Transcranial focused ultrasound to the posterior cingulate cortex modulates default mode network and subjective experience: an fMRI pilot study.

Background: Transcranial focused ultrasound (TFUS) is an emerging neuromodulation tool for temporarily altering brain activity and probing network functioning. The effects of TFUS on the default mode network (DMN) are unknown. Objective: The study examined the effects of transcranial focused ultrasound (TFUS) on the functional connectivity of the default mode network (DMN), specifically by targeting the posterior cingulate cortex (PCC). Additionally, we investigated the subjective effects of TFUS on mood, mindfulness, and self-related processing. Methods: The study employed a randomized, single-blind design involving 30 healthy subjects. Participants were randomly assigned to either the active TFUS group or the sham TFUS group. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted before and after the TFUS application. To measure subjective effects, the Toronto Mindfulness Scale, the Visual Analog Mood Scale, and the Amsterdam Resting State Questionnaire were administered at baseline and 30 min after sonication. The Self Scale and an unstructured interview were also administered 30 min after sonication. Results: The active TFUS group exhibited significant reductions in functional connectivity along the midline of the DMN, while the sham TFUS group showed no changes. The active TFUS group demonstrated increased state mindfulness, reduced Global Vigor, and temporary alterations in the sense of ego, sense of time, and recollection of memories. The sham TFUS group showed an increase in state mindfulness, too, with no other subjective effects. Conclusions: TFUS targeted at the PCC can alter DMN connectivity and cause changes in subjective experience. These findings support the potential of TFUS to serve both as a research tool and as a potential therapeutic intervention.

Improvements in mindfulness, interoceptive and emotional awareness, emotion regulation, and interpersonal emotion management following completion of an online emotional skills training program.

Socioemotional skills, such as the ability to recognize, understand, and regulate the emotions of self and others, are associated with both physical and emotional health. The present study tested the effectiveness of a recently validated online training program for increasing these emotional skills in adults. In this study, 448 participants (323 female) were randomly assigned to complete this training program or a placebo control program. Among those who completed the training program or placebo (N = 326), the training program led to improved scores post-training on measures of interoceptive and emotional awareness, mindfulness, emotion recognition, and emotion regulation strategies (e.g., reduced emotion suppression and greater impulse control) relative to placebo. In a smaller group of participants who also completed a 6-month follow-up visit (N = 94), sustained improvements were observed on several measures in those who completed the training program, while the placebo group instead showed decreased performance. This suggested a potentially protective effect against emotional challenges associated with the COVID-19 pandemic occurring during this time. These results suggest that this online training program shows promise in improving emotional skills relevant to adaptive social and emotional functioning, and that it might be useful as an intervention within at-risk populations and those with emotional disorders associated with reduced application of these skills. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A pull to be close: The differentiating effects of oxytocin and grief stimulus type on approach behavior in complicated grief.

Theoretical models of complicated grief (CG) suggest that maladaptive motivational tendencies (e.g., perseverative proximity-seeking of the deceased; excessive avoidance of reminders) interfere with a person's ability to recover from their loved one's death. Due in part to conflicting evidence, little mechanistic understanding of how these behaviors develop in grief exists. We sought to (1) identify behavioral differences between CG and non-CG groups based on approach/avoidance bias for grief-, deceased-, and social-related stimuli, and (2) test the role of the neuropeptide oxytocin in shaping approach/avoidance bias. Widowed older adults with (n = 17) and without (n = 22) CG completed an approach/avoidance task measuring implicit bias for both personalized and non-specific grief-related stimuli (among other stimuli). In a double-blinded, randomized, counterbalanced design, each participant attended both an intranasal oxytocin session and a placebo session. Aims were to (1) identify differential effects of CG and stimulus type on implicit approach/avoidance bias [placebo session], and (2) investigate interactive effects of CG, stimulus type, and oxytocin vs. placebo on approach/avoidance bias [both sessions]. In the placebo session, participants in the non-CG group demonstrated an approach bias across all stimuli. Intranasal oxytocin had an overall slowing effect on the CG group's response times. Further, oxytocin decreased avoidance bias in response to photos of the deceased spouse in the CG group only. Findings support the hypothesis that oxytocin has a differential effect on motivational tendency in CG compared to non-CG, strengthening evidence for its role in CG. Findings also emphasize the need to consider differences in personalized vs. generic stimuli when designing grief-relevant tasks.

