Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.

BACKGROUND: While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. METHODS: Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. RESULTS: Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LIMITATIONS: The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month. CONCLUSION: More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method.

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Investigating the variability of prefrontal tDCS effects on working memory: An individual E-field distribution study.

Transcranial direct current stimulation (tDCS) over the prefrontal cortex has the potential to enhance working memory by means of a weak direct current applied to the scalp. However, its effects are highly variable and possibly dependent on individual variability in cortical architecture and head anatomy. Unveiling sources of heterogeneity might improve fundamental and clinical application of tDCS in the field. Therefore, we investigated sources of tDCS variability of prefrontal 1.5 mA tDCS, 3 mA tDCS and sham tDCS in 40 participants (67.5% women, mean age 24.7 years) by associating simulated electric field (E-field) magnitude in brain regions of interest (dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and subgenual ACC) and working memory performance. Emotional and non-emotional 3-back paradigms were used. In the tDCS protocol analysis, effects were only significant for the 3 mA group, and only for the emotional tasks. In the individual E-field magnitude analysis, faster responses in non-emotional, but not in the emotional task, were associated with stronger E-fields in all brain regions of interest. Concluding, individual E-field distribution might explain part of the variability of prefrontal tDCS effects on working memory performance and in clinical samples. Our results suggest that tDCS effects might be more consistent or improved by applying personalizing current intensity, although this hypothesis should be confirmed by further studies.

Structural connectome alterations in anxious dogs: a DTI-based study.

Anxiety and fear are dysfunctional behaviors commonly observed in domesticated dogs. Although dogs and humans share psychopathological similarities, little is known about how dysfunctional fear behaviors are represented in brain networks in dogs diagnosed with anxiety disorders. A combination of diffusion tensor imaging (DTI) and graph theory was used to investigate the underlying structural connections of dysfunctional anxiety in anxious dogs and compared with healthy dogs with normal behavior. The degree of anxiety was assessed using the Canine Behavioral Assessment & Research Questionnaire (C-BARQ), a widely used, validated questionnaire for abnormal behaviors in dogs. Anxious dogs showed significantly decreased clustering coefficient ([Formula: see text]), decreased global efficiency ([Formula: see text]), and increased small-worldness (σ) when compared with healthy dogs. The nodal parameters that differed between the anxious dogs and healthy dogs were mainly located in the posterior part of the brain, including the occipital lobe, posterior cingulate gyrus, hippocampus, mesencephalon, and cerebellum. Furthermore, the nodal degree ([Formula: see text]) of the left cerebellum was significantly negatively correlated with "excitability" in the C-BARQ of anxious dogs. These findings could contribute to the understanding of a disrupted brain structural connectome underlying the pathological mechanisms of anxiety-related disorders in dogs.

Combining transcranial direct current stimulation with group cognitive behavioral therapy developed to treat rumination: a clinical pilot study.

Background: As part of repetitive negative thinking (RNT), rumination is a maladaptive cognitive response style to stress or negative mood which can increase the risk of depression and may prohibit complete recovery. Cognitive behavioral therapy (CBT) and transcranial direct current stimulation (tDCS) both proved to be effective in decreasing rumination. However, the combined effects of tDCS and CBT interventions on rumination have not yet been explored. The first aim of this pilot study is to investigate whether the combination of tDCS and CBT has an accumulating positive effect on modulating state rumination. The second aim is to assess the feasibility and safety profile of the proposed combined approach. Method: Seventeen adults aged 32-60 years, suffering from RNT, were referred by their primary care professional to participate in an 8-week group intervention for RNT ("Drop It") comprising 8 sessions of CBT. Before each CBT session, patients underwent one double-blinded prefrontal active (2 mA for 20 min) or sham tDCS (anode over F3, cathode over the right supraorbital region) combined with an internal cognitive attention task focused on individual RNT, i.e., online tDCS priming. During each session, the Brief State Rumination Inventory was used to assess state rumination. Results: A mixed effects model analysis revealed no significant differences between the stimulation conditions, weekly sessions, or their interaction in terms of state rumination scores. Conclusion: Overall, the combination of online tDCS priming followed by group CBT was found to be safe and feasible. On the other hand, no significant additional effects of this combined approach on state rumination were established. Although our pilot study may have been too small to find significant clinical effects, future larger RCT studies on combined tDCS-CBT treatment protocols may reevaluate the selection of internal cognitive attention tasks and more objective neurophysiological measurements, consider the optimal timing of the combination (concurrently or sequentially), or may add additional tDCS sessions when following CBT.

