Left egocentric neglect in early subacute right-stroke patients is related to damage of the superior longitudinal fasciculus.

A typical consequence of stroke in the right hemisphere is unilateral spatial neglect. Distinct forms of neglect have been described, such as space-based (egocentric) and object-based (allocentric) neglect. However, the relationship between these two forms of neglect is still far from being understood, as well as their neural substrates. Here, we further explore this issue by using voxel lesion symptoms mapping (VLSM) analyses on a large sample of early subacute right-stroke patients assessed with the Apples Cancellation Test. This is a sensitive test that simultaneously measures both egocentric and allocentric neglect. Behaviourally, we found no correlation between egocentric and allocentric performance, indicating independent mechanisms supporting the two forms of neglect. This was confirmed by the VLSM analysis that pointed out a link between a damage in the superior longitudinal fasciculus and left egocentric neglect. By contrast, no association was found between brain damage and left allocentric neglect. These results indicate a higher probability to observe egocentric neglect as a consequence of white matter damages in the superior longitudinal fasciculus, while allocentric neglect appears more "globally" related to the whole lesion map. Overall, these findings on early subacute right-stroke patients highlight the role played by white matter integrity in sustaining attention-related operations within an egocentric frame of reference

Mapping spatial neglect symptoms in the brain: a preliminary report from a single case.

Background Following injury to the right parietal cortex, patients typically show unilateral spatial neglect, a complex syndrome associated with a reduced capability to orient attentional resources toward the contralateral side of space [1]. Visual extinction is one of the most prominent symptoms of unilateral spatial neglect. In visual extinction, a transient stimulus presented in the right hemifield ‘extinguishes’ from awareness an homologue stimulus simultaneously presented in the left hemifield. This is thought to be a consequence of the residual activity of the left – non damaged – parietal cortex [1-4]. Surprisingly, however, this hypothesis has been largely unexplored to date in real neglect patients. Here we used functional magnetic resonance imaging (fMRI) to identify brain regions contributing to visual extinction in a stroke patient with unilateral spatial neglect and in four healthy controls. Method During fMRI, all participants were presented with a target stimulus (i.e., a black square of 2x2°; 10° apart from the central fixation point), that equiprobably appeared on either the left, right or both hemifields. Participants pressed one of three response buttons to indicate the hemifield(s) of appearance of the target, left, right, or bilateral. Results Behaviourally, we found 100% accuracy in control subjects, irrespective of the target side, left, right or bilateral. By contrast, the neglect patient systematically failed to detect bilateral targets (0% of accuracy). Importantly, “bilateral” targets were perceived by the patient as “right” targets in the great majority of trials (93,75%). Moreover, the patient showed a decreased capability in detecting left (44%) vs. right targets (100%). The fMRI analysis revealed in the patient a greater activation of the left posterior parietal cortex, namely of the left angular gyrus (x, y, z = -44, -68, 30), when comparing detection of bilateral vs. unilateral (left and right) targets. The same comparison revealed no significant activations in the control group. Conclusions Our findings provides empirical evidence that confirm the crucial role played by the left parietal cortex during visual extinction in spatial neglect, providing important insights for the current models of unilateral spatial neglect

Mapping spatial neglect symptoms in patients with stroke

Background Following injury to the right parietal cortex (e.g. right-sided stroke), patients typically show unilateral spatial neglect, a complex syndrome associated with a reduced capability to orient attentional resources toward the contralateral side of space. One of the most prominent symptoms is the visual extinction in which a transient stimulus presented in the right hemifield ‘extinguishes’ from awareness an homologue stimulus simultaneously presented in the left hemifield. This is thought to be a consequence of the residual activity of the left – non damaged – parietal cortex. Surprisingly, however, this hypothesis has been largely unexplored to date in real neglect patients. In this study we used functional magnetic resonance imaging (fMRI) to identify brain regions contributing to visual extinction assessing three groups of subjects: right-sided stroke patients with (N = 3) or without unilateral spatial neglect (N = 3) and age-/gender-matched healthy controls (N = 10). Method During fMRI, all participants were presented with a target stimulus (i.e., a black square of 2x2°; 10° apart from the central fixation point), that equiprobably appeared on either the left, right or both hemifields. Participants pressed one of three response buttons to indicate the hemifield(s) of appearance of the target, left, right, or bilateral. Results We found 100% accuracy in control subjects, irrespective of the target side, left, right or bilateral. By contrast, neglect patients failed to detect bilateral targets (16,3% of accuracy). Importantly, “bilateral” targets were perceived by neglect patients as “right” targets in the great majority of trials (66,25%). Moreover, neglect patients showed a decreased capability in detecting left (48,8%) vs. right targets (86,3%). The fMRI analysis revealed a greater task-related activity of the left fronto-parietal cortex in neglect vs. non-neglect patients and controls. Conclusions Our findings provide empirical evidence that confirm the crucial role played by the residual neural resources in the left fronto-parietal cortex during visual extinction in spatial neglect, providing important insights for the current models of unilateral spatial neglect in patients with right-sided stroke

Using task-based fMRI to understand attentional mechanisms in healthy controls

Background. Hemispatial neglect is a complex syndrome associated with a reduced capability to orient attentional resources toward the contralateral side of space, that involves a collection of symptoms. We used three functional magnetic resonance imaging (fMRI) tasks (i.e., visual search, VS; line bisection, LB; extinction, EX), performed by 25 healthy subjects, to investigate the behavioral and neural correlates under these symptoms. Procedure. During fMRI, participants were presented with: 1. VS: an array containing 8-12 stimuli such as O-like (target) and Q-like (distractors) shapes projected on both sides 2. LB: a bisected line covering 18° of visual angle 3. EX: a black square (target) of 2x2° that equiprobably appeared on either the left, right or both hemifields Participants pressed one of three response buttons to indicate: left, right and bilateral (i.e., for EX) or central (i.e., for LB). Results fMRI data showed an increased activation in the right angular gyrus comparing bilateral vs. unilateral stimulus in EX, and a bilateral occipital activation comparing high vs. low load stimulus in VS, highlighting that in both cases subjects make an effort performing the task. These results are confirmed behaviourally, in fact subjects are less accurate when they are presented with bilateral (97,8% vs. 99,5% in unilateral) and high load (88,9% vs. 93,1% low load) stimulus. There are no significant activations regarding LB task. Conclusions We found that in healthy conditions the right attentional network is involved in processing simultaneous stimuli and bilateral visual cortex is involved in processing the high load of stimuli. Our findings provide a prior knowledge that can be used to compare with attentional mechanisms in neglect patients performing the same tasks. This will allow us to cluster at least three neglect symptoms, in terms of brain activations raised from compensation mechanisms, due to brain impairments

A recellularized human colon model identifies cancer driver genes

Refined cancer models are needed to bridge the gap between cell-line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. 38 candidate invasion driver genes were identified, 17 of which have been previously implicated in colorectal cancer progression, including TCF7L2, TWIST2, MSH2, DCC and EPHB1/2. Six invasion driver genes that to our knowledge have not been previously described were validated in vitro using cell proliferation, migration and invasion assays, and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose-and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for ge-netic vaccine development, especially when robust CD8 response is needed