Influence of spatial information on responses of tonically active neurons in the monkey striatum

Previous studies have demonstrated that tonically active neurons (TANs) in the primate striatum play an important role in the detection of rewarding events. However, the influence of the spatial features of stimuli or actions required to obtain reward remains unclear. Here, we examined the activity of TANs in the striatum of monkeys trained to make spatially directed movements elicited by visual stimuli presented ipsilaterally or contralaterally to the moving arm. Among 181 neurons responding to the trigger stimulus, 127 (70%) were nonselective for stimulus location and 54 (30%) responded to only one location of the stimulus. Most of the selective responses (63%) occurred when the stimulus was presented contralaterally to the moving arm. To examine whether TAN responses are related to the location of the stimulus or to the direction of the movement, we tested a subset of the trigger-responsive neurons (n = 44) in a condition that elicited reaching toward or away from the stimulus. By comparing TAN activity between the two conditions, we found that half of the responses can be interpreted as being related to the location of the stimulus, one quarter to the direction of movement, and one quarter to the context in which stimulus-movement combination occurs. These results demonstrate that TANs are not limited to motivational processing, but may play a role in the processing of spatial attributes of stimulus and/or movement as well. These response properties suggest that TANs are involved in the flexible shifting of motor responses during spatially directed behavior.     

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO,SITO, and AMCLI societies

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain diagnostic procedures, and antiviral intervention forced the panel to use the methods of consensus for shaping some recommendations. Recommendations concerning the two types of transplant were given for the following issues: assessment of pretransplant CMV serostatus, immunological monitoring after transplant, CMV prophylaxis with antivirals, CMV preemptive strategy, and CMV prophylaxis with immunoglobulin infusion and with adoptive immunotherapy. The questions raised by and the recommendations resulting from this consensus conference project may contribute to the improvement of certain crucial aspects of the management of CMV infections in allo‐HSCT and in SOT populations.     

Dravet syndrome: Early clinical manifestations and cognitive outcome in 37 Italian patients

Aims of our study were to describe the early clinical features of Dravet syndrome (SMEI) and the neurological, cognitive and behavioral outcome. The clinical history of 37 patients with clinical diagnosis of SMEI, associated with a point mutation of SCN1A gene in 84% of cases, were reviewed with particular attention to the symptoms of onset. All the patients received at least one formal cognitive and behavior evaluation. Epilepsy started at a mean age of 5.7 months; the onset was marked by isolated seizure in 25 infants, and by status epilepticus in 12; the first seizure had been triggered by fever, mostly of low degree in 22 infants; the first EEG was normal in all cases. During the second year of life difficult-to-treat seizures recurred, mostly triggered by fever, hot bath, and intermittent lights and delay in psychomotor development became evident. At the last evaluation, performed at a mean age of 16 ± 6.9 years, mental retardation was present in 33 patients, associated with behavior disorders in 21. Our data indicate that the most striking features of SMEI are: the early onset of seizures in a previously healthy child, the long duration of the first seizure, the presence of focal ictal symptoms, and sensitivity to low-grade fever. Diagnosis of SMEI may be proposed by the end of the first year of life, and a definite diagnosis can be established during the second year based on the peculiar seizure-favoring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between high seizure frequency and cognitive impairment support the role of epilepsy in the clinical outcome, even if a role of channelopathy cannot be ruled out.     

Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization

To test a prediction of our previous computational model of cortico‐hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI‐adapted category‐learning task that has two phases, an initial phase in which associations are learned through trial‐and‐error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning‐related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Hum Brain Mapp 35:3122–3131, 2014. © 2013 Wiley Periodicals, Inc .     

Calcitonin gene-related peptide as inflammatory mediator

Sensory neuropeptides have been proposed to play a key role in the pathogenesis of a number of respiratory diseases such as asthma, chronic obstructive pulmonary disease or chronic cough. Next to prominent neuropeptides such as tachykinins or vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) has long been suggested to participate in airway physiology and pathophysiology. CGRP is a 37 amino-acid peptide which is expressed by nerve fibers projecting to the airways and by pulmonary neuroendocrine cells. The most prominent effects of CGRP in the airways are vasodilatation and in a few instances bronchoconstriction. A further pulmonary effect of CGRP is the induction of eosinophil migration and the stimulation of beta-integrin-mediated T cell adhesion to fibronectin at the site of inflammation. By contrast, CGRP inhibits macrophage secretion and the capacity of macrophages to activate T-cells, indicating a potential anti-inflammatory effect. Due to the complex pulmonary effects of CGRP with bronchoconstriction and vasodilatation and diverse immunomodulatory actions, potential anti-asthma drugs based on this peptide have not been established so far. However, targeting the effects of CGRP may be of value for future strategies in nerve modulation.     

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience

PURPOSE: This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. METHODS: We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1-23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. RESULTS: Patients have been treated for 1-18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3-4 months on ketogenic diet. CONCLUSION: This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9-12 months.