Stimulation of the dorsolateral prefrontal cortex modulates brain cue reactivity to reward (un)availability.

Brain imaging studies have shown that stimulation of the left dorsolateral prefrontal cortex (dlPFC), which plays a pivotal role in high-order cognitive control processes, modulates brain reactivity to reward-related cues. Nevertheless, the impact of contextual factors such as reward availability (the reward that is depicted in the cue exposure task) on such modulation effect remains unclear. Here we tested whether a single session of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dlPFC differently impacts brain reactivity to cues signalling either availability or unavailability of a sports betting opportunity. Employing a within-subject design (verum versus sham HF-rTMS) among thirty-two frequent sports bettors, we first observed that, as compared to the sham condition, verum HF-rTMS modulated brain reactivity to game cues prior to being made (un)available for betting, through simultaneous increases (posterior insula and caudate nucleus) and decreases (occipital pole) in brain activation. Second, verum HF-rTMS led to increased ventral striatal activity towards cues available for betting but did not modulate brain response to cues unavailable for betting. Taken together, these findings demonstrate that transient stimulation of the left dlPFC led to a general modulation in brain activity in responses to cues, and that this effect is only partly dependent on cues signalling for reward (un)availability.

Network analysis reveals abnormal functional brain circuitry in anxious dogs.

Anxiety is a common disease within human psychiatric disorders and has also been described as a frequently neuropsychiatric problem in dogs. Human neuroimaging studies showed abnormal functional brain networks might be involved in anxiety. In this study, we expected similar changes in network topology are also present in dogs. We performed resting-state functional MRI on 25 healthy dogs and 13 patients. The generic Canine Behavioral Assessment & Research Questionnaire was used to evaluate anxiety symptoms. We constructed functional brain networks and used graph theory to compare the differences between two groups. No significant differences in global network topology were found. However, focusing on the anxiety circuit, global efficiency and local efficiency were significantly higher, and characteristic path length was significantly lower in the amygdala in patients. We detected higher connectivity between amygdala-hippocampus, amygdala-mesencephalon, amygdala-thalamus, frontal lobe-hippocampus, frontal lobe-thalamus, and hippocampus-thalamus, all part of the anxiety circuit. Moreover, correlations between network metrics and anxiety symptoms were significant. Altered network measures in the amygdala were correlated with stranger-directed fear and excitability; altered degree in the hippocampus was related to attachment/attention seeking, trainability, and touch sensitivity; abnormal frontal lobe function was related to chasing and familiar dog aggression; attachment/attention seeking was correlated with functional connectivity between amygdala-hippocampus and amygdala-thalamus; familiar dog aggression was related to global network topology change. These findings may shed light on the aberrant topological organization of functional brain networks underlying anxiety in dogs.

Double the dose, double the impact? Effects of iTBS on salivary cortisol in stressed healthy volunteers.

There is a growing interest in applying double-dose repetitive transcranial Magnetic Stimulation (rTMS) as a therapeutic tool for stress-related psychiatric disorders. Such stimulation protocols may shorten the treatment duration and may result in faster symptom improvement. Currently, theta-burst stimulation (TBS) protocols have gained attention because of their significantly reduced treatment duration, compared to conventional rTMS. However, the effect of one or twice daily rTMS sessions remains unclear in relation to stress. Using a two-period cross-over design, we examined the impact of double-dosed intermittent (TBS) over the left dorsolateral prefrontal cortex on stress responses (salivary cortisol) in thirty-eight healthy participants after being stressed by a validated psychosocial stress task: the Trier Social Stress Test. After the first active iTBS session, as contrasted to sham, no differential effects on salivary output were observed. However, after the second active session, there was a significantly smaller decrease of salivary cortisol concentrations in the active iTBS condition compared to sham. Our results suggest that double-dosed iTBS after being stressed might differently affect stress recovery compared to a single session of iTBS.

