast, the targets located by the other methods were relatively close together with less dispersion, and did not differ in anticorrelation with the SGC, implying their limitation of the therapeutic efficacy and possible interchangeability of them.

Targeting the left DLPFC and right VLPFC in unmarried romantic relationship breakup (love trauma syndrome) with intensified electrical stimulation: A randomized, single-blind, parallel-group, sham-controlled study.

BACKGROUND: Ending a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables. METHODS: In this randomized, sham-controlled, single-blind parallel trial, we assessed the efficacy of an intensified anodal stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) with two montages (left DLPFC vs right VLPFC) to reduce love trauma symptoms. 36 participants with love trauma syndrome were randomized in three tDCS condition (left DLPFC, right VLPFC, sham stimulation). LTS symptoms, treatment-related outcome variables (depressive state, anxiety, emotion regulation, positive and negative affect), and cognitive functions were assessed before, right after, and one month after intervention. RESULTS: Both DLPFC and VLPFC protocols significantly reduced LTS symptoms, and improved depressive state and anxiety after the intervention, as compared to the sham group. The improving effect of the DLPFC protocol on love trauma syndrome was significantly larger than that of the VLPFC protocol. For emotion regulation and positive and negative affect, improved regulation of emotions and positive affect and reduced negative affect were revealed after intervention in the two real stimulation conditions compared to the sham. For cognitive functions, no significant difference was observed between the groups, but again a positive effect of intervention within groups in the real stimulation conditions (DLPFC and VLPFC) was found for most components of the cognitive tasks. CONCLUSIONS: Enhancement of left DLPFC and right VLPFC activity with intensified stimulation improves LTS symptoms and treatment-related variables. For LTS symptoms, DLPFC stimulation was more efficient than VLPFC stimulation., For the other variables, no significant difference was observed between these two stimulation groups. These promising results require replication in larger trials.

No Impact of Tdcs on Stress-Induced State Rumination and no Influence of Executive Control and Trait Rumination: A Double-Blind Sham-Controlled Within-Subjects Study.

Objective: Rumination is conceptualized as a critical transdiagnostic vulnerability and maintenance factor for affective dysregulation and related emotional disorders. Recent research has pointed to transcranial direct current stimulation (tDCS) as a novel therapeutic tool for alleviating rumination, especially stress-induced rumination. However, the mechanisms of action underlying this effect remain unclear, particularly regarding the potential moderating role of executive control and trait-like rumination. Therefore, in this study, we investigated the impact of anodal tDCS on stress-induced rumination and the potential moderating influence of executive control and trait-like rumination on this efect. Method: Forty participants from the general community (i.e., unselected sample) took part in a double-blind within-subjects design study wherein we compared anodal stimulation over the left dorsolateral prefrontal cortex(dlPFC) with a sham-stimulation procedure. Participants completed an N-back task, reflecting executive control, during tDCS stimulation, followed by a stress-induction protocol wherein we assessed stress-induced state rumination. Results: We found no significant effect of tDCS on stress-induced state rumination and no modulation by executive control or trait rumination. Post-hoc Bayesian analyses corroborated these results and even supported the hypothesis that anodal tDCS does not impact stress-induced rumination. Conclusions: From a clinical perspective, our results are at odds with the current outlook that tDCS is a viable tool for reducing rumination, particularly stress-induced rumination. However, we firmly believe that the results of null-finding studies, such as those from this study, are particularly valuable for future iterations and meta-researchon tDCS as a potential tool for targeting transdiagnostic processes, such as rumination. We also addressed methodological limitations and directions for future research in this area.

Reliability of the TMS-evoked potential in dorsolateral prefrontal cortex.

We currently lack a reliable method to probe cortical excitability noninvasively from the human dorsolateral prefrontal cortex (dlPFC). We recently found that the strength of early and local dlPFC transcranial magnetic stimulation (TMS)-evoked potentials (EL-TEPs) varied widely across dlPFC subregions. Despite these differences in response amplitude, reliability at each target is unknown. Here we quantified within-session reliability of dlPFC EL-TEPs after TMS to six left dlPFC subregions in 15 healthy subjects. We evaluated reliability (concordance correlation coefficient [CCC]) across targets, time windows, quantification methods, regions of interest, sensor- vs. source-space, and number of trials. On average, the medial target was most reliable (CCC = 0.78) and the most anterior target was least reliable (CCC = 0.24). However, all targets except the most anterior were reliable (CCC > 0.7) using at least one combination of the analytical parameters tested. Longer (20 to 60 ms) and later (30 to 60 ms) windows increased reliability compared to earlier and shorter windows. Reliable EL-TEPs (CCC up to 0.86) were observed using only 25 TMS trials at a medial dlPFC target. Overall, medial dlPFC targeting, wider windows, and peak-to-peak quantification improved reliability. With careful selection of target and analytic parameters, highly reliable EL-TEPs can be extracted from the dlPFC after only a small number of trials.

The effects of prefrontal tDCS and hf-tRNS on the processing of positive and negative emotions evoked by video clips in first- and third-person.

