About
240
Publications
51,108
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
7,677
Citations
Introduction
Dr. Khalsa received MD and PhD (neuroscience) degrees at the University of Iowa. He completed residency training in Psychiatry at UCLA, serving as the program Chief Resident and Chief Resident in the UCLA Anxiety Disorders Clinic. He subsequently joined the department as an Assistant Professor in Residence in the Adult Psychiatry Division at UCLA. In 2015, Dr. Khalsa joined the Laureate Institute for Brain Research in Tulsa, Oklahoma, as the Director of Clinical Studies. Dr. Khalsa’s research investigates brain-body communication to 1) better understand how human beings perceive cardiorespiratory sensation, 2) determine whether there is dysfunctional cross-talk between the body and brain in psychiatric illness, and 3) develop novel brain-body interventions for anxiety and eating disorders.
Publications
Publications (240)
Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body’s internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, driv...
The present paper considers recent progress in our understanding of the afferent/ascending neural pathways and neural circuits of interoception. Of particular note is the extensive role of rostral neural systems, including cortical systems, in the recognition of internal body states, and the reciprocal role of efferent/descending systems in the reg...
Purpose of Review
Abnormal interoception has been consistently observed across eating disorders despite limited inclusion in diagnostic conceptualization. Using the alimentary tract as well as recent developments in interoceptive neuroscience and predictive processing as a guide, the current review summarizes evidence of gastrointestinal interocept...
Importance:
β-Adrenergic stimulation elicits heart palpitations and dyspnea, key features of acute anxiety and sympathetic arousal, yet no neuroimaging studies have examined how the pharmacologic modulation of interoceptive signals is associated with fear-related neurocircuitry in individuals with generalized anxiety disorder (GAD).
Objective:
T...
Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the body’s interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a...
Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered fu...
Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualised meditation practices and designed various meditation interventions (MIs), that have shown therapeutic efficacy for disorders including d...
Interoception is crucial for human health as it constitutes the afferent component of the brain-body feedback loop that is essential for maintaining physiological equilibrium. Disruption in interoceptive processes is increasingly recognized as a common thread across numerous psychiatric disorders, suggesting that enhanced understanding and targetin...
Interoception is crucial for human health as it constitutes the afferent component of the brain-body feedback loop that is essential for maintaining physiological equilibrium. Disruption in interoceptive processes is increasingly recognized as a common thread across numerous psychiatric disorders, suggesting that enhanced understanding and targetin...
Major depressive disorder has a point prevalence of 5% of the world population and is the main cause of disability, with up to a third of patients not responding to first-line treatments. Surgical neuromodulation is offered to only an anecdotal proportion of these patients, because while these methods are curative in some individuals, the proportio...
Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered fu...
A subset of major depressive disorder (MDD) is characterized by immune system dysfunction, but the intracellular origin of these immune changes remains unclear. Here we tested the hypothesis that abnormalities in endoplasmic reticulum (ER) stress, inflammasome activity and mitochondrial biogenesis contribute to the development of systemic inflammat...
Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal or limbic regions on the sensation and regulation of...
Objective
There is currently a lack of validated questionnaires designed specifically to assess mental health within patients with chronic gastroduodenal symptoms. This research describes the multi-phase process used to develop and validate a novel mental health scale for patients with chronic gastroduodenal symptoms, the Alimetry® Gut-Brain Wellbe...
Current theories suggest individuals with methamphetamine use disorder (iMUDs) have difficulty considering long-term outcomes in decision-making, which could contribute to risk of relapse. Aversive interoceptive states (e.g., stress, withdrawal) are also known to increase this risk. The present study analyzed computational mechanisms of planning in...
Elevated anxiety and uncertainty avoidance are known to exacerbate maladaptive choice in individuals with affective disorders. However, the differential roles of state vs. trait anxiety remain unclear, and underlying computational mechanisms have not been thoroughly characterized. In the present study, we investigated how a somatic (interoceptive)...
Background
Reduced Environmental Stimulation Therapy via floatation (floatation-REST) is a behavioral intervention designed to attenuate exteroceptive sensory input to the nervous system. Prior studies in anxious and depressed individuals demonstrated that single sessions of floatation-REST are safe, well-tolerated, and associated with an acute anx...
The integration of large language models (LLMs) into mental healthcare and research heralds a potentially transformative shift, one offering enhanced access to care, efficient data collection, and innovative therapeutic tools. This paper reviews the development, function, and burgeoning use of LLMs in psychiatry, highlighting their potential to enh...
