Visuospatial attention disturbance in Duchenne muscular dystrophy

AIM The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to investigate attentional function in individuals with DMD. METHOD Twenty-five males (mean age 12y; SD 2y 2mo) with DMD and 25 healthy males (mean age 12y; SD 2y) were tested in a visuospatial task (Posner computerized test). They were instructed to respond as quickly as possible to a lateralized visual target stimulus with the ipsilateral hand. Their attention was automatically orientated by a peripheral prime stimulus or, alternatively, voluntarily orientated by a central spatially informative cue. RESULTS The main result obtained was that the attentional effect (sum of the benefit and the cost of attention) did not differ between the two groups in the case of automatic attention (p=0.846) but was much larger for individuals with DMD than for comparison individuals in the case of voluntary attention (p < 0.001). INTERPRETATION The large voluntary attentional effect exhibited by the participants with DMD seems similar to that of younger children, suggesting that the disease is associated with delayed maturation of voluntary attention mechanisms.

The role of medial parieto occipital cortex in visuospatial attention and reach planning: electrophysiological studies in human and non-human primates

We usually perform actions in a dynamic environment and changes in the location of a target for an upcoming action require both covert shifts of attention and motor planning update. In this study we tested whether, similarly to oculomotor areas that provide signals for overt and covert attention shifts, covert attention shifts modulate activity in cortical area V6A, which provides a bridge between visual signals and arm-motor control. We performed single cell recordings in monkeys trained to fixate straight-ahead while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention demonstrating that visual, motor, and attentional responses can occur in combination in single neurons of V6A. This modulation in an area primarily involved in visuo-motor transformation for reaching suggests that also reach-related regions could directly contribute in the shifts of spatial attention necessary to plan and control goal-directed arm movements. Moreover, to test whether V6A is causally involved in these processes, we have performed a human study using on-line repetitive transcranial magnetic stimulation over the putative human V6A (pV6A) during an attention and a reaching task requiring covert shifts of attention and reaching movements towards cued targets in space. We demonstrate that the pV6A is causally involved in attention reorienting to target detection and that this process interferes with the execution of reaching movements towards unattended targets. The current findings suggest the direct involvement of the action-related dorso-medial visual stream in attentional processes, and a more specific role of V6A in attention reorienting. Therefore, we propose that attention signals are used by the V6A to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly appears at an unattended location.

Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

Lateral asymmetry of voluntary attention orienting

We recently demonstrated that automatic attention favors the right side of space and, in the present study, we investigated whether voluntary attention also favors this side. Six reaction time experiments were conducted. In each experiment, 12 new 18-25-year-old male right-handed individuals were tested. In Experiments 1, 2, 3 (a, b) and 4 (a, b), tasks with increasing attentional demands were used. In Experiments 1, 2, 3a, and 4a, attention was oriented to one or both sides by means of a central spatially informative visual cue. A left or right side visual target appeared 100, 300, or 500 ms later. Attentional effects were observed in the four experiments. In Experiments 2, 3a and 4a, these effects were greater when the cue indicated the right side than when it indicated the left side (respectively: 16 ± 10 and 44 ± 6 ms, P = 0.015, for stimulus onset asynchrony of 500 ms in Experiment 2; 38 ± 10 and 70 ± 7 ms, P = 0.011, for Experiment 3a, and 23 ± 11 and 61 ± 10 ms, P = 0.009, for Experiment 4a). In Experiments 3b and 4b, the central cue pointed to both sides and was said to be non-relevant for task performance. In these experiments right and left reaction times did not differ. The most conservative interpretation of the present findings is that voluntary attention orienting favors the right side of space, particularly when a difficult task has to be performed.

Lateral asymmetry of voluntary attention orienting

We recently demonstrated that automatic attention favors the right side of space and, in the present study, we investigated whether voluntary attention also favors this side. Six reaction time experiments were conducted. In each experiment, 12 new 18-25-year-old male right-handed individuals were tested. In Experiments 1, 2, 3 (a, b) and 4 (a, b), tasks with increasing attentional demands were used. In Experiments 1, 2, 3a, and 4a, attention was oriented to one or both sides by means of a central spatially informative visual cue. A left or right side visual target appeared 100, 300, or 500 ms later. Attentional effects were observed in the four experiments. In Experiments 2, 3a and 4a, these effects were greater when the cue indicated the right side than when it indicated the left side (respectively: 16 ± 10 and 44 ± 6 ms, P = 0.015, for stimulus onset asynchrony of 500 ms in Experiment 2; 38 ± 10 and 70 ± 7 ms, P = 0.011, for Experiment 3a, and 23 ± 11 and 61 ± 10 ms, P = 0.009, for Experiment 4a). In Experiments 3b and 4b, the central cue pointed to both sides and was said to be non-relevant for task performance. In these experiments right and left reaction times did not differ. The most conservative interpretation of the present findings is that voluntary attention orienting favors the right side of space, particularly when a difficult task has to be performed.

