Low pre-stimulus EEG alpha power amplifies visual awareness but not visual sensitivity.

Pre-stimulus oscillatory neural activity has been linked to the level of awareness of sensory stimuli. More specifically, the power of low-frequency oscillations (primarily in the alpha-band, i.e., 8-14 Hz) prior to stimulus onset is inversely related to measures of subjective performance in visual tasks, such as confidence and visual awareness. Intriguingly, the same EEG signature does not seem to influence objective measures of task performance (i.e., accuracy). We here examined whether this dissociation holds when stringent accuracy measures are used. Previous EEG-studies have employed 2-alternative forced choice (2-AFC) discrimination tasks to link pre-stimulus oscillatory activity to correct/incorrect responses as an index of accuracy/objective performance at the single-trial level. However, 2-AFC tasks do not provide a good estimate of single-trial accuracy, as many of the responses classified as correct will be contaminated by guesses (with the chance correct response rate being 50%). Here instead, we employed a 19-AFC letter identification task to measure accuracy and the subjectively reported level of perceptual awareness on each trial. As the correct guess rate is negligible (~5%), this task provides a purer measure of accuracy. Our results replicate the inverse relationship between pre-stimulus alpha/beta-band power and perceptual awareness ratings in the absence of a link to discrimination accuracy. Pre-stimulus oscillatory phase did not predict either subjective awareness or accuracy. Our results hence confirm a dissociation of the pre-stimulus EEG power-task performance link for subjective versus objective measures of performance, and further substantiate pre-stimulus alpha power as a neural predictor of visual awareness.

Editorial for special issue on neglect rehabilitation.

It is clear already that in current and future years more people will suffer from stroke, whether related to COVID-19 or not, and given its prevalence, many more people's lives will be affected by neglect. Here we hope to have contributed to its possible amelioration with highlights of the latest thinking on neglect diagnosis, prevalence and treatment.

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.Trial registration: ClinicalTrials.gov identifier: NCT02401724.

Efficacy of home-based visuomotor feedback training in stroke patients with chronic hemispatial neglect.

Hemispatial neglect is a severe cognitive condition frequently observed after a stroke, associated with unawareness of one side of space, disability and poor long-term outcome. Visuomotor feedback training (VFT) is a neglect rehabilitation technique that involves a simple, inexpensive and feasible training of grasping-to-lift rods at the centre. We compared the immediate and long-term effects of VFT vs. a control training when delivered in a home-based setting. Twenty participants were randomly allocated to an intervention (who received VFT) or a control group (n = 10 each). Training was delivered for two sessions by an experimenter and then patients self-administered it for 10 sessions over two weeks. Outcome measures included the Behavioural Inattention Test (BIT), line bisection, Balloons Test, Landmark task, room description task, subjective straight-ahead pointing task and the Stroke Impact Scale. The measures were obtained before, immediately after the training sessions and after four-months post-training. Significantly greater short and long-term improvements were obtained after VFT when compared to control training in line bisection, BIT and spatial bias in cancellation. VFT also produced improvements on activities of daily living. We conclude that VFT is a feasible, effective, home-based rehabilitation method for neglect patients that warrants further investigation with well-designed randomised controlled trials on a large sample of patients.

Trial-by-trial co-variation of pre-stimulus EEG alpha power and visuospatial bias reflects a mixture of stochastic and deterministic effects.

Human perception of perithreshold stimuli critically depends on oscillatory EEG activity prior to stimulus onset. However, it remains unclear exactly which aspects of perception are shaped by this pre-stimulus activity and what role stochastic (trial-by-trial) variability plays in driving these relationships. We employed a novel jackknife approach to link single-trial variability in oscillatory activity to psychometric measures from a task that requires judgement of the relative length of two line segments (the landmark task). The results provide evidence that pre-stimulus alpha fluctuations influence perceptual bias. Importantly, a mediation analysis showed that this relationship is partially driven by long-term (deterministic) alpha changes over time, highlighting the need to account for sources of trial-by-trial variability when interpreting EEG predictors of perception. These results provide fundamental insight into the nature of the effects of ongoing oscillatory activity on perception. The jackknife approach we implemented may serve to identify and investigate neural signatures of perceptual relevance in more detail.

