T1‐Weighted MRI shows stage‐dependent substantia nigra signal loss in Parkinson's disease

Depigmentation of the substantia nigra is a conspicuous pathological feature of Parkinson's disease and related to a loss of neuromelanin. Similar to melanin, neuromelanin has paramagnetic properties resulting in signal increase on specific T1‐weighted magnetic resonance imaging. The aim of this study was to assess signal changes in the substantia nigra in patients with Parkinson's disease using an optimized neuromelanin‐sensitive T1 scan. Ten patients with Parkinson's disease and 12 matched controls underwent high‐resolution T1‐weighted magnetic resonance imaging with magnetization transfer effect at 3T. The size and signal intensity of the substantia nigra pars compacta were determined as the number of pixels with signal intensity higher than background signal intensity + 3 standard deviations and regional contrast ratio. Patients were subclassified as early stage (n = 6) and late stage (n = 4) using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr Parkinson's disease staging scale. The T1 hyperintense area in the substantia nigra was substantially smaller in patients compared with controls (?60%, P < .01), and contrast was reduced (?3%, P < .05). Size reduction was even more pronounced in more advanced disease (?78%) than in early‐stage disease (?47%). We present preliminary findings using a modified T1‐weighted magnetic resonance imaging technique showing stage‐dependent substantia nigra signal reduction in Parkinson's disease as a putative marker of neuromelanin loss. Our data suggest that reduction in the size of neuromelanin‐rich substantia nigra correlates well with postmortem observations of dopaminergic neuron loss. Further validation of our results could potentially lead to development of a new biomarker of disease progression in Parkinson's disease. © 2011 Movement Disorder Society     

Processing consequences of superfluous and missing prosodic breaks in auditory sentence comprehension

This ERP study investigates whether a superfluous prosodic break (i.e., a prosodic break that does not coincide with a syntactic break) has more severe processing consequences during auditory sentence comprehension than a missing prosodic break (i.e., the absence of a prosodic break at the position of a syntactic break). Participants listened to temporarily ambiguous sentences involving a prosody–syntax match or mismatch. The disambiguation of these sentences was always lexical in nature in the present experiment. This contrasts with a related study by Pauker, Itzhak, Baum, and Steinhauer (2011), where the disambiguation was of a lexical type for missing PBs and of a prosodic type for superfluous PBs. Our results converge with those of Pauker et al. (2011): superfluous prosodic breaks lead to more severe processing problems than missing prosodic breaks. Importantly, the present results extend those of Pauker et al. (2011) showing that this holds when the disambiguation is always lexical in nature. Furthermore, our results show that the way listeners use prosody can change over the course of the experiment which bears consequences for future studies.     

Effect of Wii-intervention on balance of children with poor motor performance

The purpose of this study was to investigate the effects of training with the Wii-balance board on balance and balance-related skills of children with poor motor performance. Twenty-nine children (23 boys, 6 girls; aged 7–12 years) participated in this study and were randomly assigned to an experimental and control group. All children scored below the 16th percentile on a standardized test of motor ability and balance skills (Movement Assessment Battery for children (M-ABC-2)). Before and after a six-week Wii-intervention (M = 8 h, 22 min, SD = 53 min), the balance skills of the experimental group and control group were measured with the M-ABC-2 and the Bruininks–Oseretsky test of motor proficiency (BOT-2). Both groups improved on all tests. The M-ABC-2 and the BOT-2 total balance-scores of the experimental group improved significantly from pre to post intervention, whereas those of the control group showed no significant progress. This resulted in significant interaction-effects, favoring the experimental children. No transfer-effects of the intervention on balance-related skills were demonstrated. Our findings showed that the Wii-balance board is an effective intervention for children with poor balance control. Further development and investigation of the intervention could be directed toward the implementation of the newly acquired balance-skills in daily life.     

