Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations.

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.

IgE Ratio in Tears: A Predictive Tool of Ocular Allergic Inflammation.

PURPOSE: To demonstrate the tear IgE (measured/exuded) ratio (R) as a useful biological marker of ocular allergy in order to distinguish severe from less severe inflammatory status. METHODS: Tear samples and sera from 78 ocular allergy patients and 19 control subjects were analyzed. Total IgE and albumin were measured for calculating the tear IgE-R defining two subgroups (SG) of samples: R ≥ 4-SG and R < 4-SG. Eosinophil cationic protein, Th1 and Th2 cytokines (IFN-γ, IL-4, -5, -6, -8 and -10) and protein electrophoretic profiles were also investigated in tears. RESULTS: The R < 4-SG compared to the R ≥ 4-SG shows higher levels of tear albumin, eosinophil cationic protein, and Th1 and Th2 cytokines. Moreover, each subgroup presents a specific protein profile. CONCLUSION: This study showed that an IgE-R lower than four must be carefully interpreted as a warning sign of a severe inflammatory context and should be also associated with an exploration of immunological profile.

Blindness and social trust: The effect of early visual deprivation on judgments of trustworthiness.

Investigating the impact of early visual deprivation on evaluations related to social trust has received little attention to date. This is despite consistent evidence suggesting that early onset blindness may interfere with the normal development of social skills. In this study, we investigated whether early blindness affects judgments of trustworthiness regarding the actions of an agent, with trustworthiness representing the fundamental dimension in the social evaluation. Specifically, we compared performance between a group of early blind individuals with that of sighted controls in their evaluation of trustworthiness of an agent after hearing a pair of two positive or two negative social behaviors (impression formation). Participants then repeated the same evaluation following the presentation of a third (consistent or inconsistent) behavior regarding the same agent (impression updating). Overall, blind individuals tended to give similar evaluations compared to their sighted counterparts. However, they also valued positive behaviors significantly more than sighted controls when forming their impression of an agent's trustworthiness. Moreover, when inconsistent information was provided, blind individuals were more prone to revise their initial evaluation compared to controls. These results suggest that early visual deprivation may have a dramatic effect on the evaluation of social factors such as trustworthiness.

Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS.

Transcranial direct current stimulation (tDCS) has recently emerged as a promising approach to enhance neurorehabilitative outcomes. However, little is known about how the local electrical field generated by tDCS relates to underlying neuroplastic changes and behavior. To address this question, we present a case study analysis of an individual with hemianopia due to stroke and who benefited from a combined visual rehabilitation training and tDCS treatment program. Activation associated with a visual motion perception task (obtained by functional magnetic resonance imaging; fMRI) was used to characterize local changes in brain activity at baseline and after training. Individualized, high-resolution electrical field modeling reproducing precise cerebral and lesioned tissue geometry, predicted distortions of current flow in peri-lesional areas and diffuse clusters of peak electric fields. Using changes in fMRI signal as an index of cortical recovery, correlations to the electrical field map were determined. Significant correlations between the electrical field and change in fMRI signal were region specific including cortical areas under the anode electrode and peri-lesional visual areas. These patterns were consistent with effective tDCS facilitated rehabilitation. We describe the methodology used to analyze tDCS mechanisms through combined fMRI and computational modeling with the ultimate goal of developing a rationale for individualized therapy.

Clinical impact of a real-time PCR assay for rapid identification of Staphylococcus aureus and determination of methicillin resistance from positive blood cultures.