Methamphetamine Use Disorder (MUD) is associated with substantially reduced quality of life. Yet, decisions to use persist, due in part to avoidance of anticipated withdrawal states. However, the specific cognitive mechanisms underlying this decision process, and possible modulatory effects of aversive states, remain unclear. Here, 56 individuals w...
Recent Bayesian theories of interoception suggest that perception of bodily states rests upon a precision-weighted integration of afferent signals and prior beliefs. In a previous study, we fit a computational model of perception to behavior on a heartbeat tapping task to test whether aberrant precision-weighting could explain misestimation of card...
Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain neuronal-enriched extracellular vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMR...
Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualised meditation practices and designed various meditation interventions (MIs), that have shown therapeutic efficacy for disorders including d...
This multimodal brain imaging study investigated functional MRI (fMRI) neural processing of cardiac interoceptive signals in 38 patients with functional neurological disorder (FND) compared to 38 healthy controls (HCs). Additionally, we characterized how brain fMRI responses during heartbeat counting (interoception) vs. tone counting (exteroception...
Background
The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing. The insula and dorsal anterior cingulate cortex (dACC) are brain regions that may be involved in generating the HEP. Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique...
Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered fu...
Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered fu...
Glucagon‐like peptide 1 (GLP‐1) receptor agonists are revolutionizing obesity and type 2 diabetes treatment, delivering remarkable weight loss outcomes. These medications, leveraging the effects of the insulin‐regulating hormone GLP‐1 via actions on peripheral and central nervous system targets, have raised hopes with their bariatric surgery‐rivali...
Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of...
Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered fu...
Background: Despite being the most common psychiatric comorbidity, underlying brain and behavioral processes characterizing anxious depression are not well understood. Affective startle modulation is a process that separately probes appetitive/defensive systems and is altered transdiagnostically in individuals with mood and anxiety disorders. This...
A subset of major depressive disorder (MDD) is characterized by immune system dysfunction, but the intracellular origin of these immune changes remains unclear. Here we tested the hypothesis that abnormalities in the endoplasmic reticulum (ER) stress, inflammasome activity and mitochondrial biogenesis contribute to the development of systemic infla...
Background
Sensitivity to threat with dysregulation of fear learning is thought to contribute to the development of psychiatric disorders, including anxiety disorders (AD) and major depressive disorder (MDD). However, fewer studies have examined fear learning in MDD than in AD. Nearly half of individuals with MDD have an AD and the comorbid diagnos...
Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal, or limbic regions on the sensation and regulation o...
Recent computational theories of interoception suggest that perception of bodily states rests upon an expected reliability- or precision-weighted integration of afferent signals and prior beliefs. The computational psychiatry framework further suggests that aberrant precision-weighting may lead to misestimation of bodily states, potentially hinderi...
Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of...
Objective
Binge eating disorder (BED) is the most common eating disorder, and yet only one pharmacotherapy (lisdexamfetamine), which has known abuse-potential, is FDA-approved. Topiramate is also commonly prescribed off-label for binge eating but has many contraindications. In contrast, the glucagon-like peptide-1 (GLP1) analog semaglutide has prof...
Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of medications currently approved by the US Food and Drug Administration for weight loss and glycemic control in individuals with obesity and type 2 diabetes. These medications mimic the effects of GLP-1, an endogenous hormone that regulates insulin and glucagon secretion and increases s...
Background
Body image disturbance and anxiety are core features of anorexia nervosa (AN), a psychiatric disorder with one of the highest mortality rates. This study examined the efficacy of a novel non-pharmacological treatment, floatation-REST (Reduced Environmental Stimulation Therapy) on body image disturbance and anxiety in inpatients with AN....
Major depressive disorder (MDD) is associated with immunologic and metabolic alterations linked to central processing dysfunctions, including attenuated reward processing. This study investigated the associations between inflammation, metabolic hormones (leptin, insulin, adiponectin), and reward-related brain processing in MDD patients with high (M...
Posttraumatic stress disorder (PTSD) is a psychiatric condition characterized by sustained symptoms, including reexperiencing, hyperarousal, avoidance, and mood alterations, following exposure to a traumatic event. Although symptom presentations in PTSD are heterogeneous and incompletely understood, they likely involve interactions between neural c...
Background:
Decision-making under approach-avoidance conflict (AAC; e.g., sacrificing quality of life to avoid feared outcomes) may be affected in multiple psychiatric disorders. Recently, we used a computational (active inference) model to characterize information processing differences during AAC in individuals with depression, anxiety and/or su...