Age-related reduction of hemispheric lateralisation for spatial attention: An EEG study.

A group-level visuospatial attention bias towards the left side of space (pseudoneglect) is consistently observed in young adults, which is likely to be a consequence of right parieto-occipital dominance for spatial attention. Conversely, healthy older adults demonstrate a rightward shift of this behavioural bias, hinting that an age-related reduction of lateralised neural activity may occur within visuospatial attention networks. We compared young (aged 18-25) and older (aged 60-80) adults on a computerised line bisection (landmark) task whilst recording event-related potentials (ERPs). Full-scalp cluster mass permutation tests identified a larger right parieto-occipital response for long lines compared to short in young adults (confirming Benwell et al., 2014a) which was not present in the older group. To specifically investigate age-related differences in hemispheric lateralisation, cluster mass permutation tests were then performed on a lateralised EEG dataset (RH-LH electrodes). A period of right lateralisation was identified in response to long lines in young adults, which was not present for short lines. No lateralised clusters were present for either long or short lines in older adults. Additionally, a reduced P300 component amplitude was observed for older adults relative to young. We therefore report here, for the first time, an age-related and stimulus-driven reduction of right hemispheric control of spatial attention in older adults. Future studies will need to determine whether this is representative of the normal aging process or an early indicator of neurodegeneration.

Parieto-occipital cortex shows early target selection to faces in a reflexive orienting task.

It is well established that human faces induce stronger involuntary orienting responses than other visual objects. Yet, the timing of this preferential orienting response at the neural level is still unknown. Here, we used an antisaccade paradigm to investigate the neural dynamics preceding the onset of reflexive and voluntary saccades elicited by human faces and nonface visual objects, normalized for their global low-level visual properties. High-density event-related potentials (ERPs) were recorded in observers as they performed interleaved pro- and antisaccades toward a lateralized target. For reflexive saccades, we report an ERP modulation specific to faces as early as 40-60 ms following stimulus onset over parieto-occipital sites, further predicting the speed of saccade execution. This was not linked to differences in the programming of the saccadic eye movements, as it occurred early in time. For the first time, we present electrophysiological evidence of early target selection to faces in reflexive orienting responses over parieto-occipital cortex that facilitates the triggering of saccades toward faces. We argue for a 2-stage process in the representation of a face in involuntary spatial orienting with an initial, rapid implicit processing of the visual properties of a face, followed by subsequent stimulus categorization depicted by the N170 component.

On the neural origin of pseudoneglect: EEG-correlates of shifts in line bisection performance with manipulation of line length.

Healthy participants tend to show systematic biases in spatial attention, usually to the left. However, these biases can shift rightward as a result of a number of experimental manipulations. Using electroencephalography (EEG) and a computerized line bisection task, here we investigated for the first time the neural correlates of changes in spatial attention bias induced by line-length (the so-called line-length effect). In accordance with previous studies, an overall systematic left bias (pseudoneglect) was present during long line but not during short line bisection performance. This effect of line-length on behavioral bias was associated with stronger right parieto-occipital responses to long as compared to short lines in an early time window (100-200ms) post-stimulus onset. This early differential activation to long as compared to short lines was task-independent (present even in a non-spatial control task not requiring line bisection), suggesting that it reflects a reflexive attentional response to long lines. This was corroborated by further analyses source-localizing the line-length effect to the right temporo-parietal junction (TPJ) and revealing a positive correlation between the strength of this effect and the magnitude by which long lines (relative to short lines) drive a behavioral left bias across individuals. Therefore, stimulus-driven left bisection bias was associated with increased right hemispheric engagement of areas of the ventral attention network. This further substantiates that this network plays a key role in the genesis of spatial bias, and suggests that post-stimulus TPJ-activity at early information processing stages (around the latency of the N1 component) contributes to the left bias.

Probing sustained attention and fatigue across the lifespan.