Development and validation of an online emotional intelligence training program.

Introduction: Emotional intelligence (EI) is associated with a range of positive health, wellbeing, and behavioral outcomes. The present article describes the development and validation of an online training program for increasing EI abilities in adults. The training program was based on theoretical models of emotional functioning and empirical literature on successful approaches for training socioemotional skills and resilience. Methods: After an initial design, programming, and refinement process, the completed online program was tested for efficacy in a sample of 326 participants (72% female) from the general population. Participants were randomly assigned to complete either the EI training program (n = 168) or a matched placebo control training program (n = 158). Each program involved 10-12 hours of engaging online content and was completed during either a 1-week (n = 175) or 3-week (n = 151) period. Results: Participants who completed the EI training program showed increased scores from pre- to post-training on standard self-report (i.e., trait) measures of EI (relative to placebo), indicating self-perceived improvements in recognizing emotions, understanding emotions, and managing the emotions of others. Moreover, those in the EI training also showed increased scores in standard performance-based (i.e., ability) EI measures, demonstrating an increased ability to strategically use and manage emotions relative to placebo. Improvements to performance measures also remained significantly higher than baseline when measured six months after completing the training. The training was also well-received and described as helpful and engaging. Discussion: Following a rigorous iterative development process, we created a comprehensive and empirically based online training program that is well-received and engaging. The program reliably improves both trait and ability EI outcomes and gains are sustained up to six months post-training. This program could provide an easy and scalable method for building emotional intelligence in a variety of settings.

The within-person association of relative left frontal activity and vagally mediated heart rate variability not moderated by history of depression.

Motivated by the Neurovisceral Integration Model (NVI) of cardiac vagal control, we investigated the relationship between relative left frontal activity (rLFA) and vagally mediated heart rate variability or respiratory sinus arrhythmia (RSA) in 287 participants, half of whom had a history of depression. We hypothesized that there would be a within-person association of rLFA and RSA such that when RSA is lower rLFA would also be lower (Hypothesis I). Moreover, it was hypothesized that this within-subject association would be moderated by a history of depression (Hypothesis II). Metrics of rLFA and RSA were derived from concurrent electroencephalogram and electrocardiogram recordings. The logarithmic difference in EEG alpha power between the homologous right and left electrodes (Ln (Right/Left)) in the frontal region was used to index rLFA. A Hilbert transform was applied to the mean-centered and bandpass-filtered (0.12-.40 Hz) inter-beat interval (IBI) time series to get a fine-grained measure (in the time domain) of RSA. A linear mixed ANOVA model with rLFA as the dependent variable and RSA as the main fixed effect found that participants had less rLFA during epochs when they had lower RSA, which was consistent with the prediction from Hypothesis I. Contrary to the prediction from Hypothesis II, the within-person association of RSA and rLFA was not moderated by a history of depression. However, the association between RSA and rLFA varied across the four pairs of frontal electrodes that we examined. Thus, more research is needed to determine the spatial extent of this association, e.g., examining the relationship between source-localized rLFA and RSA.

Development and validation of a computer program for measuring emotional awareness in German-The geLEAS (German electronic Levels of Emotional Awareness Scale).

Introduction: Emotional awareness is the ability to identify, interpret, and verbalize the emotional responses of oneself and those of others. The Levels of Emotional Awareness Scale (LEAS) is an objective performance inventory that accurately measures an individual's emotional awareness. LEAS assessments are typically scored manually and are therefore both time consuming and cognitively demanding. This study presents a German electronic scoring program for the LEAS (geLEAS), the first non-English computerized assessment approach of the LEAS. Methods: Data were collected from a healthy German community sample (N = 208). We developed a modern software for computerizing LEAS scoring, an open-source text-based emotion assessment tool called VETA (Verbal Emotion in Text Assessment). We investigated if the software would arrive at similar results as hand scoring in German and if emotional awareness would show similar associations to sociodemographic information and psychometric test results as in previous studies. Results: The most frequently used scoring method of the geLEAS shows excellent internal consistency (α = 0.94) and high correlations with hand scoring (r = 0.97, p < 0.001). Higher emotional awareness measured by the geLEAS is associated with female gender, older age, and higher academic achievement (all p < 0.001). Moreover, it is linked to the ability to identify emotions in facial expressions (p < 0.001) and more accurate theory of mind functioning (p < 0.001). Discussion: An automated method for evaluating emotional awareness greatly expands the ability to study emotional awareness in clinical care and research. This study aims to advance the use of emotional awareness as a clinical and scientific parameter.

Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder.

Whole-body hyperthermia (WBH) shows promise for the treatment of major depressive disorder (MDD). Because MDD is associated with increased inflammation, and anti-inflammatory agents show some promise as antidepressants, the current study sought to identify the acute and longer-term immune effects of WBH in participants with MDD and to explore whether these effects associate with the procedure's antidepressant properties. Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (n = 16) or sham treatment (n = 14). Hamilton Depression Rating Scale (HDRS) scores were assessed at baseline and 1, 2, 4, and 6 weeks post-treatment (WBH vs. sham), and plasma cytokine concentrations were assessed at baseline, immediately post-treatment, and 1 and 4 weeks post-treatment. As previously reported, WBH produced a rapid and sustained antidepressant effect. When compared to sham, WBH increased plasma interleukin (IL)-6 immediately post-treatment (time by treatment: χ2(3, N=108) = 47.33, p < 0.001), while having no effect on other cytokines acutely and no impact on IL-6, or any other cytokine, at 1 or 4 weeks post treatment. In the study sample as a whole, increased IL-6 post-treatment was associated with reduced HDRS depression scores over the 6 weeks of follow-up (F(1, 102.3) = 6.74, p = 0.01). These results suggest a hitherto unrecognized relationship between hyperthermia, the immune system, and depression, and may point to WBH as a novel modality for exploring behavioral effects of IL-6 when the cytokine is activated in isolation from the inflammatory mediators with which it frequently travels.

Evaluating EEG complexity metrics as biomarkers for depression.

Nonlinear EEG analysis offers the potential for both increased diagnostic accuracy and deeper mechanistic understanding of psychopathology. EEG complexity measures have previously been shown to positively correlate with clinical depression. In this study, resting state EEG recordings were taken across multiple sessions and days with both eyes open and eyes closed conditions from a total of 306 subjects, 62 of which were in a current depressive episode, and 81 of which had a history of diagnosed depression but were not currently depressed. Three different EEG montages (mastoids, average, and Laplacian) were also computed. Higuchi fractal dimension (HFD) and sample entropy (SampEn) were calculated for each unique condition. The complexity metrics showed high internal consistency within session and high stability across days. Higher complexity was found in open-eye recordings compared to closed eyes. The predicted correlation between complexity and depression was not found. However, an unexpected sex effect was observed, in which males and females exhibited different topographic patterns of complexity.

Altered electroencephalography resting state network coherence in remitted MDD.

Individuals with remitted depression are at greater risk for subsequent depression and therefore may provide a unique opportunity to understand the neurophysiological correlates underlying the risk of depression. Research has identified abnormal resting-state electroencephalography (EEG) power metrics and functional connectivity patterns associated with major depression, however little is known about these neural signatures in individuals with remitted depression. We investigate the spectral dynamics of 64-channel EEG surface power and source-estimated network connectivity during resting states in 37 individuals with depression, 56 with remitted depression, and 49 healthy adults that did not differ on age, education, and cognitive ability across theta, alpha, and beta frequencies. Average reference spectral EEG surface power analyses identified greater left and midfrontal theta in remitted depression compared to healthy adults. Using Network Based Statistics, we also demonstrate within and between network alterations in LORETA transformed EEG source-space coherence across the default mode, fronto-parietal, and salience networks where individuals with remitted depression exhibited enhanced coherence compared to those with depression, and healthy adults. This work builds upon our currently limited understanding of resting EEG connectivity in depression, and helps bridge the gap between aberrant EEG power and brain network connectivity dynamics in this disorder. Further, our unique examination of remitted depression relative to both healthy and depressed adults may be key to identifying brain-based biomarkers for those at high risk for future, or subsequent depression.

Transcranial focused ultrasound modulates the emergence of learned helplessness via midline theta modification.

