Mitigating the impact of air pollution on dementia and brain health: Setting the policy agenda.

BACKGROUND: Emerging research suggests exposure to high levels of air pollution at critical points in the life-course is detrimental to brain health, including cognitive decline and dementia. Social determinants play a significant role, including socio-economic deprivation, environmental factors and heightened health and social inequalities. Policies have been proposed more generally, but their benefits for brain health have yet to be fully explored. OBJECTIVE AND METHODS: Over the course of two years, we worked as a consortium of 20+ academics in a participatory and consensus method to develop the first policy agenda for mitigating air pollution's impact on brain health and dementia, including an umbrella review and engaging 11 stakeholder organisations. RESULTS: We identified three policy domains and 14 priority areas. Research and Funding included: (1) embracing a complexities of place approach that (2) highlights vulnerable populations; (3) details the impact of ambient PM2.5 on brain health, including current and historical high-resolution exposure models; (4) emphasises the importance of indoor air pollution; (5) catalogues the multiple pathways to disease for brain health and dementia, including those most at risk; (6) embraces a life course perspective; and (7) radically rethinks funding. Education and Awareness included: (8) making this unrecognised public health issue known; (9) developing educational products; (10) attaching air pollution and brain health to existing strategies and campaigns; and (11) providing publicly available monitoring, assessment and screening tools. Policy Evaluation included: (12) conducting complex systems evaluation; (13) engaging in co-production; and (14) evaluating air quality policies for their brain health benefits. CONCLUSION: Given the pressing issues of brain health, dementia and air pollution, setting a policy agenda is crucial. Policy needs to be matched by scientific evidence and appropriate guidelines, including bespoke strategies to optimise impact and mitigate unintended consequences. The agenda provided here is the first step toward such a plan.

Maximizing Telerehabilitation for Patients With Visual Loss After Stroke: Interview and Focus Group Study With Stroke Survivors, Carers, and Occupational Therapists.

BACKGROUND: Visual field defects are a common consequence of stroke, and compensatory eye movement strategies have been identified as the most promising rehabilitation option. There has been a move toward compensatory telerehabilitation options, such as the Durham Reading and Exploration (DREX) training app, which significantly improves visual exploration, reading, and self-reported quality of life. OBJECTIVE: This study details an iterative process of liaising with stroke survivors, carers, and health care professionals to identify barriers and facilitators to using rehabilitation tools, as well as elements of good practice in telerehabilitation, with a focus on how the DREX package can be maximized. METHODS: Survey data from 75 stroke survivors informed 12 semistructured engagement activities (7 focus groups and 5 interviews) with 32 stroke survivors, 10 carers, and 24 occupational therapists. RESULTS: Thematic analysis identified key themes within the data. Themes identified problems associated with poststroke health care from both patients' and occupational therapists' perspectives that need to be addressed to improve uptake of this rehabilitation tool and telerehabilitation options generally. This included identifying additional materials or assistance that were required to boost the impact of training packages. The acute rehabilitation setting was an identified barrier, and perceptions of technology were considered a barrier by some but a facilitator by others. In addition, 4 key features of telerehabilitation were identified: additional materials, the importance of goal setting, repetition, and feedback. CONCLUSIONS: The data were used to try to overcome some barriers to the DREX training and are further discussed as considerations for telerehabilitation in general moving forward.

Near and far space: Understanding the neural mechanisms of spatial attention.

Visuospatial neglect is a multicomponent syndrome, and one dissociation reported is between neglect for near (peripersonal) and far (extrapersonal) space. Owing to patient heterogeneity and extensive lesions, it is difficult to determine the precise neural mechanisms underlying this dissociation using clinical methodology. In this study, transcranial magnetic stimulation was used to examine the involvement of three areas in the undamaged brain, while participants completed a conjunction search task in near and far space. The brain areas investigated were right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), each of which has been implicated in visuospatial processing. The results revealed a double dissociation, whereby rPPC was involved for search in near space only, whilst rVO only became necessary when the task was completed in far space. These data provide clear evidence for a dorsal and ventral dissociation between the processing of near and far space, which is compatible with the functional roles previously attributed to the two streams. For example, the involvement of the dorsal stream in near space reflects its role in vision for action, because it is within this spatial location that actions can be performed. The results also revealed that rFEF is involved in the processing of visual search in both near and far space and may contribute to visuospatial attention and/or the control of eye-movements irrespective of spatial frame. We discuss our results with respect to their clear ramifications for clinical diagnosis and neurorehabilitation.

