Site- and frequency-specific enhancement of visual search performance with online individual alpha frequency (IAF) repetitive transcranial magnetic stimulation (rTMS) to the inferior frontal junction.

In this study, repetitive transcranial magnetic stimulation was applied to either the right inferior frontal junction or the right inferior parietal cortex during a difficult aerial reconnaissance search task to test its capacity to improve search performance. Two stimulation strategies previously found to enhance cognitive performance were tested: The first is called "addition by subtraction," and the second condition utilizes a direct excitatory approach by applying brief trains of high-frequency repetitive transcranial magnetic stimulation immediately before task trials. In a within-subjects design, participants were given active or sham repetitive transcranial magnetic stimulation at either 1 Hz or at 1 Hz above their individual peak alpha frequency (IAF + 1, mean 11.5 Hz), delivered to either the right inferior frontal junction or the right inferior parietal cortex, both defined with individualized peak functional magnetic resonance imaging (fMRI) activation obtained during the visual search task. Results indicated that among the 13 participants who completed the protocol, only active IAF + 1 stimulation to inferior frontal junction resulted in significant speeding of reaction time compared to sham. This site- and frequency-specific enhancement of performance with IAF + 1 repetitive transcranial magnetic stimulation applied immediately prior to task trials provides evidence for the involvement of inferior frontal junction in guiding difficult visual search, and more generally for the use of online repetitive transcranial magnetic stimulation directed at specific functional networks to enhance visual search performance.

Visual Performance and Sports: A Scoping Review.

Vision is central to success in nearly all sports, and there is an emerging body of research investigating the links between visual abilities and athletic performance. This preregistered scoping review seeks to clarify the topics of study, methodologies used, populations under investigation, researchers, and disciplines driving this field. Systematic searches of English-language articles were conducted in PubMed and Web of Science, with additional literature identified through bibliographic searches. Six hundred sixty-seven articles published between 1976 and 2023 were identified with 547 empirical studies, 58 review articles, 20 commentaries, and 4 meta-analyses, among others. Among the empirical papers, 411 reported on visual assessments and 98 on vision training interventions. The most represented sports included baseball, soccer, basketball, and cricket, with over 150 articles reporting on professional, elite, or Olympic athletes. This scoping review describes the breadth of this emerging field, identifies its strengths and weaknesses, and provides recommendations for future improvement.

Suitability of Automated Writing Measures for Clinical Trial Outcome in Writer's Cramp.

BACKGROUND: Writer's cramp (WC) dystonia is a rare disease that causes abnormal postures during the writing task. Successful research studies for WC and other forms of dystonia are contingent on identifying sensitive and specific measures that relate to the clinical syndrome and achieve a realistic sample size to power research studies for a rare disease. Although prior studies have used writing kinematics, their diagnostic performance remains unclear. OBJECTIVE: This study aimed to evaluate the diagnostic performance of automated measures that distinguish subjects with WC from healthy volunteers. METHODS: A total of 21 subjects with WC and 22 healthy volunteers performed a sentence-copying assessment on a digital tablet using kinematic and hand recognition softwares. The sensitivity and specificity of automated measures were calculated using a logistic regression model. Power analysis was performed for two clinical research designs using these measures. The test and retest reliability of select automated measures was compared across repeat sentence-copying assessments. Lastly, a correlational analysis with subject- and clinician-rated outcomes was performed to understand the clinical meaning of automated measures. RESULTS: Of the 23 measures analyzed, the measures of word legibility and peak accelerations distinguished subjects with WC from healthy volunteers with high sensitivity and specificity and demonstrated smaller sample sizes suitable for rare disease studies, and the kinematic measures showed high reliability across repeat visits, while both word legibility and peak accelerations measures showed significant correlations with the subject- and clinician-rated outcomes. CONCLUSIONS: Novel automated measures that capture key aspects of the disease and are suitable for use in clinical research studies of WC dystonia were identified. © 2022 International Parkinson and Movement Disorder Society.

