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Introduction: Homonymous visual field defects (HVFDs) following acquired brain lesions affect independent living by hampering several activities of everyday life. Available treatments are intensive and week- or month-long. Transcranial Direct current stimulation (tDCS), a plasticity-modulating non-invasive brain stimulation technique, could be combined with behavioral trainings to boost their efficacy or reduce treatment duration. Some promising attempts have been made pairing occipital tDCS with visual restitution training, however less is knows about which area/network should be best stimulated in association with compensatory approaches, aimed at improving exploratory abilities, such as multisensory trainings. Methods: In a proof-of-principle, sham-controlled, single-blind study, 15 participants with chronic HVFDs underwent four one-shot sessions of active or sham anodal tDCS applied over the ipsilesional occipital cortex, the ipsilesional or contralesional posterior parietal cortex. tDCS was delivered during a compensatory multisensory (audiovisual) training. Before and immediately after each tDCS session, participants carried out a visual detection task, and two visual search tasks (EF and Triangles search tests). Accuracy (ACC) and response times (RTs) were analyzed with generalized mixed models. We investigated differences in baseline performance, clinical-demographic and lesion factors between tDCS responders and non-responders, based on post-tDCS behavioral improvements. Lastly, we conducted exploratory analyses to compare left and right brain-damaged participants. Results: RTs improved after active ipsilesional occipital and parietal tDCS in the visual search tasks, while no changes in ACC were detected. Responders to ipsilesional occipital tDCS (Triangle task) had shorter disease duration and smaller lesions of the parietal cortex and the superior longitudinal fasciculus. On the other end, on the EF test, those participants with larger damage of the tempo

Patients suffering from Unilateral Spatial Neglect (USN) fail to pay attention to, respond to, and report sensory events occurring in the contralesional side of space. The traditional neuropsychological assessment of USN is based on paper-and-pencil tests, whose data recording and scoring may be subjected to human error. The utilization of technological devices can be expected to improve the assessment of USN. Therefore, we built Neurit.Space, a modified digital version of three paper-and-pencil tests, widely used to detect signs of USN, namely: Bells Cancellation, Line Bisection and Five Elements Drawing Test. Administration and data processing is fully automatic. Twelve right brain-damaged patients (six with and six without USN) and 12 age- and education-balanced healthy participants were enrolled in the study. All participants were administered both the computerized and the paper-and-pencil versions of the tests. The results of this preliminary study showed good sensitivity, specificity, and usability of Neurit.Space, suggesting that these digital tests are a promising tool for the evaluation of USN, both in clinical and in research settings.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 “neglect” patients exhibited clear signs of neglect on our task as compared to “non-neglect” patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

Temporal Binding Window (TBW) represents a reliable index of efficient multisensory integration process, which allows individuals to infer which sensory inputs from different modalities pertain to the same event. TBW alterations have been reported in some neurological and neuropsychiatric disorders and seem to negatively affects cognition and behavior. So far, it is still unknown whether deficits of multisensory integration, as indexed by an abnormal TBW, are present even in Multiple Sclerosis. We addressed this issue by testing 25 participants affected by relapsing–remitting Multiple Sclerosis (RRMS) and 30 age-matched healthy controls. Participants completed a simultaneity judgment task (SJ2) to assess the audio-visual TBW; two unimodal SJ2 versions were used as control tasks. Individuals with RRMS showed an enlarged audio-visual TBW (width range = from − 166 ms to + 198 ms), as compared to healthy controls (width range = − 177/ + 66 ms), thus showing an increased tendency to integrate temporally asynchronous visual and auditory stimuli. Instead, simultaneity perception of unimodal (visual or auditory) events overall did not differ from that of controls. These results provide first evidence of a selective deficit of multisensory integration in individuals affected by RRMS, besides the well-known motor and cognitive impairments. The reduced multisensory temporal acuity is likely caused by a disruption of the neural interplay between different sensory systems caused by multiple sclerosis.

Visuo-motor adaptation to optical prisms (Prism Adaptation, PA), displacing the visual scene laterally, is a behavioral method used for the experimental investigation of visuomotor plasticity, and, in clinical settings, for temporarily ameliorating and rehabilitating unilateral spatial neglect. This study investigated the building up of PA, and the presence of the typically occurring subsequent Aftereffects (AEs) in a brain-damaged patient (TMA), suffering from apperceptive agnosia and a right visual half-field defect, with bilateral atrophy of the parieto-occipital cortices, regions involved in PA and AEs. Base-Right prisms and control neutral lenses were used. PA was achieved by repeated pointing movements toward three types of stimuli: visual, auditory, and bimodal audio-visual. The presence and the magnitude of AEs were assessed by proprioceptive, visual, visuo-proprioceptive, and auditory-proprioceptive straight-ahead pointing tasks. The patient’s brain connectivity was investigated by Diffusion Tensor Imaging (DTI). Unlike control participants, TMA did not show any adaptation to prism exposure, but her AEs were largely preserved. These findings indicate that AEs may occur even in the absence of PA, as indexed by the reduction of the pointing error, showing a dissociation between the classical measures of PA and AEs. In the PA process, error reduction, and its feedback, may be less central to the building up of AEs, than the sensorimotor pointing activity per se.