The causal role of the cerebral hemispheres in positive and negative emotion processing remains uncertain. The Right Hemisphere Hypothesis proposes right hemispheric superiority for all emotions, while the Valence Hypothesis suggests the left/right hemisphere's primary involvement in positive/negative emotions, respectively. To address this, emotional video clips were presented during dorsolateral prefrontal cortex (DLPFC) electrical stimulation, incorporating a comparison of tDCS and high frequency tRNS stimulation techniques and manipulating perspective-taking (first-person vs third-person Point of View, POV). Four stimulation conditions were applied while participants were asked to rate emotional video valence: anodal/cathodal tDCS to the left/right DLPFC, reverse configuration (anodal/cathodal on the right/left DLPFC), bilateral hf-tRNS, and sham (control condition). Results revealed significant interactions between stimulation setup, emotional valence, and POV, implicating the DLPFC in emotions and perspective-taking. The right hemisphere played a crucial role in both positive and negative valence, supporting the Right Hemisphere Hypothesis. However, the complex interactions between the brain hemispheres and valence also supported the Valence Hypothesis. Both stimulation techniques (tDCS and tRNS) significantly modulated results. These findings support both hypotheses regarding hemispheric involvement in emotions, underscore the utility of video stimuli, and emphasize the importance of perspective-taking in this field, which is often overlooked.

High-definition turns timing-dependent: Different behavioural consequences during and following cathodal high-definition transcranial direct current stimulation (HD tDCS) in a magnitude classification task.

Neuromodulation with transcranial direct current stimulation (tDCS) can transiently alter neural activity, but its spatial precision is low. High-definition (HD) tDCS was introduced to increase spatial precision by placing additional electrodes over the scalp. Initial evaluations of HD tDCS indicated polarity-specific neurophysiological effects-similar to conventional tDCS albeit with greater spatial precision. Here, we compared the effects of cathodal tDCS or HD tDCS in a 4 × 1 configuration over prefrontal cortex (PFC) regions on behavioural outcomes in a magnitude classification task. We report results on overall performance, on the numerical distance effect as a measure of numerical processing, and on the spatial-numerical associations of response codes (SNARC) effect, which was previously affected by prefrontal tDCS. Healthy volunteers (n = 68) received sham or cathodal HD tDCS at 1 mA over the left dorsolateral prefrontal cortex (DLPFC) or the left inferior frontal gyrus (IFG). Results were compared to an identical protocol with conventional cathodal tDCS to the left PFC versus sham (n = 64). Mixed effects models showed performance gains relative to sham tDCS in all conditions after tDCS (i.e. 'offline'), whereas montages over PFC and DLPFC already showed performance gains during tDCS (i.e. 'online'). In contrast to conventional tDCS, HD tDCS did not reduce the SNARC effect. Neither condition affected numerical processing, as expected. The results suggest that HD tDCS with cathodal polarity might require further adjustments (i.e. regarding tDCS intensity) for effective modulations of cognitive-behavioural performance, which could be achieved by individualised current density in electric field modelling.

The impact of transcranial direct current stimulation on attention bias modification in children with ADHD.

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.

Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer's Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study.

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD).

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.

Real-world retrospective study of repetitive transcranial magnetic stimulation (TMS) treatment for bipolar and unipolar depression using TMS registry data in Tokyo.

Despite the prevalence of empirical practice, evidence supporting the use of repetitive transcranial magnetic stimulation (rTMS) in treating bipolar depression (BD) is sparse compared to that for unipolar depression. Therefore, this study aimed to conduct a retrospective observational analysis using TMS registry data to compare the efficacy of rTMS treatment for BD and unipolar depression. Data from 20 patients diagnosed with unipolar and BD were retrospectively extracted from the TMS registry to ensure age and sex matching. The primary outcomes of this registry study were measured using the 21-item Hamilton Depression Rating Scale (HAM-D21) and Montgomery-Åsberg Depression Rating Scale (MADRS). Analysis did not reveal significant differences between the two groups in terms of depression severity, motor threshold, or stimulus intensity at baseline. Similarly, no significant differences were observed in absolute or relative changes in the total HAM-D21 and MADRS scores. Furthermore, the response and remission rates following rTMS treatment did not differ significantly between groups. The only adverse event reported in this study was scalp pain at the stimulation site; however, the incidence and severity were not significantly different between the groups. In conclusion, this retrospective study, using real-world TMS registry data, suggests that rTMS treatment for BD could be as effective as that for unipolar depression. These findings underscore the need for further validation in prospective randomized controlled trials with larger sample sizes.

Comprehensive elucidation of resting-state functional connectivity in anorexia nervosa by a multicenter cross-sectional study.

BACKGROUND: Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs). METHODS: We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons. RESULTS: Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction). CONCLUSION: Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

Relationship Between the Parietal Cortex and Task Switching: Transcranial Direct Current Stimulation Combined with an Event-related Potential Study.

