Biology subjects

Savill, N.

Publications and source records attributed to Savill, N..

5 recordsLinked to original sources

bioRxiv2025

Diverse ways of holding verbal information in mind revealed with functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation: Individual differences in left anterior parietal cortex

Cognitive neuroscience has identified brain systems that reliably underpin specific abilities, including verbal short-term memory. However, there is no simple mapping between anatomy and function; moreover, brains are differently organised across people. In two functional magnetic resonance imaging studies, and using transcranial magnetic brain stimulation to test causality, we characterised differences in the neural processes supporting verbal short-term memory in healthy participants who varied in their use of semantic information. In group analyses, left anterior inferior parietal cortex showed the expected pattern for a "phonological buffer" -- this site was responsive to phonological tasks and verbal short-term memory for meaningless items. However, the functions of this site differed across the sample; individuals with the strongest "semantic reliance" in short-term memory (showing higher imageability effects and poorer nonword performance) showed weaker phonological responses. They also showed more activation when maintaining meaningful word sequences in short-term memory, compared with nonwords. In these semantically-reliant participants, left anterior inferior parietal cortex showed stronger functional connectivity to limbic and default mode regions during nonword rehearsal. While inhibitory stimulation to phonologically responsive regions disrupted nonwords more than words in people with good phonological short-term memory, these effects were reversed when verbal short-term memory was more semantically reliant. These findings show that left anterior inferior parietal cortex supports the maintenance of different kinds of verbal information across individuals.

neuroscience↗

bioRxiv2023

Single-Molecule Morphology of Topologically Digested Olympic Networks

The kinetoplast DNA (kDNA) is the archetype of a two-dimensional Olympic network, composed of thousands of DNA minicircles and found in the mitochondrion of certain parasites. The evolution, replication and self-assembly of this structure are fascinating open questions in biology that can also inform us how to realise synthetic Olympic networks in vitro. To obtain a deeper understanding of the structure and assembly of kDNA networks, we sequenced the Crithidia fasciculata kDNA genome and performed high-resolution Atomic Force Microscopy (AFM) and analysis of kDNA networks that had been partially digested by selected restriction enzymes. We discovered that these topological perturbations lead to networks with significantly different geometrical features and morphologies with respect to the unperturbed kDNA, and that these changes are strongly dependent on the class of DNA circles targeted by the restriction enzymes. Specifically, cleaving maxicircles leads to a dramatic reduction in network size once adsorbed onto the surface, whilst cleaving both maxicircles and a minor class of minicircles yields non-circular and deformed structures. We argue that our results are a consequence of a precise positioning of the maxicircles at the boundary of the network, and we discuss our findings in the context of kDNA biogenesis, design of artificial Olympic networks and detection of in vivo perturbations.

biophysics↗

bioRxiv2023

When is a slender not a slender? The cell-cycle arrest and scarcity of slender parasites challenges the role of bloodstream trypanosomes in infection maintenance

The development of Trypanosoma brucei in its mammalian host is marked by a distinct morphological change as replicative "slender" forms differentiate into cell-cycle arrested "stumpy" forms in a quorum-sensing dependent manner. Although stumpy forms dominate chronic infections at the population level, the proportion of replicative parasites at the individual cell level and the irreversibility of arrest in the bloodstream is unclear. Here, we experimentally demonstrate that developmental cell cycle arrest is definitively irreversible in acute and chronic infections in mice. Furthermore, analysis of replicative capacity and single-cell transcriptome profiling reveals a temporal hierarchy, whereby cell-cycle arrest and appearance of a stumpy-like transcriptome precedes irreversible commitment and morphological change. Unexpectedly, we show that proliferating parasites are exceptionally scarce in the blood after infections are established. This challenges the ability of bloodstream trypanosomes to sustain infection by proliferation or antigenic variation, these parasites instead being overwhelmingly adapted for transmission.

microbiology↗

bioRxiv2018

Individual differences in reading comprehension and off-task thought relate to perceptually-coupled and decoupled cognition

Although the default mode network (DMN) is associated with off-task states, recent evidence shows it can support tasks. This raises the question of how DMN activity can be both beneficial and detrimental to task performance. The decoupling hypothesis proposes that these opposing states occur because DMN supports modes of cognition driven by external input, as well as retrieval states unrelated to input. To test this account, we capitalised on the fact that during reading, regions in DMN are thought to represent the meaning of words through their coupling with visual cortex; the absence of visual coupling should occur when the attention drifts off from the text. We examined individual differences in reading comprehension and off-task thought while participants read an expository text in the laboratory, and related variation in these measures to (i) the neural response during reading in the scanner (Experiment 1), and (ii) patterns of intrinsic connectivity measured in the absence of a task (Experiment 2). The responsiveness of a region of DMN in middle temporal gyrus (MTG) to orthographic inputs during reading predicted good comprehension, while intrinsic decoupling of the same site from visual cortex at rest predicted more frequent off-task thought. In addition, good comprehension was associated with greater intrinsic connectivity between MTG and medial prefrontal regions also within DMN, demonstrating that DMN coupling can support task performance, not only off-task states. These findings indicate that the opposing roles of DMN in cognition reflect its capacity to support both perceptually-coupled and decoupled cognition.

neuroscience↗

bioRxiv2017

Dynamic semantic cognition: Characterising coherent and controlled conceptual retrieval through time using magnetoencephalography and chronometric transcranial magnetic stimulation

Distinct neural processes are thought to support the retrieval of semantic information that is (i) coherent with strongly-encoded aspects of knowledge, and (ii) non-dominant yet relevant for the current task or context. While the brain regions that support coherent and controlled patterns of semantic retrieval are relatively well-characterised, the temporal dynamics of these processes are not well-understood. This study used magnetoencephalography (MEG) and dual-pulse chronometric transcranial magnetic stimulation (cTMS) in two separate experiments to examine temporal dynamics within the temporal lobe during the retrieval of strong and weak associations. MEG results revealed a dissociation within left temporal cortex: anterior temporal lobe (ATL) showed greater oscillatory response for strong than weak associations, while posterior middle temporal gyrus (pMTG) showed the reverse pattern. In the cTMS experiment, stimulation of ATL at ~150ms disrupted the efficient retrieval of strong associations, indicating a necessary role for ATL in coherent conceptual activations. Stimulation of pMTG at the onset of the second word disrupted the retrieval of weak associations, suggesting this site may maintain information about semantic context from the first word, allowing engagement of semantic control. Together these studies provide converging evidence for a functional dissociation within the temporal lobe, across both tasks and time.

neuroscience↗