Biology subjects

Mosley, P.

Publications and source records attributed to Mosley, P..

3 recordsLinked to original sources

bioRxiv2022

A snapshot of brain and cognition in healthy mid-life and older adults

Deficits in memory are seen as a canonical sign of ageing and a prodrome to dementia in older adults. However, the nature of cognitive and brain changes across a wider aperture of adulthood is not well known. We quantify the relationship between cognitive function and brain morphology from mid-life to older adulthood, and the influence of age, sex, amyloid and genetic risk for dementia. We analyzed three observational cohorts (PISA, AIBL, ADNI) with cognitive, genetic and neuroimaging measures comprising a total of 1570 healthy mid-life and older adults (mean age 72, range 49-90 years, 1330 males) and 1365 age- and sex-matched adults with mild cognitive impairment or Alzheimers disease. Among healthy adults, we find robust modes of co-variation between regional sulcal width and multidomain cognitive function that change from mid-life to the older age range. The most prominent cortical changes in mid-life are predominantly associated with changes in executive functions, whereas they are most strongly associated with poorer memory function in older age. These cognitive changes are accompanied by an age-dependent pattern of sulcal widening. Amyloid exerts a weak, but significant, influence on cognition, but not on sulcal width. The APOE {varepsilon}4 allele also exerts a weak influence on cognition, but only significantly in the (larger and older) AIBL cohort. These findings provide new insights into brain and cognition in mid-life and older adults, suggesting that cognitive screening in mid-life cohorts should encompass executive functions as well as memory.

neuroscience↗

bioRxiv2019

Left prefrontal connectivity links subthalamic stimulation with depressive symptoms in Parkinson’s disease

ObjectiveSubthalamic nucleus deep brain stimulation (STN-DBS) in Parkinsons Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS which have been reported to improve, worsen or remain unchanged. MethodsDepressive symptoms before and after STN-DBS surgery were documented in 116 PD patients from three DBS centers (Berlin, Queensland, Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTA) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as test-set for which depressive symptom change was predicted. ResultsStructural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity. InterpretationFibers linking the STN electrode with left prefrontal areas predicted worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

neuroscience↗

bioRxiv2018

Subjective estimates of uncertainty and volatility during gambling predict impulsivity after subthalamic deep brain stimulation for Parkinson’s disease

1Subthalamic deep brain stimulation (STN-DBS) for Parkinsons disease may modulate chronometric and instrumental aspects of choice behaviour, including motor inhibition, decisional slowing, and value sensitivity. However, it is not well known whether STN-DBS affects more complex aspects of decision-making, such as the influence of subjective estimates of uncertainty on choices. In this study, thirty-eight participants with Parkinsons disease played a virtual casino prior to subthalamic DBS (whilst on medication) and again, three-months postoperatively (whilst on stimulation). At the group level, there was a small but statistically significant postoperative decrease in impulsivity, as quantified by the Barratt Impulsiveness Scale (BIS). The gambling behaviour of participants (bet increases, slot machine switches and double or nothing gambles) was associated with this self-reported measure of impulsivity. However, there was a large variance in outcome amongst participants, and we were interested in whether individual differences in subjective estimates of uncertainty (specifically, volatility) were related to differences in pre- and postoperative impulsivity. To examine these individual differences, we fit a computational model (the Hierarchical Gaussian Filter, HGF), to choices made during slot machine game play as well as a simpler reinforcement learning model based on the Rescorla-Wagner formalism. The HGF was superior in accounting for the behaviour of our participants, suggesting that participants incorporated beliefs about environmental uncertainty when updating their beliefs about gambling outcome and translating these beliefs into action. A specific aspect of subjective uncertainty, the participants estimate of the tendency of the slot machines winning probability to change (volatility), increased subsequent to DBS. Additionally, the decision temperature of the response model decreased post-operatively, implying greater stochasticity in the belief-to-choice mapping of participants. Model parameter estimates were significantly associated with impulsivity; specifically, increased uncertainty was related to increased postoperative impulsivity. Moreover, changes in these parameter estimates were significantly associated with the maximum post-operative change in impulsivity over a six month follow up period. Our findings suggest that impulsivity in persons with Parkinsons disease may be influenced by subjective estimates of uncertainty (environmental volatility) and implicate a role for the subthalamic nucleus in the modulation of outcome certainty. Furthermore, our work outlines a possible approach to characterising those persons who become more impulsive after subthalamic DBS, an intervention in which non-motor outcomes can be highly variable.

neuroscience↗