Modulation of cortical excitability can speed up blindsight but not improve it.

Blindsight has been widely investigated and its properties documented. One property still debated and contested is the puzzling absence of phenomenal visual percepts of visual stimuli that can be detected with perfect accuracy. We investigated the possibility that phenomenal visual percepts of exogenous visual stimuli in patient GY might be induced by using transcranial direct current stimulation. High contrast and low contrast stimuli were presented as a moving grating in his blind hemifield. When left area MT/V5 was anodally stimulated during the presentation of high-contrast gratings, he never reported a phenomenal percept of a moving grating but showed perfect blindsight performance. When applied along with low contrast gratings, for which accuracy was titrated to 60-70 %, performance did not improve but responses were significantly faster. Cathodal stimulation had no effect. Results are explained in the framework of GY's reorganized cortical connexions and oscillatory patterns known to be involved in awareness in GY. The apparent presence of phenomenal visual percepts in earlier studies is shown to be a semantic confusion about what he means when he says that he sees in his blind field.

Uncovering the social determinants of brain injury rehabilitation.

Social determinants of health (SDH), such as social isolation and loneliness, are often more frequently experienced in brain injury survivors. The paper explores the personal experiences of loneliness among brain injury survivors during lockdown to negate health inequalities and improve rehabilitation for this population in the future. Twenty-four brain injury survivors participated in semi-structured interviews and questionnaires relating to loneliness, resilience and wellbeing. Three themes (the experience of loneliness, loneliness during the pandemic and loneliness after the pandemic) explored survivors' experiences of loneliness generally post-brain injury, but also chronicle how these feelings developed in lockdown and survivors' feelings regarding society returning to 'normal'. Future interventions should focus on reframing survivors' beliefs regarding societal expectations and minimise the pressure they experience to keep up with their peers physically and emotionally. Additionally, we recommend creating accessible peer support options for all brain injury survivors as an important step for alleviating loneliness.

Inhibition of return impairs phosphene detection.

Efficient visual exploration requires the ability to select possible target locations via spatial attention and to deselect previously inspected locations via inhibition of return (IOR). Although a great deal is known about the effects of spatial attention on processing in visual cortex, much less is known about the effects of IOR on early visual areas. One possibility is that IOR acts in an opposite way to spatial attention, such that, whereas spatial attention enhances target related neural signals in visual cortex, IOR suppress target-related signals. Using a novel dual-coil TMS protocol, we found that IOR reduced the probability of detecting a TMS-induced phosphene in extrastriate cortex (V5). Specifically, a nonpredictive spatial precue presented 500 or 800 msec before stimulation significantly reduced the probability of detecting a phosphene when the precue appeared contralaterally to the site of stimulation (i.e., ipsilaterally to the potential location of the phosphene), compared with ipsilaterally or centrally presented cues. This result demonstrates that IOR facilitates visual exploration by directly affecting the strength of target-related signals in extrastriate visual cortex. This result is consistent with neurophysiological models of attention, which postulate that IOR modulates perception by biasing competition between sensory representations.

The effects of induced optical blur on visual search performance and training.

Visual search is a task often used in the rehabilitation of patients with cortical and non-cortical visual pathologies such as visual field loss. Reduced visual acuity is often comorbid with these disorders, and it remains poorly defined how low visual acuity may affect a patient's ability to recover visual function through visual search training. The two experiments reported here investigated whether induced blurring of vision (from 6/15 to 6/60) in a neurotypical population differentially affected various types of feature search tasks, whether there is a minimal acceptable level of visual acuity required for normal search performance, and whether these factors affected the degree to which participants could improve with training. From the results, it can be seen that reducing visual acuity did reduce search speed, but only for tasks where the target was defined by shape or size (not colour), and only when acuity was worse than 6/15. Furthermore, searching behaviour was seen to improve with training in all three feature search tasks, irrespective of the degree of blurring that was induced. The improvement also generalised to a non-trained search task, indicating that an enhanced search strategy had been developed. These findings have important implications for the use of visual search as a rehabilitation aid for partial visual loss, indicating that individuals with even severe comorbid blurring should still be able to benefit from such training.

