An exploration of ocular fixation in Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy

Since the basal ganglia are thought to have a role in controlling ocular fixation it is expected that patients with parkinsonian conditions would show impaired performance in fixation tasks. Our study examines ocular fixation in patients with a range of parkinsonian conditions (Idiopathic Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy). Eye movements were recorded from 44 patients and 50 age matched control subjects during ocular fixation both with and without a visible target. The data for each patient were then characterised in terms of fixation periods and saccadic intrusions (SI). Patient groups exhibited larger and more frequent SI as well as greater displacement from the fixation target. Patients with Progressive Supranuclear Palsy exhibit larger SI than control subjects when fixation targets are visible, this difference is reversed in the absence of a fixation target. Patients with Multiple System Atrophy show increased frequency of SI both with and without a visible target. Our findings show that ocular fixation is impaired in patients with parkinsonian conditions and may prove useful as part of an oculomotor profile to aid with the differentiation of parkinsonian conditions.     

Pubertal testosterone influences threat-related amygdala–orbitofrontal cortex coupling

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala–orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala–OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed.     

Recombinant adeno-associated virus (AAV) drives constitutive production of glutamate decarboxylase in neural cell lines.

Many neurological disorders result directly or indirectly from the loss of inhibitory function. Engineering the production of GABA, an inhibitory neurotransmitter, may therefore be able at least partly to restore the lost inhibition seen in epilepsy, Parkinson's disease, or Huntington's disease. In this article, we describe a set of recombinant adeno-associated viruses (AAVs) that can deliver cDNAs encoding the GABA-producing enzyme, glutamate decarboxylase (GAD), directly into neural cells. We have characterized these recombinant AAVs in several cell lines derived from the CNS. These recombinant AAVs effectively transduced all neural cell lines, although with different efficiencies. Transduction occurred in both proliferating and nonproliferating cells, but actively proliferating cell lines had approximately six times greater transduction efficiency than nonproliferating cells. Furthermore, these AAVs maintained long-term expression of GAD in an astrocytic cell line for at least seven passages. These recombinant AAVs are promising vehicles for investigating the potential therapeutic effects of GABA in animal models of epilepsy and neurodegenerative diseases.     

Functional symptoms in inflammatory bowel disease and their potential influence in misclassification of clinical status

Background : Functional symptoms occur in inflammatory bowel disease probably more than in the general population. Existing disease indices rely heavily on symptoms that may be organic or functional. This may explain inconsistencies between recent therapeutic trials in inflammatory bowel disease. Clinically, misinterpretation can lead to over‐treatment of functional symptoms with potent agents, and to under‐treatment of inflammatory bowel disease when inflammatory features are more subtle. Aim : To assess functional symptoms in inflammatory bowel disease and to devise simple means of their evaluation. Methods : Patients with Crohn's disease, ulcerative colitis, and irritable bowel syndrome completed questionnaires, generating inflammatory bowel disease and irritable bowel syndrome indices. Data from outliers selected as exemplars were employed to create a new index. Results : One hundred and ninety patients completed questionnaires. Overall, Crohn's and irritable bowel syndrome patients had similar functional features. The new scoring system was based on the eight apparently discriminant symptoms. Prospective evaluation in a separate cohort of 180 inflammatory bowel disease patients yielded scores that are independent of established indices, inflammatory markers and psychometric scores. Conclusions : Patients with Crohn's report comparable rates of apparently functional symptoms to those with irritable bowel syndrome. A new score has been developed to help in their identification. This has the potential to guide therapeutic decisions and optimize future trial recruitment.