Biology subjects

Khalsa, S. S.

Publications and source records attributed to Khalsa, S. S..

7 recordsLinked to original sources

bioRxiv2024

Low-intensity focused ultrasound to the human insular cortex differentially modulates the heartbeat-evoked potential: a proof-of-concept study

BackgroundThe 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. ObjectiveProof-of-concept study to determine whether LIFU modulation of the anterior insula (AI), posterior insula (PI), and dACC influences the HEP. MethodsIn a within-subject, repeated-measures design, healthy human participants (n=16) received 10 minutes of stereotaxically targeted LIFU to the AI, PI, dACC or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was change in HEP amplitudes. Relationships between LIFU pressure and HEP changes were examined using linear mixed modelling. Peripheral indices of visceromotor output including heart rate and heart rate variability (HRV) were explored between conditions. ResultsRelative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; this was partially explained by increased LIFU pressure. LIFU did not affect time or frequency dependent measures of HRV. ConclusionsThese results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. Our findings have implications for the causal role of these areas in bottom-up heart-brain communication that could guide future work investigating the HEP as a marker of interoceptive processing in healthy and clinical populations.

neuroscience↗

bioRxiv2023

Sensing, Feeling, and Regulating: Investigating the Association of Focal Brain Damage with Voluntary Respiratory and Motor Control

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. Participants performed a respiratory regulation task across regular and irregular frequencies ranging from 6 to 60 breaths per minute (bpm), with a counterbalanced hand motor control task. Interoceptive and affective states induced by each condition were assessed via questionnaire and autonomic signals were indexed via skin conductance. Participants with focal lesions to the bilateral frontal lobe, right insula/basal ganglia, and left medial temporal lobe showed reduced performance than individually matched healthy comparisons during the breathing and motor tasks. They also reported significantly higher anxiety during the 60-bpm regular and irregular breathing trials, with anxiety correlating with difficulty in rapid breathing specifically within this group. This study demonstrates that damage to frontal, temporal, or limbic regions is associated with abnormal voluntary respiratory and motor regulation and tachypnea-related anxiety, highlighting the role of the forebrain in affective and motor responses during breathing. HighlightsO_LIImpaired human respiratory regulation is associated with cortical/subcortical brain lesions C_LIO_LIFrontolimbic/temporal regions contribute to rhythmic breathing and hand motor control C_LIO_LIFrontolimbic/temporal damage is associated with anxiety during tachypnea/irregular breathing C_LIO_LIThe human forebrain is vital for affective and interoceptive experiences during breathing C_LI

neuroscience↗

bioRxiv2023

The unique face of anxious depression: Increased sustained threat circuitry response during fear acquisition

BackgroundSensitivity 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 diagnosis has worse outcomes. The current study used propensity matching to examine the hypothesis that AD+MDD shows greater neural correlates of fear learning than MDD, suggesting that the co-occurrence of AD+MDD is exemplified by exaggerated defense related processes. Methods195 individuals with MDD (N = 65) or AD+MDD (N=130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. ResultsMDD and AD+MDD showed significantly different patterns of activation for [CSplus- CSminus] in the medial amygdala ({eta}p2=0.009), anterior insula ({eta}p2=0.01), dorsolateral prefrontal cortex ({eta}p2=0.002), dorsal anterior cingulate cortex ({eta}p2=0.01), mid-cingulate cortex ({eta}p2=0.01) and posterior cingulate cortex ({eta}p2=0.02). These differences were driven by greater activation to the CS+ in late conditioning phases in ADD+MDD relative to MDD. ConclusionsAD+MDD showed a pattern of increased sustained activation in regions identified with fear learning. Effects were consistently driven by the threat condition, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, and self-relevant processing. These findings help to elucidate the fear signaling mechanisms involved in the pathophysiology of comorbid anxiety and depression, thereby highlighting promising treatment targets for this prevalent treatment group.

neuroscience↗

bioRxiv2022

Functional dissection of neural connectivity in generalized anxiety disorder

Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on the null-hypothesis significance testing (NHST) framework limits the identification and characterization of disorder-relevant relationships. In this preregistered study, we applied a Bayesian statistical framework as well as NHST to the analysis of resting-state fMRI scans from females with GAD and demographically matched healthy comparison females. Eleven a-priori hypotheses about functional correlativity (FC) were evaluated using Bayesian (multilevel model) and frequentist (t-test) inference. Reduced FC between the ventromedial prefrontal cortex (vmPFC) and the posterior-mid insula (PMI) was confirmed by both statistical approaches. FC between the vmPFC-anterior insula, the amygdala-PMI, and the amygdala-dorsolateral prefrontal cortex (dlPFC) region pairs did not survive multiple comparison correction using the frequentist approach. However, the Bayesian model provided evidence for these region pairs having decreased FC in the GAD group. Leveraging Bayesian modeling, we demonstrate decreased FC of the vmPFC, insula, amygdala, and dlPFC in females with GAD. Exploiting the Bayesian framework revealed FC abnormalities between region pairs excluded by the frequentist analysis, as well as other previously undescribed regions, demonstrating the benefits of applying this statistical approach to resting state FC data.

neuroscience↗

bioRxiv2021

Characterising the Photoplethysmography Pulse Waveform for Use in Human Neuroscience: The Hybrid Excess and Decay (HED) Model

Photoplethysmography (PPG) offers a widely-used, convenient and non-invasive approach to monitoring basic indices of cardiovascular function such as heart rate and blood oxygenation. However, while the pulse waveform, generated by PPG comprises features that are shaped by physiological and psychological factors, it is frequently overlooked in analyses of such data. We suggest that studies could be enriched by exploiting the possibilities afforded by a systematic analysis of PPG waveforms. To do this we initially require a robust and automated means of characterising it, thereby allowing us to examine variations across individuals and between different physiological and psychological contexts. We present a psychophysiologically-relevant model, the Hybrid Excess and Decay (HED) Model, which characterises pulse wave morphology in terms of three underlying pressure waves and a decay function. We show that these parameters capture PPG data with a high degree of precision and, moreover, are sensitive to specific, physiologically-relevant changes within individuals. We present the theoretical and practical basis for the model and demonstrate its performance when applied to a pharmacological dataset of 105 participants receiving intravenous administrations of the sympathomimetic drug isoproterenol (Isoprenaline). We conclude by discussing the possible value in using the HED model to complement standard measures of PPG outputs.

neuroscience↗

bioRxiv2021

Neural indicators of human gut feelings

Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the bodys 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 vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with a more rapid detection of the stimulation and reduced reaction time variability. Stomach stimulation induced early and late neural responses in parieto-occipital leads near the midline. Moreover, these gastric evoked potentials showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. These findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut-brain interactions in healthy and clinical populations.

neuroscience↗

bioRxiv2020

Confirmatory evidence that healthy individuals can adaptively adjust prior expectations and interoceptive precision estimates

Theoretical proposals have previously been put forward regarding the computational basis of interoception. Following on this, we recently reported using an active inference approach to 1) quantitatively simulate interoceptive computation, and 2) fit the model to behavior on a cardiac awareness task. In the present work, we attempted to replicate our previous results in an independent group of healthy participants. We provide evidence confirming our previous finding that healthy individuals adaptively adjust prior expectations and interoceptive sensory precision estimates based on task context. This offers further support for the utility of computational approaches to characterizing the dynamics of interoceptive processing.

neuroscience↗