The physiology of intraoperative error: using electrokardiograms to understand operator performance during robot-assisted surgery simulations.

BACKGROUND: No platform for objective, synchronous and on-line evaluation of both intraoperative error and surgeon physiology yet exists. Electrokardiogram (EKG) metrics have been associated with cognitive and affective features that are known to impact surgical performance but have not yet been analyzed in conjunction with real-time error signals using objective, real-time methods. METHODS: EKGs and operating console point-of-views (POVs) for fifteen general surgery residents and five non-medically trained participants were captured during three simulated robotic-assisted surgery (RAS) procedures. Time and frequency-domain EKG statistics were extracted from recorded EKGs. Intraoperative errors were detected from operating console POV videos. EKG statistics were synchronized with intraoperative error signals. RESULTS: Relative to personalized baselines, IBI, SDNN and RMSSD decreased 0.15% (S.E. 3.603e-04; P = 3.25e-05), 3.08% (S.E. 1.603e-03; P < 2e-16) and 1.19% (S.E. 2.631e-03; P = 5.66e-06), respectively, during error. Relative LF RMS power decreased 1.44% (S.E. 2.337e-03; P = 8.38e-10), and relative HF RMS power increased 5.51% (S.E. 1.945e-03; P < 2e-16). CONCLUSIONS: Use of a novel, on-line biometric and operating room data capture and analysis platform enabled detection of distinct operator physiological changes during intraoperative errors. Monitoring operator EKG metrics during surgery may help improve patient outcomes through real-time assessments of intraoperative surgical proficiency and perceived difficulty as well as inform personalized surgical skills development.

Neurobehavioral measures of coincidence anticipation timing.

Coincidence anticipation (CA) refers to the ability to coordinate responses to the arrival of a moving object. This study investigates the neurobehavioral processes that underlie CA through the measurement of electroencephalography (EEG) recorded during a CA task on a 17-foot plastic rail with evenly spaced LED lights. Participants responded at the anticipated moment a sequence of successively lit LEDs coincided with a stationary target. Healthy young adult participants (Mage = 21) performed six blocks with movement at 20, 30, or 40 mph and the direction either inbound or outbound relative to the participant. Behavioral results demonstrated a main effect of speed and an interaction between speed and direction, with outbound motion producing early responses and inbound motion producing delayed responses that increased at greater speeds. EEG demonstrated characteristic P1, N2, and P3-like visual evoked potentials (VEPs). VEP amplitudes revealed a significant direction by channel interaction for the P1, indicative of more medial responses for inbound motion. Significant laterality differences were present in the N2, whereas the P3 component produced significant main effects and interactions of speed and direction. This novel combination of three-dimensional CA with EEG demonstrates systematic brain responses that are tuned for motion speed and sensitive to different egocentric motion patterns thereby shedding new light on the mechanism of human visual-motor control.

Enhancing Cognitive Restructuring with Concurrent Repetitive Transcranial Magnetic Stimulation: A Transdiagnostic Randomized Controlled Trial.

INTRODUCTION: Emotional dysregulation constitutes a serious public health problem in need of novel transdiagnostic treatments. OBJECTIVE: To this aim, we developed and tested a one-time intervention that integrates behavioral skills training with concurrent repetitive transcranial magnetic stimulation (rTMS). METHODS: Forty-six adults who met criteria for at least one DSM-5 disorder and self-reported low use of cognitive restructuring (CR) were enrolled in a randomized, double-blind, sham-controlled trial that used a between-subjects design. Participants were taught CR and underwent active rTMS applied at 10 Hz over the right (n = 17) or left (n = 14) dorsolateral prefrontal cortex (dlPFC) or sham rTMS (n = 15) while practicing reframing and emotional distancing in response to autobiographical stressors. RESULTS: Those who received active left or active right as opposed to sham rTMS exhibited enhanced regulation (ds = 0.21-0.62) as measured by psychophysiological indices during the intervention (higher high-frequency heart rate variability, lower regulation duration). Those who received active rTMS over the left dlPFC also self-reported reduced distress throughout the intervention (d = 0.30), higher likelihood to use CR, and lower daily distress during the week following the intervention. The procedures were acceptable and feasible with few side effects. CONCLUSIONS: These findings show that engaging frontal circuits simultaneously with cognitive skills training and rTMS may be clinically feasible, well-tolerated and may show promise for the treatment of transdiagnostic emotional dysregulation. Larger follow-up studies are needed to confirm the efficacy of this novel therapeutic approach.

