Individual EEG profiling of attention deficits in left spatial neglect: A pilot study.

Electrophysiological group studies in brain-damaged patients can be run to capture the EEG correlates of specific cognitive impairments. Nonetheless, this procedure is not adequate to characterize the inter-individual variability present in major neuropsychological syndromes. We tested the possibility of getting a reliable individual EEG characterization of deficits of endogenous orienting of spatial attention in right-brain damaged (RBD) patients with left spatial neglect (N+). We used a single-trial topographical analysis (STTA; [39] of individual scalp EEG topographies recorded during leftward and rightward orienting of attention with central cues in RBD patients with and without (N-) neglect and in healthy controls (HC). We found that the STTA successfully decoded EEG signals related to leftward and rightward orienting in five out of the six N+, five out of the six N- patients and in all the six HC. In agreement with findings from conventional average-group studies, successful classifications of EEG signals in N+ were observed during the 400-800 ms period post-cue-onset, which reflects preserved voluntary engagement of attention resources (ADAN component). These results suggest the possibility of acquiring reliable individual EEG profiles of neglect patients.

Number space is made by response space: Evidence from left spatial neglect.

Whether the semantic representation of numbers is endowed with an intrinsic spatial component, so that smaller numbers are inherently represented to the left of larger ones on a Mental Number Line (MNL), is a central matter of debate in numerical cognition. To gain an insight into this issue, we investigated the performance of right brain damaged patients with left spatial neglect (N+) in a bimanual Magnitude Comparison SNARC task and in a uni-manual Magnitude Comparison Go/No-Go task (i.e. "is the number smaller or larger than 5?"). While the first task requires the use of contrasting left/right spatial codes for response selection, the second task does not require the use of these codes. In line with previous evidence, in the SNARC task N+ patients displayed a significant asymmetry in Reaction Times (RTs), with slower RTs to number "4", that was immediately precedent to the numerical reference "5", with respect to the number "6", that immediately followed the same reference. This RTs asymmetry was correlated with lesion of white matter tracts, i.e. Fronto-Occipital-Fasciculus, that allows prefrontal Ba 8 and 46 to regulate the distribution of attention on sensory and memory traces in posterior occipital, temporal and parietal areas. In contrast, no similar RTs asymmetry was found in the Go/No-Go task. These findings suggest that while in the SNARC task numbers get mentally organised from left-to-right as a function of their increasing magnitude, so that N+ patients display a delay in the processing of number-magnitudes that are immediately smaller than a given numerical reference, in the Go/No-Go task no left-to-right organization is activated. These results support the idea that it is the use of contrasting left/right spatial codes, whether motor or conceptual, that triggers the generation of a spatially left-to-right organised MNL and that the representation of number magnitude is not endowed with an inherent spatial component.

How to trigger and keep stable directional Space-Number Associations (SNAs).

Humans are prone to mentally organise the ascending series of integers according to reading habits so that in western cultures small numbers are positioned to the left of larger ones on a mental number line. Despite 140 years since seminal observations by Sir Francis Galton (Galton, 1880a, b), the functional mechanisms that give rise to directional Space-Number Associations (SNAs) remain elusive. Here, we contrasted three different experimental conditions, each including a different version of a Go/No-Go task with intermixed numerical and arrow-targets (Shaki and Fischer, 2018; Pinto et al., 2019a). We show that directional SNAs are not "all or none" phenomena. We demonstrate that SNAs get progressively less noisy and more stable the more contrasting small/large magnitude-codes and contrasting left/right spatial-codes are explicitly and fully combined in the task set. The analyses of the time-course of space-number congruency effects showed that both the absence and presence of the SNA were independent of the speed of reaction times. In agreement with our original proposal (Aiello et al., 2012), these findings show that conceptualising the ascending series of integers in spatial terms depends on the use of spatial codes in the numerical task at hand rather than on the presence of an inherent spatial dimension in the semantic representation of numbers. This evidence suggests that directional SNAs, like the SNARC effect, are secondary to the primary transfer of spatial response codes to number stimuli, rather than deriving from a primary congruency or incongruence between independent spatial-response and spatial-number codes.

Pre-motor deficits in left spatial neglect: An EEG study on Contingent Negative Variation (CNV) and response-related beta oscillatory activity.