Mental Health and Wellbeing of Retired Elite and Amateur Rugby Players and Non-contact Athletes and Associations with Sports-Related Concussion: The UK Rugby Health Project.

BACKGROUND: Concerns have intensified over the health and wellbeing of rugby union and league players, and, in particular, about the longer-term effects of concussion. The purpose of this study was to investigate whether there were differences in mental health, sleep and alcohol use between retired elite and amateur rugby code players and non-contact athletes, and to explore associations with sports-related concussion. METHODS: 189 retired elite (ER, n = 83) and amateur (AR, n = 106) rugby code players (rugby union n = 145; rugby league n = 44) and 65 former non-contact athletes (NC) were recruited to the UK Rugby Health Project between 2016 and 2018. Details on sports participation and concussion history were obtained by questionnaire, which also included questions on mental health, anger, sleep, mood, alcohol use, social connections and retirement from injury. Data were compared between sports groups (ER, AR and NC), between exposure of three or more or five or more concussions and for years in sport. RESULTS: ER reported more concussions than AR (5.9 ± 6.3 vs. 3.7 ± 6.3, p = 0.022) and NC (0.4 ± 1.0, p < 0.001). ER had a higher overall negative mental health score (indicating poor mental health) than AR (10.4 ± 6.3 vs. 7.4 ± 6.5, d = 0.47, p = 0.003) and NC (7.1 ± 4.8, d = 0.57, p = 0.006) and a lower overall positive score (indicating good mental health) than NC (8.9 ± 4.1 vs. 10.7 ± 3.4, d = 0.46, p = 0.021). Negative scores were highest and positive scores lowest in those reporting three or more concussions (d = 0.36, p = 0.008; d = 0.28, p = 0.040, respectively) or five or more concussions (d = 0.56, p < 0.001; d = 0.325, p = 0.035, respectively). Reported symptoms for sleep disruption were more prevalent in ER than NC, and in former athletes with three or more concussions (d = 0.41-0.605, p < 0.05). There were no significant differences in alcohol score (p = 0.733). Global anger score and covert anger expression was higher in former athletes with five or more concussions (d = 0.32, p = 0.035; d = 0.37, p = 0.016). AR reported greater attachment to friends than NC (d = 0.46, p = 0.033) and 20% of ER reported that they would not turn to anyone if they had a problem or felt upset about anything. CONCLUSION: There was a significantly higher prevalence of adverse mental health and sleep disruption in ER and in former athletes who reported a higher number of concussions. Anger and irritability were more prevalent in former athletes with a history of five or more concussions. Strategies are needed to address mental health and sleep disturbance in elite rugby code athletes, who are also less likely to seek help should they need it. Further research is needed to elucidate causation, and the neurobiological connection between concussion, sub-concussions and longer-term psychological health and wellbeing.

Event-related repetitive TMS reveals distinct, critical roles for right OFA and bilateral posterior STS in judging the sex and trustworthiness of faces.

Judging the sex of faces relies on cues related to facial morphology and spatial relations between features, whereas judging the trustworthiness of faces relies on both structural and expressive cues that signal affective valence. The right occipital face area (OFA) processes structural cues and has been associated with sex judgments, whereas the posterior STS processes changeable facial cues related to muscle movements and is activated when observers judge trustworthiness. It is commonly supposed that the STS receives inputs from the OFA, yet it is unknown whether these regions have functionally dissociable, critical roles in sex and trustworthiness judgments. We addressed this issue using event-related, fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Twelve healthy volunteers judged the sex of individually presented faces and, in a separate session, whether those same faces were trustworthy or not. Relative to sham stimulation, RTs were significantly longer for sex judgments when rTMS was delivered over the right OFA but not the right or left STS, and for trustworthiness judgments on male but not female faces when rTMS was delivered over the right STS or left STS but not the right OFA. Nonetheless, an analysis of the RT distributions revealed a possible critical role also for the right OFA in trustworthiness judgments, limited to faces with longer RTs, perhaps reflecting the later, ancillary use of structural cues related to the sex of the face. On the whole, our findings provide evidence that evaluations of the trustworthiness and sex of faces rely on functionally dissociable cortical regions.