Structural Controllability Predicts Functional Patterns and Brain Stimulation Benefits Associated with Working Memory.

The brain is an inherently dynamic system, and much work has focused on the ability to modify neural activity through both local perturbations and changes in the function of global network ensembles. Network controllability is a recent concept in network neuroscience that purports to predict the influence of individual cortical sites on global network states and state changes, thereby creating a unifying account of local influences on global brain dynamics. While this notion is accepted in engineering science, it is subject to ongoing debates in neuroscience as empirical evidence linking network controllability to brain activity and human behavior remains scarce. Here, we present an integrated set of multimodal brain-behavior relationships derived from fMRI, diffusion tensor imaging, and online repetitive transcranial magnetic stimulation (rTMS) applied during an individually calibrated working memory task performed by individuals of both sexes. The modes describing the structural network system dynamics showed direct relationships to brain activity associated with task difficulty, with difficult-to-reach modes contributing to functional brain states in the hard task condition. Modal controllability (a measure quantifying the contribution of difficult-to-reach modes) at the stimulated site predicted both fMRI activations associated with increasing task difficulty and rTMS benefits on task performance. Furthermore, fMRI explained 64% of the variance between modal controllability and the working memory benefit associated with 5 Hz online rTMS. These results therefore provide evidence toward the functional validity of network control theory, and outline a clear technique for integrating structural network topology and functional activity to predict the influence of stimulation on subsequent behavior.SIGNIFICANCE STATEMENT The network controllability concept proposes that specific cortical nodes are able to steer the brain into certain physiological states. By applying external perturbation to these control nodes, it is theorized that brain stimulation is able to selectively target difficult-to-reach states, potentially aiding processing and improving performance on cognitive tasks. The current study used rTMS and fMRI during a working memory task to test this hypothesis. We demonstrate that network controllability correlates with fMRI modulation because of working memory load and with the behavioral improvements that result from a multivisit intervention using 5 Hz rTMS. This study demonstrates the validity of network controllability and offers a new targeting approach to improve efficacy.

Psychophysiological Markers of Performance and Learning during Simulated Marksmanship in Immersive Virtual Reality.

The fusion of immersive virtual reality, kinematic movement tracking, and EEG offers a powerful test bed for naturalistic neuroscience research. Here, we combined these elements to investigate the neuro-behavioral mechanisms underlying precision visual-motor control as 20 participants completed a three-visit, visual-motor, coincidence-anticipation task, modeled after Olympic Trap Shooting and performed in immersive and interactive virtual reality. Analyses of the kinematic metrics demonstrated learning of more efficient movements with significantly faster hand RTs, earlier trigger response times, and higher spatial precision, leading to an average of 13% improvement in shot scores across the visits. As revealed through spectral and time-locked analyses of the EEG beta band (13-30 Hz), power measured prior to target launch and visual-evoked potential amplitudes measured immediately after the target launch correlated with subsequent reactive kinematic performance in the shooting task. Moreover, both launch-locked and shot/feedback-locked visual-evoked potentials became earlier and more negative with practice, pointing to neural mechanisms that may contribute to the development of visual-motor proficiency. Collectively, these findings illustrate EEG and kinematic biomarkers of precision motor control and changes in the neurophysiological substrates that may underlie motor learning.

