Contralateral white noise selectively changes left human auditory cortex activity in a lexical decision task

In a previous study, we hypothesized that the approach of presenting information-bearing stimuli to one ear and noise to the other ear may be a general strategy to determine hemispheric specialization in auditory cortex (AC). In that study, we confirmed the dominant role of the right AC in directional categorization of frequency modulations by showing that fMRI activation of right but not left AC was sharply emphasized when masking noise was presented to the contralateral ear. Here, we tested this hypothesis using a lexical decision task supposed to be mainly processed in the left hemisphere. Subjects had to distinguish between pseudowords and natural words presented monaurally to the left or right ear either with or without white noise to the other ear. According to our hypothesis, we expected a strong effect of contralateral noise on fMRI activity in left AC. For the control conditions without noise, we found that activation in both auditory cortices was stronger on contralateral than on ipsilateral word stimulation consistent with a more influential contralateral than ipsilateral auditory pathway. Additional presentation of contralateral noise did not significantly change activation in right AC, whereas it led to a significant increase of activation in left AC compared with the condition without noise. This is consistent with a left hemispheric specialization for lexical decisions. Thus our results support the hypothesis that activation by ipsilateral information-bearing stimuli is upregulated mainly in the hemisphere specialized for a given task when noise is presented to the more influential contralateral ear.     

Posttraumatic stress symptoms in parents of children with acute burns

OBJECTIVE: To develop a model of risk factors for posttraumatic stress disorder (PTSD) symptoms in parents of children with burns. METHODS: Immediately following the burn and 3 months later, parents reported on their children's and their own psychological functioning and traumatic stress responses. RESULTS: Approximately 47% of the parents reported experiencing significant posttraumatic stress symptoms 3 months after the burn. Our model indicates three independent pathways to PTSD symptoms (i.e., parent-child conflict, parents' dissociation, and children's PTSD symptoms). Additionally, parents' anxiety predicted increased parent-child conflict, conflict with extended family and size of the burn predicted parents' dissociation, and size of the burn and children's dissociation predicted children's PTSD symptoms. CONCLUSIONS: This study suggests that many parents of children with burns suffer from posttraumatic stress symptoms. Interventions that target factors such as family conflict, children's symptoms, and parents' acute anxiety and dissociation may diminish the risk for PTSD.     

Learning and transfer of bimanual multifrequency patterns: effector-independent and effector-specific levels of movement representation

Current behavioural theories consider that during motor learning, an effector-independent memory representation of the acquired skill is built up. Using a transfer paradigm, we addressed the nature of the memory representation for a 2:1 multifrequency co-ordination task, requiring, for example, the left arm to cycle twice as fast as the right. After learning this 2:1 pattern, transfer to its converse pattern (i.e., the right arm cycles twice as fast as the left) revealed powerful evidence for negative transfer. The converse task arrangement revealed similar effects. These observations suggest a reconsideration of current viewpoints on movement representations, which emphasize effector independence. Based on the present findings, we propose a new model of motor memory, consisting of an abstract, effector-independent and an effector-specific layer. The abstract code is hypothesized to represent general spatiotemporal movement features, whereas the specific representation refers to effector-related movement commands. This concept is consistent with recent neuroscientific evidence in animal and human species, and invites a reconsideration of current behavioural theories of motor learning and memory.     

Characterization of the putative cholesterol transport protein metastatic lymph node 64 in the brain

Intracellular management of cholesterol is a critical process in the brain. Deficits with cholesterol transport and storage are linked to neurodegenerative disorders such as Neimann-Pick disease type C and Alzheimer's disease. One protein putatively involved in cholesterol transport is metastatic lymph node 64 (MLN64). MLN64 localizes to late endosomes which are part of the cholesterol internalization pathway. However, a detailed pattern of MLN64 expression in the brain is unclear. Using immunocytochemical and immunoblot analyses, we demonstrated the presence of MLN64 in several tissue types and various regions within the brain. MLN64 immunostaining in the CNS was heterogeneous, indicating selective expression in discrete specific cell populations and regions. MLN64 immunoreactivity was detected in glia and neurons, which displayed intracellular labeling consistent with an endosomal localization. Although previous studies suggested that MLN64 may promote steroid production in the brain, MLN64 immunoreactivity did not colocalize with steroidogenic cells in the CNS. These results demonstrate that MLN64 is produced in the mouse and human CNS in a restricted pattern of expression, suggesting that MLN64 serves a cell-specific function in cholesterol transport.     

Density-dependent decay in HIV-1 dynamics

The decay of HIV-1-infected cell populations after treatment with antiretroviral therapy has been measured using simple exponential decay models. These models are unlikely to be realistic over periods longer than a few months, however, because the population dynamics of HIV are complex. We considered an alternate model developed by Perelson and colleagues that extends the standard model for biphasic viral load decline and allows for nonlinear log decay of infected cell populations. Using data from 6 children on highly active antiretroviral therapy (HAART) and a single parameter in the new model, the assumption of log linear decay of infected cell populations is tested. Our analysis indicates that the short-lived and long-lived infected cell populations do not decay according to a simple exponential model. Furthermore, the resulting estimates of time to eradication of infected cell compartments are dramatically longer than those previously reported (eg, decades vs. years for long-lived infected cell populations and years vs. weeks for short-lived infected cell populations). Furthermore, estimates of the second-phase decay rates are significantly different than 0 for most children when obtained using the Perelson biphasic decay model. In contrast, this rate is not significantly different than 0 when the density-dependent decay model is used for parameter estimation and inference. Thus, the density-dependent decay model but not the simple exponential decay model is consistent with recent data showing that even under consistent HAART-mediated suppression of viral replication, decay rates of infected cell reservoirs decay little over several years. This suggests that conclusions about long-term viral dynamics of HIV infection based on simple exponential decay models should be carefully re-evaluated.     

