A proto-architecture for innate directionally selective visual maps.

Self-organizing artificial neural networks are a popular tool for studying visual system development, in particular the cortical feature maps present in real systems that represent properties such as ocular dominance (OD), orientation-selectivity (OR) and direction selectivity (DS). They are also potentially useful in artificial systems, for example robotics, where the ability to extract and learn features from the environment in an unsupervised way is important. In this computational study we explore a DS map that is already latent in a simple artificial network. This latent selectivity arises purely from the cortical architecture without any explicit coding for DS and prior to any self-organising process facilitated by spontaneous activity or training. We find DS maps with local patchy regions that exhibit features similar to maps derived experimentally and from previous modeling studies. We explore the consequences of changes to the afferent and lateral connectivity to establish the key features of this proto-architecture that support DS.

Deterioration of the auditory brainstem response in children with type 3 Gaucher disease.

Enzyme replacement therapy (ERT) has improved the quality of life in patients with Gaucher disease (GD). An emerging concern is whether ERT can also halt the neurologic progression in type 3 GD. The authors examined the auditory brainstem response (ABR) in eight children with type 3 GD undergoing high-dose ERT and found a consistent deterioration in ABR response. They conclude that ERT does not halt brainstem degeneration and that alternative therapies must be sought.

Optimal impedance control for task achievement in the presence of signal-dependent noise.

There is an infinity of impedance parameter values, and thus different co-contraction levels, that can produce similar movement kinematics from which the CNS must select one. Although signal-dependent noise (SDN) predicts larger motor-command variability during higher co-contraction, the relationship between impedance and task performance is not theoretically obvious and thus was examined here. Subjects made goal-directed, single-joint elbow movements to either move naturally to different target sizes or voluntarily co-contract at different levels. Stiffness was estimated as the weighted summation of rectified EMG signals through the index of muscle co-contraction around the joint (IMCJ) proposed previously. When subjects made movements to targets of different sizes, IMCJ increased with the accuracy requirements, leading to reduced endpoint deviations. Therefore without the need for great accuracy, subjects accepted worse performance with lower co-contraction. When subjects were asked to increase co-contraction, the variability of EMG and torque both increased, suggesting that noise in the neuromotor command increased with muscle activation. In contrast, the final positional error was smallest for the highest IMCJ level. Although co-contraction increases the motor-command noise, the effect of this noise on the task performance is reduced. Subjects were able to regulate their impedance and control endpoint variance as the task requirements changed, and they did not voluntarily select the high impedance that generated the minimum endpoint error. These data contradict predictions of the SDN-based theory, which postulates minimization of only endpoint variance and thus require its revision.

Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consensus statements.

UNLABELLED: Gaucher disease is caused by defective activity of glucocerebrosidase. The resulting accumulation of glucocerebroside in the lysosomes of visceral macrophages in various tissue and organ compartments leads to multiple manifestations, including hepatosplenomegaly, anemia, thrombocytopenia, growth retardation and skeletal disease. The most prevalent form of Gaucher disease is the non-neuronopathic (type 1) variant, which lacks primary involvement of the central nervous system. Traditionally, this has been referred to as the 'adult type'; however, 66% of individuals with symptomatic non-neuronopathic Gaucher disease manifest in childhood. Onset in childhood is usually predictive of a severe, rapidly progressive phenotype and children with non-neuronopathic Gaucher disease are at high risk for morbid complications. Enzyme therapy with recombinant human glucocerebrosidase in childhood can restore health in reversible manifestations and prevent the development of irreversible symptoms. A heightened focus on pediatric Gaucher disease is therefore needed. Although some correlation has been found between genotype and phenotype, mutation analysis is of limited value in disease prognosis. Management of pediatric Gaucher disease should be underpinned by a thorough assessment of the phenotype at baseline with regular monitoring thereafter. Excluding neuronopathic disease is recommended as the first step. Subsequently, baseline evaluation should focus on staging of different storage tissues, particularly the bone the involvement of which results in the greatest long-term morbidity. These organ assessments are recommended because bone disease severity may not correlate with disease severity in other organs and vice versa. In addition, different organs may respond differently to therapy. Initial assessment of each organ system can enable setting of realistic and individualized goals. CONCLUSION: A thorough approach to baseline assessment will improve the understanding of childhood Gaucher disease, optimizing management to minimize impairment of growth and development and prevent irreversible symptoms.

