James M. Shine

Jaan Aru, Matthew Larkum, James M. Shine

Interactions with large language models have led to the suggestion that these models may soon be conscious. From the perspective of neuroscience, this position is difficult to defend. For one, the inputs to large language models lack the embodied, embedded information content characteristic of our sensory contact with the world around us. Secondly, the architecture of large language models is missing key features of the thalamocortical system that have been linked to conscious awareness in mammals. Finally, the evolutionary and developmental trajectories that led to the emergence of living conscious organisms arguably have no parallels in artificial systems as envisioned today. The existence of living organisms depends on their actions, and their survival is intricately linked to multi-level cellular, inter-cellular, and organismal processes culminating in agency and consciousness.

Yifei Sun, James M. Shine, Robert D. Sanders et al.

The white matter of the brain is organised into axonal bundles that support long-range neural communication. Although diffusion MRI (dMRI) enables detailed mapping of these pathways through tractography, how white matter pathways directly facilitate large-scale neural synchronisation remains poorly understood. We developed a data-driven framework that integrates dMRI and functional MRI (fMRI) to model the dynamic coupling supported by white matter tracks. Specifically, we employed track dynamic functional connectivity (Track-DFC) to characterise functional coupling of remote grey matter connected by individual white matter tracks. Using independent component analysis followed by k-medoids clustering, we derived functionally-coherent clusters of white matter tracks from the Human Connectome Project young adult cohort. When applied to the HCP ageing cohort, these clusters exhibited widespread age-related declines in both functional coupling strength and temporal variability. Importantly, specific clusters encompassing pathways linking control, default mode, attention, and visual systems significantly mediated the relationship between age and cognitive performance. Together, these findings depict the functional organisation of white matter tracks and provide a powerful tool to study brain ageing and cognitive decline.

Alejandro Rodriguez-Garcia, Christopher J. Whyte, Brandon R. Munn et al.

Biological and artificial learning systems alike confront the plasticity-stability dilemma. In the brain, neuromodulators such as acetylcholine and noradrenaline relieve this tension by tuning neuronal gain and inhibitory gating, balancing segregation and integration of circuits. Fed by dense cholinergic and noradrenergic projections from the ascending arousal system, layer-5 pyramidal neurons in the cerebral cortex offer a relevant substrate for understanding these dynamics. When distal dendritic signals coincide with back-propagating action potentials, calcium plateaus turn a single somatic spike into a high-gain burst, and interneuron inhibition sculpts the output. These properties make layer-5 cells gain-tunable amplifiers that translate neuromodulatory cues into flexible cortical activity. To capture this mechanism we developed a two-compartment Izhikevich model for pyramidal neurons and single-compartment somatostatin (SOM) and parvalbumin (PV) interneurons, linked by Gaussian connectivity and spike-timing-dependent plasticity (STDP). The soma and apical dendrite are so coupled that somatic spikes back-propagate, while dendritic plateaus can switch the soma from regular firing to bursting by shifting reset and adaptation variables. We show that stronger dendritic drive or tighter coupling raise gain by increasing the likelihood of calcium-triggered somatic bursts. In contrast, dendritic-targeted inhibition suppresses gain, while somatic-targeted inhibition raises the firing threshold of neighboring neurons, thus gating neurons output. Notably, bursting accelerates STDP, supporting rapid synaptic reconfiguration and flexibility. This suggests that brief gain pulses driven by neuromodulators could serve as an adaptive two-timescale optimization mechanism, effectively modulating the synaptic weight updates.