Biology subjects

Sweeney, J.

Publications and source records attributed to Sweeney, J..

5 recordsLinked to original sources

bioRxiv2024

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

neuroscience↗

bioRxiv2021

Brain-wide neural co-activations in resting human

Spontaneous neural activity in human as assessed with resting-state functional magnetic resonance imaging (fMRI) exhibits brain-wide coordinated patterns in the frequency of <0.1Hz. However, fast brain-wide networks at the timescales of neuronal events (milliseconds to sub-seconds) and their spatial, spectral, and propagational characteristics remain unclear due to the temporal constraints of hemodynamic signals. With milli-second resolution and whole-head coverage, scalp-based electroencephalography (EEG) provides a unique window into brain-wide networks with neuronal-timescale dynamics, shedding light on the organizing principles of brain function. Using state-of-the-art signal processing techniques, we reconstructed cortical neural tomography from resting-state EEG and extracted component-based co-activation patterns (cCAPs). These cCAPs revealed brain-wide intrinsic networks and their dynamics, indicating the configuration/reconfiguration of resting human brains into recurring and propagating functional states, which are featured with the prominent spatial phenomena of global patterns and anti-state pairs of co-(de)activations. Rich oscillational structures across a wide frequency band (i.e., 0.6Hz, 5Hz, and 10Hz) were embedded in the dynamics of these functional states. We further identified a superstructure that regulated between-state propagations and governed a significant aspect of brain-wide network dynamics. These findings demonstrated how resting-state EEG data can be functionally decomposed using cCAPs to reveal rich structures of brain-wide human neural activations.

neuroscience↗

bioRxiv2019

Inspiratory muscle training in young, race-fit Thoroughbred racehorses during a period of detraining

Although inspiratory muscle training (IMT) is reported to improve inspiratory muscle strength in humans little has been reported for horses. We tested the hypothesis that IMT would maintain and/or improve inspiratory muscle strength variables measured in Thoroughbreds during detraining. Thoroughbreds from one training yard were placed into a control (Con, n=3 males n=7 females; median age 2.2{+/-}0.4 years) or treatment group (Tr, n=5 males, n=5 females; median age 2.1{+/-}0.3 years) as they entered a detraining period at the end of the racing/training season. The Tr group underwent eight weeks of IMT twice a day, five days per week using custom-made training masks with resistance valves and an incremental threshold of breath-loading protocol. An inspiratory muscle strength test to fatigue using an incremental threshold of breath-loading was performed in duplicate before (T0) and after four (T1) and eight weeks (T2) of IMT/no IMT using a custom-made testing mask and a commercial testing device. Inspiratory measurements included the total number of breaths achieved during the test, average load, peak power, peak volume, peak flow, energy and the mean peak inspiratory muscle strength index (IMSi). Data was analysed using a linear mixed effects model, P[≤]0.05 significant. There were no differences for inspiratory measurements between groups at T0. Compared to T0, the total number of breaths achieved (P=0.02), load (P=0.003) and IMSi (P=0.01) at T2 had decreased for the Con group while the total number of breaths achieved (P<0.001), load (P=0.03), volume (P=0.004), flow (P=0.006), energy (P=0.01) and IMSi (P=0.002) had increased for the Tr group. At T2 the total number of breaths achieved (P<0.0001), load (P<0.0001), volume (P=0.02), energy (P=0.03) and IMSi (P<0.0001) were greater for the Tr than Con group. In conclusion, our results support that IMT can maintain and/or increase aspects of inspiratory muscle strength for horses in a detraining programme.

physiology↗

bioRxiv2019

Prolonged oral coenzyme Q10-β-cyclodextrin supplementation increases plasma CoQ10 concentration and skeletal muscle complex I+III activity in young, untrained healthy Thoroughbreds

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transport chain (ETC). Decreased skeletal muscle CoQ10 content may result in decreased ETC activity and energy production. This study aimed to test the hypothesis that prolonged supplementation with oral CoQ10 will increase plasma CoQ10 concentrations and skeletal muscle CoQ10 content in young, healthy untrained Thoroughbreds. Nineteen Thoroughbreds (27.5{+/-}9.7 months old; 11 males, 8 females) from one farm and maintained on a grass pasture with one grain meal per day were supplemented orally once per day for 9 weeks with 1.5 mg/kg body weight of a CoQ10-{beta}-cyclodextrin inclusion complex. Whole-blood and skeletal muscle biopsies were collected before (T0) and after (T1) 9 weeks of supplementation. Plasma CoQ10 concentrations were determined via high-performance liquid chromatography. Skeletal muscle mitochondrial ETC combined complex I+III enzyme activity (an indirect measurement of CoQ10 content) was assessed spectrophotometrically and normalised to mitochondrial abundance. Results were analysed using a paired two-tailed Students t-test with P[≤]0.05 significant. Horses accepted supplementation with no adverse effects. The mean change in plasma CoQ10 concentration from T0 to T1 was significantly greater than zero (0.13{+/-}0.02 vs. 0.25{+/-}0.03 {micro}g/ml, mean difference 0.12{+/-}0.03; P=0.004), although variability in absorbance resulted in only a 58% response rate. The mean change in skeletal muscle complex I+III activity from T0 to T1 was significantly greater than zero (0.36{+/-}0.04 vs. 0.59{+/-}0.05 pmol/min/mg of muscle, mean difference 0.23{+/-}0.05; P=0.0004), although T1 values for 3/19 horses decreased on average by 23% below T0 values. In conclusion, prolonged oral supplementation of the diet of young, healthy untrained Thoroughbreds with CoQ10 increased mean plasma CoQ10 concentration by 99% and mean skeletal muscle complex I+III activity by 65% with variability in absorbance among horses. Additional research is warranted investigating training and exercise effects on skeletal muscle CoQ10 content in CoQ10 supplemented and un-supplemented Thoroughbreds.

biochemistry↗

bioRxiv2017

Common variants of NRXN1, LRP1B and RORA are associated with increased ventricular volumes in psychosis - GWAS findings from the B-SNIP deep phenotyping study

Schizophrenia, Schizoaffective, and Bipolar Disorders share common illness traits, intermediate phenotypes and a partially overlapping polygenic basis. We performed GWAS on deep phenotyping data, including structural MRI and DTI, clinical, and behavioral scales from 1,115 cases and controls. Significant associations were observed with two cerebrospinal fluid volumes: the temporal horn of left lateral ventricle was associated with NRXN1, and the volume of the cavum septum pellucidum was associated with LRP1B and RORA. Both volumes were associated with illness. Suggestive associations were observed with local gyrification indices, fractional anisotropy and age at onset. The deep phenotyping approach allowed unexpected genetic sharing to be found between phenotypes, including temporal horn of left lateral ventricle and age at onset.

genetics↗