BACKGROUND: Helplessness and hopelessness are states closely related to depressive disorders. They ensue following the anticipated absence of valid behavioral options to alleviate an aversive state. One neural structure involved in the detection of such options, is the cingulate cortex (CC), which conveys the evaluation of behavior against the value of its outcome. Accordingly, CC-related EEG measures are thought to correlate to feedback evaluation but also to anxious and conflict-related states, signaling the need for further adaptation to current requirements. Against this background, this study investigated the role of CC functioning in the emergence and prevention of helpless/hopeless states by applying low-intensity transcranial focused ultrasound (litFUS) neuromodulation prior to a learned helplessness task. METHOD: In a randomized controlled double blind experimental setup with 55 participants, litFUS was used to inhibit the right lateral prefrontal cortex (lPFC), a region closely connected to CC modulation. Participants were instructed to play 8 games of chess against a computer that was unbeatable to them, while an EEG was recorded. Theta oscillation in midline electrodes, playing performance and self-rate measures on cognitive, affective and physiological parameters were assessed. RESULTS: The results show a considerable influence of litFUS neuromodulation of the lPFC on midline theta activity (Fz and Pz electrode position) which in turn correlated to several psychological variables including self-report data on emotion, cognition, and arousal as well as behavioral measures (playing performance). LIMITATIONS: Due to the small sample size and sample characteristics, results cannot be generalized to the field of clinical application. A replication of results in larger samples and in context of other sonication parameters is needed to increase the robustness of results and to maximize the efficacy of litFUS application. CONCLUSIONS: We conclude that the development of learned helplessness/hopelessness could be positively influenced in its course by litFUS neuromodulation of the right lPFC. In line with previous results, especially the posterior midline electrode Pz seems to be an interesting target for further research in this field as theta activity at this electrode is correlated to control perception and motivated behavior. To our knowledge, this is the first study to use neuromodulation to monitor and manipulate the development of helplessness in the laboratory.

A comparison of nomothetic and individualized alpha frequency approaches to measuring frontal EEG alpha asymmetry.

Frontal alpha asymmetry (FAA) is considered to be a reliable marker of affective processing and psychopathology. Traditionally, the magnitude of alpha is calculated by taking the average over a nomothetic fixed frequency window (e.g., 8 to 13 Hz). Alternatively, methods have been proposed to extract individualized alpha frequency (IAF) peaks and windows in hopes of improving the reliability and validity of signal detection. However, no study has compared the nomothetic to IAF approaches to examine the reliability and validity of resting FAA in a large well-characterized data set. In this study, we assessed the psychometric performance of the standard fixed window approach, a PZ-alpha based IAF approach and a global-alpha based IAF windows detection approach on a previously collected EEG data set (8 recordings per subject collected on four occasions across two weeks). Our results revealed that resting FAA calculated with these three different methods are highly correlated at all frontal regions (mean r = .98). The stability across the 8 recordings over the two weeks also showed no substantial difference between approaches as indicated by intraclass correlations. Moreover, internal-consistency reliability, validity with respect to measures of emotion and emotion-related psychopathology and state-trait Structure equation model (SEM) fitting were evaluated and yielded no significant differences across methods. Our results supported the overall reliability and validity of two different IAF approaches to assessing resting FAA but fail to find any incremental advantage over nomothetic approaches to defining alpha bands. Guidelines for methods selection for future research are provided.

Dwelling in prolonged grief: Resting state functional connectivity during oxytocin and placebo administration.

Clinical theories of adaptation in bereavement highlight a need for flexible shifting between mental states. However, prolonged motivational salience of the deceased partner may be a complicating factor, particularly when coupled with perseverative thinking about the loss. We investigated how prolonged grief symptoms might relate to resting state functional brain network connectivity in a sample of older adults (n = 38) who experienced the death of a partner 6-36 months prior, and whether intranasal oxytocin (as a neuropeptide involved in pair-bonding) had differential effects in participants with higher prolonged grief symptoms. Higher scores on the Inventory of Complicated Grief (ICG) were associated with lower anticorrelation (i.e., higher functional connectivity) between the defaultretrosplenial - cingulo-operculardACC network pair. Intranasal oxytocin increased functional connectivity in the same defaultretrosplenial - cingulo-operculardACC circuit but ICG scores did not moderate effects of oxytocin, contrary to our prediction. Higher ICG scores were associated with longer dwell time in a dynamic functional connectivity state featuring positive correlations among default, frontoparietal, and cingulo-opercular networks, across both placebo and oxytocin sessions. Dwell time was not significantly affected by oxytocin, and higher prolonged grief symptoms were not associated with more variability in dynamic functional connectivity states over the scan. Results offer preliminary evidence that prolonged grief symptoms in older adults are associated with patterns of static and time-varying functional network connectivity and may specifically involve a default network-salience-related circuit that is sensitive to oxytocin.