Effects of HF-rTMS over the left and right DLPFC on proactive and reactive cognitive control.

Previous research supports the distinction between proactive and reactive control. Although the dorsolateral prefrontal cortex (DLPFC) has been consistently related to these processes, lateralization of proactive and reactive control is still under debate. We manipulated brain activity to investigate the role of the left and right DLPFC in proactive and reactive cognitive control. Using a single-blind, sham-controlled crossover within-subjects design, 25 young healthy females performed the 'AX' Continuous Performance Task after receiving sham vs active high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to increase left and right DLPFC activity. Reaction times (RTs) and pupillometry were used to assess patterns of proactive and reactive cognitive control and task-related resource allocation, respectively. We observed that, compared to sham, HF-rTMS over the left DLPFC increased proactive control. After right DLPFC HF-rTMS, participants showed slower RTs on AX trials, suggesting more reactive control. However, this latter result was not supported by RTs on BX trials (i.e. the trial that specifically assess reactive control). Pupil measures showed a sustained increase in resource allocation after both active left and right HF-rTMS. Our results with RT data provide evidence on the role of the left DLPFC in proactive control and suggest that the right DLPFC is implicated in reactive control.

Effects of combined theta burst stimulation and transcranial direct current stimulation of the dorsolateral prefrontal cortex on stress.

OBJECTIVE: Research suggests that the combination of different non-invasive brain stimulation techniques, such as intermittent theta-burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), could enhance the effects of stimulation. Studies investigating the combination of tDCS and iTBS over the dorsolateral prefrontal cortex (DLPFC) are lacking. In this within-subjects study, we evaluated the additive effects of iTBS with tDCS on psychophysiological measures of stress. METHOD: Sixty-eight healthy individuals were submitted to a bifrontaltDCS + iTBS and shamtDCS + iTBS protocol targeting the DLPFC with a one-week interval. The Maastricht Acute Stress Test was used to activate the stress system after stimulation. Stress reactivity and recovery were assessed using physiological and self-report measures. RESULTS: The stressor evoked significant psychophysiological changes in both stimulation conditions. However, no evidence was found for differences between them in stress reactivity and recovery. Participants reported more pain and feelings of discomfort to the bifrontaltDCS + iTBS protocol. CONCLUSION: In this study set-up, iTBS plus tDCS was not superior to iTBS in downregulating stress in healthy subjects. SIGNIFICANCE: There is no evidence for an effect of combined tDCS-iTBS of the DLPFC on stress according to the parameters employed in our study. Future studies should explore other stimulation parameters, additive approaches and/or neurobiological markers.

The Role of the Cerebellum in Social and Non-Social Action Sequences: A Preliminary LF-rTMS Study.

An increasing number of studies demonstrated the involvement of the cerebellum in (social) sequence processing. The current preliminary study is the first to investigate the causal involvement of the cerebellum in sequence generation, using low-frequency repetitive transcranial magnetic stimulation (LF-rTMS). By targeting the posterior cerebellum, we hypothesized that the induced neuro-excitability modulation would lead to altered performance on a Picture and Story sequencing task, which involve the generation of the correct chronological order of various social and non-social stories depicted in cartoons or sentences. Our results indicate that participants receiving LF-rTMS over the cerebellum, as compared to sham participants, showed a stronger learning effect from pre to post stimulation for both tasks and for all types of sequences (i.e. mechanical, social scripts, false belief, true belief). No differences between sequence types were observed. Our results suggest a positive effect of LF-rTMS on sequence generation. We conclude that the cerebellum is causally involved in the generation of sequences of social and nonsocial events. Our discussion focuses on recommendations for future studies.

Is twice daily LF-rTMS a viable treatment option for treatment-resistant OCD? Results from an open-label feasibility study.

Several reports point to the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant obsessive-compulsive disorder (OCD). This study aimed to evaluate the safety and efficacy of rTMS targeting the dmPFC in the treatment of treatment-resistant OCD patients. Twelve patients received 20 sessions of low-frequency (LF) rTMS (1 Hz, 1200 pulses) in a twice daily protocol during 10 weekdays. Y-BOCS and IDS scores modestly but significantly decreased after treatment and at follow-up and HADS anxiety improved at follow-up. LF rTMS may improve OCD, anxiety, and depressive symptoms in treatment-resistant OCD and was a safe and well-tolerated treatment.