Background: To quantify the degree of ganglion cell degeneration through spectral domain optical coherence tomography (SD-OCT) in adult patients with post-stroke homonymous visual field defect. Methods: Fifty patients with acquired visual field defect due to stroke (mean age = 61 years) and thirty healthy controls (mean age = 58 years) were included. Mean deviation (MD) and pattern standard deviation (PSD), average peripapillary retinal nerve fibre layer thickness (pRNLF-AVG), average ganglion cell complex thickness (GCC-AVG), global loss volume (GLV) and focal loss volume (FLV) were measured. Patients were divided according to the damaged vascular territories (occipital vs. parieto-occipital) and stroke type (ischaemic vs. haemorrhagic). Group analysis was conducted with ANOVA and multiple regressions. Results: pRNFL-AVG was significantly decreased among patients with lesions in parieto-occipital territories compared to controls and to patients with lesions in occipital territories (p =.04), with no differences with respect to stroke type. GCC-AVG, GLV and FLV differed in stroke patients and controls, regardless of stroke type and involved vascular territories. Age and elapsed time from stroke had a significant effect on pRNFL-AVG and GCC-AVG (p <.01), but not on MD and PSD. Conclusions: Reduction of SD-OCT parameters occurs following both ischaemic and haemorrhagic occipital stroke, but it is larger when the injury extends to parietal territories and increases as time since stroke increases. The size of visual field defect is unrelated to SD-OCT measurements. Macular GCC thinning appeared to be more sensitive than pRNFL in detecting retrograde retinal ganglion cell degeneration and its retinotopic pattern in stroke.

Unilateral spatial neglect (USN) is a neuropsychological syndrome, typically caused by lesions of the right hemisphere, whose features are the defective report of events occurring in the left (contralesional) side of space and the inability to orient and set up actions leftwards. Multisensory integration mechanisms, largely spared in USN patients, may temporally modulate spatial orienting. In this pilot study, the effects of an intensive audio-visual Multisensory Stimulation (MS) on USN were assessed, and compared with those of a treatment that ameliorates USN, Prismatic Adaptation (PA). Twenty USN stroke patients received a 2-week treatment (20 sessions, twice per day) of MS or PA. The effects of MS and PA were assessed by a set of neuropsychological clinical tests (target cancellation, line bisection, sentence reading, personal neglect, complex drawing) and the Catherine Bergego Scale for functional disability. Results showed that MS brought about an amelioration of USN deficits overall comparable to that induced by PA; personal neglect was improved only by MS, not by PA. The clinical gains of the MS treatment were not influenced by duration of disease and lesion volume, and they persisted up to one month post-treatment. In conclusion, MS represents a novel and promising rehabilitation procedure for USN.

Motor learning interacts with and shapes experience-dependent cerebral plasticity. In stroke patients with paresis of the upper limb, motor recovery was proposed to reflect a process of re-learning the lost/impaired skill, which interacts with rehabilitation. However, to what extent stroke patients with hemiparesis may retain the ability of learning with their affected limb remains an unsolved issue, that was addressed by this study. Nineteen patients, with a cerebrovascular lesion affecting the right or the left hemisphere, underwent an explicit motor learning task (finger tapping task, FTT), which was performed with the paretic hand. Eighteen age-matched healthy participants served as controls. Motor performance was assessed during the learning phase (i.e., online learning), as well as immediately at the end of practice, and after 90 min and 24 h (i.e., retention). Results show that overall, as compared to the control group, stroke patients, regardless of the side (left/right) of the hemispheric lesion, do not show a reliable practice-dependent improvement; consequently, no retention could be detected in the long-term (after 90 min and 24 h). The motor learning impairment was associated with subcortical damage, predominantly affecting the basal ganglia; conversely, it was not associated with age, time elapsed from stroke, severity of upper-limb motor and sensory deficits, and the general neurological condition. This evidence expands our understanding regarding the potential of post-stroke motor recovery through motor practice, suggesting a potential key role of basal ganglia, not only in implicit motor learning as previously pointed out, but also in explicit finger tapping motor tasks.

