Biology subjects

Finch, A.

Publications and source records attributed to Finch, A..

5 recordsLinked to original sources

bioRxiv2025

Hemispheric laterality of the putamen predicts pseudoneglect

Healthy individuals tend to exhibit a subtle leftward attentional bias, a phenomenon termed pseudoneglect. While this bias is thought to reflect a right-hemisphere dominance when allocating spatial attention, the contribution of subcortical structures remains poorly understood. Although lesion and neuroimaging studies in clinical populations have implicated asymmetries in the basal ganglia and thalamus to dysfunction in spatial attention, it remains unclear whether naturally occurring subcortical asymmetries in healthy individuals predict behavioural biases in spatial attention. In this study, we investigated whether volumetric asymmetries in subcortical structures are associated with biases in spatial attention in a non-clinical population. This was achieved by using the landmark task to assess spatial biases, alongside acquiring T1-weighted MRI data from 44 healthy participants. The subcortical regions were segmented using the FIRST algorithm to estimate the volumetric asymmetry of specific regions. We found that variability in pseudoneglect was predicted by the degree of leftward lateralisation of putamen volume, indicating that the putamen contributes to the magnitude of spatial attention biases. This also suggests that the left putamen may support right-hemisphere neocortical dominance through the indirect pathway. These findings bridge anatomical and behavioural measures, highlighting the functional relevance of subcortical asymmetry in shaping attentional processes in the healthy brain. Our findings pave the way for early diagnosis of neurological disorders associated with subcortical atrophies including Parkinsons Disease and dementia. Significance StatementHemispheric dominance in cortical networks shape attentional biases, but the role of subcortical structures remains poorly understood. Here we show that natural variability in the lateralisation of the putamen predicts individual differences in pseudoneglect--a subtle leftward bias in spatial attention observed in healthy adults. Using MRI and psychophysics, we demonstrate that greater leftward putamen asymmetry is associated with stronger leftward bias, independent of eye dominance and microsaccadic behaviour, and moderated by handedness. These findings reveal a structural subcortical basis for attentional asymmetries and suggest that simple behavioural measures could serve as non-invasive markers of early subcortical changes relevant to disorders such as Parkinsons disease, Alzheimers disease, and ADHD.

neuroscience↗

bioRxiv2023

Accommodation and wavelength: the effect of longitudinal chromatic aberration on the stimulus-response curve.

The longitudinal chromatic aberration (LCA) of the eye creates a chromatic blur on the retina that is an important cue for accommodation. While this mechanism can work optimally in broadband illuminants such as daylight, it is not clear how the system responds to the narrowband illuminants used by many modern displays. Here, we measured pupil and accommodative responses as well as visual acuity under narrowband LED illuminants of different peak wavelengths. Observers were able to accommodate under narrowband light and compensate for the LCA of the eye, with no difference in the variability of the steady-state accommodation response between narrowband and broadband illuminants. Intriguingly, our subjects compensated more fully for LCA at nearer distances. That is, the difference in accommodation to different wavelengths became larger when the object was placed nearer the observer, causing the slope of the accommodation response curve to become shallower for shorter wavelengths and steeper for longer ones. Within the accommodative range of observers, accommodative errors were small and visual acuity normal. When comparing between illuminants, when accommodation was accurate, visual acuity was worst for blue narrowband light. This cannot be due to the sparser spacing for S-cones, since our stimuli had equal luminance and thus activated M-cones roughly equally. It is likely because ocular LCA changes more rapidly at shorter wavelength, and so the finite spectral bandwidth of LEDs corresponds to a greater dioptric range at shorter wavelengths. This effect disappears for larger accommodative errors, due to the increased depth-of-focus of the eye.

physiology↗

bioRxiv2020

Default Mode Network Ventral Hub Connectivity Associated with Memory Impairment in Temporal Lobe Epilepsy Surgery

In patients undergoing surgery for intractable temporal lobe epilepsy, the relationship between the default mode network and patients neurocognitive outcome remains unclear. The objective of this study is to employ non-invasive network mapping to identify the relationship between subdivisions of the default mode network and neurocognitive function before and after epilepsy surgery in patients with temporal lobe epilepsy. Twenty-seven medically patients with medically refractory temporal lobe epilepsy were prospectively enrolled and received resting state functional MRI and neuropsychological testing both pre- and post-operatively. Connectivity within the default mode network was modeled and average connectivity within the networks was calculated. Higher pre-operative connectivity in the ventral default mode network hub correlated with impaired baseline performance in a visual memory task. Post-operatively, a decrease in ventral but not dorsal default mode network connectivity was correlated with a deterioration of verbal and logical memory after surgery. Overall, higher connectivity in the ventral default mode network hub was associated with poor memory function in patients with temporal lobe epilepsy both before and after temporal lobe surgery. Pre-operatively, higher ventral connectivity was associated with worse visual function. Post-operatively, decreased connectivity of the ventral and dorsal default mode network was correlated with a greater decrease in logical and verbal memory when compared with the pre-operation baseline. An imbalance in default mode network connectivity towards the ventral stream and more widespread epilepsy networks may be used to predict memory impairments following surgical intervention and may lead to more tailored surgical decision making based on this non-invasive network modeling.

neuroscience↗

bioRxiv2020

The hepatic compensatory response to elevated systemic sulfide impairs medium chain fat oxidation and promotes diabetes

Impaired hepatic glucose and lipid metabolism are hallmarks of type-2 diabetes. Increased sulfide production from cysteine, or sulfide-donor compounds, may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver-enriched mitochondrial SOP enzyme thiosulfate sulfur-transferase (Tst-/- mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia and fatty liver, despite whole-body insulin-sensitisation. Unexpectedly, hepatic sulfide levels were normal in Tst-/- mice, a result of homeostatic induction of mitochondrial sulfide disposal and glutathione excretion associated with net suppression of protein persulfidation and nuclear respiratory factor-2 target proteins. Proteomic and persulfidomic profiling converged on gluconeogenesis and hepatic lipid metabolism and revealed a selective deficit in medium-chain fatty acid oxidation in Tst-/- mice. We reveal a critical role for TST in hepatic metabolism that raises implications for sulfide-donor strategies in the context of liver function and metabolic disease.

physiology↗

bioRxiv2018

Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence

Cellular senescence is triggered by diverse stimuli and is characterised by long-term growth arrest and secretion of cytokines and chemokines (termed the SASP - senescence-associated secretory phenotype). Senescence can be organismally beneficial as it can prevent the propagation of damaged or mutated clones and stimulate their clearance by immune cells. However, it has recently become clear that senescence also contributes to the pathophysiology of aging through the accumulation of damaged cells within tissues. Here we describe that inhibition of the reaction catalysed by LSG1, a GTPase involved in the biogenesis of the 60S ribosomal subunit, leads to a robust induction of cellular senescence. Perhaps surprisingly, this was not due to ribosome depletion or translational insufficiency, but rather through perturbation of endoplasmic reticulum (ER) homeostasis and a dramatic upregulation of the cholesterol biosynthesis pathway. This cholesterol/ER signature is shared with several other forms of senescence and contributes to the cell cycle arrest in oncogene-induced senescence (OIS). Furthermore, targetting of LSG1 resulted in amplification of the cholesterol/ER signature and restoration of a robust cellular senescence response in transformed cells, suggesting potential therapeutic uses of LSG1 inhibition.

cancer biology↗