K. Luan Phan

• M.D.
• Chair at The Ohio State University

No prior work has directly compared the impacts of transcranial photobiomodulation (tPBM) and transcranial magnetic stimulation (TMS) on the human brain. This within-subjects pilot study compares the effects of tPBM and TMS of human somatomotor cortex on brain structural and functional connectivity. Eight healthy participants underwent four lab vis...

Introduction Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), are thought to weaken neurocognitive processes. However, past experimental research examining the acute effects of THC on neurocognition has produced mixed results. The current study aims to advance this literature through application of computational m...

Poor inhibitory control and exaggerated threat reactivity are two well‐established risk factors for suicide. Theory suggests that these two factors may interact to influence suicide risk, although few studies have directly tested these relationships. In the present study, we examined the unique and interactive effects of inhibitory control (IC) and...

Background Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds promise for the treatment of brain-based disorders. Studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets, including the amygdala; however, limited research has explored how tFUS impacts large-s...

Introduction. Deaths related to drug overdose and suicide in the United States have increased nearly 500% and 35%, respectively over the last two decades. The human and economic costs to society associated with these deaths of despair are immense. Great efforts and substantial investments have been made in treatment and prevention, yet these effort...

Background Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds immense promise for the treatment of brain-based disorders. Several studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets including the amygdala; however, limited research has explored how tFUS...

Background A developing theory and recent research suggest that heightened reactivity to uncertain stressors or threats may be an important individual difference factor that facilitates excessive drinking as a means of avoidance-based coping and characterizes individuals with current and past alcohol use disorder (AUD). Neuroimaging studies of unpr...

Background Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [...

Background: Discovery of modifiable factors influencing subjective withdrawal experience might advance opioid use disorder (OUD) research and precision treatment. This study explores one factor - withdrawal catastrophizing - a negative cognitive and emotional orientation toward withdrawal characterized by excessive fear, worry or inability to diver...

Subclinical symptoms of obsessive–compulsive disorder (i.e., obsessive compulsive symptoms, or “OCS”) cause functional impairment, including for youth without full-syndrome OCD. Further, despite high rates of OCS in youth with anxiety disorders, knowledge of OCS in the context of specific anxiety disorders is limited. The present study seeks to: (1...

Background: Social anxiety disorder (SAD) has been associated with alterations in amygdala and hippocampal volume but there is mixed evidence for the direction of volumetric alterations. Additionally, little is known about the involvement distinct subfields of these regions in the pathophysiology of SAD. Methods: T1-weighted MRI images from a large...

Individual differences in reactivity to unpredictable threat (U‐threat) have repeatedly been linked to symptoms of anxiety and drinking behavior. An emerging theory is that individuals who are hyper‐reactive to U‐threat experience chronic anticipatory anxiety, hyperarousal, and are vulnerable to excessive alcohol use via negative reinforcement proc...

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...

Background Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generaliz...

Background: Effective biomarkers of cognitive behavioral therapy (CBT) response provide information beyond available behavioral or self-report measures and may optimize treatment selection for patients based on likelihood of benefit. No single biomarker reliably predicts CBT response. In this study, we evaluated patterns of brain connectivity assoc...

Background: Recent studies have begun to examine how signals in the brain correspond to the underlying white matter structure using tools from the field of graph signal processing (GSP) to quantify brain function 'alignment' to brain network topology. Here, we apply this framework for the first time towards a transdiagnostic cohort of internalizin...

Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to...

Fibromyalgia and opioid use disorder (OUD) are highly impactful chronic illnesses with substantially overlapping psychosocial, biological, and clinical features. Little previous research has examined interactions between fibromyalgia and OUD. Limiting such research has been the previous requirement of a clinical examination to diagnose fibromyalgia...

Individuals with internalizing psychopathologies (IPs) demonstrate a negativity bias in emotion and self-related processing that contributes to negative interpretation of neutral information. However, most neuroimaging studies of emotional experience in IPs do not specifically investigate reactivity to neutral stimuli. Thus, little is known about t...