Task switching refers to a set of cognitive processes involved in shifting attention from one task to another. In recent years, researchers have applied transcranial direct current stimulation (tDCS) to investigate the causal relationship between the parietal cortex and task switching. However, results from available studies are highly inconsistent. This may be due to the unclear understanding of the underlying mechanisms. Therefore, the current study utilized event-related potential (ERP) analysis to investigate the modulatory effects of tDCS on task-switching processes. Twenty-four subjects were recruited to perform both predictable and unpredictable parity/magnitude tasks under anodal (RA) and sham conditions. The results showed no significant changes in behavioral performance. However, marked tDCS-induced ERP changes were observed. Specifically, for the predictable task switching, compared with the sham condition, the target-N2 component occurred significantly earlier for switch trials than repeat trials under the RA condition in males, while no difference was found in females. For unpredictable task switching, under the sham condition, the P2 peak was significantly larger for switch trials compared with repeat trials, whereas this difference was not observed under the RA condition. These results indicated the causal relationship between the right parietal cortex and exogenous adjustment processes involved in task switching. Moreover, anodal tDCS over the right parietal cortex may lead to the manifestation of gender differences.

The effect of high-frequency rTMS over left DLPFC and fluid abilities on goal neglect.

Goal neglect refers to when an aspect of task instructions is not utilised due to increased competition between goal representations, an attentional limit theoretically linked to working memory. In an attempt to alleviate goal neglect and to investigate the association between dorsolateral prefrontal cortex (DLPFC)-supported working memory and goal neglect, we used high-frequency repetitive transcranial magnetic stimulation to the left DLPFC whilst participants completed the letter-monitoring task, a measure of goal neglect, and an N3-back task, a working memory task known to be affected by rTMS of the left DLPFC, following 20 min of active and sham stimulation (run on separate days). We found increased accuracy on the N3-back task in addition to decreased goal neglect in the active compared to sham condition when controlling for age and fluid abilities (as assessed by matrix reasoning performance). Furthermore, analysis showed that active stimulation improvements on both the N3-back and letter-monitoring tasks were greater for those with higher fluid abilities. These findings provide support for the link between the DLPFC-support working memory and goal neglect. Increased performance on the N3-back task also supports the literature reporting a link between left DLPFC and verbal working memory. Results are evaluated in the context of potential use to alleviate symptoms of disorders related to goal neglect.

Combining transcranial magnetic stimulation with training to improve social cognition impairment in schizophrenia: a pilot randomized controlled trial.

Schizophrenia is a severe, chronic mental disorder that profoundly impacts patients' everyday lives. The illness's core features include positive and negative symptoms and cognitive impairments. In particular, deficits in the social cognition domain showed a tighter connection to patients' everyday functioning than the other symptoms. Social remediation interventions have been developed, providing heterogeneous results considering the possibility of generalizing the acquired improvements in patients' daily activities. In this pilot randomized controlled trial, we investigated the feasibility of combining fifteen daily cognitive and social training sessions with non-invasive brain stimulation to boost the effectiveness of the two interventions. We delivered intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC). Twenty-one patients were randomized into four groups, varying for the assigned stimulation condition (real vs. sham iTBS) and the type of cognitive intervention (training vs. no training). Clinical symptoms and social cognition tests were administered at five time points, i.e., before and after the treatment, and at three follow-ups at one, three, and six months after the treatments' end. Preliminary data show a trend in improving the competence in managing emotion in participants performing the training. Conversely, no differences were found in pre and post-treatment scores for emotion recognition, theory of mind, and attribution of intentions scores. The iTBS intervention did not induce additional effects on individuals' performance. The methodological approach's novelty and limitations of the present study are discussed.

Dopamine D2 receptor antagonist modulates rTMS-induced pain experiences and corticospinal excitability dependent on stimulation targets / El antagonista del receptor de dopamina D2 modula las experiencias de dolor inducidas por rTMS y la excitabilidad corticoespinal dependiendo de los objetivos de estimulación

Both the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) rTMS have the potential to reduce certain chronic pain conditions. However, the analgesic mechanisms remain unclear, in which M1- and DLPFC-rTMS may have different impact on the release of dopamine receptor D2 neurotransmissions (DRD2). Using a double-blind, randomised, sham- and placebo-controlled design, this study investigated the influence of DRD2 antagonist on rTMS-induced analgesia and corticospinal excitability across the M1 and DLPFC. Healthy participants in each group (M1, DLPFC, or Sham) received an oral dose of chlorpromazine or placebo before the delivery of rTMS in two separate sessions. Heat pain and cortical excitability were assessed before drug administration and after rTMS intervention. DRD2 antagonist selectively abolished the increased heat pain threshold induced by DLPFC stimulation and increased pain unpleasantness. The absence of analgesic effects in DLPFC stimulation was not accompanied by plastic changes in the corticospinal pathway. In contrast, DRD2 antagonist increased corticospinal excitability and rebalanced excitation-inhibition relationship following motor cortex stimulation, although there were no clear changes in pain experiences. These novel findings together highlight the influence of dopaminergic neurotransmission on rTMS-induced analgesia and corticospinal excitability dependent on stimulation targets.(AU)