Biology subjects

Payne, B.

Publications and source records attributed to Payne, B..

5 recordsLinked to original sources

bioRxiv2024

Low-intensity focused ultrasound to the insula and dorsal anterior cingulate has site-specific and pressure dependent effects on pain during measures of central sensitization

BackgroundThe insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. Objective/HypothesisInvestigate the effect of low-intensity focused ultrasound (LIFU) pressure to the anterior insula (AI), posterior insula (PI) or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). MethodsN = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 minute LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. ResultsLIFU to the PI significantly attenuated pain ratings in both TSP and the CPM protocols. LIFU to the dACC only affected TSP pain ratings. LIFU to AI had no effect on either TSP or CPM pain ratings. LIFU pressure modulated group means but did not affect overall group differences. ConclusionsLIFU to the PI and dACC differentially affected central sensitization. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.

neuroscience↗

bioRxiv2023

Non-invasive modulation of the human dorsal anterior cingulate attenuates acute pain perception and homeostatic cardiovascular responses

Homeostasis is the process of maintaining physiologic balance in the body that is critical for maintaining health and is dysfunctional in several disorders like chronic pain. The dorsal anterior cingulate cortex (dACC) is a critical brain area for homeostatic cardiovascular responses and pain processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for an effect on behavioral and cardiac autonomic responses using a transient heat pain stimulus. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included perceived pain ratings, homeostatic measures including heart-rate variability, blood pressure, EDR response as well as the amplitude of the contact heat-evoked potential (CHEP). LIFU reduced pain ratings by 1.08 {+/-} 0.21 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 25.1% reduction in the N1-P1 CHEP amplitude driven primarily by effects on the P1 amplitude. Our results demonstrate LIFU to the dACC reduces perceived pain and alters homeostatic cardiovascular responses to a transient heat pain stimulus. These results have implications for the causal understanding of human pain and autonomic processing in the dACC and the potential for future therapeutics for pain relief and homeostatic modulation. SIGNIFICANCE STATEMENTNew lines of inquiry now demonstrate cardiac homeostatic signals like heart rate variability (HRV) are aberrant in mental health disorders, addiction, and chronic pain and may contribute to their underlying etiology. The dorsal anterior cingulate cortex (dACC) is a key homeostatic center with direct influences on cardiovascular autonomic function, but its depth precludes direct access without invasive surgery. For the first time in humans, we demonstrate low-intensity focused ultrasound (LIFU) can non-invasively and selectively modulate the dACC to reduce acute pain perception and homeostatic cardiovascular responses as well as pain processing signals. This work helps establish a causal role of the dACC in pain perception and homeostatic signaling with potential future clinical applications in chronic pain and neuropsychological populations.

neuroscience↗

bioRxiv2023

Non-invasive neuromodulation of sub-regions of the human insula differentially affect pain processing and heart-rate variability

The insula is a portion of the cerebral cortex folded deep within the lateral sulcus covered by the overlying opercula of the inferior frontal lobe and superior portion of the temporal lobe. The insula has been parsed into sub-regions based upon cytoarchitectonics and structural and functional connectivity with multiple lines of evidence supporting specific roles for each of these sub-regions in pain processing and interoception. In the past, causal interrogation of the insula was only possible in patients with surgically implanted electrodes. Here, we leverage the high spatial resolution combined with the deep penetration depth of low-intensity focused ultrasound (LIFU) to non-surgically modulate either the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact head evoked potentials (CHEPs) and time-frequency power as well as autonomic measures including heart-rate variability (HRV) and electrodermal response (EDR). N = 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, EDR and EEG recording. LIFU was delivered to either the AI (anterior short gyrus), PI (posterior longus gyrus) or under an inert sham condition time-locked to the heat stimulus. Results demonstrate that single-element 500 kHz LIFU is capable of individually targeting specific gyri of the insula. LIFU to both AI and PI similarly reduced perceived pain ratings but had differential effects on EEG activity. LIFU to PI affected earlier EEG amplitudes around 300 milliseconds whereas LIFU to AI affected EEG amplitudes around 500 milliseconds. In addition, only LIFU to the AI affected HRV as indexed by an increase in standard deviation of N-N intervals (SDNN) and mean HRV low frequency power. There was no effect of LIFU to either AI or PI on EDR or blood pressure. Taken together, LIFU looks to be an effective method to individually target sub-regions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus. These data have implications for the treatment of chronic pain and several neuropsychological diseases like anxiety, depression and addiction that all demonstrate abnormal activity in the insula concomitant with dysregulated autonomic function.

neuroscience↗

bioRxiv2022

The Codon Statistics Database: a Database of Codon Usage Bias

MotivationMost amino acids can be encoded by a set of synonymous codons. Often, for any given amino acid, certain codons are significantly more used than others, a phenomenon known as codon usage bias. The genomes of different species differ in the frequencies at which they use each codon (e.g., a codon that is highly used in one species may be lowly used in another species). In addition, within any given genome, genes differ in their degree of codon bias, with highly expressed genes being more likely to use preferred codons. Knowing the codons that are preferred by a certain genome, and the amount of codon bias exhibited by each gene, has multiple applications (e.g., in heterologous expression, gene prediction, or phylogenetic inference). ResultsWe have developed the Codon Statistics Database, an online database that contains codon usage statistics for all the species with reference or representative genomes in RefSeq. The user can search for any species and access two sets of tables. One set lists, for each codon, the frequency, the Relative Synonymous Codon Usage (RSCU), and whether the codon is preferred. Another set of tables lists, for each gene, its GC content, Effective Number of Codons (ENC), Codon Adaptation Index (CAI), and frequency of optimal codons (Fop). Equivalent tables can be accessed for 1) all nuclear genes, 2) nuclear genes encoding ribosomal proteins, 3) mitochondrial genes and 4) chloroplastic genes (if available in the relevant assembly). The user can also search for any taxonomic group (e.g., "primates") and obtain a table comparing all the species in the group. AvailabilityThe database is free to access without registration at http://codonstatsdb.unr.edu.

bioinformatics↗

bioRxiv2019

Mechanism of processive telomerase catalysis revealed by high-resolution optical tweezers

Telomere maintenance by telomerase is essential for continuous proliferation of human cells and is vital for the survival of stem cells and 90% of cancer cells. To compensate for telomeric DNA lost during DNA replication, telomerase processively adds GGTTAG repeats to chromosome ends by copying the template region within its RNA subunit. Between repeat additions, the RNA template must be recycled. How telomerase remains associated with substrate DNA during this critical translocation step remains unknown. Using a newly developed single-molecule telomerase activity assay utilizing high-resolution optical tweezers, we demonstrate that stable substrate DNA binding at an anchor site within telomerase facilitates the processive synthesis of telomeric repeats. After release of multiple telomeric repeats from telomerase, we observed folding of product DNA into G-quadruplex structures. Our results provide detailed mechanistic insights into telomerase catalysis, a process of critical importance in aging and cancer.

biochemistry↗