Suicidality is prevalent in Social Anxiety Disorder (SAD) and Major Depressive Disorder (MDD). Limited data indicate the reward positivity (RewP), a neurophysiological index of reward responsivity, and subjective capacity for pleasure may serve as brain and behavioral assays for suicide risk though this has yet to be examined in SAD or MDD in the c...

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a gl...

Rumination and worry are forms of repetitive negative thinking (RNT) commonly associated with internalizing psychopathologies, although less is known about RNT in trauma-exposed individuals with internalizing psychopathologies. Separate lines of research show RNT also plays a role in problematic sleep, which is frequently experienced after trauma e...

Background: Current clinical assessments of Posttraumatic stress disorder (PTSD) rely solely on subjective symptoms and experiences reported by the patient, rather than objective biomarkers of the illness. Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. Here...

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level infere...

A number of studies of posttraumatic stress disorder (PTSD) report thinner cerebral cortical gyri using gyrus-based analysis or thinner foci within the gyri using vertex-based analysis. However, the locations of these findings are inconsistent across studies, and the spatial transformations required during vertex-based analysis may affect the focal...

Recent studies have begun to examine the extent to which signals in the brain correspond to the underlying white matter structure by using tools from the field of graph signal processing to quantify brain function alignment to brain network topology. Here, we apply this framework for the first time towards a transdiagnostic cohort of internalizing...

Research indicates that heightened anticipatory anxiety underlies several forms of psychopathology. Anticipatory anxiety can be reliably and objectively measured in the laboratory using the No-Predictable-Unpredictable (NPU) threat paradigm. The NPU paradigm is an ideal research tool for the NIH ‘Fast-Fail’ approach of screening promising compounds...

Background Knowledge of the neural mechanisms underlying increased disease burden in the anxiety disorders that is unaccounted for by individual categorical diagnoses could lead to improved clinical care. Here, we tested the utility of a joint fMRI-EEG neurobiological profile characterized by overvaluation of negative stimuli (amygdala) in combinat...

Background Internalizing psychopathologies (IPs) are highly comorbid and exhibit substantial overlap, such as aberrant affective reactivity. Neural reactivity to emotional images, measured via the late positive potential (LPP) event‐related potential (ERP) component, has been utilized to index affective reactivity in IPs. The LPP is often examined...

Self-reported histories of mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) symptoms are prevalent among post-9/11 veterans. Both are associated with subjective and often overlapping symptom complaints, but variably with objective neuropsychological test performances. These outcomes are seldom explored in relation to life...

Introduction: Central sensitization (CS) involves dysfunctional central nervous system pain modulation resulting in heightened pain perception. Central sensitization is not commonly assessed among patients with opioid use disorder (OUD), despite the fact that pain has been implicated in the development, maintenance, and relapse of OUD and chronic...

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (...

Background Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is c...

The reward positivity (RewP) event-related potential is a well-validated measure of reward processing implicated in internalizing psychopathologies. The RewP is thought to reflect reward reactivity in the mesocorticolimbic system; however, it is not clear how the RewP is related to the functional connectivity of reward-related brain regions. The cu...

The transition to becoming a mother involves numerous emotional challenges, and the ability to effectively keep negative emotions in check is critical for parenting. Evidence suggests that experiencing socioeconomic disadvantage interferes with parenting adaptations and alters neural processes related to emotion regulation. The present study examin...

Objective: Posttraumatic stress disorder (PTSD) and alcohol use (AU) are highly prevalent and comorbid among post-9/11 U.S. military veterans. Both issues are associated with working memory (WM) deficits, but have rarely been studied concurrently in cognitive studies of post-9/11 veterans. They also have been measured inconsistently, with variable...