L'incidence de l'alternance des taches sur les processus de l'attention : indices électrophysiologiques chez l'humain.

Connue pour augmenter les temps de réponse et les erreurs, l’alternance des tâches est considérée par les industriels comme un point de friction humain depuis plusieurs décennies. Pourtant malgré l’important nombre d’études sur l’alternance des tâches, peu s'intéressent à l'électrophysiologie humaine et au déploiement de l’attention visuospatiale. Le travail qui suit décrit notre incursion destinée à approfondir les connaissances autant sur les paradigmes d’alternance de tâche que les composantes électrophysiologiques typiquement reliées au déploiement de l’attention visuospatiale telles la N2pc ou la Ppc récemment décrite par Corriveau et al. (2012). Afin d’examiner les modulations des composantes électrophysiologiques sus nommées en fonction des coûts d’alternance, un paradigme d’alternance des tâches regroupant des blocs mixtes (avec alternance) et des blocs purs (sans alternance) a été utilisé. Les résultats démontrent un impact du coût d’alternance sur la latence de la N2pc, ce qui reflète comme attendu d’un processus de contrôle cognitif descendant sur la sélection attentionnelle visospatiale. De manière plus surprenante, des modulations de Ppc ont été observées, tandis que cette composante était jusqu’alors comprise comme une composante principalement reliée à une activité ascendante de bas niveau de traitement. Cette modulation de Ppc suggère l'existence d’un autre mécanisme de modulation attentionnelle antérieur à la N2pc.

Endogenous-like orienting of visual attention in rats

This study investigated the orienting of visual attention in rats using a 3-hole nose-poke task analogous to Posner, Information processing in cognition: the Loyola Symposium, Erlbaum, Hillsdale, (1980) covert attention task for humans. The effects of non-predictive (50% valid and 50% invalid) and predictive (80% valid and 20% invalid) peripheral visual cues on reaction times and response accuracy to a target stimulus, using Stimuli-Onset Asynchronies (SOAs) varying between 200 and 1,200 ms, were investigated. The results showed shorter reaction times in valid trials relative to invalid trials for both subjects trained in the non-predictive and predictive conditions, particularly when the SOAs were 200 and 400 ms. However, the magnitude of this validity effect was significantly greater for subjects exposed to predictive cues, when the SOA was 800 ms. Subjects exposed to invalid predictive cues exhibited an increase in omission errors relative to subjects exposed to invalid non-predictive cues. In contrast, valid cues reduced the proportion of omission errors for subjects trained in the predictive condition relative to subjects trained in the non-predictive condition. These results are congruent with those usually reported for humans and indicate that, in addition to the exogenous capture of attention promoted by both predictive and non-predictive peripheral cues, rats exposed to predictive cues engaged an additional slower process equivalent to human`s endogenous orienting of attention. To our knowledge, this is the first demonstration of an endogenous-like process of covert orienting of visual attention in rats.

Automatic attention lateral asymmetry in visual discrimination tasks

There is evidence that automatic visual attention favors the right side. This study investigated whether this lateral asymmetry interacts with the right hemisphere dominance for visual location processing and left hemisphere dominance for visual shape processing. Volunteers were tested in a location discrimination task and a shape discrimination task. The target stimuli (S2) could occur in the left or right hemifield. They were preceded by an ipsilateral, contralateral or bilateral prime stimulus (S1). The attentional effect produced by the right S1 was larger than that produced by the left S1. This lateral asymmetry was similar between the two tasks suggesting that the hemispheric asymmetries of visual mechanisms do not contribute to it. The finding that it was basically due to a longer reaction time to the left S2 than to the right S2 for the contralateral S1 condition suggests that the inhibitory component of attention is laterally asymmetric.