The full identification and susceptibility profile of staphylococci from positive blood cultures (BCs) generally takes 24-48 h using phenotypic methods. The aim of this prospective study was to evaluate the clinical impact of a real-time PCR strategy for rapid identification of staphylococci and determination of methicillin resistance directly from positive BCs. During a 12-month period, 250 episodes of positive BCs with organism morphology resembling staphylococci were enrolled. Two strategies were compared: conventional (n = 128) using standard phenotypic methods or rapid (n = 122) using a real-time PCR assay that is able to detect specific genes of Staphylococcus aureus (nuc and sa442) and the encoding gene for methicillin resistance (mecA). Overall, 97 episodes (39%) were clinical-significant bloodstream infections. The prevalence of methicillin resistance of S. aureus was 24%. A favorable outcome (defined as clinical cure with resolution of signs and no evidence of recurrence or relapse at 12 weeks follow-up) was observed in similar proportions of episodes with (58%) or without (60%) PCR testing (p 0.8). In multivariate analyses, age and infection due to methicillin-susceptible S. aureus (adjusted OR 0.96, 95% CI 0.93-0.99; and adjusted OR 3.11, 95% CI 1.12-8.65, respectively) were the unique factors independently associated with a favorable outcome. Among the 153 episodes of contaminated BCs, similar proportions received unjustified antibiotic therapy (PCR strategy: 17%, conventional testing: 10%; p 0.33). In a setting with a moderate level of methicillin-resistant S. aureus and relatively high contamination of BCs, real-time PCR testing was not beneficial compared to conventional methods.

Development of a cortical visual neuroprosthesis for the blind: the relevance of neuroplasticity.

Clinical applications such as artificial vision require extraordinary, diverse, lengthy and intimate collaborations among basic scientists, engineers and clinicians. In this review, we present the state of research on a visual neuroprosthesis designed to interface with the occipital visual cortex as a means through which a limited, but useful, visual sense could be restored in profoundly blind individuals. We review the most important physiological principles regarding this neuroprosthetic approach and emphasize the role of neural plasticity in order to achieve desired behavioral outcomes. While full restoration of fine detailed vision with current technology is unlikely in the immediate near future, the discrimination of shapes and the localization of objects should be possible allowing blind subjects to navigate in a unfamiliar environment and perhaps even to read enlarged text. Continued research and development in neuroprosthesis technology will likely result in a substantial improvement in the quality of life of blind and visually impaired individuals.

Higher-order motion processing in the pulvinar.

Thalamic nuclei have long been considered as passive relay stations for sensory signals en route to the cerebral cortex, where higher level processing occurs. In recent years, it has been proposed that thalamic nuclei may actively participate in the processing of specific information in conjunction with cortical areas. In support of this hypothesis, we recently discovered that neurons in the main extrageniculate visual nucleus, the pulvinar, exhibit higher-order visual properties that were, until now, only associated with higher-order cortical areas. Pulvinar neurons can indeed code the veridical direction of a moving plaid pattern, indicating that these cells can integrate ambiguous signals into a coherent percept. This finding as well as our demonstration that there are cortico-thalamo-cortical loops involved in complex motion analysis open promising avenues in unraveling the function of the pulvinar complex in normal vision.

Responses of neurons in the cat posteromedial lateral suprasylvian cortex to moving texture patterns.

The posteromedial lateral suprasylvian cortex represents a point of convergence between the geniculostriate and extrageniculostriate visual pathways. Given its purported role in motion analysis and the conflicting reports regarding the texture sensitivity of this area, we have investigated the response properties of cells in PMLS to moving texture patterns ("visual noise"). In contrast to previous reports, we have found that a large majority of cells (80.1%) responds to the motion of a texture pattern with sustained discharges. In general, responses to noise were more broadly tuned for direction compared to gratings; however, direction selectivity appeared more pronounced in response to noise. The majority of cells was selective for drift velocity of the noise pattern (mean optimal velocity: 26.7 degrees /s). Velocity tuning was comparable to that of its principal thalamic input, the lateral posterior pulvinar nucleus. In general, responsiveness of cells in the posteromedial lateral suprasylvian cortex increased with increasing texture element size, although some units were tuned to smaller element sizes than the largest presented. Finally, the magnitude of these noise responses was dependent on the area of the visual field stimulated. In general, a stimulus corresponding to roughly twice the size of the receptive field was required to elicit an equivalent half-maximal response to that for gratings. The results of this study indicate that the majority of cells in the posteromedial lateral suprasylvian cortex can be driven by the motion of a fine texture field, and highlight the importance of this area in motion analysis.

Motion integration in a thalamic visual nucleus.