Paediatric non-neuronopathic Gaucher disease: recommendations for treatment and monitoring.

UNLABELLED: In individuals with non-neuronopathic Gaucher disease, childhood manifestations are usually predictive of a more severe phenotype. Although children with Gaucher disease are at risk of irreversible disease complications, early intervention with an optimal dose of enzyme therapy can prevent the development of complications and ensure adequate, potentially normal, development through childhood and adolescence. Very few, if any, children diagnosed by signs and symptoms should go untreated. Evidence suggests that disease severity, disease progression and treatment response in different organs where glucocerebroside accumulates are often non-uniform in affected individuals. Therefore, serial monitoring of the affected compartments is important. This should include a thorough physical examination at 6- to 12-monthly intervals. Neurological assessment should be performed to rule out neurological involvement and should be undertaken periodically thereafter in children who are considered to have risk factors for developing neuronopathic disease. Haematological and biochemical markers, such as haemoglobin, platelet counts and chitotriosidase levels, should be assessed every 3 months initially, but when clinical goals have been met through treatment with enzyme therapy, the frequency can be reduced to every 12 to 24 months. Careful monitoring of bone disease is vitally important, as the resulting sequelae are associated with the greatest level of morbidity. By combining various imaging modalities, the skeletal complications of non-neuronopathic Gaucher disease can be effectively monitored so that irreversible skeletal pathology is avoided and pain due to bone involvement is diminished or eliminated. Monitoring must include regular psychosocial, functional status and quality-of-life evaluation, as well as consistent assessment of therapeutic goal attainment and necessary dosage adjustments based on the patient's progress. CONCLUSION: Through comprehensive and serial monitoring, ultimately, a therapeutic dose of enzyme therapy that achieves sustained benefits can be found for each child with non-neuronpathic Gaucher disease.

Vertical optokinetic nystagmus and saccades in normal human subjects.

PURPOSE: Optokinetic stimulation induces nystagmus that can be used to test the saccadic and visual-tracking systems in some patients with voluntary gaze palsies. The purpose of this study was to characterize vertical optokinetic nystagmus (OKN) in normal human subjects, comparing the dynamic properties of the quick phases with voluntary saccades of similar size and measuring the slow-phase responses to visual stimuli with a range of spatial and temporal frequencies. METHODS: Vertical OKN and saccades were recorded in 10 healthy adult subjects (age range, 24-54 years) using the magnetic search coil technique. The optokinetic (OK) stimulus subtended 72 degrees horizontally and 60 degrees vertically, consisted of black-and-white stripes with a spatial frequency of 0.04, 0.08, or 0.16 cyc/deg, and moved vertically at 10 to 50 deg/s. Vertical and horizontal saccades to visual targets separated by 1 degrees to 10 degrees were also elicited. RESULTS: Over 95% of quick phases were less than 10 degrees in amplitude; voluntary saccades of this amplitude range were slightly faster than quick phases of similar size. The amplitude-peak velocity relationships and amplitude-duration relationships of upward and downward fast movements (saccades or quick phases) were similar. Most vertical slow-phase OK responses showed greater gain for upward stimulus motion. OK gain decreased with increasing stimulus speed and increased spatial frequency, so that there was a general decrease in slow-phase velocity gain with increasing temporal frequency. CONCLUSIONS: In this study, the best OK responses were obtained using stripes with lower spatial frequencies and lower stripe speeds (0.4 cyc/deg at 10 deg/s). The dynamic properties of vertical quick phases of nystagmus are similar enough to those of voluntary saccades for OK stimulation to be used as a clinical test of the vertical saccadic system in individuals with voluntary gaze palsy.