Biology subjects

Bishop, S. J.

Publications and source records attributed to Bishop, S. J..

4 recordsLinked to original sources

bioRxiv2025

Exploring the impact of social relevance on the cortical tracking of speech: viability and temporal response characterisation

Human speech is inherently social. Yet our understanding of the neural substrates underlying continuous speech perception relies largely on neural responses to monologues, leaving substantial uncertainty about how social interactions shape the neural encoding of speech. Here, we bridge this gap by studying how EEG responses to speech change when the input includes a social element. In Experiment 1, we compared the neural encoding of synthesised undirected monologues, directed monologues, and dialogues. In Experiment 2, we extended this by using podcasts, addressing the additional challenges of real speech dialogue, such as dysfluency. Using temporal response function analyses, we show that the presence of a social component strengthens the cortical tracking of the speech envelope, despite identical acoustic properties. Neural responses to synthesised speech showed a strong correlation with those for real speech podcasts, with a stronger alignment emerging for more socially-relevant speech material. In addition, we demonstrate that robust neural indices of sound and lexical-level processing can be derived using real podcast recordings despite the presence of dysfluencies. Finally, we present a simulation to put to the test the robustness of temporal response function analyses under increasing levels of dysfluency. Together, these findings highlighting the impact of social elements in shaping auditory neural processing, providing a framework for future investigation and analysis of social speech listening and speech interaction. Significance StatementHuman speech is rarely produced or processed in a social vacuum. Yet, our understanding of continuous speech neurophysiology mostly comes from experiments involving speech monologues. This study reveals how social context modulates the neural encoding of speech. We directly contrast neural signals recorded when participants listened to monologues and dialogues, using controlled material from speech synthesis and real podcast recordings. We found that the social element amplifies the neural encoding of speech features, reflecting greater engagement. We also show strong correlation between synthetic and real podcast neural responses, scaling with social relevance. Finally, we demonstrate that lexical processing can be measured robustly even amid natural dysfluencies. These insights advance our understanding of speech neurophysiology, informing future research on social speech.

neuroscience↗

bioRxiv2025

Dual process impairments in reinforcement learning and working memory systems underlie learning deficits in physiological anxiety

Anxiety has been robustly linked to deficits in frontal executive function including working memory (WM) and attentional control processes. However, although anxiety has also been associated with impaired performance on learning tasks, computational investigations of reinforcement learning (RL) impairment in anxiety have yielded mixed results. WM processes are known to contribute to learning behavior in parallel to RL processes and to modulate the effective learning rate as a function of load. However, WM processes have typically not been modeled in investigations of anxiety and RL. In the current study, we leveraged an experimental paradigm (RLWM) which manipulates the relative contributions of WM and RL processes in a reinforcement learning and retention task using multiple stimulus set sizes. Using a computational model of interactive RL and WM processes, we investigated whether individual differences in physiological or cognitive anxiety impacted task performance via deficits in RL or WM. Elevated physiological, but not cognitive, anxiety scores were strongly associated with worse performance during learning and retention testing across all set sizes. Computationally, higher physiological anxiety scores were significantly related to reduced learning rate and increased rate of WM decay. To highlight the importance of modeling WM contributions to learning, we considered the effect of fitting RL models without WM modules to the data. Here we found that reduced learning performance for higher physiological anxiety was at least partially misattributed to stochastic decision noise in 9 out of 10 RL-only models considered. These findings reveal a dual-process impairment in learning in anxiety that is linked to a more physiological than cognitive anxiety phenotype. More broadly, this work also points to the importance of accounting for the contribution of WM to RL when investigating psychopathology-related deficits in learning.

neuroscience↗

bioRxiv2022

Identification of KNX-002, a novel inhibitor of Toxoplasma motility targeting the Class XIV myosin, TgMyoA

Toxoplasma gondii is a widespread apicomplexan parasite that can cause severe disease in its human hosts. The ability of T. gondii and other apicomplexan parasites to invade into, egress from, and move between cells of the hosts they infect is critical to parasite virulence and disease progression. An unusual and highly conserved parasite myosin motor (TgMyoA) plays a central role in T. gondii motility. The goal of this work was to test whether pharmacological inhibition of TgMyoA can alter disease progression in an animal model of infection. To this end, we sought to identify small molecule inhibitors of TgMyoA by screening a collection of 50,000 structurally diverse small molecules for inhibitors of the recombinant motors actin-activated ATPase activity. The top hit to emerge from the screen, KNX-002, inhibited TgMyoA with little to no effect on any of the vertebrate myosins tested. KNX-002 was also active against parasites, inhibiting parasite motility and growth in culture in a dose-dependent manner. We used chemical mutagenesis, selection in KNX-002, and targeted sequencing to identify a mutation in TgMyoA (T130A) that renders the recombinant motor less sensitive to compound. Compared to wild-type parasites, parasites expressing the T130A mutation showed reduced sensitivity to KNX-002 in motility and growth assays, confirming TgMyoA as a biologically relevant target of KNX-002. Finally, KNX-002 was shown to slow disease progression in mice infected with wild-type parasites, but not parasites expressing the resistance-conferring TgMyoA T130A mutation. These data demonstrate the specificity of KNX-002 for TgMyoA, both in vitro and in vivo, and validate TgMyoA as a druggable target for toxoplasmosis. Since TgMyoA is essential for virulence, conserved in apicomplexan parasites, and distinctly different from the myosins found in humans, pharmacological inhibition of MyoA offers a promising new approach to treating the devastating diseases caused by T. gondii and other apicomplexan parasites.

microbiology↗

bioRxiv2020

Executive modulation of brain reward systems endows goals with value

People often learn from the outcomes of their actions, even when these outcomes do not involve material rewards or punishments. How does our brain provide this flexibility? We combined behavior, computational modeling, and functional neuroimaging to probe whether learning from transient goals harnesses the same circuitry that supports learning from secondary reinforcers. Behavior and neuroimaging revealed that "one-shot" transient goals (abstract fractal images seen once) can act as a substitute for rewards during instrumental learning, and produce reliable reward-like signals in dopaminergic reward circuits. Moreover, we found evidence that prefrontal correlates of executive control may play a role in shaping these responses in reward circuits. These results suggest that learning from abstract goal outcomes is supported by an interplay between high-level representations in prefrontal cortex and low-level responses in subcortical reward circuits. This interaction may allow humans to perform reinforcement learning over flexible, arbitrarily abstract reward functions.

neuroscience↗