How we perceive and interpret signals from others’ behavior, known as social-emotional information processing (SEIP), is key when responding to social threat. Impulsively aggressive individuals, behaviorally, demonstrate impaired SEIP for encoding relevant social stimuli, attribution of intent of the other person in the interaction, and responding...

Background Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). Methods Neuroimaging and clinical data were aggregated fro...

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging meth...

Background Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method Adult subjects (N = 2229; 56.2% male) aged 18–69...

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings, and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders, studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associat...

Background Emotion regulation (ER) strategies (i.e., reappraisal, suppression) and repetitive negative thinking (RNT) tendencies (i.e., brooding rumination, worry) are transdiagnostic and contribute to the maintenance of internalizing psychopathologies. Cognitive Behavioral Therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both...

Guided by developmental psychopathology and dual-risk frameworks, the present study examined the interplay between childhood maltreatment and maternal major depression history in relation to neural reward responsiveness in youth. The sample consisted of 96 youth (ages 9–16; M = 12.29 years, SD = 2.20; 68.8% female) drawn from a large metropolitan c...

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through th...

Anterior cingulate cortex (ACC) response during attentional control in the context of task-irrelevant emotional faces is a promising biomarker of cognitive behavioral therapy (CBT) outcome in patients with social anxiety disorder (SAD). However, it is unclear whether this biomarker extends to major depressive disorder (MDD) and is specific to CBT o...

One sex differences in the perception of emotion is that females, particularly those with high anxiety, often show heightened identification of fearful faces. To better understand the causal role of glucocorticoids in this sex difference, we examine these associations in people with HIV(PWH) where emotion perception is impaired and mental health di...

Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that b...

Background : Individuals with intermittent explosive disorder (IED) are reported to exhibit amygdala (AMYG) hyper-activation to anger faces during functional magnetic resonance imaging (fMRI). However, it remains unknown if emotional experience is different in study participants with IED compared with healthy controls (HC). Thus, we examined the co...

Background Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (...

Background Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative...

Early life adversity (ELA) increases the risk of problematic alcohol use and alcohol use disorder (AUD). However, it is unclear why some but not all ELA-exposed individuals develop problematic alcohol use. Research is needed to determine how this environmental risk factor interacts with underlying neurobehavioral vulnerabilities to problem alcohol...

Anxiety disorders (ADs) are common and difficult to treat. While research suggests ADs are characterized by an imbalance between bottom-up and top-down attention processes and that effective treatments work by correcting this dysfunction, there is insufficient data to explain how and for whom treatments work. The late positive potential (LPP), an e...

Background Resting-state graph-based network edges can be powerful tools for identification of mood disorders. We address whether these edges can be integrated with RDoC constructs, for accurate identification of mood-disorder related markers, while minimizing active symptoms of disease. Methods We compared 132 individuals with currently remitted...

Early parenting relies on emotion regulation capabilities, as mothers are responsible for regulating both their own emotional state and that of their infant during a time of new parenting-related neural plasticity and potentially increased stress. Previous research highlights the importance of frontal cortical regions in facilitating effective emot...

Background: Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings, and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders, studies have not examined its neural basis. We hypothesized that maladaptive SFA would be associated...

Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to...

Objective We examined the impact of post-traumatic stress disorder (PTSD) on both prospective (PM) and retrospective (RM) memory performance among a cross-sectional veteran sample. Method Data from tests of PM/RM memory and PTSD, anxiety, depression and sleep disturbance symptoms were examined among a prospectively recruited sample of 26 veterans...

Objective: The relative contribution of individual cognitive behavioral therapy (CBT) components to treatment outcomes for child anxiety disorders (CADs) is unclear. Recent meta-analyses suggest that exposure may be the primary active ingredient in CBT for CADs, and that relaxation may be relatively less effective. This brief report tests the hypot...

Network diffusion models are a common and powerful way to study the propagation of information through a complex system, they and offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with impaired information diffusion capacity using the structural basis that b...