Absence of placeholders abolishes exogenous attention effect in a peripheral cueing procedure

Most studies of exogenous visuospatial attention use placeholders indicating the regions where the stimuli appear on the screen. Preliminary results from our laboratory provided evidence that the attentional effect is more frequently observed when placeholders are used in these experimental procedures. Four experiments were carried out. Experiment 1 aimed at confirming the finding that the attentional effect of a spatially non-informative cue (S1) observed in the presence of placeholders disappears in their absence. The results confirmed this finding. Experiments 2, 3, and 4 examined several possible processes that could explain this finding. Experiment 2 investigated if the contribution of a faster disengagement of attention from the cued location or a stronger forward masking could explain the absence of attentional effect when no placeholders were used. Experiment 3 investigated if increased difficulty in discrimination of the target (S2) from S1 would favor the appearance of the attentional effect in the absence of placeholders. Experiment 4 investigated if an insufficient focusing of attention towards the cued location could explain the absence of attentional effect when no placeholders were used. The results of the three experiments indicated that placeholders act by reducing the discriminability of the S2. This would presumably lead to the adoption of an attentional set that favors the mobilization of attention by the S1

Human brain regions required for the dividing and switching of attention between two features of a single object

This combined PET and ERP study was designed to identify the brain regions activated in switching and divided attention between different features of a single object using matched sensory stimuli and motor response. The ERP data have previously been reported in this journal [64]. We now present the corresponding PET data. We identified partially overlapping neural networks with paradigms requiring the switching or dividing of attention between the elements of complex visual stimuli. Regions of activation were found in the prefrontal and temporal cortices and cerebellum. Each task resulted in different prefrontal cortical regions of activation lending support to the functional subspecialisation of the prefrontal and temporal cortices being based on the cognitive operations required rather than the stimuli themselves. (C) 2003 Elsevier Science B.V. All rights reserved.

Pseudoneglect and visual attention networks

Pseudoneglect represents the tendency for healthy individuals to show a slight but consistent bias in favour of stimuli appearing in the left visual field. The bias is often measured using variants of the line bisection task. An accurate model of the functional architecture of the visuospatial attention system must account for this widely observed phenomenon, as well as for modulation of the direction and magnitude of the bias within individuals by a variety of factors relating to the state of the participant and/or stimulus characteristics. To date, the neural correlates of pseudoneglect remain relatively unmapped. In the current thesis, I employed a combination of psychophysical measurements, electroencephalography (EEG) recording and transcranial direct current stimulation (tDCS) in an attempt to probe the neural generator(s) of pseudoneglect. In particular, I wished to utilise and investigate some of the factors known to modulate the bias (including age, time-on-task and the length of the to-be-bisected line) in order to identify neural processes and activity that are necessary and sufficient for the lateralized bias to arise. Across four experiments utilising a computerized version of a perceptual line bisection task, pseudoneglect was consistently observed at baseline in healthy young participants. However, decreased line length (experiments 1, 2 and 3), time-on-task (experiment 1) and healthy aging (experiment 3) were all found to modulate the bias. Specifically, all three modulations induced a rightward shift in subjective midpoint estimation. Additionally, the line length and time-on-task effects (experiment 1) and the line length and aging effects (experiment 3) were found to have additive relationships. In experiment 2, EEG measurements revealed the line length effect to be reflected in neural activity 100 – 200ms post-stimulus onset over source estimated posterior regions of the right hemisphere (RH: temporo-parietal junction (TPJ)). Long lines induced a hemispheric asymmetry in processing (in favour of the RH) during this period that was absent in short lines. In experiment 4, bi-parietal tDCS (Left Anodal/Right Cathodal) induced a polarity-specific rightward shift in bias, highlighting the crucial role played by parietal cortex in the genesis of pseudoneglect. The opposite polarity (Left Cathodal/Right Anodal) did not induce a change in bias. The combined results from the four experiments of the current thesis provide converging evidence as to the crucial role played by the RH in the genesis of pseudoneglect and in the processing of visual input more generally. The reduction in pseudoneglect with decreased line length, increased time-on-task and healthy aging may be explained by a reduction in RH function, and hence contribution to task processing, induced by each of these modulations. I discuss how behavioural and neuroimaging studies of pseudoneglect (and its various modulators) can provide empirical data upon which accurate formal models of visuospatial attention networks may be based and further tested.