Body image disturbance (BID) is a diagnostic feature of anorexia nervosa (AN), with few reliable, unbiased visual markers. We examined test-retest reliability of Somatomap, a 2-dimensional(2D) and 3-dimensional(3D) digital assessment of BID. Fifty-nine AN inpatients performed test-retest by a) outlining body concern areas on a 2D avatar; and b) usi...
Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on null-hypothesis significance testing (NHST) limits the identification of disorder-relevant relationships. In this preregistered study, we applied both a Bayesian statistical framework and...
Background: Reduced Environmental Stimulation Therapy via floatation (floatation-REST) is a behavioral intervention designed to attenuate exteroceptive sensory input to the nervous system. Pilot studies in anxious and depressed individuals demonstrated that single sessions of floatation-REST are safe, well-tolerated, and associated with acute anxio...
As the sense of the body's internal state, interoception represents the afferent component of the brain-body feedback loop essential for linking internal sensation with body regulation, thereby minimizing erroneous feedback and maintaining homeostasis. The anticipation of potential future interoceptive states enables organisms to take regulatory ac...
Aims:
To test whether there are sex differences in the relationship between impulsivity and amphetamine use disorder (AMP).
Design:
Naturalistic cross-sectional design.
Setting:
Tulsa 1000 study in Tulsa, Oklahoma, USA.
Participants:
Two groups, AMP+ (29F, 20M) and AMP- (57F, 33M).
Measurements:
UPPS-P Impulsive Behavior Scale and a stop s...
Background:
Repetitive negative thinking (RNT) is a symptom that can negatively impact the treatment and course of common psychiatric disorders such as depression and anxiety. We aimed to characterize behavioral and genetic correlates of RNT to infer potential contributors to its genesis and maintenance.
Methods:
We applied a machine learning (M...
Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain Neuronal-Enriched Extracellular Vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMR...
Anxiety and depression commonly co-occur, yet the underlying brain and behavioral processes are poorly understood. Here we examined the hypothesis that individuals with comorbid anxiety and depression would show increased fearful reactivity to an aversive interoceptive perturbation relative to depressed-only individuals. One-hundred and eighty anxi...
The parasympathetic nervous system via the vagus nerve exerts profound influence over the heart. Together with the sympathetic nervous system, the parasympathetic nervous system is responsible for fine-tuned regulation of all aspects of cardiovascular function, including heart rate, rhythm, contractility, and blood pressure. In this review, we high...
Background
Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exp...
The central nervous system (CNS) exerts a strong regulatory influence over the cardiovascular system in response to environmental demands. Floatation-REST (Reduced Environmental Stimulation Therapy) is an intervention that minimizes stimulation from the environment, yet little is known about the autonomic consequences of reducing external sensory i...
Background
Depression (MDD) is associated with an unusually large amount of individual disability and societal costs as well as unsatisfactory outcomes with well-established therapies, including psychotropic drugs and different types of psychotherapy. Based on increasing interest in modulation of brain circuits involved in specific symptoms of depr...
Background
Anorexia nervosa (AN) is characterized by low body weight, disturbed eating, body image disturbance, anxiety, and interoceptive dysfunction. However, the neural processes underlying these dysfunctions in AN are unclear. This investigation combined an interoceptive pharmacological probe, the peripheral beta-adrenergic agonist isoprotereno...
Ibuprofen, a non-steroidal, anti-inflammatory drug, modulates inflammation but may also have neuroprotective effects on brain health that are poorly understood. Astrocyte-enriched extracellular vesicles (AEEVs) facilitate cell-to-cell communication and – among other functions - regulate inflammation and metabolism via microribonucleic acids (miRNAs...
Background: Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive-compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of ex...
Rationale
At least six different types of antidepressant treatments have been shown to either increase the neuroprotective kynurenine pathway (KP) metabolite, kynurenic acid (KynA), or decrease the neurotoxic KP metabolite, quinolinic acid (QA). Nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen have shown some efficacy in the treatm...
Empathic communications between a patient and therapist are an essential component of psychotherapy. However, objective neural markers of the quality of the psychotherapeutic relationship have been elusive. Here we conceptualize how a neuroscience-informed approach involving real-time neurofeedback, facilitated via existing functional magnetic reso...
Repetitive negative thinking (RNT) is a transdiagnostic symptom associated with poor outcomes in major depressive disorder (MDD). MDD