Publications by authors named "Sahib Khalsa"

Objective: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND.

Methods: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients.

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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 enhance mental healthcare through improved diagnostic accuracy, personalized care, and streamlined administrative processes. It is also acknowledged that LLMs introduce challenges related to computational demands, potential for misinterpretation, and ethical concerns, necessitating the development of pragmatic frameworks to ensure their safe deployment.

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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 functional neuroimaging study of 46 individuals with anxiety, depression, and/or eating disorders (ADE) and 46 propensity-matched healthy comparisons (HC), comparing their neural activity across two interoceptive tasks differentially recruiting top-down or bottom-up processing within the same scan session. During an interoceptive attention task, top-down attention was voluntarily directed towards cardiorespiratory or visual signals.

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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 depression, pain, addiction, and anxiety. Over the past decade, neuroimaging has examined the neuroscientific basis of meditation practices, effects, states, and outcomes for clinical and non-clinical populations.

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  • The study investigates how focused ultrasound (LIFU) can modify brain responses tied to heartbeat, known as heartbeat evoked potentials (HEP), and focuses on specific brain regions like the insula and dorsal anterior cingulate cortex (dACC).
  • Healthy participants received targeted LIFU while their brain activity (EEG) and heart activity (ECG) were monitored, with the main goal of observing changes in HEP amplitudes.
  • Results showed that LIFU to the posterior insula reduced HEP amplitudes, but it did not alter heart rate or variability, indicating the potential for targeting brain areas to influence interoceptive processing.
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  • * Using functional imaging, the research found that AnxMDD participants showed significantly greater brain activation in key areas related to fear processing when exposed to threatening stimuli compared to those with MDD alone.
  • * The findings imply that comorbid anxiety may influence fear-related brain responses, pinpointing areas for potential treatment strategies in individuals who suffer from both depression and anxiety, which are often more challenging to treat.
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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 inflammation in MDD. RT-qPCR was used to measure mRNA expression of key organellar genes from peripheral blood mononuclear cells (PBMCs) isolated from 186 MDD and 67 healthy control (HC) subjects.

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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 Wellbeing (AGBW) Survey.

Methods: A patient-centered multi-phase process was implemented.

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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 breathing patterns.

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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.

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  • This study looked at how anxiety affects people's ability to make choices, especially those with mental health issues like depression and anxiety.
  • Researchers tested how breathing exercises that make someone feel anxious impacted decision-making in people who usually have high anxiety levels.
  • They found that while people with anxiety usually try to seek more information, this desire decreased when they felt anxious, leading to slower learning and worse choices.
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Background: Reduced Environmental Stimulation Therapy (REST) is a behavioral intervention that systematically attenuates external sensory input to the nervous system. Previous studies have demonstrated acute anxiolytic and antidepressant effects of single sessions of REST in anxious individuals, however the duration and time course of these effects is unknown. In the current study, we used experience sampling and multiple sessions of REST to explore the time course of the anxiolytic and antidepressant effects over a 48-hour time period.

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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 anxiolytic and antidepressant effect that persists for over 48 hours. However, the feasibility of using floatation-REST as a repeated intervention in anxious and depressed populations has not been well-investigated.

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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.

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  • Recent research in Bayesian theories indicates that how we perceive bodily states depends on a combination of incoming signals and our prior beliefs about those signals.
  • A study involving heartbeat tapping showed that healthy individuals adapt their perception of cardiac signals during breath-holding, while those with anxiety or related disorders do not adjust their perception, indicating a problem with how they weight these signals.
  • Expanding a previous study with a larger sample size confirmed these findings and suggests that future research could look into how understanding interoceptive precision might help improve treatment outcomes and identify new therapeutic targets.
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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 (fMRI) to identify the contribution of gene regulatory pathways, in particular micro-RNA (miR) 93, to interoceptive dysfunction in MDD. Individuals with MDD (n = 41) and healthy comparisons (HC; n = 35) provided blood samples and completed an interoceptive attention task during fMRI.

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  • Good communication between a patient and a therapist is really important in therapy.
  • Researchers want to find ways to measure how well this communication is working by using brain scans and technology like fMRI and EEG.
  • They suggest new methods that could help both patients and therapists have a better experience, but they also think about the challenges and limitations of these methods for the future.
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Background: Major depressive disorder has a complex, bidirectional relationship with metabolic dysfunction, but the neural correlates of this association are not well understood.

Methods: In this cross-sectional investigation, we used a 2-step discovery and confirmatory strategy utilizing 2 independent samples (sample 1: 288 participants, sample 2: 196 participants) to examine the association between circulating indicators of metabolic health (leptin and adiponectin) and brain structures in individuals with major depressive disorder.

Results: We found a replicable inverse correlation between leptin levels and cortical surface area within essential brain areas responsible for emotion regulation, such as the left posterior cingulate cortex, right pars orbitalis, right superior temporal gyrus, and right insula (standardized beta coefficient range: -0.

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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 that can selectively target sub-regions of the insula and dACC to better understand their contributions to the HEP.

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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-rivaling results. However, questions remain about their long-term safety and efficacy.

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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 cardiovascular signaling differentially affects the heartbeat-evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.

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Article Synopsis
  • A study investigates the immune dysfunction associated with major depressive disorder (MDD) and its potential intracellular origins, focusing on endoplasmic reticulum (ER) stress, inflammasome activity, and mitochondrial biogenesis.
  • Researchers analyzed mRNA expression in blood samples from 186 individuals with MDD and 67 healthy controls, finding significant increases in ER stress and mitochondrial biogenesis genes in the MDD group.
  • The results suggest that abnormalities in these cellular processes may contribute to systemic inflammation observed in MDD, shedding light on potential biological mechanisms behind the disorder.
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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 functional neuroimaging study of 46 individuals with anxiety, depression, and/or eating disorders (ADE) and 46 propensity-matched healthy comparisons (HC), comparing their neural activity across two interoceptive tasks differentially recruiting top-down or bottom-up processing within the same scan session. During an interoceptive attention task, top-down attention was voluntarily directed towards cardiorespiratory or visual signals, whereas during an interoceptive perturbation task, intravenous infusions of isoproterenol (a peripherally-acting beta-adrenergic receptor agonist) were administered in a double-blinded and placebo-controlled fashion to drive bottom-up cardiorespiratory sensations.

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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 profound effects on central satiety signaling leading to reduced food intake, and has been approved for the treatment of obesity based on its efficacy and safety profile.

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