Spatial attention in cognitive healthy ageing

In young adults, spatial attention typically manifests in a processing advantage for the left side of space (“pseudoneglect”)(Bowers & Heilman, 1980), whereas older adults tend to display no strongly lateralised bias, or a preference towards the right side of space (Benwell, Thut, Grant, & Harvey, 2014; Schmitz & Peigneux, 2011). However in addition, in recent studies, pseudoneglect has also been found to be maintained into old age (Brooks, Darling, Malvaso, & Della Sala, 2016; Brooks, Sala, & Darling, 2014; Friedrich, Hunter, & Elias, 2018). This suggests that the traditional view of an attenuated spatial asymmetry bias with increasing age may be too simplistic and that the spatial biases observed could be sensitive to a range of influences besides age. In addition, the traditionally observed shifts in spatial asymmetry in older adults have been attributed to neuroanatomical changes in the right hemisphere (with age), however as yet, there is limited evidence linking neurophysiological results to such behavioural shifts. To this end, for older adults, spatial attention research lacks systematic investigation of intra- and inter-task consistency. In the first of the four experiments of this thesis, I built on an earlier study which investigated young adults (Learmonth, Gallagher, Gibson, Thut, & Harvey, 2015, see 2018), and addressed this issue by investigating the magnitude and direction of spatial asymmetry in older adults aged between 60 to 86 years in five commonly used spatial tasks (line bisection, landmark, grey and grating scales and lateralised visual detection). I also compared the obtained spatial biases to a driving task. Results confirmed a stable retest reliability of all spatial tasks across two testing days in older adults. The line bisection and greyscales tasks elicited significant left spatial biases, in accordance with pseudoneglect, while the other tasks showed no significant biases to either side of space. Interestingly, in the driving task a right bias emerged for older adult and was stable across testing sessions. Yet, it failed to correlate with the other spatial measures. In comparison to the young adults’ sample from Learmonth et al. (2015, 2018), only the landmark task was age sensitive. However, none of the task showed significant inter task correlations. This replicates the findings of Learmonth et al. (2015, 2018) for an older age group. So in view of my findings of no significant inter-task correlations, as well as the inconsistent directions of the observed spatial biases for the older adults, I present supporting evidence that pseudoneglect is a multi-component phenomenon and highly task sensitive. Each task may reflect a distinct neural mechanism, likely to be impacted differently by age or other non- spatial modulators. In fact, the influence of other non -spatial modulators on spatial attention was the central topic of the other three experiments presented in Chapters 3 and 4. I employed a dual task paradigm (Chapters 3 and 4) and electroencephalography (EEG) (Chapter 4 only) to investigate behaviourally as well as neurophysiologically if an increase in attentional load has a reducing effect on spatial asymmetry and whether this would be more pronounced with old age. Interestingly, for the last experiment including EEG (Chapter 4) in particular, results showed that although older adults perform similarly well to young adults on a behavioural level, changes are visible on a neuronal level. Specifically, I found that older adults showed an age related reduction in the right hemisphere, for right lateralized targets at the early stages of stimuli processing, indexed by the N1 component, which was absent in young adults. Moreover, the results suggest that older adults used additional neuronal recruitment in the later stages of stimuli processing (P3), to compensate for increased task difficulty and increased resource allocation, likely improving the behavioural results of the older adults so that they were similar to young adults. The work presented in this thesis thus suggest that ageing per se does not result in an attenuated spatial asymmetry (that would be seen as equal to a decline in spatial attention ability). Instead I would argue that, independently of age, a set of underlying non spatial factors (such as load for example) influence the magnitude and direction of spatial asymmetry. In addition, additional neuronal recruitment and intrinsic mechanisms are used in older adults to compensate for possible deficits and this results in maintained performance in this age group