Psychopathic tendencies are selectively associated with reduced emotional awareness in the context of early adversity.

It is unclear at present whether psychopathic tendencies are associated with lower or higher levels of emotional awareness (EA). Given that psychopathy includes a proficiency for manipulating others, one might expect an elevated ability to identify and use information about others' emotions. On the other hand, empathic deficits in psychopathy could arise from reduced emotional awareness. Further, heterogeneity in psychopathy may also play a role, wherein 'secondary' psychopathy is associated with early adversity and high negative affect, while 'primary' psychopathy is not. In this paper, we tested the relationship between EA and psychopathic tendencies in 177 undergraduate students (40 males) who completed the levels of emotional awareness scale (LEAS), the triarchic psychopathy measure (TPM), the affective (empathy-related) subscales of the interpersonal reactivity index (IRI), and two measures of early adversity: the childhood experiences of care and abuse questionnaire (CECA) and the childhood trauma questionnaire (CTQ). We found that lower LEAS scores were associated with higher TPM and lower IRI empathy scores, but these relationships were primarily present in those with early adversity and high negative affect. This suggests that lower EA may be selectively associated with higher levels of secondary psychopathy, while those with higher levels of primary psychopathy remain capable of higher EA.

Attention and regulation during emotional word comprehension in older adults: Evidence from event-related potentials and brain oscillations.

Older adults often show a positivity bias effect during picture processing, focusing more on positive than negative information. It is unclear whether this positivity bias effect generalizes to language and whether arousal matters. The present study investigated how age affects emotional word comprehension with varied valence (positive, negative) and arousal (high, low). We recorded older and younger participants' brainwaves (EEG) while they read positive/negative and high/low-arousing words and pseudowords, and made word/non-word judgments. Older adults showed increased N400s and left frontal alpha decreases (300-450 ms) for low-arousing positive as compared to low-arousing negative words, suggesting an arousal-dependent positivity bias during lexical retrieval. Both age groups showed similar LPPs to negative words. Older adults further showed a larger mid-frontal theta increase (500-700 ms) than younger adults for low-arousing negative words, possibly indicating down-regulation of negative meanings of low-arousing words. Altogether, our data supported the strength and vulnerability integration model of aging.

Improvements in well-being and cardiac metrics of stress following a yogic breathing workshop: Randomized controlled trial with active comparison.

ObjectiveCompare two distinct psychosocial stress-management workshops.ParticipantsUndergraduate and graduate students (n = 69 for analysis, completed April 2017).MethodsParticipants were randomized to one of two workshops (Sudarshan Kriya Yoga, SKY; Wisdom On Wellness, WOW), matched in terms of duration, group size, etc. Outcomes were questionnaires and psychophysiological response to laboratory stress induction at pre, post, and 3-month follow-up.ResultsSKY and WOW participants demonstrated similar workshop ratings and retention rates. SKY demonstrated greater improvements on a number of self-report measures relative to WOW, including perceived stress, sleep, social connectedness, distress, anxiety, depression, conscientiousness, self-esteem, and life satisfaction. Both groups improved in terms of heart rate measures of stress reactivity, however, these outcomes were partially related to changes in resting values at post-workshop and follow-up.ConclusionsThese findings offer insight into unique patterns of change between yogic breathing, acceptance-based approaches to stress management versus cognitively based approaches.

Psilocybin for the Treatment of Obsessive-Compulsive Disorders.

