Differences between endogenous attention to spatial locations and sensory modalities.

Vibell et al. (J Cogn Neurosci 19:109-120, 2007) reported that endogenously attending to a sensory modality (vision or touch) modulated perceptual processing, in part, by the relative speeding-up of neural activation (i.e., as a result of prior entry). However, it was unclear whether it was the fine temporal discrimination required by the temporal-order judgment task that was used, or rather, the type of attentional modulation (spatial locations or sensory modalities) that was responsible for the shift in latencies that they observed. The present study used a similar experimental design to evaluate whether spatial attention would also yield similar latency effects suggestive of prior entry in the early visual P1 potentials. Intriguingly, while the results demonstrate similar neural latency shifts attributable to spatial attention, they started at a somewhat later stage than seen in Vibell et al.'s study. These differences are consistent with different neural mechanisms underlying attention to a specific sensory modality versus to a spatial location.

Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.

Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

CREB engages C/EBPδ to initiate leukemogenesis.

cAMP response element binding protein (CREB) is frequently overexpressed in acute myeloid leukemia (AML) and acts as a proto-oncogene; however, it is still debated whether such overactivation alone is able to induce leukemia as its pathogenetic downstream signaling is still unclear. We generated a zebrafish model overexpressing CREB in the myeloid lineage, which showed an aberrant regulation of primitive hematopoiesis, and in 79% of adult CREB-zebrafish a block of myeloid differentiation, triggering to a monocytic leukemia akin the human counterpart. Gene expression analysis of CREB-zebrafish revealed a signature of 20 differentially expressed human homologous CREB targets in common with pediatric AML. Among them, we demonstrated that CREB overexpression increased CCAAT-enhancer-binding protein-δ (C/EBPδ) levels to cause myeloid differentiation arrest, and the silencing of CREB-C/EBPδ axis restored myeloid terminal differentiation. Then, C/EBPδ overexpression was found to identify a subset of pediatric AML affected by a block of myeloid differentiation at monocytic stage who presented a significant higher relapse risk and the enrichment of aggressive signatures. Finally, this study unveils the aberrant activation of CREB-C/EBPδ axis concurring to AML onset by disrupting the myeloid cell differentiation process. We provide a novel in vivo model to perform high-throughput drug screening for AML cure improvement.

Temporal order is coded temporally in the brain: early event-related potential latency shifts underlying prior entry in a cross-modal temporal order judgment task.

The speeding-up of neural processing associated with attended events (i.e., the prior-entry effect) has long been proposed as a viable mechanism by which attention can prioritize our perception and action. In the brain, this has been thought to be regulated through a sensory gating mechanism, increasing the amplitudes of early evoked potentials while leaving their latencies unaffected. However, the majority of previous research has emphasized speeded responding and has failed to emphasize fine temporal discrimination, thereby potentially lacking the sensitivity to reveal putative modulations in the timing of neural processing. In the present study, we used a cross-modal temporal order judgment task while shifting attention between the visual and tactile modalities to investigate the mechanisms underlying selective attention electrophysiologically. Our results indicate that attention can indeed speed up neural processes during visual perception, thereby providing the first electrophysiological support for the existence of prior entry.

Illusory movements of the contralesional hand in patients with body image disorders.

OBJECTIVES: In the present study, we assess whether illusory sensations of movement can be elicited in patients with right brain damage (RBD). METHODS: Ten RBD patients (three with disorders of bodily representations) were asked to report whether movements of their right hand induced any illusory somatic or motor sensations. Inquiries on anomalous sensation of movement of the left hand were carried out while subjects: 1) observed the moving hand in a mirror propped vertically along the parasagittal plane; 2) looked directly at the moving hand; 3) looked at the still hand; 4) kept their eyes closed. Twelve healthy subjects served as controls. RESULTS: Movement of the right hand induced a very clear sensation of movement of the left, contralesional hand in two patients affected by body image disorders. Remarkably, this occurred mainly while subjects were looking in the mirror, that is, when conflicts between visual, somatic, and motor information were maximal. In no condition did control subjects report any consistent anomalous evoked movement or sensation. CONCLUSIONS: Illusory movements of the left, plegic hand contingent upon sensorimotor conflicts can be evoked in brain damaged patients with body image disorders.

The role of auditory cues in modulating the perception of electric toothbrushes.

Recent research shows that what people hear can influence what they feel. We investigated whether the perception of an electric toothbrush might also be affected by the sound that it makes. Participants were required to make stereotypical brushing movements with a standard electric toothbrush while they rated either the pleasantness or the roughness of the vibrotactile stimulation they felt on their teeth. The results demonstrate that the perception of the sensations experienced during toothbrush use were systematically altered by variations in the auditory feedback elicited by the brushing action. Participants reported that the toothbrush felt more pleasant and less rough when either the overall sound level was reduced, or when just the high-frequency sounds were attenuated. These results highlight the significant role that auditory cues can play in modulating the perception and evaluation of everyday products in use, and provide a paradigm for future study in this area.

Neuropsychological evidence that somatic stimuli are spatially coded according to multiple frames of reference in a stroke patient with tactile extinction.

A right-brain damaged patient with pure tactile extinction was asked to report series of single or double light, brief touches delivered to both hands, the thumb or the pinkie of a single hand, the sides of a single index. The stimulated hand was positioned palm up or palm down, in front of or behind the patient, in anatomic or crossed position. In double touch conditions, stimuli coded as left-sided were extinguished not only when delivered to both hands, but also when delivered on a single hand or a single finger. The findings suggest that tactile stimuli may be coded as left or right according to multiple body anchors that are dynamically scaled from the corporeal midline, to axes centered on a single hand or finger.