Mapping and modulating spatial attention asymmetries in young and older adults

Healthy young adults demonstrate a group-level, systematic preference for stimuli presented in the left side of space relative to the right (‘pseudoneglect’) (Bowers & Heilman, 1980). This results in an overestimation of features such as size, brightness, numerosity and spatial frequency in the left hemispace, probably as a result of right cerebral hemisphere dominance for visuospatial attention. This spatial attention asymmetry is reduced in the healthy older population, and can be shifted entirely into right hemispace under certain conditions. Although this rightward shift has been consistently documented in behavioural experiments, there is very little neuroimaging evidence to explain this effect at a neuroanatomical level. In this thesis, I used behavioural methodology and electroencephalography (EEG) to map spatial attention asymmetries in young and older adults. I then use transcranial direct current stimulation (tDCS) to modulate these spatial biases, with the aim of assessing age-related differences in response to tDCS. In the first of three experiments presented in this thesis, I report in Chapter Two that five different spatial attention tasks provide consistent intra-task measures of spatial bias in young adults across two testing days. There were, however, no inter-task correlations between the five tasks, indicating that pseudoneglect is at least partially driven by task-dependent patterns of neural activity. In Chapter Three, anodal tDCS was applied separately to the left (P5) and right (P6) posterior parietal cortex (PPC) in young and older adults, with an aim to improve the detection of stimuli appearing in the contralateral visual field. There were no age differences in response to tDCS, but there were significant differences depending on baseline performance. Relative to a sham tDCS protocol, tDCS applied to the right PPC resulted in maintained visual detection across both visual fields in adults who were good at the task at baseline. In contrast, left PPC tDCS resulted in reduced detection sensitivity across both visual fields in poor performers. Finally, in Chapter Four, I report a right-hemisphere lateralisation of EEG activity in young adults that was present for long (but not short) landmark task lines. In contrast, older adults demonstrated no lateralised activity for either line length, thus providing novel evidence of an age-related reduction of hemispheric asymmetry in older adults. The results of this thesis provide evidence of a highly complex set of factors that underlie spatial attention asymmetries in healthy young and older adults.

Human cortical processing of colour and pattern

The present study investigates human visual processing of simple two-colour patterns using a delayed match to sample paradigm with positron emission tomography (PET). This study is unique in that we specifically designed the visual stimuli to be the same for both pattern and colour recognition with all patterns being abstract shapes not easily verbally coded composed of two-colour combinations. We did this to explore those brain regions required for both colour and pattern processing and to separate those areas of activation required for one or the other. We found that both tasks activated similar occipital regions, the major difference being more extensive activation in pattern recognition. A right-sided network that involved the inferior parietal lobule, the head of the caudate nucleus, and the pulvinar nucleus of the thalamus was common to both paradigms. Pattern recognition also activated the left temporal pole and right lateral orbital gyrus, whereas colour recognition activated the left fusiform gyrus and several right frontal regions. (C) 2001 Wiley-Liss, Inc.

EEG alpha activity reflects motor preparation rather than the mode of action selection

Alpha-band activity (8-13 Hz) is not only suppressed by sensory stimulation and movements, but also modulated by attention, working memory and mental tasks, and could be sensitive to higher motor control functions. The aim of the present study was to examine alpha oscillatory activity during the preparation of simple left or right finger movements, contrasting the external and internal mode of action selection. Three preparation conditions were examined using a precueing paradigm with S1 as the preparatory and S2 as the imperative cue: Full, laterality instructed by S1; Free, laterality freely selected and None, laterality instructed by S2. Time-frequency (TF) analysis was performed in the alpha frequency range during the S1-S2 interval, and alpha motor-related amplitude asymmetries (MRAA) were also calculated. The significant MRAA during the Full and Free conditions indicated effective external and internal motor response preparation. In the absence of specific motor preparation (None), a posterior alpha event-related desynchronization (ERD) dominated, reflecting the main engagement of attentional resources. In Full and Free motor preparation, posterior alpha ERD was accompanied by a midparietal alpha event-related synchronization (ERS), suggesting a concomitant inhibition of task-irrelevant visual activity. In both Full and Free motor preparation, analysis of alpha power according to MRAA amplitude revealed two types of functional activation patterns: (1) a motor alpha pattern, with predominantly midparietal alpha ERS and large MRAA corresponding to lateralized motor activation/visual inhibition and (2) an attentional alpha pattern, with dominating right posterior alpha ERD and small MRAA reflecting visuospatial attention. The present results suggest that alpha oscillatory patterns do not resolve the selection mode of action, but rather distinguish separate functional strategies of motor preparation.

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.