Biology subjects

Petitet, P.

Publications and source records attributed to Petitet, P..

5 recordsLinked to original sources

bioRxiv2021

Hypersensitivity to uncertainty is key feature of subjective cognitive impairment

With an increasingly ageing global population, more people are presenting with concerns about their cognitive function, but not all have an underlying neurodegenerative diagnosis. Subjective cognitive impairment (SCI) is a common condition describing self-reported deficits in cognition without objective evidence of cognitive impairment. Many individuals with SCI suffer from depression and anxiety, which have been hypothesised to account for their cognitive complaints. Despite this association between SCI and affective features, the cognitive and brain mechanisms underlying SCI are poorly understood. Here, we show that people with SCI are hypersensitive to uncertainty and that this might be a key mechanism accounting for their affective burden. Twenty-seven individuals with SCI performed an information sampling task, where they could actively gather information prior to decisions. Across different conditions, SCI participants sampled faster and obtained more information than matched controls to resolve uncertainty. Remarkably, despite their urgent sampling behaviour, SCI participants were able to maintain their efficiency. Hypersensitivity to uncertainty indexed by this sampling behaviour correlated with the severity of affective burden including depression and anxiety. Analysis of MRI resting functional connectivity revealed that both uncertainty hypersensitivity and affective burden were associated with stronger insular-hippocampal connectivity. These results suggest that altered uncertainty processing is a key mechanism underlying the psycho-cognitive manifestations in SCI and implicate a specific brain network target for future treatment.

neuroscience↗

bioRxiv2020

GABA relates to functional connectivity changes and retention in visuomotor adaptation

Motor adaptation is fundamental to maintaining accurate movements under changing conditions, but the neurochemical basis of human motor adaptation is not well understood. Here, we used an ultra-high-field MR multimodal acquisition to address the hypothesis that M1 GABA and M1-Cerebellar functional connectivity would relate to retention of adaptation, but not acquisition of adaptation. As such, we demonstrate higher baseline M1 [GABA] relates to greater retention but does not relate to adaptation-acquisition. This relationship is mediated by change in M1-Cerebellar functional connectivity: higher M1 [GABA] relates to a decreased M1-Cerebellar connectivity, resulting in greater retention. These findings showed anatomical, neurochemical and behavioural specificity: As expected, no relationship was found between retention and a control metabolite, retention and connectivity change between control regions and between M1 [GABA] and behaviour in a control condition. The implication of a mechanistic link from neurochemistry to retention advances our understanding of population variability in retention and provides a step towards therapeutic interventions to restore motor abilities.

neuroscience↗

bioRxiv2020

Age-related decline in cortical inhibitory tone strengthens motor memory

Ageing disrupts the finely tuned excitation/inhibition balance (E:I) across cortex, driven by a natural decline in inhibitory tone ({gamma}-amino butyric acid, GABA). This causes functional decrements. However, in young adults, experimentally lowering GABA in sensorimotor cortex enhances adaptation memory. Therefore, using a cross-sectional design, here we tested the hypothesis that as sensorimotor cortical GABA declines naturally with age, adaptation memory would increase, and the former would explain the latter. Results confirmed this prediction. To probe causality, we used brain stimulation to further lower sensorimotor cortical GABA during adaptation. Across individuals, how stimulation changed memory depended on sensorimotor cortical E:I. In those with low E:I, stimulation increased memory; in those with high E:I stimulation reduced memory. Thus, we identify a form of motor memory that improves naturally with age, depends causally on sensorimotor cortex neurochemistry, and may be a potent target for motor skill preservation strategies in healthy ageing and neurore-habilitation.

neuroscience↗

bioRxiv2018

Causal explanation of individual differences in human sensorimotor memory formation

Sensorimotor cortex mediates the formation of adaptation memory. Individuals differ in the rate at which they acquire, retain, and generalize adaptation. We present a mechanistic explanation of the neurochemical and computational causes of this variation in humans. Neuroimaging identified structural, functional and neurochemical covariates of a computational parameter that determines memory persistence. To establish causality, we increased sensorimotor cortex excitability during adaptation, using transcranial direct current stimulation. As predicted, this increased retention. Inter-individual variance in the stimulation-induced E:I increase predicted the computational change, which predicted the memory gain. These relations did not hold, and memory was unchanged, with stimulation applied before adaptation. This cognitive state dependent effect was modulated by the BDNF val66met genetic polymorphism. Memory was enhanced by stimulation in Val/Val carriers only, implicating a mechanistic role for activity-dependent BDNF secretion. Sensorimotor cortex E:I causally determines the time constant of memory persistence, explaining phenotypic variation in adaptation decay.

neuroscience↗

bioRxiv2017

Towards a neuro-computational account of prism adaptation

Prism adaptation has a long history as an experimental paradigm used to investigate the functional and neural processes that underlie sensorimotor control. In the neuropsychology literature, functional explanations of prism adaptation are typically framed within a traditional cognitive psychology box-and-arrow framework that distinguishes putative component functions thought to give rise to behaviour (i.e. strategic control versus spatial realignment). However, this kind of theoretical framework lacks precision and explanatory power. Here, we advocate for a computational framework that offers several advantages: 1) an algorithmic explanatory account of the computations and operations that drive behaviour; 2) expressed in quantitative mathematical terms; 3) embedded within a principled theoretical framework (Bayesian decision theory, state-space modelling); 4) that offers a means to generate and test quantitative behavioural predictions. This computational framework offers a route toward mechanistic explanations of prism adaptation behaviour. Thus it constitutes a conceptual advance compared to the traditional theoretical framework. In this paper, we illustrate how Bayesian decision theory and state-space models offer principled explanations for a range of behavioural phenomena in the field of prism adaptation (e.g. visual capture, magnitude of visual versus proprioceptive realignment, spontaneous recovery and dynamics of adaptation memory). We argue that this explanatory framework offers to advance understanding of the functional and neural mechanisms that implement prism adaptation behaviour, by enabling quantitative tests of hypotheses that go beyond mere descriptive mapping claims that brain area X is (somehow) involved in psychological process Y.

neuroscience↗