Trait fatigues reflects tiredness that persists throughout a prolonged period, whereas state fatigue is a short-term reaction to intense or prolonged effort. We investigated the impact of sustained attention (using the SART) on both trait and state fatigue levels in the general population. An online version of the SART was undertaken by 115 participants, stratified across the whole adult lifespan. While pre-task trait fatigue was a strong indicator of the initial state fatigue levels, undergoing the task itself induced an increase in reported subjective state fatigue, and an accompanying reduction in subjective energy rating. Consistent with this finding, greater subjective state fatigue levels were associated with reduced accuracy. In addition, age was the best predictor of inter-participant accuracy (the older the participants, the greater the accuracy), and learning (i.e., task duration reducing reaction times). Moreover, a ceiling effect occurred where participants with higher trait fatigue did not experience greater state fatigue changes relative to those with low trait scores. In summary, we found improved accuracy in older adults, as well as a tight coupling between state fatigue and SART performance decline (in an online environment). The findings warrant further investigation into fatigue as a dynamic, task-dependent state and into SART performance as an objective measure and inducer of fatigue.

The role of right temporal lobe structures in off-line action: evidence from lesion-behavior mapping in stroke patients.

Recent evidence suggests the possibility that not all action modes depend on dorsal visual stream processing but that off-line nontarget-directed actions, such as antipointing, require additional and even distinct neural networks when compared with target-directed online actions. Here, we explored this potential dissociation in a group of 11 patients with left visual neglect, a syndrome characterized by a loss of awareness of the contralesional side of space. Ten healthy participants and 10 right hemisphere-damaged patients without neglect served as controls. Participants had to point either directly toward targets presented on their left or right (i.e., propointing) or to the mirror position in the opposite hemispace (i.e., antipointing). Compared with both control groups, neglect patients showed reduced accuracy when antipointing but not propointing. Lesion-behavior mapping revealed that the areas critically associated with these deficits were located in the middle and superior temporal and parahippocampal gyri. We argue that neglect patients present specific deficits only when the visuomotor task taps into more perceptual representations thought to rely on ventral visual stream processing and that our results indicate that right temporal brain regions are implicated in these off-line actions.

Effects of Rhythmic Transcranial Magnetic Stimulation in the Alpha-Band on Visual Perception Depend on Deviation From Alpha-Peak Frequency: Faster Relative Transcranial Magnetic Stimulation Alpha-Pace Improves Performance.

Alpha-band oscillatory activity over occipito-parietal areas is involved in shaping perceptual and cognitive processes, with a growing body of electroencephalographic (EEG) evidence indicating that pre-stimulus alpha-band amplitude relates to the subjective perceptual experience, but not to objective measures of visual task performance (discrimination accuracy). The primary aim of the present transcranial magnetic stimulation (TMS) study was to investigate whether causality can be established for this relationship, using rhythmic (alpha-band) TMS entrainment protocols. It was anticipated that pre-stimulus 10 Hz-TMS would induce changes in subjective awareness ratings but not accuracy, in the visual hemifield contralateral to TMS. To test this, we administered 10 Hz-TMS over the right intraparietal sulcus prior to visual stimulus presentation in 17 participants, while measuring their objective performance and subjective awareness in a visual discrimination task. Arrhythmic and 10 Hz sham-TMS served as control conditions (within-participant design). Resting EEG was used to record individual alpha frequency (IAF). A study conducted in parallel to ours with a similar design but reported after we completed data collection informed further, secondary analyses for a causal relationship between pre-stimulus alpha-frequency and discrimination accuracy. This was explored through a regression analysis between rhythmic-TMS alpha-pace relative to IAF and performance measures. Our results revealed that contrary to our primary expectation, pre-stimulus 10 Hz-TMS did not affect subjective measures of performance, nor accuracy, relative to control-TMS. This null result is in accord with a recent finding showing that for influencing subjective measures of performance, alpha-TMS needs to be applied post-stimulus. In addition, our secondary analysis showed that IAF was positively correlated with task accuracy across participants, and that 10 Hz-TMS effects on accuracy-but not awareness ratings-depended on IAF: The slower (or faster) the IAF, relative to the fixed 10 Hz TMS frequency, the stronger the TMS-induced performance improvement (or worsening), indicating that 10 Hz-TMS produced a gain (or a loss) in individual performance, directly depending on TMS-pace relative to IAF. In support of recent reports, this is evidence for alpha-frequency playing a causal role in perceptual sensitivity likely through regulating the speed of sensory sampling.

Parietal alpha tACS shows inconsistent effects on visuospatial attention.

