Biology subjects

Doyle, H.

Publications and source records attributed to Doyle, H..

4 recordsLinked to original sources

bioRxiv2024

Ramping dissociates motor and cognitive sequences in the parietal and prefrontal cortices

Humans complete different types of sequences as a part of everyday life. These sequences can be divided into two important categories: those that are abstract, in which the steps unfold according to a rule at super-second to minute time scale, and those that are motor, defined solely by individual movements and their order which unfold at the sub-second to second timescale. For example, the sequence of making spaghetti consists of abstract tasks (preparing the sauce and cooking the noodles) and nested motor actions (stir pasta water). Previous work shows neural activity increases (ramps) in the rostrolateral prefrontal (RLPFC) during abstract sequence execution (Desrochers et al., 2015, 2019). During motor sequence production, activity occurs in regions of the prefrontal cortex (Yewbrey et al., 2023). However, it remains unknown if ramping is a signature of motor sequence production as well or solely an attribute of abstract sequence monitoring and execution. We tested the hypothesis that significant ramping activity occurs during motor sequence production in the RLPFC. Contrary to our hypothesis, we did not observe significant ramping activity in the RLPFC during motor sequence production, but we found significant ramping activity in bilateral inferior parietal cortex, in regions distinct from those observed during an abstract sequence task. Our results suggest different prefrontal-parietal circuitry may underlie abstract versus motor sequence execution.

neuroscience↗

bioRxiv2024

Cognitive sequences in obsessive-compulsive disorder are supported by frontal cortex ramping activity and mediated by symptom severity

Completing sequences is a routine part of daily life. Many are abstract, defined by a rule governing the order rather than the identity of individual steps (e.g., getting dressed). In obsessive-compulsive disorder (OCD), excessive ritualistic behaviors suggest a disruption in abstract sequence completion. Executing abstract sequences requires at least two levels in a hierarchy of cognitive control: abstract sequential control (tracking steps) and task switching (shifting between tasks). While task switching has been studied in OCD, little is known in a sequential context. Understanding both hierarchical control types is key to uncovering how abstract sequences with nested task switches are processed in OCD. Previous studies showed that the rostrolateral prefrontal cortex (RLPFC) supports abstract sequence monitoring in healthy individuals with an increase in activity across each sequence, a dynamic known as "ramping". Ramping outside the RLPFC is potentially indicative of other sequence-related processes such as progress towards a goal and increasing working memory load. Therefore, we hypothesized that abstract sequential control deficits would correspond to altered ramping dynamics in RLPFC and other cortical regions. Second, we predicted task switching deficits in OCD, coupled with altered activity in cortical regions canonically implicated in task level control. We found partial support for both hypotheses. Abstract sequential control did not show behavioral differences in OCD but did show increased overall ramping in the anterior cingulate cortex (ACC) and superior frontal sulcus (SFS) and ramping differences in additional, novel cortical regions according to abstract sequence complexity. In contrast, behavioral differences were observed for task switching in OCD without neural differences between the groups. Together, these results suggest a group of areas support sequential control differentially in OCD than in healthy controls, despite behavioral similarity, and that this observation is likely not the result of neural deficits in task switching. These findings thus provide insight into OCD during complex behaviors more similar to daily life where sequence and task level control are intertwined and may inform future potential treatment.

neuroscience↗

bioRxiv2021

Bacteria modulate tamoxifen-induced death via host fatty acid metabolism

Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER-positive breast cancer, but that at high doses kills both ER-positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find that different bacteria dramatically modulate tamoxifen toxicity in C. elegans, with a three-order of magnitude difference between animals fed Escherichia coli, Comamonas aquatica, and Bacillus subtilis. Remarkably, host fatty acid (FA) biosynthesis mitigates tamoxifen toxicity, and different bacteria provide the animal with different FAs, resulting in distinct FA profiles. Surprisingly these bacteria modulate tamoxifen toxicity by different death mechanisms, some of which are modulated by FA supplementation and others by antioxidants. Together, this work reveals a complex interplay between microbiota, FA metabolism and tamoxifen toxicity that may provide a blueprint for similar studies in more complex mammals.

systems biology↗

bioRxiv2018

Taxonomic revision of Leopold and Rudolf Blaschka Glass Models of Invertebrates 1888 Catalogue, with correction of authorities

The glass models of invertebrates crafted by Leopold and Rudolf Blaschka were made between 1863 and 1889. Production ceased when the glassmakers turned their attention to what is now known as the Ware Collection of Blaschka Glass Models of Plants, created for the Harvard Museum of Natural History. Nearly 130 years have passed since their last published catalogue of species in 1888 and the nomenclature they applied is now a confusing mix that includes many junior synonyms and unavailable names. This is an issue for many museums and universities which owns Blaschka models as uncertain identifications may compromised interpretation of this rediscovered legacy. Nowadays, many museums and universities hold collections of those glass invertebrates but misspelled, mislabelled or simply apply the century old taxonomy of 1888. Here, we provide a valuable resource for curators and enthusiasts alike. We studied and updated the final catalogue 1888 from the Blaschkas Dresden-based workshop. We first focused on major taxonomical changes from taxa to species, as well as on an analysis of the acknowledged authorities. We found that only 35.3% of the models retain their original names, while 3.7% lack any known synonym and their identity remains open to interpretation. Finally, two of the authorities listed in the catalogue, Ernst Haeckel and Philip Henry Gosse, were incorrectly acknowledged for an extensive range of models. This study is the first of its kind on the Blaschka collection, and it will help in the identification and naming of Blaschka models worldwide.

scientific communication and education↗