Review: Vision and On-field Performance: A Critical Review of Visual Assessment and Training Studies with Athletes.

SIGNIFICANCE: Sports vision is an emerging field that seeks to establish the relationships between visual function and sports performance. Here we provide the first critical review of empirical studies that attempt to link visual assessments and vision training to competitive game performance.Vision is essential to producing controlled movement, and therefore, it is intuitive that better visual abilities should relate to better sporting performance. This notion has been central to the field of sports vision, an area of study that seeks to determine the visual skills that underlie optimal sports performance and investigate approaches to train these abilities to improve sports performance. Although this field now contains hundreds of published articles addressing visual assessment and training in athletes, relatively few have attempted to directly link these capabilities to on-field production statistics from competitive matches. The objectives of this article are both to describe the theoretical and experimental framework necessary for such research and to critically review the empirical literature that has attempted to directly link visual assessments and/or training to athletic performance. We begin by describing why such associations are important and then provide an evidence-based framework for evaluating the quality of research in this domain. This is followed by a summary and review of the qualified literature that has addressed either relationships between baseline assessments and game performance or the effects of visual training interventions on game performance. Based on this review, it is concluded that, despite promising evidence supporting the role of vision in sports performance and improvements due to training, the specialty is still in need of methodological improvements. It is recommended that studies aim for larger better-powered studies, consistent and precise outcome measures, and greater scientific rigor such as obtained through randomized placebo-controlled designs with pre-registration of hypotheses.

Effects of repetitive transcranial magnetic stimulation on resting-state connectivity: A systematic review.

The brain is organized into networks that reorganize dynamically in response to cognitive demands and exogenous stimuli. In recent years, repetitive transcranial magnetic stimulation (rTMS) has gained increasing use as a noninvasive means to modulate cortical physiology, with effects both proximal to the stimulation site and in distal areas that are intrinsically connected to the proximal target. In light of these network-level neuromodulatory effects, there has been a rapid growth in studies attempting to leverage information about network connectivity to improve neuromodulatory control and intervention outcomes. However, the mechanisms-of-action of rTMS on network-level effects remain poorly understood and is based primarily on heuristics from proximal stimulation findings. To help bridge this gap, the current paper presents a systematic review of 33 rTMS studies with baseline and post-rTMS measures of fMRI resting-state functional connectivity (RSFC). Literature synthesis revealed variability across studies in stimulation parameters, studied populations, and connectivity analysis methodology. Despite this variability, it is observed that active rTMS induces significant changes on RSFC, but the prevalent low-frequency-inhibition/high-frequency-facilitation heuristic endorsed for proximal rTMS effects does not fully describe distal connectivity findings. This review also points towards other important considerations, including that the majority of rTMS-induced changes were found outside the stimulated functional network, suggesting that rTMS effects tend to spread across networks. Future studies may therefore wish to adopt conventions and systematic frameworks, such as the Yeo functional connectivity parcellation atlas adopted here, to better characterize network-level effect that contribute to the efficacy of these rapidly developing noninvasive interventions.

Examining the Role of Lateral Parietal Cortex in Emotional Distancing Using TMS.

We recently proposed a neurocognitive model of distancing-an emotion regulation tactic-with a focus on the lateral parietal cortex. Although this brain area has been implicated in both cognitive control and self-projection processes during distancing, fMRI work suggests that these processes may be dissociable here. This preregistered (NCT03698591) study tested the contribution of left temporoparietal junction (TPJ) to distancing using repetitive transcranial magnetic stimulation. We hypothesized that inhibiting left TPJ would decrease the efficiency of distancing but not distraction, another regulation tactic with similar cognitive control requirements, thus implicating this region in the self-projection processes unique to distancing. Active and sham continuous theta burst stimulation (cTBS) were applied to 30 healthy adults in a single-session crossover design. Tactic efficiency was measured using online reports of valence and effort. The stimulation target was established from the group TPJ fMRI activation peak in an independent sample using the same distancing task, and anatomical MRI scans were used for individual targeting. Analyses employed both repeated-measures ANOVA and analytic procedures tailored to crossover designs. Irrespective of cTBS, distancing led to greater decreases in negative valence over time relative to distraction, and distancing effort decreased over time while distraction effort remained stable. Exploratory analyses also revealed that active cTBS made distancing more effortful, but not distraction. Thus, left TPJ seems to support self-projection processes in distancing, and these processes may be facilitated by repeated use. These findings help to clarify the role of lateral parietal cortex in distancing and inform applications of distancing and distraction.