Recent neuropsychological evidence suggests that acquired brain lesions can, in some instances, abolish the ability to integrate inputs from different sensory modalities, disrupting multisensory perception. We explored the ability to perceive multisensory events, in particular the integrity of audio-visual processing in the temporal domain, in brain-damaged patients with visual field defects (VFD), or with unilateral spatial neglect (USN), by assessing their sensitivity to the 'Sound-Induced Flash Illusion' (SIFI). The study yielded two key findings. Firstly, the 'fission' illusion (namely, seeing multiple flashes when a single flash is paired with multiple sounds) is reduced in both left- and right-brain-damaged patients with VFD, but not in right-brain-damaged patients with left USN. The disruption of the fission illusion is proportional to the extent of the occipital damage. Secondly, a reliable 'fusion' illusion (namely, seeing less flashes when a single sound is paired with multiple flashes) is evoked in USN patients, but neither in VFD patients nor in healthy participants. A control experiment showed that the fusion, but not the fission, illusion is lost in older participants (>50 year-old), as compared with younger healthy participants (<30 year-old). This evidence indicates that the fission and fusion illusions are dissociable multisensory phenomena, altered differently by impairments of visual perception (i.e. VFD) and spatial attention (i.e. USN). The occipital cortex represents a key cortical site for binding auditory and visual stimuli in the SIFI, while damage to right-hemisphere areas mediating spatial attention and awareness does not prevent the integration of audio-visual inputs in the temporal domain.

We have investigated the capacity of two human immunodeficiency virus type 1-derived lentivectors, differing in the presence of a ll8-bp pol fragment containing the cPPT/CTS element, to transduce human normal primary cells of different hematopoietic lineages. Infection of resting monocytes with a high multiplicity of infection (MOI > 10) revealed that the lentivirus carrying the pol fragment (cPPT) is effective, transducing 75% of cells compared with 36% for the no-cPPT vector. Even at low MOIs (≤1) the cPPT vector still shows a better transduction efficiency than the no-cPPT vector. Moreover, transduction does not require dendritic cell differentiation. In contrast, infection of nonactivated T lymphocytes showed that both vectors, tested at high MOIs, can transduce a small, although measurable, percentage of cells (up to 10%), which may correspond to Gla "activated" cells as detected by simultaneous staining of DNA and RNA, in our cultures in the presence of medium alone. Furthermore, we show that the sole addition of interleukin 2 or interleukin 15 represents a full proliferative signal under our conditions and permits high transduction efficiency (up to 30% with the cPPT vector and 15% with the no-cPPT vector). Still higher transduction of T lymphocytes can be achieved after stimulation with phytohemagglutinin and interleukin 2 (up to 78% with the cPPT vector vs. 42% with the no-cPPT vector). Finally, both viruses do not transduce either resting or proliferating tonsillar B lymphocytes.

Moloney murine leukemia virus (MMLV)-based vectors have been widely used in vitro and in clinical studies. Subsequently, HIV-1 derived lentivectors were introduced1 in which the env, vif, vpr, vpu and nef genes are deleted.2 Another version of the lentivector has been developed which contains a 118 bp non-coding sequence from the HIV-1 pol gene.3,4 We compare the capacity of these different retroviruses5-7 to transduce human hematopoietic lines.

Adaptation to optical prisms displacing the visual scene laterally is a widely investigated instance of visuo-motor plasticity, also because prism adaptation (PA) has been extensively used as a treatment for right-brain-damaged patients suffering from left spatial neglect. The lateral visual displacement brought about by prisms, as indexed by a pointing error in the direction of the displacement, is progressively corrected through repeated pointings: after prism removal, a shift in the direction opposite to the prism-induced deviation occurs in visual, proprioceptive, and visuo-proprioceptive straight-ahead tasks (aftereffects, AEs). The cerebellum and the posterior parietal cortex (PPC) are key components of the bilateral cerebral network subserving the AEs, and the reduction of the pointing error during prism exposure in PA. We report the experimental study of a patient with bilateral occipital and left cerebellar damage, who showed a preserved reduction of the pointing errors to rightward displacing prisms, but not the leftward AEs in the proprioceptive straight-ahead task; instead, visual-proprioceptive and visual AEs were preserved. Anodal transcranial Direct Current Stimulation (tDCS) over the left PPC restored the leftward proprioceptive AEs, and anodal tDCS over the left cerebellum abolished the rightward deviation. Conversely, stimulation over the right PPC or the right cerebellum was ineffective. These results provide novel evidence for neuromodulatory effects of tDCS on defective AEs, through the stimulation over dedicated cortical regions.

This study investigates whether the rubber hand illusion (RHI) can induce a remission of somatoparaphrenia, a somatic delusion usually following righthemisphere damage, which typically manifests as a defective sense of ownership of one's contralesional body parts. First, we show that patients with somatoparaphrenia can experience a reliable RHI, exhibiting illusory effects similar to those reported by healthy participants. Moreover, synchronous touches applied to the patients' visible disowned left hand (rather than to the rubber hand), and to their right invisible unimpaired hand, induce an immediate self-attribution of the disowned hand, without affecting other sensorimotor or attentional disorders. The higher-level representation of the body concerned with ownership, deranged as a somatic delusion in patients with somatoparaphrenia, is penetrable, and can be restored by multisensory stimulations. © 2014 American Academy of Neurology.