Individual resting-state frontocingular functional connectivity predicts the intermittent theta burst stimulation response to stress in healthy female volunteers.

Intermittent theta burst stimulation (iTBS) delivered to the dorsolateral prefrontal cortex (DLPFC) has been investigated as a promising treatment for stress and stress-related mental disorders such as major depression, yet large individual differences in responsiveness demand further exploration and optimization of its effectiveness. Clinical research suggests that resting-state functional connectivity (rsFC) between the DLPFC and the anterior cingulate cortex (ACC) can predict iTBS treatment response in depression. The present study aimed to investigate whether rsFC between the left DLPFC and ACC subregions could predict the degree to which the stress system is affected by iTBS. After assessment of baseline resting-state fMRI data, 34 healthy female participants performed the Trier Social Stress Test on two separate days, each followed by active or sham iTBS over the left DLPFC. To evaluate iTBS effects on the stress-system, salivary cortisol was measured throughout the procedure. Our results showed that a stronger negative correlation between the left DLPFC and the caudal ACC was linked to a larger attenuation of stress-system sensitivity during active, but not during sham iTBS. In conclusion, based on individual rsFC between left DLPFC and caudal ACC, iTBS could be optimized to more effectively attenuate deregulation of the stress system.

Theta-burst stimulation and frontotemporal regulation of cardiovascular autonomic outputs: The role of state anxiety.

Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying top-down control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of top-down neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation.

The effect of neurostimulation applied to the left dorsolateral prefrontal cortex on post-stress adaptation as a function of depressive brooding.

Depressive brooding following a stressful event predicts negative affect and neuroendocrine responses related to psychological stress. The dorsolateral prefrontal cortex (DLPFC) has been associated with the top-down regulation of thoughts and emotions, and abnormal neural activity within this region has been associated with increased psychological stress and ruminative thinking. The aim of this study was to investigate whether the modulation of the DLPFC could have beneficial effects on ruminative thoughts and the endocrine response following a self-relevant stressor. Using a sham-controlled within-subjects crossover-design, two sessions of intermittent theta-burst stimulation (iTBS) were administered over the left DLPFC to thirty-eight healthy-volunteers after they were confronted with a social-evaluative stressor, the Trier Social Stress Test. To assess stress recovery, momentary rumination was measured before and after a resting period subsequent to the encounter with the stressor. In addition, cortisol levels were measured between and after the two iTBS sessions that were applied during the stress recovery phase. Overall, iTBS did not significantly influence ruminative thinking and cortisol secretion during the stress recovery phase. However, taking into account participants ruminative tendencies, our results revealed that for participants with higher levels of brooding ruminative thinking remained stable after iTBS, whereas in the sham condition there was a marginal significant increase in ruminative thinking. Moreover, only after iTBS, there was a significant reduction in cortisol secretion (i.e. a faster return to baseline as compared to sham) for high brooders during the recovery from the stressor. These results show that the prefrontal cortex plays a role in stress recovery mechanisms in individuals who are more vulnerable for psychopathology.

The influence of personality on the effect of iTBS after being stressed on cortisol secretion.

Over the last years, individualization of repetitive Transcranial Magnetic Stimulation (rTMS) parameters has been a focus of attention in the field of non-invasive stimulation. It has been proposed that in stress-related disorders personality characteristics may influence the clinical outcome of rTMS. However, the underlying physiological mechanisms as to how personality may affect the rTMS response to stress remains to be clarified. In this sham-controlled crossover study, after being stressed by the Trier Social Stress Test, 38 healthy females received two sessions of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex. To take possible personality influences into account, they also completed the Temperament and Character Inventory. Mood and salivary cortisol were assessed throughout the experimental protocol. Overall, two iTBS sessions did not significantly alter mood or influenced cortisol secretion. When taking into account personality features, higher scores on the character dimension Cooperativeness was related to decreased cortisol output, only when active iTBS was administered after the social stressor. In line with other studies, personality features such as the character dimension Cooperativeness may be of particular interest to explain individual neurobiological responses to neurostimulation.

Prefrontal TDCS attenuates medial prefrontal connectivity upon being criticized in individuals scoring high on perceived criticism.