Visual-motor expertise in athletes: Insights from semiparametric modelling of 2317 athletes tested on the Nike SPARQ Sensory Station.

Elite athletes not only run faster, hit harder, and jump higher, but also see and react better. However, the specific visual-motor skills that differentiate high-achieving athletes are still not well understood. In this paper we examine 2317 athletes (1871 male) tested on the Nike SPARQ Sensory Station, a digital test battery measuring visual, perceptual and motor skills relevant for sports performance. We develop a multivariate Gaussian transformation model to robustly estimate visual-motor differences by level, gender, and sport type. Results demonstrate that visual-motor performance is superior for athletes at higher levels, with males faster at near-far eye movements and females faster at eye-hand reaction times. Interestingly, athletes who play interceptive sports such as baseball and tennis exhibit better measures of visual clarity, contrast sensitivity and simple reaction time, while athletes from strategic sports like soccer and basketball have higher measures of spatial working memory. These findings provide quantitative evidence of domain-specific visual expertise in athletes.

Visual abilities distinguish pitchers from hitters in professional baseball.

This study aimed to evaluate the possibility that differences in sensorimotor abilities exist between hitters and pitchers in a large cohort of baseball players of varying levels of experience. Secondary data analysis was performed on 9 sensorimotor tasks comprising the Nike Sensory Station assessment battery. Bayesian hierarchical regression modelling was applied to test for differences between pitchers and hitters in data from 566 baseball players (112 high school, 85 college, 369 professional) collected at 20 testing centres. Explanatory variables including height, handedness, eye dominance, concussion history, and player position were modelled along with age curves using basis regression splines. Regression analyses revealed better performance for hitters relative to pitchers at the professional level in the visual clarity and depth perception tasks, but these differences did not exist at the high school or college levels. No significant differences were observed in the other 7 measures of sensorimotor capabilities included in the test battery, and no systematic biases were found between the testing centres. These findings, indicating that professional-level hitters have better visual acuity and depth perception than professional-level pitchers, affirm the notion that highly experienced athletes have differing perceptual skills. Findings are discussed in relation to deliberate practice theory.

Cortical Brain Activity Reflecting Attentional Biasing Toward Reward-Predicting Cues Covaries with Economic Decision-Making Performance.

Adaptive choice behavior depends critically on identifying and learning from outcome-predicting cues. We hypothesized that attention may be preferentially directed toward certain outcome-predicting cues. We studied this possibility by analyzing event-related potential (ERP) responses in humans during a probabilistic decision-making task. Participants viewed pairs of outcome-predicting visual cues and then chose to wager either a small (i.e., loss-minimizing) or large (i.e., gain-maximizing) amount of money. The cues were bilaterally presented, which allowed us to extract the relative neural responses to each cue by using a contralateral-versus-ipsilateral ERP contrast. We found an early lateralized ERP response, whose features matched the attention-shift-related N2pc component and whose amplitude scaled with the learned reward-predicting value of the cues as predicted by an attention-for-reward model. Consistently, we found a double dissociation involving the N2pc. Across participants, gain-maximization positively correlated with the N2pc amplitude to the most reliable gain-predicting cue, suggesting an attentional bias toward such cues. Conversely, loss-minimization was negatively correlated with the N2pc amplitude to the most reliable loss-predicting cue, suggesting an attentional avoidance toward such stimuli. These results indicate that learned stimulus-reward associations can influence rapid attention allocation, and that differences in this process are associated with individual differences in economic decision-making performance.