Transcranial alternating current stimulation (tACS) is a popular technique that has been used for manipulating brain oscillations and inferring causality regarding the brain-behaviour relationship. Although it is a promising tool, the variability of tACS results has raised questions regarding the robustness and reproducibility of its effects. Building on recent research using tACS to modulate visuospatial attention, we here attempted to replicate findings of lateralized parietal tACS at alpha frequency to induce a change in attention bias away from the contra- towards the ipsilateral visual hemifield. 40 healthy participants underwent tACS in two separate sessions where either 10 Hz tACS or sham was applied via a high-density montage over the left parietal cortex at 1.5 mA for 20 min, while performance was assessed in an endogenous attention task. Task and tACS parameters were chosen to match those of previous studies reporting positive effects. Unlike these studies, we did not observe lateralized parietal alpha tACS to affect attention deployment or visual processing across the hemifields as compared to sham. Likewise, additional resting electroencephalography immediately offline to tACS did not reveal any notable effects on individual alpha power or frequency. Our study emphasizes the need for more replication studies and systematic investigations of the factors that drive tACS effects.

Memory-guided saccade processing in visual form agnosia (patient DF).

According to Milner and Goodale's model (The visual brain in action, Oxford University Press, Oxford, 2006) areas in the ventral visual stream mediate visual perception and oV-line actions, whilst regions in the dorsal visual stream mediate the on-line visual control of action. Strong evidence for this model comes from a patient (DF), who suffers from visual form agnosia after bilateral damage to the ventro-lateral occipital region, sparing V1. It has been reported that she is normal in immediate reaching and grasping, yet severely impaired when asked to perform delayed actions. Here we investigated whether this dissociation would extend to saccade execution. Neurophysiological studies and TMS work in humans have shown that the posterior parietal cortex (PPC), on the right in particular (supposedly spared in DF), is involved in the control of memory-guided saccades. Surprisingly though, we found that, just as reported for reaching and grasping, DF's saccadic accuracy was much reduced in the memory compared to the stimulus-guided condition. These data support the idea of a tight coupling of eye and hand movements and further suggest that dorsal stream structures may not be sufficient to drive memory-guided saccadic performance.

No neglect-specific deficits in reaching tasks.

It is well established that patients with hemispatial neglect present with severe visuospatial impairments, but studies that have directly investigated visuomotor control have revealed diverging results, with some studies showing that neglect patients perform relatively better on such tasks. The present study compared the visuomotor performance of patients with and without neglect after right-hemisphere stroke with those of age-matched controls. Participants were asked to point either directly towards targets or halfway between two stimuli, both with and without visual feedback during movement. Although we did not find any neglect-specific impairment, both patient groups showed increased reaction times to leftward stimuli as well as decreased accuracies for open loop leftward reaches. We argue that these findings agree with the view that neglect patients code spatial parameters for action veridically. Moreover, we suggest that lesions in the right hemisphere may cause motor deficits irrespective of the presence of neglect and we performed an initial voxel-lesion symptom analysis to assess this. Lesion-symptom analysis revealed that the reported deficits did not result from damage to neglect-associated areas alone, but were further associated with lesions to crucial nodes in the visuomotor control network (the basal ganglia as well as occipito-parietal and frontal areas).

Looking away from faces: influence of high-level visual processes on saccade programming.

Human faces capture attention more than other visual stimuli. Here we investigated whether such face-specific biases rely on automatic (involuntary) or voluntary orienting responses. To this end, we used an anti-saccade paradigm, which requires the ability to inhibit a reflexive automatic response and to generate a voluntary saccade in the opposite direction of the stimulus. To control for potential low-level confounds in the eye-movement data, we manipulated the high-level visual properties of the stimuli while normalizing their global low-level visual properties. Eye movements were recorded in 21 participants who performed either pro- or anti-saccades to a face, car, or noise pattern, randomly presented to the left or right of a fixation point. For each trial, a symbolic cue instructed the observer to generate either a pro-saccade or an anti-saccade. We report a significant increase in anti-saccade error rates for faces compared to cars and noise patterns, as well as faster pro-saccades to faces and cars in comparison to noise patterns. These results indicate that human faces induce stronger involuntary orienting responses than other visual objects, i.e., responses that are beyond the control of the observer. Importantly, this involuntary processing cannot be accounted for by global low-level visual factors.

Modelling contralesional movement slowing after unilateral brain damage.