The involvement of posterior parietal cortex in feature and conjunction visuomotor search.

Successful interaction with the environment often involves the identification and localization of an item. Right posterior parietal cortex (rPPC) is necessary for the completion of conjunction but not feature visual search, regardless of the attentional requirements. One account for this dissociation is that the rPPC is primarily involved in processing spatial information. For target identification, conjunction tasks require that spatial information is used to determine if features occur at the same location, whereas feature search does not require such a process. This account suggests that if the requirement to localize the target is made explicit, then rPPC may also be necessary for feature search. This was examined using TMS and by manipulating the response mode: Participants were either required to press a button indicating the presence/absence of the target or else had to point to the target. TMS over rPPC did not disrupt performance of the feature task when a button press was required but significantly increased response time and movement time for the same task in the pointing condition. Conjunction search in both response conditions was significantly impaired by TMS. Performance on a task that required pointing to a target in the absence of distractors and thus did not involve visual search was unaffected by rPPC stimulation. We conclude that rPPC is involved in coding and representing spatial information and is therefore crucial when the task requires determining whether two features spatially co-occur or when search is combined with explicit target localization via a visuomotor transformation.

Spatial priming in visual search: memory for body-centred information.

Spatial priming allows memory for target locations to be evaluated, whereby when a target appears in the same location across trials, participants become more efficient at locating it and consequently their search times decrease. Previously, we reported priming effects when the location of a target was repeated with respect to the participant's body but not when it was repeated relative to their eye position; therefore, suggesting that body-centred information is available after a delay of at least a few seconds (Ball et al. in Exp Brain Res 204:585-594, 2010). However, we were unable to rule out the possibility that stable allocentric cues within the room may have contributed to the priming effects that we observed. In this current study, we introduced a condition where despite participants moving to a new location between trials, their position relative to the target was maintained. This movement disrupted any potential room-based cues about the target location. While we replicated our previous finding of priming when the location of the target was repeated relative to the viewer when no movement was required, we also found robust priming effects when participants moved to a new location in between trials. Thus, we provide clear evidence that in our spatial priming task, the location of the target was being coded in a body-centred reference frame and that this information is available after a delay.

Visual exploration training is no better than attention training for treating hemianopia.

Patients with homonymous visual field defects experience disabling functional impairments as a consequence of their visual loss. Compensatory visual exploration training aims to improve the searching skills of these patients in order to help them to cope more effectively. However, until now the efficacy of this training has not been compared to that of a control intervention. Given that exploration training uses the visual search paradigm, which is known to require visual attention, in this study the efficacy of the technique was compared with training that requires visual attention but not exploration. Participants completed either exploration training (n = 21), or attention training followed by exploration training (n = 21). Assessment of the visual field, visual search, reading and activities of daily living were performed before and after each intervention that the participants completed. The results revealed that both the exploration training and the attention training led to significant improvements in most of the visual tasks. For most of the tasks exploration training did not prove superior to attention training, and for reading both types of intervention failed to yield any benefits. The results indicate that attention plays a large role in the rehabilitation of homonymous visual field defects.

A body-centred frame of reference drives spatial priming in visual search.

Spatial priming in visual search is a well-documented phenomenon. If the target of a visual search is presented at the same location in subsequent trials, the time taken to find the target at this repeated target location is significantly reduced. Previous studies did not determine which spatial reference frame is used to code the location. At least two reference frames can be distinguished: an observer-related frame of reference (egocentric) or a scene-based frame of reference (allocentric). While past studies suggest that an allocentric reference frame is more effective, we found that an egocentric reference frame is at least as effective as an allocentric one (Ball et al. Neuropsychologia 47(6):1585-1591, 2009). Our previous study did not identify which specific egocentric reference frame was used for the priming: participants could have used a retinotopic or a body-centred frame of reference. Here, we disentangled the retinotopic and body-centred reference frames. In the retinotopic condition, the position of the target stimulus, when repeated, changed with the fixation position, whereas in the body-centred condition, the position of the target stimulus remained the same relative to the display, and thus to the body-midline, but was different relative to the fixation position. We used a conjunction search task to assess the generality of our previous findings. We found that participants relied on body-centred information and not retinotopic cues. Thus, we provide further evidence that egocentric information, and specifically body-centred information, can persist for several seconds, and that these effects are not specific to either a feature or a conjunction search paradigm.