Right Brain Damaged patients with left spatial neglect (N+), are characterised by poor allocation of attention in the contralesional left side of space. In a recent study (Lasaponara et al., 2018) we showed during orienting of spatial attention with endogenous central cues, both the EEG markers reflecting the early phases of orienting (Early Directing Attention Negativity) and those reflecting the late setting-up of sensory facilitation in the visual cortex (Late Directing Attention Positivity) are disturbed in N+ when these patients attend the left side of space. In the healthy brain, endogenous cues also elicit EEG activity related to the preparation of manual responses to upcoming spatial targets. Here, we wished to expand on our previous findings and investigate the EEG correlates of cue-related response preparation in N+ patients. To this aim we investigated the Contingent Negative Variation (CNV) response and the pre-motor Beta-oscillatory activity evoked by spatially informative central cues during the performance of a Posner task. Due to concomitant contralesional motor impairments, N+ an N- patients performed the task only with the ipsilesional right-hand. Compared to healthy controls and patients without neglect, N+ displayed a pathological suppression of CNV component that was independent of cue direction. In addition, the amplitude of the CNV in response to right-pointing cues was positively correlated with neglect severity in line bisection. N+ also displayed a pathological enhancement of pre-motor Beta oscillations over the left hemisphere during the time period that preceded manual responses to targets in the left side of space, particularly to invalidly cued ones. Synchronization in the Beta-band (ERS) was also correlated with lower detection rate and slower RTs to Invalid targets in the left side of space. These results provide new insights on the premotor components of the spatial orienting deficits suffered by patients with left spatial neglect and can help improving its diagnosis and rehabilitation.

Expectancy modulates pupil size both during endogenous orienting and during re-orienting of spatial attention: A study with isoluminant stimuli.

We have recently demonstrated that when endogenous orienting of spatial attention is guided by central directional cues that reliably predict the position of lateral targets. Pupil Dilation (PDil) is higher as compared with directional cues that do not predict target position. These findings were interpreted as reflecting different levels of Locus Coeruleus-Noradrenergic activity during endogenous orienting. In contrast to this, we were not able to highlight reliable differences between PDil responses to infrequent invalid targets that are associated with predictive cues and frequent invalid targets that are associated with non-predictive ones. These null findings might have been due to the spurious influence of transitory changes in luminance at the moment of target presentation or to the short time window used for the analysis of target-related changes in PDil. Here, we re-explored cue- and target-related changes in PDil using cue and target stimuli that were kept isoluminant to their background and long lasting cue and target periods for data recording and analysis. We fully replicate our previous cue-related results and, in addition, we demonstrate that infrequent invalid targets in the predictive experimental condition evoke larger PDil as compared with frequent ones. Analyses with Linear Mixed Models highlighted that both during the cue and target period, higher levels of PDil were associated with slower reaction times. These findings confirm that PDil is a reliable marker of the expectancy components of endogenous cue-related and exogenous target-related orienting of spatial attention.

EEG Correlates of Preparatory Orienting, Contextual Updating, and Inhibition of Sensory Processing in Left Spatial Neglect.

Studies with event-related potentials have highlighted deficits in the early phases of orienting to left visual targets in right-brain-damaged patients with left spatial neglect (N+). However, brain responses associated with preparatory orienting of attention, with target novelty and with the detection of a match/mismatch between expected and actual targets (contextual updating), have not been explored in N+. Here in a study in healthy humans and brain-damaged patients of both sexes we demonstrate that frontal activity that reflects supramodal mechanisms of attentional orienting (Anterior Directing Attention Negativity, ADAN) is entirely spared in N+. In contrast, posterior responses that mark the early phases of cued orienting (Early Directing Attention Negativity, EDAN) and the setting up of sensory facilitation over the visual cortex (Late Directing Attention Positivity, LDAP) are suppressed in N+. This uncoupling is associated with damage of parietal-frontal white matter. N+ also exhibit exaggerated novelty reaction to targets in the right side of space and reduced novelty reaction for those in the left side (P3a) together with impaired contextual updating (P3b) in the left space. Finally, we highlight a drop in the amplitude and latency of the P1 that over the left hemisphere signals the early blocking of sensory processing in the right space when targets occur in the left one: this identifies a new electrophysiological marker of the rightward attentional bias in N+. The heterogeneous effects and spatial biases produced by localized brain damage on the different phases of attentional processing indicate relevant functional independence among their underlying neural mechanisms and improve the understanding of the spatial neglect syndrome.SIGNIFICANCE STATEMENT Our investigation answers important questions: are the different components of preparatory orienting (EDAN, ADAN, LDAP) functionally independent in the healthy brain? Is preparatory orienting of attention spared in left spatial neglect? Does the sparing of preparatory orienting have an impact on deficits in reflexive orienting and in the assignment of behavioral relevance to the left space? We show that supramodal preparatory orienting in frontal areas is entirely spared in neglect patients though this does not counterbalance deficits in preparatory parietal-occipital activity, reflexive orienting, and contextual updating. This points at relevant functional dissociations among different components of attention and suggests that improving voluntary attention in N+ might be behaviorally ineffective unless associated with stimulations boosting the response of posterior parietal-occipital areas.

