Biology subjects

Walton, M.

Publications and source records attributed to Walton, M..

5 recordsLinked to original sources

bioRxiv2022

Reward Bases: Instantaneous reward revaluation with temporal difference learning

AO_SCPLOWBSTRACTC_SCPLOWAn influential theory posits that dopaminergic neurons in the mid-brain implement a model-free reinforcement learning algorithm based on temporal difference (TD) learning. A fundamental assumption of this model is that the reward function being optimized is fixed. However, for biological creatures the reward function can fluctuate substantially over time depending on the internal physiological state of the animal. For instance, food is rewarding when you are hungry, but not when you are satiated. While a variety of experiments have demonstrated that animals can instantly adapt their behaviour when their internal physiological state changes, under current thinking this requires model-based planning since the standard model of TD learning requires retraining from scratch if the reward function changes. Here, we propose a novel and simple extension to TD learning that allows for the zero-shot (instantaneous) generalization to changing reward functions. Mathematically, we show that if we assume the reward function is a linear combination of reward basis vectors, and if we learn a value function for each reward basis using TD learning, then we can recover the true value function by a linear combination of these value function bases. This representational scheme allows instant and perfect generalization to any reward function in the span of the reward basis vectors as well as possesses a straightforward implementation in neural circuitry by parallelizing the standard circuitry required for TD learning. We demonstrate that our algorithm can also reproduce behavioural data on reward revaluation tasks, predict dopamine responses in the nucleus accumbens, as well as learn equally fast as successor representations while requiring much less memory.

neuroscience↗

bioRxiv2021

An intrinsic endothelial dysfunction causes cerebral small vessel disease

Small Vessel Disease (SVD) is the leading cause of vascular dementia, causes a quarter of strokes, and worsens stroke outcomes(1, 2). The disease is characterised by cerebral small vessel and white matter pathology, but the underlying mechanisms are poorly understood. Classically, the microvascular and tissue damage has been considered secondary to extrinsic factors, such as hypertension, consisting of microvessel stiffening, impaired vasoreactivity and blood-brain barrier dysfunction identified in human sporadic SVDs. However, increasing evidence points to an underlying vulnerability to SVD-related brain damage, not just extrinsic factors. Here, in a novel normotensive transgenic rat model where the phospholipase flippase Atp11b is deleted, we show pathological, imaging and behavioural changes typical of those in human sporadic SVD, but that occur without hypertension. These changes are due to an intrinsic endothelial cell dysfunction, identified in vessels of the brain white matter and the retina, with pathological evidence of vasoreactivity and blood-brain barrier deficits, which precipitate a secondary maturation block in oligodendroglia and myelin disruption around the small vessels. This highlights that an intrinsic endothelial dysfunction may underlie vulnerability to human sporadic SVD, providing alternative therapeutic targets to prevent a major cause of stroke and dementia.

neuroscience↗

bioRxiv2019

Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques

One of the most influential accounts of central orbitofrontal cortex- that it mediates behavioral flexibility - has been challenged by the finding that discrimination reversal in macaques -the classic test of behavioral flexibility -is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.

neuroscience↗

bioRxiv2018

Time efficient preparation methods for MRI brain scanning in awake young children and factors associated with success

ObjectiveYoung children are often unable to remain still for magnetic resonance imaging (MRI). Various preparation methods have been reported to avoid sedation or anesthesia, with mixed success rates and feasibility. Here we describe a time-efficient preparation method and factors associated with successful scanning in young chdilren.\n\nWe recruited 134 children aged 2.0-5.0 years for an MRI study. Some children completed a training session on a mock scanner, and all children received a 15-20 minute introduction to scanning procedures immediately before their scan. We compared success between children receiving mock scanner training or not, and evaluated demographic or cognitive factors that predicted success.\n\nResults97 children (72%) completed at least one sequence successfully; 64 children provided high-quality data for all 3 sequences. Cognitive scores were higher in successful children, but children who received mock scanner training were less likely to be successful. A case-controlled comparison of children matched on age, gender, and cognitive scores found no differences between children receiving training or not.\n\nWe present a quick method for preparing young children for awake MRI scans. Our data suggests limited advantages of mock scanner preparation for healthy young children, and that cognitive abilities may help predict success.

neuroscience↗

bioRxiv2017

Brain white matter structure and language ability in preschool-aged children

Brain alterations are associated with reading and language difficulties in older children, but little research has investigated relationships between early language skills and brain white matter structure during the preschool period. We studied 68 children aged 3.0-5.6 years who underwent diffusion tensor imaging and participated in assessments of Phonological Processing and Speeded Naming. Tract-based spatial statistics and tractography revealed relationships between Phonological Processing and fractional anisotropy and mean diffusivity in bilateral ventral white matter pathways, the corpus callosum, and corticospinal tracts. The relationships observed in left ventral pathways are consistent with studies in older children, and demonstrate that structural markers for language difficulties are apparent as young as 3 years of age. Our findings in right hemisphere areas that are not as commonly found in adult studies suggest that young children rely on a widespread network for language processing that becomes more specialized with age.

neuroscience↗