Background Early Life Adversity (ELA) is consistently linked to chronic, treatment-resistant depression and anxiety. Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) represent the two first-line treatments for internalizing disorders. However, little is known about the efficacy of these therapies for individual...

Introduction Cortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. T...

Background Rumination and worry are repetitive negative thinking (RNT) tendencies that contribute to the development and maintenance of internalizing psychopathologies. Accruing data suggest rumination and worry represent overlapping and unique transdiagnostic cognitive processes. Yet, prior neuroimaging research has mostly focused on rumination in...

Introduction Disruptions in neural measures of reward responsiveness are implicated in risk for and the development of Substance Use Disorders (SUDs) in general, but it is not clear if this is also true for Cannabis Use Disorder (CUD). To date, no studies have examined neural reward responsiveness in cannabis users using EEG. Methods Cannabis user...

Background Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis us...

Social-emotional information processing (SEIP) is critical for appropriate human interaction. It is composed of processes that underlie how we behave towards others, especially in response to adverse social threat. We conducted a study in 26 healthy participants who completed a validated Video-SEIP (V-SEIP) task in the fMRI scanning environment. Th...

Trauma exposure is prevalent, associated with multiple forms of psychopathology, and thought to alter the neurobiological substrates of threat processing. The late positive potential (LPP) is an event-related potential (ERP) that may be a clinically useful probe of the neurobiology of threat processing. Despite evidence that combat-exposed veterans...

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnorma...

Background Alcohol use disorder (AUD) remains an unresolved source of morbidity and mortality. Psychopharmacological challenge studies and neuroimaging experiments are two methods used to identify risk of problematic substance use. The present study combined these two approaches by examining associations between self-reported stimulation, sedation,...

Background Neuroimaging studies have shown variance in brain response to emotional faces predicts cognitive behavioral therapy (CBT) outcome. An important next step is to determine if individual differences in neural predictors of CBT response represent distinct patient groups. Methods In total, 90 patients with internalizing disorders completed a...

Background: Anxiety is associated with aberrant patterns of cortical thickness in regions implicated in emotion regulation. However, few studies have examined cortical thickness differences between individuals with anxiety and healthy controls (HCs) across development, particularly during childhood when cortical thinning begins and anxiety risk in...

The error‐related negativity (ERN) is an event‐related potential that reflects error monitoring. Enhanced ERN indicates sensitivity to performance errors and is a correlate of anxiety disorders. In contrast, youth with externalizing problems exhibit a reduced ERN, suggesting decreased error monitoring. Anxiety and externalizing problems commonly co...

Objective: The present study explored both embedded symptom (SVT) and performance (PVT) validity test scores within a post- 9/11 veteran sample to elucidate the degree to which there is concordance between validity indicators, as well as how frequently one SVT and four PVT indicators were failed in screened mild traumatic brain injury (mTBI) and di...

Background Alterations in resting‐state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre‐ and post‐treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. Methods Sixty‐four combat veterans with PTSD were randomly ass...

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA‐Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega‐analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...

One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested...

Identifying neurobehavioral correlates of suicidal ideation can help detect those most vulnerable for suicide among high-risk groups, such as those with internalizing psychopathology. Individuals with elevated sensitivity to uncertain threat (U-threat) have a strong preference for known outcomes relative to unknown outcomes and often experience hig...

This study examined the impact of perceived social support on mental health and psychosocial functioning in combat veterans after military deployment, including veterans with post-traumatic stress disorder (PTSD) and veterans with comorbid PTSD and alcohol use disorder. Veterans ( n = 139; female = 23) completed self-report and clinician-administer...

Structural differences in the amygdala (AMG) are implicated in anxiety and observed among individuals with generalized (GAD) and social anxiety (SAD) disorders. Findings have been mixed, perhaps because studies rarely examine differences between GAD and SAD, test comorbidity, or examine age-related differences. We tested AMG volume differences amon...