The role of the left dorsolateral prefrontal cortex in attentional bias.

The DLPFC is thought to be critically involved in maintaining attention away from behaviourally irrelevant information, and in the establishment of attentional control settings. These play an important role in the phenomenon of top-down bias to features in the visual field - also known as attentional bias. This paper probes the involvement of the left DLPFC in attentional bias by manipulating its cortical excitability via tDCS and then analysing these effects following an induced attentional bias towards the colour green. Although both anodal and cathodal tDCS over the left DLPFC decrease distractibility caused by biased but irrelevant objects, further interrogation of our data reveals theoretically differential mechanisms for each type of stimulation. Anodal tDCS appears to increase cognitive control over attentional bias-related items that are behaviourally irrelevant, allowing for their efficient disregard. In contrast, cathodal tDCS appears to lessen the overall effect of the induced attentional bias, potentially by reducing the influence of top-down modulated attentional control settings thus preventing the implementation of the control setting favouring green items. These results suggest a potential causal role of the left DLPFC in the cognitive mechanism underlying attentional bias.

Real-world applications in vision and attention: How to help patients find their (golf) balls again.

The loss of visual function is a common and debilitating effect of brain injury. Such effects include the inability to attend to the contralesional part of space (visual neglect) and loss of vision in part of the visual field in both eyes (homonymous visual field defects). The underlying mechanism of these functional deficits are varied which explains why no one intervention is effective in their treatment. In this chapter, we examine the cognitive neuroscience that underlies visual performance and attention with particular focus on what we know about visual exploration using search tasks in the laboratory. We then discuss how this knowledge has informed the development of interventions for poor visual function and how these can be maximized.

The Limitations of Reward Effects on Saccade Latencies: An Exploration of Task-Specificity and Strength.

Saccadic eye movements are simple, visually guided actions. Operant conditioning of specific saccade directions can reduce the latency of eye movements in the conditioned direction. However, it is not clear to what extent this learning transfers from the conditioned task to novel tasks. The purpose of this study was to investigate whether the effects of operant conditioning of prosaccades to specific spatial locations would transfer to more complex oculomotor behaviours, specifically, prosaccades made in the presence of a distractor (Experiment 1) and antisaccades (Experiment 2). In part 1 of each experiment, participants were rewarded for making a saccade to one hemifield. In both experiments, the reward produced a significant facilitation of saccadic latency for prosaccades directed to the rewarded hemifield. In part 2, rewards were withdrawn, and the participant made a prosaccade to targets that were accompanied by a contralateral distractor (Experiment 1) or an antisaccade (Experiment 2). There were no hemifield-specific effects of the reward on saccade latency on the remote distractor effect or antisaccades, although the reward was associated with an overall slowing of saccade latency in Experiment 1. These data indicate that operant conditioning of saccadic eye movements does not transfer to similar but untrained tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor system.

Investigating the roles of medial prefrontal and superior temporal cortex in source monitoring.

Source monitoring, or the ability to recall the origin of information, is a crucial aspect of remembering past experience. One facet of this, reality monitoring, refers to the ability to distinguish between internally generated and externally generated information, biases in which have previously been associated with auditory verbal hallucinations in schizophrenia. Neuroimaging evidence suggests that medial prefrontal and superior temporal (STG) regions may play a role in reality monitoring for auditory verbal information, with evidence from a previous neurostimulation experiment also suggesting that modulation of excitability in STG may affect reality monitoring task performance. Here, two experiments are reported that used transcranial direct current stimulation (tDCS) to modulate excitability in medial prefrontal and superior temporal cortex, to further investigate the role of these brain regions in reality monitoring. In the first experiment (N = 36), tDCS was applied during the encoding stage of the task, while in the second experiment, in a separate sample (N = 36), it was applied during the test stage. There was no effect of tDCS compared to a sham condition in either experiment, with Bayesian analysis providing evidence for the null hypothesis in both cases. This suggests that tDCS applied to superior temporal or medial prefrontal regions may not affect reality monitoring performance, and has implications for theoretical models that link reality monitoring to the therapeutic effect of tDCS on auditory verbal hallucinations.