Thalamic nuclei have long been regarded as passive relay stations for sensory information en route to higher level processing in the cerebral cortex. Recently, physiological and theoretical studies have reassessed the role of the thalamus and it has been proposed that thalamic nuclei may actively participate with cortical areas in processing specific information. In support of this idea, we now show that a subset of neurons in an extrageniculate visual nucleus, the lateral-posterior pulvinar complex, can signal the true direction of motion of a plaid pattern, indicating that thalamic cells can integrate different motion signals into a coherent moving percept. This is the first time that these computations have been found to occur outside the higher-order cortical areas. Our findings implicate extrageniculate cortico-thalamo-cortical loops in the dynamic processing of image motion, and, more generally, as basic computational modules involved in analysing specific features of complex visual scenes.

Dose-dependent inhibitory effects of angiotensin II on visual responses of the rat superior colliculus: AT1 and AT2 receptor contributions.

Angiotensin II (Ang II) has traditionally been regarded as a peripherally circulating and acting hormone involved in fluid homeostasis and blood pressure regulation. With the rather recent localization of Ang II receptors within the mammalian brain, renewed interest has emerged in the hope of elucidating the central impact and function of this hormone. One region that has been clearly demonstrated to express Ang II receptors is the superior colliculus (SC). This mesencephalic structure plays an important role in sensory visuomotor integration. Receptors for Ang II (of both the AT1 and AT2 subtypes) have been localized within the superficial layers of this structure, i.e. the areas that are visually responsive. In the hopes of characterizing the role of Ang II in the SC, we have attempted to physiologically activate these receptors in vivo and observe the effects of Ang II on visually evoked responses. In the attempt to identify the receptor subtype(s) responsible in mediating these effects, Ang II was injected concomitantly with selective receptor ligands. Experiments were performed on adult rats prepared in classical fashion for electrophysiological studies. Through microinjection of Ang II, and the simultaneous recording of visually evoked potentials to flash stimulation, we have observed that this peptide yields a strong suppressive effect on visual neuronal activity. By injecting Ang II at various concentrations (10(-3)-10(-10) M), we have further observed that the effects of this peptide express a dose-related dependency. Injection of Ang II in progressively more ventral layers yielded less pronounced effects, demonstrating physiologically the discrete localization of these receptors in the stratum griseum superficiale. Coinjection of Ang II with Losartan yielded a near complete blockade of Ang II suppressive effects, suggesting that AT1 receptors play a prominent role in mediating these responses. However, coinjection of Ang II with PD 123,319 yielded a slight, yet significant partial blockade. Coinjection of Ang II with both the AT1 and AT2 receptor antagonists yielded a complete blockade of the Ang II effect. Finally, some of the results suggest that the AT2 receptor ligand CGP 42,112 may possess agonist properties. Taken together, these findings suggest that the AT1 receptor is predominantly involved in mediating Ang II responses in the SC and there also appears to be some indication of AT2 receptor involvement. However, the underlying mechanisms (such as receptor interactions), the exact specificity of the ligands used, and the possibility of other receptor subtype implication have yet to be explored fully.

Neuromodulatory effects of angiotensin II in the visual layers of the rat superior colliculus.

Recent autoradiographic studies have revealed the presence of both AT1 and AT2 angiotensin II (AngII) receptor subtypes in the superficial layers of the rat superior colliculus (SC). We have investigated the effects of activating these receptors on visually evoked potentials (VEP) in the SC of adult rats. A recording injecting microelectrode filled with AngII was lowered into the superficial layers of the SC. AngII was injected at concentrations varying from 10(-4) to 10(-10) M. Injection of the peptide yielded a reduction in the amplitude of the VEP. This reduction usually occurred within 2-3 min following AngII injection with a 50% recovery of most of the signal 20-30 min thereafter. AngII did not modify the signal when injected in collicular layers ventral to the stratum opticum. Furthermore, concomitant injection of AngII with the specific AT, receptor antagonist Losartan failed to reduce the evoked response suggesting that the effects of AngII in the SC are likely mediated by AT1 receptors.