Effective interaction with the world requires the brain to signal behaviourally relevant events and organise an appropriate and timely motor response to such events. Unilateral brain lesion typically results in a reduction and slowing of motor behaviour directed to contralesional space. Accumulator models of choice and reaction time can distinguish between two possible functional causes of this deficit: slowed extraction of evidence in favour of a motor response or an increase in the required amount of evidence for response generation. Three patients with unilateral damage to the right hemisphere were tested on a visually guided saccade task. All three patients showed a dramatic increase in the latency of their responses to targets in the contralesional visual field. We fit their saccade latency distributions with a number of competing accumulator models that embody the alternative functional causes of this deficit. The latency difference between the two hemifields was best accounted for as an increase in the amount of evidence required for a contralesional response.

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.

Both dorsal and ventral attention network nodes are implicated in exogenously driven visuospatial anticipation.

Neuroimaging and transcranial magnetic stimulation (TMS) studies have implicated a dorsal fronto-parietal network in endogenous attention control and a more ventral set of areas in exogenous attention shifts. However, the extent and circumstances under which these cortical networks overlap and/or interact remain unclear. Crucially, whereas previous studies employed experimental designs that tend to confound exogenous with endogenous attentional engagement, we used a cued target discrimination paradigm that behaviourally dissociates exogenous from endogenous attention processes. Participants engaged with endogenous attention cues, while simultaneous apparent motion cues were driving exogenous attention along the motion path towards or away from the target position. To interfere with dorsal or ventral attention networks, we delivered neuronavigated double-pulse TMS over either right intraparietal sulcus (rIPS) or right temporo-parietal junction (rTPJ) towards the end of the cue target interval, and compared the effects to a sham-TMS condition. For sham-TMS, endogenous and exogenous cueing both benefitted discrimination accuracy. Target discrimination was enhanced at validly versus invalidly cued locations (endogenous cueing benefit) as well as when targets appeared in versus out of the motion path (exogenous cueing benefit), despite motion being uninformative and task-irrelevant, replicating previous findings. Interestingly, both rIPS- and rTPJ-TMS abolished attention benefits from exogenous cueing, while endogenous cueing benefits were unaffected. Our findings provide evidence against independent involvement of the dorsal and ventral attention network nodes in exogenous attention processes.

Effects of aging and exposure duration on perceptual biases in chimeric face processing.

Experiments using chimeric faces, where the left and the right hand side of the face are different, have shown that observers tend to bias their responses toward the information on the left. Here we investigate the effects of aging as well as exposure duration on this leftward bias. Forty female and male blended as well as chimeric faces were presented to 24 young and 23 elderly adults in either sub-saccadic 100 msec, 300 msec or free view conditions. We found firstly that an increase in exposure duration resulted in an increase in the degree of leftward perceptual biases, irrespective of age, in line with hypotheses stressing the contribution of scanning to chimeric face processing. Secondly, fundamental differences in the perceptual biases between the groups were found in so far that the younger subjects demonstrated significant perceptual biases to chimeric face stimuli even at sub-saccadic exposure durations, whilst for older adults this was the case for the 300 msec and free view conditions only. This differential perceptual activity can be viewed in terms of either reduced right hemispheric function, or increased bilateral function as a possible consequence of elderly adults experiencing the task as more effortful.

Age-related differences in corrected and inhibited pointing movements.

It has been widely reported that aging is accompanied by a decline in motor skill performance and in particular, it has been shown that older subjects take longer to adapt their ongoing reach in response to a target location shift. In the present experiment, we investigated the influence of aging on the ability to perform trajectory corrections in response to a target jump, but also assessed inhibition by asking a younger and an older group of participants to either adapt or stop their ongoing movement in response to a target location change. Results showed that although older subjects took longer to initiate, execute, correct and inhibit an ongoing reach, they performed both tasks with the same level of accuracy as the younger sample. Moreover, the slowing was also observed when older subjects were asked to point to stationary targets. Our findings thus indicate that aging does not specifically influence the ability to perform or inhibit fast online corrections to target location changes, but rather produces a general slowing and increased variability of movement planning, initiation and execution to both perturbed and stationary targets. For the first time, we demonstrate that aging is not accompanied by a decrease in the inhibition of motor control.