Light social drinkers are more distracted by irrelevant information from an induced attentional bias than heavy social drinkers.

It is well established that alcoholics and heavy social drinkers show a bias of attention towards alcohol-related items. Previous research suggests that there is a shared foundation of attentional bias, which is linked to attentional control settings. Specifically, attentional bias relates to a persistent selection of a Feature Search Mode which prioritises attentional bias-related information for selection and processing. However, no research has yet examined the effect of pre-existing biases on the development of an additional attentional bias. This paper seeks to discover how pre-existing biases affect the formation of a new, additional attentional bias. Twenty-five heavy and 25 light social drinkers, with and without a pre-existing bias to alcohol-related items, respectively, had an attentional bias towards the colour green induced via an information sheet. They then completed a series of one-shot change detection tasks. In the critical task, green items were present but task-irrelevant. Irrelevant green items caused significantly more interference for light than heavy social drinkers. This somewhat counter intuitive result is likely due to heavy drinkers having more experience in exerting cognitive control over attentional biases, something not previously observed in investigations of the effects of holding an attentional bias. Our findings demonstrate for the first time that an established attentional bias significantly modulates future behaviour.

The Pain Divide: a cross-sectional analysis of chronic pain prevalence, pain intensity and opioid utilisation in England.

OBJECTIVES: Our central research question was, in England, are geographical inequalities in opioid use driven by health need (pain)? To answer this question, our study examined: (1) if there are regional inequalities in rates of chronic pain prevalence, pain intensity and opioid utilisation in England; (2) if opioid use and chronic pain are associated after adjusting for individual-level and area-level confounders. DESIGN: Cross-sectional study design using data from the Health Survey for England 2011. SETTING: England. PRIMARY AND SECONDARY OUTCOME MEASURES: Chronic pain prevalence, pain intensity and opioid utilisation. PARTICIPANTS: Participant data relating to chronic pain prevalence, pain intensity and opioid usage data were obtained at local authority level from the Health Survey for England 2011; in total, 5711 respondents were included in our analysis. METHODS: Regional and local authority data were mapped, and a generalised linear model was then used to explore the relationships between the data. The model was adjusted to account for area-level and individual-level variables. RESULTS: There were geographical variations in chronic pain prevalence, pain intensity and opioid utilisation across the English regions-with evidence of a 'pain divide' between the North and the South, whereby people in the North of England more likely to have 'severely limiting' or 'moderately limiting' chronic pain. The intensity of chronic pain was significantly and positively associated with the use of opioid analgesics. CONCLUSIONS: There are geographical differences in chronic pain prevalence, pain intensity and opioid utilisation across England-with evidence of a 'pain divide'. Given the public health concerns associated with the long-term use of opioid analgesics-and their questionable activity in the management of chronic pain-more guidance is needed to support prescribers in the management of chronic pain, so the initiation of opioids can be avoided.

Time course of the involvement of the ventral and dorsal visual processing streams in a visuospatial task.

A previous transcranial magnetic stimulation (TMS) study [Ellison, A., & Cowey, A. (2006). TMS can reveal contrasting functions of the dorsal and ventral visual processing streams. Experimental Brain Research, 175, 618-625] showed that both the dorsal and ventral cortical visual processing streams are involved in the processing of a task in which judgement of relative spatial position is required. In order to determine whether both streams are active in a parallel or serial manner, a double pulse TMS (20 Hz) experiment was carried out to expose peaks of disruption, indicative of when each of the areas under investigation is most potently involved. Results show that TMS over lateral occipital cortex produces greater disruption of performance than that provoked by TMS over posterior parietal cortex, significantly so when applied at 50 and 100 ms post-visual array onset. Both areas showed peaks of disruption up to 350 ms after visual stimulus onset. The results are discussed with respect to why each of these areas is involved in this task and what the pattern of their involvement reveals.