BACKGROUND: Recovery of motor function after stroke may depend on a balance of activity in the neural network involving the affected and the unaffected motor cortices. OBJECTIVE: To assess whether transcranial direct current stimulation (tDCS) can increase the training-induced recovery of motor functions. METHODS: In an exploratory study, 14 patients with chronic stroke and mean Fugl-Meyer Upper Extremity Motor Assessment of 29 (range = 8-50) entered a double-blind sham-controlled study, aimed to investigate neurophysiological and behavioral effects of bihemispheric tDCS (cathodal stimulation of the unaffected motor cortex and anodal stimulation of the affected motor cortex), combined with constraint-induced movement therapy (CIMT). RESULTS: Patients in both groups demonstrated gains on primary outcome measures, that is, Jebsen Taylor Hand Function Test, Handgrip Strength, Motor Activity Log Scale, and Fugl-Meyer Motor Score. Gains were larger in the active tDCS group. Neurophysiological measurements showed a reduction in transcallosal inhibition from the intact to the affected hemisphere and increased corticospinal excitability in the affected hemisphere only in the active tDCS/CIMT group. Such neurophysiological changes correlated with the magnitude of the behavioral gains. Both groups showed a reduction in corticospinal excitability of the unaffected hemisphere. CONCLUSIONS: CIMT alone appears effective in modulating local excitability but not in removing the imbalance in transcallosal inhibition. Bihemispheric tDCS may achieve this goal and foster greater functional recovery.

This study explores whether brain polarization could be effective in modulating multisensory audiovisual interactions in the human brain, as measured by the 'sound-induced flash illusion' (Shams et al., 2000). In different sessions, healthy participants performed the task while receiving anodal, cathodal, or sham tDCS (2 mA, 8 min) to the occipital, temporal, or posterior parietal cortices. We found that up- or down-regulating cortical excitability by tDCS can facilitate or reduce audiovisual illusions, depending on the current polarity, the targeted area, and the illusory percept. Specifically, the perceptual 'fission' of a single flash, due to multiple beeps, was increased after anodal tDCS of the temporal cortex, and decreased after anodal stimulation of the occipital cortex. A reversal of such effects was induced by cathodal tDCS. Conversely, the perceptual 'fusion' of multiple flashes due to a single beep was unaffected by tDCS. This evidence adds novel clues on the cortical substrate of the generation of the sound-flash illusion, and opens new attractive possibilities for modulating multisensory perception in humans: tDCS appears to be an effective tool to modulate the conscious visual experience associated with multisensory interactions, by noninvasively shifting cortical excitability within occipital or temporal areas. (C) 2010 Elsevier Ltd. All rights reserved.

Recent evidence suggests that behavioural gains induced by behavioural training are maximized when combined with techniques of cortical neuromodulation, such as transcranial Direct Current Stimulation (tDCS). Here we address the validity of this appealing approach by investigating the effect of coupling a multisensory visual field exploration training with tDCS of the posterior parietal cortex (PPC). The multisensory visual field exploration training consisted in the practice of visual search through the systematic audio-visual stimulation of the visual field. Neurologically unimpaired participants performed a bimodal exploration training for 30 min, while simultaneously receiving anodal-excitatory PPC tDCS or sham tDCS. In two different experiments, the left and the right hemisphere were stimulated. Outcome measures included visual exploration speed at different time intervals during the training, and the post-training effects on tests assessing visual scanning and visuo-spatial orienting. Results show that PPC tDCS applied to the right, but not to the left, hemisphere increases the training-induced behavioural improvement of visual exploration, as compared to sham tDCS. In addition, right PPC tDCS brings about an improvement of covert visual orienting, in a task different from the visual search practice. In an additional experiment, we confirm that right parietal tDCS by itself, even without the associated training, can lead to enhancement of visual search. Overall, anodal PPC tDCS is a promising technique to enhance visuo-spatial abilities, when combined to a visual field exploration training task. © 2010 Elsevier B.V.

Gene manipulation and cell vaccines represent innovative strategies to enhance the immunogenicity of cancer cells. We adopted a defective lentivirus derived from the human immunodeficiency virus (HIV)-1 backbone and carrying the enhanced green fluorescent protein (EGFP) gene to transduce primary human acute myelogenous leukemia (AML) and B-precursor acute lymphoblastic leukemia (ALL) cells

Human congenital hypotransferrinemia is a rare disorder characterized by the virtual absence of transferrin in the serum. No information on the causes of the disease is known.