The mechanisms by which transcranial direct current stimulation (tDCS) influences emotional processing - and whether this is related to individual vulnerability for psychopathology - are still poorly understood. The present study aimed to investigate if one prefrontal tDCS session modulates mood and neural functional connectivity after being exposed to negative information differently in individuals low or high in perceived criticism (PC), which has been related to vulnerability for psychiatric illness. In a randomized cross-over design, one session of MRI-compatible prefrontal tDCS (neuronavigated placement of the anodal electrode at the left dorsolateral prefrontal cortex and the cathodal electrode at the right supraorbital region; vs. sham) was administered to healthy females, prior to listening to self-referential criticism. PC-dependent (low vs. high PC) changes in mood and resting-state functional connectivity patterns following tDCS and after hearing criticism were explored. After being criticized all females (low and high PC) felt angrier and more depressed, both in the active tDCS or sham tDCS condition. However, in contrast to low PC females, in high PC females prefrontal tDCS reduced connectivity between the left dorsal anterior cingulate cortex and the right dorsomedial prefrontal cortex following criticism. Despite having no differential effects on self-reported mood, prefrontal tDCS reduces medial prefrontal neural connectivity after being criticized in high PC females compared to low PC females. Depending on individual vulnerability for psychopathology, a single tDCS session differentially affects neural processing of negative emotional information, especially in brain regions involved in monitoring, experiencing and appraising/evaluating emotional material.

One MRI-compatible tDCS session attenuates ventromedial cortical perfusion when exposed to verbal criticism: The role of perceived criticism.

Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anxiety disorders, but how this application may influence emotional processes, and whether this is related to individual characteristics, is not well understood. It has been proposed that perceived criticism (PC) may represent a vulnerability factor for the development of such mental illnesses. To decipher whether neural mechanisms of action of tDCS potentially differ depending on PC status (low vs. high), we evaluated mood and brain perfusion before and after applying MRI-compatible tDCS, and after participants were exposed to verbal criticism in the scanner. Experimental design 30 healthy nondepressed females were included in a sham-controlled crossover MRI-compatible tDCS study. Brain perfusion was measured by means of arterial spin labeling (ASL) before and after tDCS applied to the left dorsolateral prefrontal cortex (DLPFC), and after hearing criticism. Before the experiment, all participants provided a rating of PC in their closest environment. Principal observations at the behavioral level, criticism made participants angrier. This was unrelated to the active or sham stimulation. After being criticized, females scoring high on PC had significantly decreased brain perfusion in the pregenual anterior cingulate cortex (pgACC) and medioprefrontal cortex (mPFC), after active tDCS but not sham. The decrease in pgACC/mPFC perfusion points to a significant impact of tDCS in brain areas related to stress responses and self-referential processes, especially in females scoring high on PC, which has been shown to be related to vulnerability for mood and anxiety disorders.

Facing temptation: The neural correlates of gambling availability during sports picture exposure.

Nowadays, sports betting has become increasingly available and easy to engage in. Here we examined the neural responses to stimuli that represent sporting events available for betting as compared to sporting events without a gambling opportunity. We used a cue exposure task in which football (soccer) fans (N = 42) viewed cues depicting scheduled football games that would occur shortly after the scanning session. In the "betting" condition, participants were instructed to choose, at the end of each block, the game (and the team) they wanted to bet on. In the "watching" condition, participants chose the game they would prefer to watch. After the scanning session, participants completed posttask rating questionnaires assessing, for each cue, their level of confidence about the team they believed would win and how much they would enjoy watching the game. We found that stimuli representing sport events available for betting elicited higher fronto-striatal activation, as well as higher insular cortex activity and functional connectivity, than sport events without a gambling opportunity. Moreover, games rated with more confidence towards the winning team resulted in greater brain activations within regions involved in affective decision-making (ventromedial prefrontal cortex), cognitive inhibitory control (medial and superior frontal gyri) and reward processing (ventral and dorsal striatum). Altogether, these novel findings offer a sensible simulation of how the high availability of sports betting in today's environment impacts on the reward and cognitive control systems. Future studies are needed to extend the present findings to a sample of football fans that includes a samilar proportion of female and male participants.