Lateralized deficit of response inhibition in early-onset schizophrenia

BACKGROUND: The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence of executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS). METHODS: Twenty-one adolescents with the onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized as paranoid (n = 10) and undifferentiated subtypes (n = 11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response. RESULTS: The undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT. CONCLUSIONS: Our results indicate a specific lateralized impairment of response inhibition in patients with undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement.     

Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators

The role of neutrophils in the immune response has long been regarded as mainly phagocytic, but recent publications have indicated the production of several cytokines by polymorphonuclear leucocytes (PMN). The results of the individual reports, however, vary considerably. In this study, we established a cytokine profile of pure human neutrophils and demonstrated that minor contamination of peripheral blood mononuclear cells (PBMCs) in PMN preparations can lead to false-positive results. In our hands, peripheral blood PMN fail to produce the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Instead, they secrete large amounts of the chemokine IL-8 and the anti-inflammatory IL-1 receptor antagonist (IL-1ra). Additionally, PMN preparations of a high purity show production of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and growth-related oncogene-alpha (GRO-alpha), as well as macrophage colony-stimulating factor (M-CSF). The neutrophil therefore represents a novelty by producing the antagonist of IL-1beta (i.e. IL-1ra) in the absence of IL-1beta itself. To support our results, we differentiated stem cells from human cord blood into PMN and monocytes, respectively. These in vitro-differentiated PMN showed the same cytokine profile as peripheral blood PMN lacking IL-1beta, while differentiated monocytes produced the expected IL-1beta in addition to IL-1ra. The clear anti-inflammatory nature of their cytokine profile enables PMN to antagonize pro-inflammatory signals in experimental conditions. It is therefore possible that PMN play a key role in immune regulation by counteracting a dysregulation of the inflammatory process. Clinical studies, in which administration of recombinant G-CSF had a favourable effect on the outcome of severe infections and even sepsis without worsening inflammation, could thus be explained by our results.     

Responses of monkey vestibular-only neurons to translation and angular rotation

Single-unit recordings were obtained from central vestibular neurons in three monkeys during passive head movements. Neurons that discharged in relation to head translation or changes in head orientation, but not eye movement ("vestibular-only," n = 154), were examined in detail. Neuronal discharge rates were analyzed during four stimulus conditions: sinusoidal head translation in the horizontal plane (0.2-4 Hz, 0.2 g peak acceleration), static head tilt in the vertical plane (+/-20 degrees ), oscillatory head tilt (0.5-2 Hz), and sinusoidal angular rotation about an earth-vertical axis (0.5 or 1 Hz). Vestibular-only cells were divided into two groups based on the regularity of their spontaneous discharge rates (CV*). One group (low-sensitivity units) exhibited regular discharge rates (CV* < 0.2), weak discharge modulation during head translation (<25 spikes . s(-1) . g(-1) at f = 1 Hz), and persistent discharge rates related to static head tilt (0.68 spikes . s(-1) . degrees (-1) of head tilt). The second group (high sensitivity neurons) exhibited irregular discharge rates (CV* > 0.2), strong discharge modulation during head translation ( approximately 100 spikes . s(-1) . g(-1) at f = 1 Hz), and little or no change in discharge rate during static head tilt (0.32 spikes . s(-1) . degrees (-1)). The firing rates of some neurons in both groups were modulated during rotation about an earth-vertical axis (42%), but the modulation was greater for neurons classified as high sensitivity units. Previous reports have described neurons similar to the high sensitivity group; however, the low sensitivity or tilt neurons have not previously been characterized. Significantly, recent theoretical models have predicted neurons with discharge patterns similar to those of low- and high-sensitivity neurons.     

Role of corvids in epidemiology of west Nile virus in southern California

The invasion of different southern California landscapes by West Nile virus (WNV) and its subsequent amplification to epidemic levels during 2004 enabled us to study the impact of differing corvid populations in three biomes: the hot Colorado desert with few corvids (Coachella Valley), the southern San Joaquin Valley (Kern County) with large western scrub-jay but small American crow populations, and the cool maritime coast (Los Angeles) with a large clustered American crow population. Similar surveillance programs in all three areas monitored infection rates in mosquitoes, seroconversion rates in sentinel chickens, seroprevalence in wild birds, numbers of dead birds reported by the public, and the occurrence of human cases. Infection rates in Culex tarsalis Coquillett and sentinel chicken seroconversion rates were statistically similar among all three areas, indicating that highly competent mosquito hosts were capable of maintaining enzootic WNV transmission among less competent and widely distributed avian hosts, most likely house sparrows and house finches. In contrast, infection rates in Culex pipiens quinquefasciatus Say were statistically higher in Kern and Los Angeles counties with elevated corvid populations than in Coachella Valley with few corvids. Spatial analyses of dead corvids showed significant clusters near known American crow roosts in Los Angeles that were congruent with clusters of human cases. In this area, the incidence of human and Cx. p. quinquefasciatus infection was significantly greater within corvid clusters than without, indicating their importance in virus amplification and as a risk factor for human infection. In contrast the uniform dispersion by territorial western scrub-jays resulted in a high, but evenly distributed, incidence of human disease in Kern County.