Right-lateralised lane keeping in young and older British drivers

Young adults demonstrate a small, but consistent, asymmetry of spatial attention favouring the left side of space (“pseudoneglect”) in laboratory-based tests of perception. Conversely, in more naturalistic environments, behavioural errors towards the right side of space are often observed. In the older population, spatial attention asymmetries are generally diminished, or even reversed to favour the right side of space, but much of this evidence has been gained from lab-based and/or psychophysical testing. In this study we assessed whether spatial biases can be elicited during a simulated driving task, and secondly whether these biases also shift with age, in line with standard lab-based measures. Data from 77 right-handed adults with full UK driving licences (i.e. prior experience of left-lane driving) were analysed: 38 young (mean age = 21.53) and 39 older adults (mean age = 70.38). Each participant undertook 3 tests of visuospatial attention: the landmark task, line bisection task, and a simulated lane-keeping task. We found leftward biases in young adults for the landmark and line bisection tasks, indicative of pseudoneglect, and a mean lane position towards the right of centre. In young adults the leftward landmark task biases were negatively correlated with rightward lane-keeping biases, hinting that a common property of the spatial attention networks may have influenced both tasks. As predicted, older adults showed no group-level spatial asymmetry on the landmark nor the line bisection task, but they maintained a mean rightward lane position, similar to young adults. The 3 tasks were not inter-correlated in the older group. These results suggest that spatial biases in older adults may be elicited more effectively in experiments involving complex behaviour rather than abstract, lab-based measures. More broadly, these results confirm that lateral biases of spatial attention are linked to driving behaviour, and this could prove informative in the development of future vehicle safety and driving technology

Intra- and inter-task reliability of spatial attention measures in healthy older adults

At present, there is a lack of systematic investigation into intra- and inter-task consistency effects in older adults, when investigating lateralised spatial attention. In young adults, spatial attention typically manifests itself in a processing advantage for the left side of space (“pseudoneglect”), whereas older adults have been reported to display no strongly lateralised bias, or a preference towards the right side. Building on our earlier study in young adults, we investigated older adults, aged between 60 to 86 years, on five commonly used spatial attention tasks (line bisection, landmark, grey and grating scales and lateralised visual detection). Results confirmed a stable test-retest reliability for each of the five spatial tasks across two testing days. However, contrary to our expectations of a consistent lack in bias or a rightward bias, two tasks elicited significant left spatial biases in our sample of older participants, in accordance with pseudoneglect (namely the line bisection and greyscales tasks), while the other three tasks (landmark, grating scales, and lateralised visual detection tasks) showed no significant biases to either side of space. This lack of inter-task correlations replicates recent findings in young adults. Comparing the two age groups revealed that only the landmark task was age sensitive, with a leftward bias in young adults and an eliminated bias in older adults. In view of these findings of no significant inter-task correlations, as well as the inconsistent directions of the observed spatial biases for the older adults across the five tested tasks, we argue that pseudoneglect is a multi-component phenomenon and highly task sensitive. Each task may engage slightly distinct neural mechanisms, likely to be impacted differently by age. This complicates generalisation and comparability of pseudoneglect effects across different tasks, age-groups and hence studies

Non-invasive brain stimulation in Stroke patients (NIBS):A prospective randomized open blinded end-point (PROBE) feasibility trial using transcranial direct current stimulation (tDCS) in post-stroke hemispatial neglect

Up to 80% of people who experience a right-hemisphere stroke suffer from hemispatial neglect. This syndrome is debilitating and impedes rehabilitation. We carried out a clinical feasibility trial of transcranial direct current stimulation (tDCS) and a behavioural rehabilitation programme, alone or in combination, in patients with neglect. Patients >4 weeks post right hemisphere stroke were randomized to 10 sessions of tDCS, 10 sessions of a behavioural intervention, combined intervention, or a control task. Primary outcomes were recruitment and retention rates, with secondary outcomes effect sizes on measures of neglect and quality of life, assessed directly after the interventions, and at 6 months follow up. Of 288 confirmed stroke cases referred (representing 7% of confirmed strokes), we randomized 8% (0.6% of stroke cases overall). The largest number of exclusions (91/288 (34%)) were due to medical comorbidities that prevented patients from undergoing 10 intervention sessions. We recruited 24 patients over 29 months, with 87% completing immediate post-intervention and 67% 6 month evaluations. We established poor feasibility of a clinical trial requiring repeated hospital-based tDCS within a UK hospital healthcare setting, either with or without behavioural training, over a sustained time period. Future trials should consider intensity, duration and location of tDCS neglect interventions