Rapid brain responses independently predict gain maximization and loss minimization during economic decision making.

Success in many decision-making scenarios depends on the ability to maximize gains and minimize losses. Even if an agent knows which cues lead to gains and which lead to losses, that agent could still make choices yielding suboptimal rewards. Here, by analyzing event-related potentials (ERPs) recorded in humans during a probabilistic gambling task, we show that individuals' behavioral tendencies to maximize gains and to minimize losses are associated with their ERP responses to the receipt of those gains and losses, respectively. We focused our analyses on ERP signals that predict behavioral adjustment: the frontocentral feedback-related negativity (FRN) and two P300 (P3) subcomponents, the frontocentral P3a and the parietal P3b. We found that, across participants, gain maximization was predicted by differences in amplitude of the P3b for suboptimal versus optimal gains (i.e., P3b amplitude difference between the least good and the best gains). Conversely, loss minimization was predicted by differences in the P3b amplitude to suboptimal versus optimal losses (i.e., difference between the worst and the least bad losses). Finally, we observed that the P3a and P3b, but not the FRN, predicted behavioral adjustment on subsequent trials, suggesting a specific adaptive mechanism by which prior experience may alter ensuing behavior. These findings indicate that individual differences in gain maximization and loss minimization are linked to individual differences in rapid neural responses to monetary outcomes.

Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.

Predictive modeling of response to repetitive transcranial magnetic stimulation in treatment-resistant depression.

Identifying predictors of treatment response to repetitive transcranial magnetic stimulation (rTMS) remain elusive in treatment-resistant depression (TRD). Leveraging electronic medical records (EMR), this retrospective cohort study applied supervised machine learning (ML) to sociodemographic, clinical, and treatment-related data to predict depressive symptom response (>50% reduction on PHQ-9) and remission (PHQ-9 < 5) following rTMS in 232 patients with TRD (mean age: 54.5, 63.4% women) treated at the University of California, San Diego Interventional Psychiatry Program between 2017 and 2023. ML models were internally validated using nested cross-validation and Shapley values were calculated to quantify contributions of each feature to response prediction. The best-fit models proved reasonably accurate at discriminating treatment responders (Area under the curve (AUC): 0.689 [0.638, 0.740], p < 0.01) and remitters (AUC 0.745 [0.692, 0.797], p < 0.01), though only the response model was well-calibrated. Both models were associated with significant net benefits, indicating their potential utility for clinical decision-making. Shapley values revealed that patients with comorbid anxiety, obesity, concurrent psychiatric medication use, and more chronic TRD were less likely to respond or remit following rTMS. Patients with trauma and former tobacco users were more likely to respond. Furthermore, delivery of intermittent theta burst stimulation and more rTMS sessions were associated with superior outcomes. These findings highlight the potential of ML-guided techniques to guide clinical decision-making for rTMS treatment in patients with TRD to optimize therapeutic outcomes.

Transcranial magnetic stimulation input-output curve slope differences suggest variation in recruitment across muscle representations in primary motor cortex.

Measurement of the input-output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects.

Multimodal smoking cessation treatment combining repetitive transcranial magnetic stimulation, cognitive behavioral therapy, and nicotine replacement in veterans with posttraumatic stress disorder: A feasibility randomized controlled trial protocol.

Tobacco-related deaths remain the leading cause of preventable death in the United States. Veterans suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies suggest the insula is integrally involved in the neurocircuitry of TUD. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a form of repetitive transcranial magnetic stimulation (rTMS) called intermittent theta burst stimulation (iTBS). iTBS has the advantage of allowing for a patterned form of stimulation delivery that we will administer at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the right post-central gyrus and the right posterior insula, withdrawal symptoms and short-term smoking cessation outcomes will improve. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n = 25) or sham-iTBS + CBT + NRT (n = 25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.