High-frequency somatosensory thalamocortical oscillations and psychopathology in schizophrenia

Human cortical somatosensory evoked potentials (SEPs), which are presumably generated in afferent thalamocortical and early cortical fibers, reveal a burst of superimposed early (N20) high-frequency oscillations (HFOs), around 600 Hz. There is increasing evidence of an imbalance of thalamocortical systems in schizophrenic patients. In order to assess correlations between somatosensory evoked oscillations and symptoms of schizophrenia, we investigated median nerve SEPs in 20 inpatients and their age-matched and gender-matched healthy controls using a multichannel EEG. Dipole source analysis and wavelet transformation were performed before and after application of a 450-Hz high-pass filter. In schizophrenics, the maximum HFOs occurred with a significantly prolonged latency. There was also a higher amplitude (energy) in the low-frequency range of the N20 component compared with the controls. Importantly, amplitudes (energy) of HFOs were inversely correlated with symptoms of formal thought disorder and delusions. Alterations of the thalamocortical somatosensory signal processing in schizophrenia with absence of an early HFO - assumed to be of inhibitory nature - could indicate a dysfunctional thalamic inhibition with increased amplitudes of N20, paralleled by enhanced positive schizophrenic symptoms.     

Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.     

Measurements of HCV neutralizing antibodies and of HCV-specific CD4+ and CD8+ cells using hepatitis C virus pseudo-particles (HCVpp)

BackgroundFor the medical management, it would be of great relevance to get a diagnostic marker predicting the outcome of infection.ObjectivesFor this purpose, the envelope antigens of the individual HCV strain in a patient was tested for their capacity to induce neutralizing antibodies and cytotoxic T lymphocytes.Study designA system for the measurement of neutralizing antibodies as well as for the stimulation of a HCV-specific T-cell response using pseudo-typed HCV particles (HCVpp) was established. A report on results of a pilot study conducted with blood specimens of 19 chronically infected patients is also presented.ResultsNeutralization of HCVpp could be measured in nearly all HCV sero-positive patient samples. Nevertheless, in more than half of the patient samples (11/19), no HCV-specific CD4+ response was detectable. In addition, HCV-specific CD8+ response was measurable in most of the patients when HCVpp were used for T-cell stimulation. Although the same antigens (HCVpp) were used, there was no relevant correlation between neutralization titers and T-cell response.ConclusionOur study shows that HCVpp are appropriate antigens for specific stimulation of lymphocytes as well as for the investigation of antibody neutralization activity.     

Odor attributes change in relation to the time of the year. Cinnamon odor is more familiar and pleasant during Christmas season than summertime

Aim of the present study was to examine whether odor attributes like pleasantness and familiarity change in relation to the time of the year. In the first part of the study a total of 100 subjects answered to questions without odor presentation whether a certain odor was more related to summertime or Christmas season. Another 41 and 51 subjects rated the familiarity and hedonicity of 12 odors either during summertime or Christmas season, respectively. Importantly, this investigation was performed at the same place within a science museum during stable environmental conditions. Subjects reported that rose odor was more related to summertime, whereas orange, cinnamon, and cloves were more associated with Christmas season with cinnamon being most intimately connected to this time of the year. Moreover, subjects showed significantly higher familiarity and pleasantness ratings when they smelled cinnamon during the Christmas season than during summertime. Taken together, this study demonstrated that attributes of some odors change throughout the year.     

Chemokines and the microenvironment in neuroectodermal tumor–host interaction

Chemokines and chemokine receptors play an important role in immune homeostasis and surveillance. Altered or defective expression of chemokines and/or chemokine receptors could lead to a disease state including autoimmune disorder or cancer. Tumors from glioblastoma, melanoma, and neuroblastoma secrete high levels of chemokines that can promote tumor growth and progression or induce stromal cells present in the tumor microenvironment to produce cytokines or chemokines which, in turn, can regulate angiogenesis, tumor growth, and metastasis. On the other hand, chemokines secreted by tumor or stromal cells can also attract leukocytes such as dendritic cells, macrophages, neutrophils, and lymphocytes which may downmodulate tumor growth. New therapies that are aimed at limiting tumor growth and progression by attracting immune effector cells to the tumor site with chemokines may hold the key to the successful treatment of cancer, although this approach may be hampered by possible tumor growth-stimulating effects of chemokines.     

Significant risk of a second melanoma in patients with a history of melanoma but no further predisposing factors

It is a well-accepted fact that melanoma patients are prone to develop further melanomas. In a cohort of 535 melanoma patients, we determined the incidence of second melanomas, as well as risk factors known to be associated with melanoma development. A retrospective analysis of patients regularly consulting our melanoma care unit revealed second or even further melanomas in 5.6% (n = 30). When compared to the overall population, melanoma patients have at least a 30-fold increased risk for the development of a second melanoma. Twenty of these 30 patients revealed none of the known predisposing conditions for multiple melanomas.