No interaction between tDCS current strength and baseline performance: a conceptual replication

Several recent studies have reported non-linear effects of transcranial direct current stimulation (tDCS), which has been attributed to an interaction between the stimulation parameters (e.g., current strength, duration) and the neural state of the cortex being stimulated (e.g., indexed by baseline performance ability, age) (see Fertonani and Miniussi, 2016). We have recently described one such non-linear interaction between current strength and baseline performance on a visuospatial attention (landmark) task (Benwell et al., 2015). In this previous study, we induced a small overall rightward shift of spatial attention across 38 participants using bi-hemispheric tDCS applied for 20 min (concurrent left posterior parietal (P5) anode and right posterior parietal (P6) cathode) relative to a sham protocol. Importantly, this shift in bias was driven by a state-dependent interaction between current intensity and the discrimination sensitivity of the participant at baseline (pre-stimulation) for the landmark task. Individuals with high discrimination sensitivity (HDS) shifted rightward in response to low- (1 mA) but not high-intensity (2 mA) tDCS, whereas individuals with low discrimination sensitivity (LDS) shifted rightward with high- but not low-intensity stimulation. However, in Benwell et al. (2015) current strength was applied as a between-groups factor, where half of the participants received 1 mA and half received 2 mA tDCS, thus we were unable to compare high and low-intensity tDCS directly within each individual. Here we aimed to replicate these findings using a within-group design. Thirty young adults received 15 min of 1 and 2 mA tDCS, and a sham protocol, each on different days, to test the concept of an interaction between baseline performance and current strength. We found no overall rightward shift of spatial attention with either current strength, and no interaction between performance and current strength. These results provide further evidence of low replicability of non-invasive brain stimulation protocols, and the need for further attempts to replicate the key experimental findings within this field

No Interaction between tDCS Current Strength and Baseline Performance:A Conceptual Replication

Several recent studies have reported non-linear effects of transcranial direct current stimulation (tDCS), which has been attributed to an interaction between the stimulation parameters (e.g., current strength, duration) and the neural state of the cortex being stimulated (e.g., indexed by baseline performance ability, age) (see Fertonani and Miniussi, 2016). We have recently described one such non-linear interaction between current strength and baseline performance on a visuospatial attention (landmark) task (Benwell et al., 2015). In this previous study, we induced a small overall rightward shift of spatial attention across 38 participants using bi-hemispheric tDCS applied for 20 min (concurrent left posterior parietal (P5) anode and right posterior parietal (P6) cathode) relative to a sham protocol. Importantly, this shift in bias was driven by a state-dependent interaction between current intensity and the discrimination sensitivity of the participant at baseline (pre-stimulation) for the landmark task. Individuals with high discrimination sensitivity (HDS) shifted rightward in response to low- (1 mA) but not high-intensity (2 mA) tDCS, whereas individuals with low discrimination sensitivity (LDS) shifted rightward with high- but not low-intensity stimulation. However, in Benwell et al. (2015) current strength was applied as a between-groups factor, where half of the participants received 1 mA and half received 2 mA tDCS, thus we were unable to compare high and low-intensity tDCS directly within each individual. Here we aimed to replicate these findings using a within-group design. Thirty young adults received 15 min of 1 and 2 mA tDCS, and a sham protocol, each on different days, to test the concept of an interaction between baseline performance and current strength. We found no overall rightward shift of spatial attention with either current strength, and no interaction between performance and current strength. These results provide further evidence of low replicability of non-invasive brain stimulation protocols, and the need for further attempts to replicate the key experimental findings within this field