Obsessive-compulsive disorder (OCD) is a highly prevalent and disabling condition for which currently available treatments are insufficiently effective and alternatives merit priority attention. Psilocybin may represent a safe and effective avenue for treatment of individuals affected by this condition. In this chapter we briefly introduce OCD symptoms, epidemiology, as well as relevant hypotheses on the mechanism of disease that may inform treatment interventions. We briefly describe currently available treatments, mechanisms of action, and efficacy limitations, as preamble to the potential use of psilocybin and perhaps similar compounds in the treatment of OCD and related conditions. Although much is reviewed throughout this book about the mechanisms of action of psychedelic agents, a focused discussion of psilocybin effects as they pertain to OCD is also included. Our experience with incidental observation, prospective research, and current explorations of psilocybin in OCD are also described.

EPOS: EEG Processing Open-Source Scripts.

BACKGROUND: Since the replication crisis, standardization has become even more important in psychological science and neuroscience. As a result, many methods are being reconsidered, and researchers' degrees of freedom in these methods are being discussed as a potential source of inconsistencies across studies. NEW METHOD: With the aim of addressing these subjectivity issues, we have been working on a tutorial-like EEG (pre-)processing pipeline to achieve an automated method based on the semi-automated analysis proposed by Delorme and Makeig. RESULTS: Two scripts are presented and explained step-by-step to perform basic, informed ERP and frequency-domain analyses, including data export to statistical programs and visual representations of the data. The open-source software EEGlab in MATLAB is used as the data handling platform, but scripts based on code provided by Mike Cohen (2014) are also included. COMPARISON WITH EXISTING METHODS: This accompanying tutorial-like article explains and shows how the processing of our automated pipeline affects the data and addresses, especially beginners in EEG-analysis, as other (pre)-processing chains are mostly targeting rather informed users in specialized areas or only parts of a complete procedure. In this context, we compared our pipeline with a selection of existing approaches. CONCLUSION: The need for standardization and replication is evident, yet it is equally important to control the plausibility of the suggested solution by data exploration. Here, we provide the community with a tool to enhance the understanding and capability of EEG-analysis. We aim to contribute to comprehensive and reliable analyses for neuro-scientific research.

Multifactorial prediction of depression diagnosis and symptom dimensions.

While depression is a leading cause of disability, prior investigations of depression have been limited by studying correlates in isolation. A data-driven approach was applied to identify out-of-sample predictors of current depression from adults (N = 217) sampled on a continuum of no depression to clinical levels. The current study used elastic net regularized regression and predictors from sociodemographic, self-report, polygenic scores, resting electroencephalography, pupillometry, actigraphy, and cognitive tasks to classify individuals into currently depressed (MDE), psychiatric control (PC), and no current psychopathology (NP) groups, as well as predicting symptom severity and lifetime MDE. Cross-validated models explained 20.6% of the out-of-fold deviance for the classification of MDEs versus PC, 33.2% of the deviance for MDE versus NP, but -0.6% of the deviance between PC and NP. Additionally, predictors accounted for 25.7% of the out-of-fold variance in anhedonia severity, 65.7% of the variance in depression severity, and 12.9% of the deviance in lifetime depression (yes/no). Self-referent processing, anhedonia, and psychosocial functioning emerged as important differentiators of MDE and PC groups. Findings highlight the advantages of using psychiatric control groups to isolate factors specific to depression.

Methods matter: An examination of factors that moderate predictions of the capability model concerning the relationship of frontal asymmetry to trait measures.

The capability model of anterior asymmetry integrates trait-related and state-related frontal asymmetry research by proposing that frontal asymmetry is dependent on relevant traits if they are activated by a situation. However, differences in experimental design and EEG recording methods haven't been fully explored. We investigated 56 participants under three different situational paradigms (virtual T-maze, mental imagery, movies), varying the stimulus and type of measurement concerning frontal asymmetry. We predicted that "strong" situational manipulations (virtual T-maze, frontal asymmetry measured as event-related desynchronization) would eclipse relationships between frontal asymmetry and relevant traits, whereas "weaker" task manipulations, measured during longer time periods, would enhance relationships to relevant traits compared to frontal asymmetry at rest. The results confirmed these expectations, stressing the importance of stimulus characteristics, trait measures and recording methods with respect to the capability model. Additionally, a revision of the capability model to an inverse U-shaped quadratic relationship might be appropriate.

Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans.

Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.