Visualising numerals: An ERPs study with the attentional SNARC task.

Inspecting or transforming the position of Arabic numbers in mental space helps everyday mathematical calculations. Nonetheless the neural and functional bases of this ability are poorly understood. Here we show that imagining the position of Arabic numbers on a horizontal mental number line speeds up the detection of targets appearing at corresponding positions in visual space. No similar advantage is found when numbers are merely perceived or classified according to their magnitude. Imagery enhanced electrophysiological activity in the extrastriate cortex contralateral to the imagined number position. Speeded detection of targets that were spatially congruent with the imagined number position was matched with enhanced C1 responses in primary visual cortex. In contrast, imagery had no effect on later target-related responses that are usually modulated by spatial attention. These results shed new light on the mechanisms that evoke sensory-like spatial representations of Arabic numbers in everyday mental computations.

Changes in predictive cuing modulate the hemispheric distribution of the P1 inhibitory response to attentional targets.

Brain activity related to orienting of attention with spatial cues and brain responses to attentional targets are influenced the probabilistic contingency between cues and targets. Compared to predictive cues, cues predicting at chance the location of targets reduce the filtering out of uncued locations and the costs in reorienting attention to targets presented at these locations. Slagter et al. (2016) have recently suggested that the larger target related P1 component that is found in the hemisphere ipsilateral to validly cued targets reflects stimulus-driven inhibition in the processing of the unstimulated side of space contralateral to the same hemisphere. Here we verified whether the strength of this inhibition and the amplitude of the corresponding P1 wave are modulated by the probabilistic link between cues and targets. Healthy participants performed a task of endogenous orienting once with predictive and once with non-predictive directional cues. In the non-predictive condition we observed a drop in the amplitude of the P1 ipsilateral to the target and in the costs of reorienting. No change in the inter-hemispheric latencies of the P1 was found between the two predictive conditions. The N1 facilitatory component was unaffected by predictive cuing. These results show that the predictive context modulates the strength of the inhibitory P1 response and that this modulation is not matched with changes in the inter-hemispheric interaction between the P1 generators of the two hemispheres.

[Bereavement and complicated grief: towards a definition of Prolonged Grief Disorder for DSM-5]. / Eventi di perdita e lutto complicato: verso una definizione di disturbo da sofferenza prolungata per il DSM-5.

Mourning is a natural response to a loss and a condition which most people experience several times during their lives. Most individuals adjust adequately to the loss of a relative, neverthless, a small but noteworthy proportion of bereaved individuals experience a syndrome of prolonged psychological distress in relation to bereavement. Prolonged distress and disability in connection with bereavement has been termed Complicated Grief (CG) or Prolonged Grief Disorder (PGD). The purpose of this paper is to analyze the literature on loss and mourning making a review of the main studies published between 1993 and 2013, identified through a search conducted on Medline/PubMed, in order to describe the epidemiological and clinical aspects of "normal" grief and "complicated" grief, pointing out the path of the clinical definition of PGD and proposed diagnostic criteria for inclusion in the next edition of the Diagnostic and Statistic Manual of Mental Disorders, Fifth edition (DSM-5). The two main diagnostic systems proposed by Horowitz and Prigerson are also compared.